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This paper presents new theoretical results on global exponential stability of cellular neural networks with time-varying delays. The stability conditions depend on external inputs, connection weights and delays of cellular neural networks. Using these results, global exponential stability of cellular neural networks can be derived, and the estimate for location of equilibrium point can also be obtained. Finally, the simulating results demonstrate the validity and feasibility of our proposed approach.

Objective: Human leukocyte antigen (HLA) haploidentical bone marrow is a potential source of donor to children for its availability. The drawback is deleterious graft versus host disease (GVHD) reaction post transplantation because of the incompatibility of HLA antigen expression between donors and recipients, in which donor T lymphocyte is stimulated to proliferate and differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound without immunogenicity, which was used to modify various proteins covalently and to prepare the versatile blood type. If mPEG modification blocks the activation of T cells in grafts, GVHD reaction probably would become less serious and transplantation might become successful. The aim of this study was to verify the improvement of haploidentical bone marrow transplantation (BMT) in a murine model by using mPEG of certain concentration to modify the grafts., Methods: Male BALB/c mice were chosen as the donor, and female CB(6)F(1) mice as the recipient. There were three groups of mPEG modification, non-modification and irradiation control, and 20 mice in each group. The modified and non-modified mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to haploidentical lethally irradiated CB(6)F(1) mice via the tail vein. After the transplant, the hematopoietic recovery, survival rate, acute graft versus host disease (aGVHD) and chromosomal karyotype were analyzed and compared with controls., Results: Seventy-five percent (15/20) of mice survived in the group of mPEG modification, while only 40% (8/20) survived in the group without the modification (chi(2) = 5.01, P = 0.025). And 100% mice died in the group of the irradiation control within 2 weeks. The hematopoietic recovery in the group of mPEG modification was show n to be faster than that in the group without modification (P < 0.05). Histopathological examination of the skin, liver and intestine showed typical signs of aGVHD, but the GVHD grading in the group of modification was less severe. The recipient mice in both groups of transplantation surviving for more than 75 days showed complete donor-type implantation by the chimerism examination., Conclusion: The modification of grafts by mPEG could alleviate aGVHD and improve the survival rate of mice after the haploidentical bone marrow transplantation.

Objective: The prognosis for neuroblastoma in advanced stage is still poor, even under conventional chemotherapy. This study aimed to investigate if very high dose chemotherapy in conjunction with autologous peripheral blood stem cell transplantation and 13-cis-retinoic acid could get excellent results in children with high risk neuroblastoma., Methods: Six children, aged from 4 to 8 years, with stage IV neuroblastoma were included in the study. The duration of the illness before admission was 1 to 12 months. Primary sites of the diseases were in the abdominal cavity (n = 5) and thoracic cavity (n = 1). All of patients had bone marrow metastasis, and one had multiple bone metastasis and orbital metastasis. All of the patients received very high dose chemotherapy, surgery, local radiation (20-30 Gy), and autologous peripheral blood stem cell transplantation as well as 13-cis retinoic acid. Induction chemotherapy included vincristine 0.67 mg/(m2 x 24 h, x 3), cyclophosphamide 2.1 g/(m2 x 24 h, x 2) and doxorubicin 25 mg/(m2 x 24 h, x 3) for 4 courses. Drugs were given as 24 hour-continuous intravenous infusion. Etopside 200 mg/(m2 x 24 h, x 3) and cisplatin 50 mg/(m2 x 24 h, x 3) were given for 2 courses. Conditioning regimen included carboplatin 400 mg/(m2.d) for 4 days, etoposide 300 mg/(m2.d) for 4 days and melphalan 70 mg/(m2.d) for 3 days. 13-cis retinoic acid 160 mg/(m2.d) started on +59 days for 6 courses, each course including 14 days therapy and 14 days rest., Results: Six patients got a complete response before stem cell transplantation. Their bone marrow metastasis disappeared and so did bone and orbital metastasis. However, marrow suppression due to very high dose chemotherapy occurred in all of the patients, which lasted for 3-4 weeks for peripheral leukocyte recovery. Fever occurred after they finished 1/3 course of chemotherapy. Infection, however, was cured with the use of Fortum and Imipenem, ect. Autologous peripheral blood stem cell transplantation was initiated and successful in all cases. Follow-up studies revealed that all the patients were in CR status 4-18 months after transplant, and the cardiac and liver and renal functions were normal. Meanwhile, bone marrow was recovered or in the process of recovery., Conclusion: The new strategies focused on very high dose chemotherapy, autologous peripheral blood stem cell transplantation and biological therapy might be a good option for patients with advance neuroblastoma.

This paper proposes a constructive approach for finding arbitrary (real or complex) roots of arbitrary (real or complex) polynomials by multilayer perceptron network (MLPN) using constrained learning algorithm (CLA), which encodes the a priori information of constraint relations between root moments and coefficients of a polynomial into the usual BP algorithm (BPA). Moreover, the root moment method (RMM) is also simplified into a recursive version so that the computational complexity can be further decreased, which leads the roots of those higher order polynomials to be readily found. In addition, an adaptive learning parameter with the CLA is also proposed in this paper; an initial weight selection method is also given. Finally, several experimental results show that our proposed neural connectionism approaches, with respect to the nonneural ones, are more efficient and feasible in finding the arbitrary roots of arbitrary polynomials.

Experiments on cryptically chiral ethanes have indicated that the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) catalyzes the hydroxylation of ethane with total retention of configuration at the carbon center attacked. This result would seem to rule out a radical mechanism for the hydroxylation chemistry, at least as mediated by this enzyme. The interpretation of subsequent experiments on n-propane, n-butane, and n-pentane has been complicated by hydroxylation at both the pro-R and pro-S secondary C-H bonds, where the hydroxylation takes place. It has been suggested that these results merely reflect presentation of both the pro-R and pro-S C-H bonds to the hot "oxygen atom" species generated at the active site, and that the oxo-transfer chemistry, in fact, proceeds concertedly with retention of configuration. In the present work, we have augmented these earlier studies with experiments on [2,2-2H2]butane and designed d,l form chiral dideuteriobutanes. Essentially equal amounts of (2R)-[3,3-2H2]butan-2-ol and (2R)-[2-2H1]butan-2-ol are produced upon hydroxylation of [2,2-2H2]butane. The chemistry is stereospecific with full retention of configuration at the secondary carbon oxidized. In the case of the various chiral deuterated butanes, the extent of configurational inversion has been shown to be negligible for all the chiral butanes examined. Thus, the hydroxylation of butane takes place with full retention of configuration in butane as well as in the case of ethane. These results are interpreted in terms of an oxo-transfer mechanism based on side-on singlet oxene insertion across the C-H bond similar to that previously noted for singlet carbene insertion (Kirmse, W., and Ozkir, I. S. (1992) J. Am. Chem. Soc. 114, 7590-7591). Finally, we discuss how even the oxene insertion mechanism, with "spin crossover" in the transition state, could lead to small amounts of radical rearrangement products, if and when such products are observed. A scheme is described that unifies the two extreme mechanistic limits, namely the concerted oxene insertion and the hydrogen abstraction radical rebound mechanism within the same over-arching framework.

In order to obtain particulate methane monooxygenase (pMMO)-enriched membranes from Methylococcus capsulatus (Bath) with high activity and in high yields, we devised a method to process cell growth in a fermentor adapted with a hollow-fiber bioreactor that allows easy control and quantitative adjustment of the copper ion concentration in NMS medium over the time course of cell culture. This technical improvement in the method for culturing bacterial cells allowed us to study the effects of copper ion concentration in the growth medium on the copper content in the membranes, as well as the specific activity of the enzyme. The optimal copper concentration in the growth medium was found to be 30 to 35 micro M. Under these conditions, the pMMO is highly expressed, accounting for 80% of the total cytoplasmic membrane proteins and having a specific activity as high as 88.9 nmol of propylene oxide/min/mg of protein with NADH as the reductant. The copper stoichiometry is approximately 13 atoms per pMMO molecule. Analysis of other metal contents provided no evidence of zinc, and only traces of iron were present in the pMMO-enriched membranes. Further purification by membrane solubilization in dodecyl beta-D-maltoside followed by fractionation of the protein-detergent complexes according to molecular size by gel filtration chromatography resulted in a good yield of the pMMO-detergent complex and a high level of homogeneity. The pMMO-detergent complex isolated in this way had a molecular mass of 220 kDa and consisted of an alphabetagamma protein monomer encapsulated in a micelle consisting of ca. 240 detergent molecules. The enzyme is a copper protein containing 13.6 mol of copper/mol of pMMO and essentially no iron (ratio of copper to iron, 80:1). Both the detergent-solubilized membranes and the purified pMMO-detergent complex exhibited reasonable, if not excellent, specific activity. Finally, our ability to control the level of expression of the pMMO allowed us to clarify the sensitivity of the enzyme to NADH and duroquinol, the two common reductants used to assay the enzyme.

Objectives: To explore the relation between tumor TNM of pancreatic cancer and treatment, and to summarize the experience in diagnosis and treatment of pancreatic cancer., Methods: The data on 321 patients with pancreatic cancer treated at our hospital between January 1990 and December 2000 were reviewed retrospectively. Radical resection and survival for various TNM stages were analyzed., Results: The rates of radical resection for stage I, stage II, stage III, stage IVA, and stage IVB were 100%, 100%, 82.6%, 12.3% and 2.1% respectively. The 1-, 3- and 5-year survivals of stage I, II were 73.3%, 40.0% and 30.0% respectively, and higher than those of other groups., Conclusions: The patients with pancreatic cancer diagnosed early can undergo radical resection. The elevation of early diagnosis rate is significant for the improvement of survival.

Aging alters numerous aspects of circadian biology, including the amplitude of rhythms generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, the site of the central circadian pacemaker in mammals, and the response of the pacemaker to environmental stimuli such as light. Although previous studies have described molecular correlates of these behavioral changes, to date only 1 study in rats has attempted to determine if there are age-related changes in the expression of genes that comprise the circadian clock itself. We used in situ hybridization to examine the effects of age on the circadian pattern of expression of a subset of the genes that comprise the molecular machinery of the circadian clock in golden hamsters. Here we report that age alters the 24-h expression profile of Clock and its binding partner Bmal1 in the hamster SCN. There is no effect of age on the 24-h profile of either Per1 or Per2 when hamsters are housed in constant darkness. We also found that light pulses, which induce smaller phase shifts in old animals than in young, lead to decreased induction of Per1, but not of Per2, in the SCN of old hamsters.

Objective: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation., Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4+ and CD8+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients., Results: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not detected in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4+ and CD8+T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4+ and CD8+ T cells from the stable survivors after liver transplantation., Conclusions: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent immune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.

Objective: To summarize our clinical experience in liver transplantation while considering the background in this field in China., Methods: Ninety-five patients who had received liver transplantation from April 1993 to March 2002 were analyzed retrospectively. Three periods were defined objectively as period I (1993 - 1997), II (1999) and III (2000 - 2002). Operative techniques, recipients, original diseases, complications and survival rates were compared among the three periods., Results: Malignant liver lesions were the main cause for liver transplantation in period I and II. The ratio of number of malignant disease to total recipients decreased gradually from period I to III (100%, 53% and 35%, respectively). The 1-year survival rate in patients with benign liver disease was 85% and the total operative mortality was 5% in period III. The incidence of hepatitis B virus reactivation or reinfection was 24% twelve months after liver transplantation. Vascular complication decreased but biliary complications did not and remained a major long-standing problem. No veno-venous bypass technique was used in period III, and its advantages were obvious when comparing with those with veno-venous bypass in period I and II., Conclusions: Strict selection of recipients, fine operative technique, familiarity with various complications and correct therapeutic methods, prophylaxis of recurrence of hepatitis B and hepatocellular carcinoma are necessary to improve long-term results of liver transplantation in China.

Objective: To sum up the experience in liver transplantation in a period of ten years at a single center., Methods: We retrospectively reviewed the clinical records of 120 patients receiving liver transplantation from April 1993 to October 2002. The patients' clinical characteristics, surgical techniques, complications and survival were compared in the phases of 1993-1997 (phase I), 1999 (phase II), and 2000-2002 (phase III)., Results: Malignant liver diseases were major indications for liver transplantation in phase I (100%) and II (53.3%), but decreased markedly in percentage in phase III (34.0%). When compared with recipients in phase I and II, the survival of recipients with benign liver diseases in phase III was significantly improved with the 3-month, 6-month and 1-year survival rates of 85.7%, 84.5% and 83.1%, respectively. For patients with malignant liver diseases, the 3-month, 6-month and 1-year survival rates were 87.4%, 81.1% and 46.0%, respectively. The reinfection rate of hepatitis B virus was 24% 12 months after transplantation. With technical refinements, the incidence of postransplantation vascular complications has significantly decreased from 29.4% in phase I and II to 4.9% in phase III. Biliary complications remained one of the major obstacles to long-term survival. No veno-venous bypass was applied in phase III, providing a promising outcome., Conclusion: Strict selection of potential recipients, technical refinement, appropriate management of vascular and biliary complications, and prophylaxis of recurrences of hepatitis B and malignant liver diseases are important to obtain long-term survival of patients receiving liver transplantation in China.

Soluble major histocompatibility complex (MHC) class I antigens released from hepatocytes and the passenger leukocyte population of the liver allograft have both been considered as important contributors for spontaneous liver tolerance upon allogeneic transplantation into fully MHC-mismatched hosts. This study was conducted to delineate the role of "passenger leukocytes" (PL) as well as local intra-graft defence mechanisms of long-term accepted liver allografts in more detail. Orthotopic liver transplantation was performed in male inbred rats as follows (n = 4-6): (i) Lewis (LEW; RT1.(l)) --> LEW; (ii) DA (RT1.(av1)) --> DA; (iii) DA --> LEW; (iv) LEW --> DA; (v) LEW (10-Gy whole body irradiation [WBI], d-7) --> DA; (vi) LEW (10-Gy WBI, d-7) --> LEW; (vii) LEW (10-Gy WBI, d-7) --> LEW (parked for 36 hours) --> DA; and (viii) LEW (10-Gy WBI, d-7) --> DA (parked for 36 hours) --> DA. The model specifically investigated the role of PLs as potential contributors to liver tolerance as WBI destroys this nonresident liver population. Characterization of Fas/FasL expression and the frequency of apoptotic cell death was performed by immunohistochemistry and TUNEL staining. Reverse transcriptase-polymerase chain reaction, by the use of Fas and FasL-specific cDNA probes, was performed on isolated hepatocytes of tolerized and rejected livers at various time points after transplantation. Animal survival in the various experimental groups was calculated using Kaplan-Meier survival statistics and related log-rank statistics as follows: (i) < 100 days; (ii) > or = 100 days; (iii) > 100 days; (iv) 11.3 +/- 1.0 day; (v) 9.0 +/- 0.5 days; (vi) > 100 days; (vii) 5/6 > 100 days; and (viii) 8.0 +/- 1.5 days. Immunohistochemistry revealed high numbers of proliferating cells in tolerized liver allografts. Apoptotic cell death of hepatocytes could be detected in both rejecting and to a lower extent in tolerized animals. Conversely, only tolerized but not rejected liver allografts revealed upregulation of FasL-expression on hepatic parenchymal cells from day 3 onwards. Irradiated LEW livers, in turn, lose their ability to survive in allogeneic DA hosts (group v) whereas they survive in syngeneic hosts (group vi), indicating that irradiation itself does not destroy the liver parenchyma. Reconstitution of irradiated LEW livers with syngeneic (group vii) but not with allogeneic (group viii) PLs restored tolerance induction. The underlying mechanisms of immune-privilege observed with liver allografts appear to share characteristics of clonal exhaustion suggesting that alloreactive lymphocytes are depleted by AICD via the FasL/Fas signal transduction pathway. The high frequency of apoptotic lymphocytes found in the portal tract of tolerized (but not rejected) LEW grafts supposes that functional FasL expression on graft hepatocytes mediates specific elimination of graft-directed effector lymphocytes. This mechanism constitutes peripheral deletion as one of the possible tolerogenic mechanisms involved. Chimerical liver grafts consisting of donor (LEW) parenchyma and host (DA) passenger leukocytes lose their tolerogenic capacity. In contrast, syngeneic reconstitution with LEW-PLs, restores liver graft acceptance upon transplantation into allogeneic DA hosts. This phenomenon is not relying on the induction of micro- or macrochimeric hosts, as no LEW PLs were found in spleen, thymus or the blood compartment from long-term surviving DA rats. Thus, non-resident liver cells contribute significantly to liver graft acceptance. Subsequently, liver tolerance appears to be mainly induced in the graft itself.

Authentic propane with known position-specific carbon isotope composition at each carbon atom was subjected to hydroxylation by the particulate and soluble methane monooxygenase (pMMO and sMMO) from Methylococcus capsulatus (Bath), and the corresponding position-specific carbon isotope content was redetermined for the product 2-propanol. Neither the reaction mediated by pMMO nor that with sMMO showed an intermolecular (12)C/(13)C kinetic isotope effect effect on the propane hydroxylation at the secondary carbon; this indicates that there is little structural change at the carbon center attacked during formation of the transition state in the rate-determining step. This finding is in line with the concerted mechanism proposed for pMMO (Bath), and suggested for sMMO (Bath), namely, direct side-on insertion of an active "O" species across the C-H bond, as has been previously reported for singlet carbene insertion.

OBJECTIVE: To evaluate the relatinship between the expression of P51, P73 and the oncogenesis and development of human gastric carcinoma. METHODS: The expression of P73 mRNA were detected both in 32 human gastric carcinoma tissues and adjacent normal gastric tissues by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Overexpressions of P73 mRNA were found in 17/32 gastric carcinoma tissues,in 2/32 adjacent normal gastric tissues.The positive expression rate of P73 mRNA in gastric carcinooma tissues was significantly higher than in adjacent normal gastric tissues( P<0.01). However, a significant correlation was found between the positive expression rate of P73 mRNA in gastric carcinoma tissues and the TNM staging(P<0.05). THe low expressions of P51A mRNA and P51B were found in all gastric carcinoma tissues and adjacent normal gastric tissues. The expression of P51A in gastric carcinoma tissues were much higher than adjacent normal gastric tissues (P<0.05). The expression of P51B is no significant correlation was observed between gastirc carcinoma tissues and adjacent normal gastric tissues. CONCLUSION: The results suggest that there is an overexpression odf P73 and P51A mRNA in gastric cancer tissues, and their expressions is relationship with oncogenesis and developnment of gastric carcinoma.

Objectives: To prevent and early diagnose hepatitis B virus reinfection and recurrent hepatitis B following liver transplantation, and to discuss the further treatment of recurrent hepatitis B., Methods: Liver transplantation recipients received lamivudine for prophylaxis of HBV reinfection. Virological and biochemical data, serum HBV DNA, and immunohistological staining for HBsAg and HBcAg in liver biopsy specimens were tested in due time., Results: Five patients with hepatitis B virus reinfection and two patients with hepatitis B recurrence were observed after liver transplantation. One patient with recurrent hepatitis B developed chronic severe hepatitis B despite treatment. One patient improved after a series of treatment., Conclusions: Hepatitis B virus reinfection or recurrent hepatitis B following liver transplantation occurs mostly 6-12 months after operation. The diagnosis of hepatitis B recurrence should be taken into account when liver biochemical data becomes poor during this period. The treatment for recurrent hepatitis B after liver transplantation includes increased dosage of lamivudine, application of famciclovir, and other liver protection measures.

Objective: To investigate the variation of functions of the heart and lung during orthotopic liver transplantation (OLT)., Methods: Pulmonary artery cannula and right radial artery cannula were indewelled before anaesthesia and the parameters of hemodynamics in different periods were monitored. Analysis of variance was used to reveal the variation among the groups. T hypothesis test in paired data was used to compare the preoperative parameters with those in each period during operation and after operation respectively, and to compare the parameters immediately after operation with those in each period after operation respectively., Results: During the operation, heart rate increased, but blood pressure decreased significantly at the beginning of no-liver period, increased again in a short period and then increased progressively 12 h after operation. Pulmonary artery pressure (PAP) increased from before the no-liver period to 60 h after operation. Pulmonary wedge pressure changed in accordance with the variation of PAP. Cardiac output was maintained at a high-output level from before operation to 60 h after operation. Systemic vascular resistance (SVR) was within the normal limits before operation, whereas pulmonary vascular resistance (PVR) was lower than normal. In the no-liver period during the operation, SVR decreased significantly. Both SVR and PVR increased progressively and returned to normal postoperatively., Conclusions: The patients undergoing OLT have a high cardiac output and low resistance obstacle before and during the operation, and will recover gradually after operation. Monitoring hemodynamics during the peri-operative period is of significance in the prevention and treatment of pneumonedema and cardiac functional insufficiency.

We studied MLN (mesenteric lymph nodes) T cell phenotype and MLN T and B cells homing properties after murine AIDS (acquired immunodeficiency syndrome) infection. Our results showed an increase in the percentage of CD4+ cells expressing CD44, CD54 and LPAM-1. There was also a decrease in the proportion of CD8+ cells but an increase in the percentage of CD8+ CD54+ cells. An increased proportion of CD11b+ (Mac1) cells suggested the recruitment of macrophages. Murine AIDS MLN cells labeled with 125I-UDR migrated back to the MLN but did not preferentially migrate to the ILP (intestinal lamina propria). Simultaneous staining for BRDU and IgA confirmed the inability of murine AIDS MLN cells to home to the ILP. These data indicate that murine AIDS infection altered the mucosal immune system while modifying MLN T cell phenotype and MLN T and B cells migratory properties.

Objective: To sum up the preliminary experience in living related liver transplantation (LRLT)., Methods: A 9-month-old male infant with biliary atresia (BA) who had undergone an unsuccessful Kasai operation was defined as a candidate for LRLT. The donor was his 30-year-old mother. Her lateral lobe of the left liver was transplanted into the infant's body as the graft. The left branches of the portal vein, left hepatic artery and left hepatic vein of the graft were end-to-end anastomosed to the portal vein, hepatic artery proper and hepatic vein of the recipient respectively. Biliary drainage was reestablished via Roux-en-Y operation., Results: The donor retained her liver function within 2 weeks after the operation. Steroid and FK506 were prescribed in immunosuppressive therapy for the recipient. The blood bilirubin level of the infant decreased to normal 2 weeks after operation. No acute rejection occurred. Biliary leakage in the early period after the transplantation was controlled by drainage, and E.coli infection was effectively treated with antibiotics. The donor and recipient are in satisfactory condition to the present., Conclusion: LRLT is advisable for children with biliary atresia.

Objective: To summarize the experience of human orthotopic liver transplantation (OLTx) in treatment of patients with end-stage hepatic disease and their perioperative management., Methods: A retrospective analysis was made on OLTx performed in 77 patients from April 1993 to September 2001 in our department included combined liver-kidney transplantation (6 patients) and living related liver transplantation (2). Among them, 76 were adults and 1 was infant (67 males and 10 females). The donors included 75 non-heart beating donors and 2 living related donors. Veno-venous bypass was used only in 45 cases during the operation. immunosuppressive agents consisted of cyclosporine, cellcept, ALG corticosteroids and FK506., Results: The one-year survival rates of grafts and recipients with benign hepatic disease were 75%. The recipients this year are surviving with good function of grafts., Conclusion: Liver transplantation is the best therapeutic method for a large number of patients with end-stage hepatic disease in China.

Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation of fully allogeneic bone marrow or blood-borne stem cells is still associated with major obstacles, such as graft-versus-host disease or cytoreductive conditioning-related toxicity. Here we show that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation of a potentially alloreactive immune response sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts. Graft survival was strictly correlated with a state of mixed chimerism, which required functional thymic host competence. Our results provide a rationale for using preimplantation-stage stem cells as vehicles in gene therapy and for the induction of long-term graft acceptance.

Objective: To explore cytomegalovirus (CMV) infection in recipients of liver transplantation (LT)., Methods: 30 recipients of LT were screened for the appearance of CMV infection by using ELISA to test anti-CMV-Ab from serum samples and using immunohistochemistry method to test CMV antigen expression and nested-PCR to amplify CMV-DNA from blood samples., Results: Four of 243 samples taken from 30 recipients came out positive of anti-CMV IgG and anti-CMV IgM with a positive rate of 100% and 1.6% respectively. 85 samples resulted in CMV antigen expression (35.0%) with the average antigen index being 4.2+/-3.1/5 X 10(4) WBC. Besides, 99 samples were found to be positive by nested-PCR with a positive rate of 40.7%. 61 samples were found to be simultaneously positive in test of CMV antigen and DNA, with a rate of 25.1%., Conclusions: Infection of CMV is common in recipients of LT. Simultaneous screening of anti-CMV-Ab, CMV-Ag and CMV-DNA after liver transplantation is very important for early diagnosis of CMV infection.

Objective: To evaluate the current status of intestinal nematode infection in Shanghai and make recommendations for further control activities., Methods: Retrospective review of the control program was made based on the change of nematode prevalence in Shanghai area since the 1950s, and challenges under the current situation were analysed., Results: The intervention measures included chemotherapy, health education, sanitary disposal of human excreta and safe water supply. With the control strategy, socio-economical development and the change of farming patterns, the prevalence of intestinal nematode infection in population was reduced by 88.5%, from 62.6% in 1955 to 8.2% in 2000. Among them, ascaris infection decreased by 89.0%, from 52.1% to 6.3%, hookworm infection decreased by 99.0%, from 12.9% to 0.1%, but pinworm infection was still as high as 18.9% in 1999., Conclusion: Prevalence of nematode infection in Shanghai was considerably reduced. To match it with the current socio-economical development in the Municipality, however, more needs to be done. Sustainable control activities and surveillance are recommended.

Objective: This study was aimed to prepare the polyclonal antibodies against type II fimbriae of actinomyces viscosus 5951., Methods: Purified type II fimbriae of actinomyces viscosus 5951 were obtained by physical and chemical ways. Then antibodies against type II fimbriae were prepared through immunity of poly ways and tested by double immunodiffusion., Results: The molecular quality of type II fimbriae was 34ku.Concentration of antibodies against type II fimbriae reached 1:64 after immunity of poly ways., Conclusion: The molecular quality of type II fimbriae was 34ku.The titre of the antibodies was 1:64, and had mild cross reaction with type I fimbriae.

Objective: To study the changes of phonetic features of Chinese speech during head-down bed-rest (HDBR) simulated weightlessness., Method: During -6 degrees HDBR in 6 healthy subjects (20-30 years), acoustic-phonetic features were analyzed., Result: The duration of utterance was slightly increase in the first two days, and recovered after the fourth day of HDBR; mean energy decreased along with time of bed rest, t-tests showed that the decrease in energy of utterances was very significant; a decrease in fundamental frequencies under HDBR was also significant., Conclusion: There were certain changes in the acoustic phonetic features under HDBR, some of them were significant.

OBJECTIVE:To preliminarily analyse the subunits and molecular weight of fimbriae of actinomyces viscosus 5951.METHODS:To do the immunoblotting test of the only II fimbriae type of mutant strain of T14V.RESULTS:It showed that there was only one 31ku band,which indicated that the fimbriae of actinomyces viscosus 5951 was composed of the same subunits of 31ku molecular weight. CONCLUSION:According to the previous reports and results of present study,the molecular weight of fimbriae of actinomyces viscosus 5951 was speculated to be 124ku and the fimbriae was composed of 4 same subunits.

Background: Coronary spasm during cardiac catheterization is not unusual. The mechanism of spasm remains uncertain, but is considered to be multifactorial. Many researchers believe that coronary spasm that develops during catheterization is partly spontaneous and partly catheter-induced. Because catheter-induced spasm results from mechanical irritation, we tried to find the iatrogenic factors that predispose patients to coronary spasm during coronary angiography., Methods: Retrospectively, we reviewed the records of 7,295 patients who underwent coronary angiography at our hospital from June, 1983 to November, 1997; coronary spasm was documented in 30 patients, who became the study group. We randomly selected 41 patients who had normal coronary arteries as the normal control group. After reviewing cine films of coronary angiography, we compared these two groups for several parameters. These parameters included the length and diameter of the left main coronary artery (LMC), the angle between the LMC and the aorta, the angle between the catheter tip and the LMC, whether the catheter tip came into contact with the vascular wall and whether there was vessel wall bulging, catheter size and catheter/LMC ratio. This angiographic data and the demographic features, including age, sex, history of hypertension, diabetes mellitus, smoking, previous myocardial infarction, family history of coronary artery disease, cholesterol and triglyceride levels and chest pain character (exertional or rest pain) were compared between the study patient group and the control group., Results: The results disclosed that larger catheter size (7.1 +/- 0.6 mm vs 6.4 +/- 0.7 mm, p < 0.001), smaller LMC diameter (4.2 +/- 0.9 mm vs 4.9 +/- 1.0 mm, p = 0.004), larger catheter/LMC ratio (0.07 +/- 0.05 vs 0.05 +/- 0.03, p = 0.022), catheter contact with the vessel wall (27/30 vs 20/41, p < 0.001) and vessel bulging (18/30 vs 5/41, p < 0.001) were related to catheter-induced coronary spasm. We found that the catheter tip coming into contact with the vessel wall, vessel wall bulging and catheter/LMC ratio (odds ratio 8.92 x 10(14)) were statistically significant factors predisposing patients to catheter-induced coronary spasm., Conclusions: Multiple factors contribute to coronary spasm. Of those, mechanical or iatrogenic factors might predispose patients to spasm during coronary catheterization. These facts deserve our attention, because iatrogenically induced spasms may be avoided by meticulously selecting catheters and manipulating them gently.

Background: Increasing evidence shows that oxidized low-density lipoprotein (ox-LDL) might play an important role in the pathogenesis of atherosclerosis. Ox-LDL is immunogenic and induces an autoantibody, which we used as a tool for measuring the content of ox-LDL in vivo., Methods: Patients who were admitted for diagnostic cardiac catheterization for typical or atypical angina pectoris were enrolled in this study. After fasting for 12 hours, a venous blood sample was drawn from the antecubital vein for testing triglyceride, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and ox-LDL autoantibody. The ox-LDL autoantibody was quantified using an enzyme linked immunosorbent assay. All patients underwent coronary angiography. Those who had more than 50% angiographic coronary luminal stenosis, were grouped into the coronary artery disease (CAD) group., Results: Sixty-four patients were enrolled in the study (male/female = 46/18; mean +/- standard deviation, age, 64 +/- 9 years). The CAD group had a significantly higher level of ox-LDL autoantibody than the non-CAD group (494.0 +/- 355.0 mU/ml vs 258.1 +/- 196.8 mU/ml, p = 0.004). However, the other lipid profiles including triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol were not statistically different between the two groups. Forty-six patients in this study had an arterial blood sample taken from the femoral artery for testing ox-LDL autoantibody. There was no significant difference between the arterial and venous samples of ox-LDL autoantibody (385.2 +/- 333.3 mU/ml vs 399.3 +/- 339.5 mU/ml, n = 46, p = 0.530)., Conclusions: Ox-LDL autoantibody was significantly higher in the CAD group. Ox-LDL may prove to play a key role in the pathogenesis of atherosclerosis. Further study of Ox-LDL and its role in the process of atherosclerosis is warranted.

Objective. The changes of auditory effect on Chinese single syllables uttered by talker under combined condition of noise and vibration were investigated. Method. The intelligibility tests were made under three conditions (quiet, 0 dB and -6 dB S/N ratios). The utterances were recorded under combined factors of noise and vibration, single factor of noise or vibration, and the control condition. Result. As compared with control group, the decrease of speech intelligibilities in combined factors groups was significant. It also occurred in most cases as compared with the single factors groups. It showed that combined effects played greater roles as S/N decreased in listening environment. As S/N was -6 dB, the intelligibilities were less than 70 percent. Conclusion. The speech production will be changed under noise and vibration, and the changes will deteriorate communication, especially in adverse listening environment. The results have important implications for communication in aerospace and military environments.

Unlabelled: Bidirectional recognition of donor- and recipient-derived immunocompetent cells has been proven to play a pivotal role for the induction of long-term unresponsiveness to allogeneic grafts. This study investigated the fate of heterotopic heart grafts with respect to the timing of subtherapeutic doses of FK-506 and with respect to the time point and type of donor antigen application, leaving space for mutual adaptation of alloreactive lymphocytes, designated as the 'WOFIE-concept' (window of opportunity for immunological engagement), originally described by R Calne., Methods: Heterotropic heart transplantation was performed using male DA (RT1.a) donor and LEW (RT1.1) recipient rats in the following groups (n = 6). FK-506 was applied intramuscularly (i.m.) using doses of 2 mg/kg x body weight per day. Donor antigen application was performed either by DA blood transfusion, 2 ml intravenously (i.v.), or by i.v. transfusion of 5 x 10(7) DA splenocytes. (i) LEW --> LEW, untreated; (ii) DA --> LEW, untreated; (iii) DA --> LEW, FK-506 days 0, 4-7; (iv) DA --> LEW, FK-506 as group (iii) plus 2 ml of DA blood 6 h post-Tx; (v) same as group (iv) but DA blood transfusion 24 h post-Tx; (vi) DA --> LEW, FK-506 as group (iii) plus DA splenocytes 6 h post-Tx; (vii) same as group (vi) but DA splenocyte transfusion 24 h post-Tx; (viii) DA --> LEW, FK-506 days 0-4 and (ix) DA --> LEW, FK-506 as group (viii) plus DA blood 6 h post-Tx. Immunohistochemical stainings (APAAP-method) of the allografts and flow cytometric analysis of recipient spleens were performed electively 3, 7 and 14 days after organ reperfusion., Results: The mean graft survival differed significantly between groups and comprised (mean +/- SD days): (i) >100, (ii) 6.5 +/- 1.0, (iii) 31.6 +/- 12.1, (iv) 44.8 +/- 10.1, (v) 29.8 +/- 14.2, (vi) 27.2 +/- 4.7, (vii) 14.6 +/- 4.2, 17.5 +/- 4.2, (viii) 17.5 +/- 4.2 and (ix) 18.8 +/- 2.8 days. Prolongation of graft survival and long-term unresponsiveness (group iv) revealed a substantially different pattern of graft infiltration., Conclusions: Effective treatment with unspecific immunosuppressants like FK-506 can be substantially improved if (i) mutual antigen recognition between donor and recipient immunocompetent cells is warranted, (ii) donor-derived blood-borne antigens are given immediately after graft reperfusion, and (iii) the type of inoculated donor antigen has a strong impact on graft survival as splenocytes which contain a large population of professional antigen-presenting cells failed to prolong graft survival after interrupted FK-506 treatment.

Immunoglobulin (Ig)A provides the initial immune barrier to viruses at mucosal surfaces. Specific IgA interrupts viral replication in polarized epithelium during receptor-mediated transport, probably by binding to newly synthesized viral proteins. Here, we demonstrate by immunoelectron microscopy that specific IgA monoclonal antibodies (mAbs) accumulate within Sendai virus-infected polarized cell monolayers and colocalize with the hemagglutinin- neuraminidase (HN) viral protein in a novel intracellular structure. Neither IgG specific for HN nor irrelevant IgA mAbs colocalize with viral protein. Treatment of cultures with viral-specific IgA but not with viral-specific IgG or irrelevant IgA decreases viral titers. These observations provide definitive ultrastructural evidence of a subcellular compartment in which specific IgA and viral envelope proteins interact, further strengthening our hypothesis of intracellular neutralization of virus by specific IgA antibodies. Our results have important implications for intracellular protein trafficking, viral replication, and viral vaccine development.

Background: Autonomic dysfunction plays an important role in the pathogenesis, treatment and prognosis of congestive heart failure (CHF). Sympathomimetic amines have been widely used in the treatment of CHF, but reports on their autonomic effects in CHF are rare. This study was designed to evaluate the effects of dopamine and dobutamine on cardiac autonomic function as assessed by heart rate variability (HRV)., Methods: Twenty patients with symptomatic CHF (systolic dysfunction) were enrolled. After recording one-hour baseline electrocardiographs (ECGs), patients were randomly selected for either dopamine (4 micrograms/kg/minute, Group A) or dobutamine (4 micrograms/kg/minute, Group B) treatment for three days. On the third day, a 24-hour ambulatory ECG was recorded and a tilt-table test was performed. Only furosemide and nitrates were allowed for adjunctive therapy. HRV was measured before and after treatment in both time and frequency domains. Frequency-domain HRV was also measured during head-up tilt., Results: After treatment, all patients improved [New York Heart Association fraction (NYHA Fc) 3.7 to 2.0]. Group A patients had higher post-treatment 24-hour HRV than those in Group B. SDNN (standard deviation of the average normal RR intervals in the entire ECG recording), SDANN (standard deviation of the average normal RR intervals for all five minute segments of an entire ECG recording) and SDNN indices in Group A were significantly higher than in Group B (90 +/- 33 ms vs 41 +/- 12 ms, 78 +/- 32 ms vs 36 +/- 11 ms, and 37 +/- 19 ms vs 16 +/- 7 ms, respectively, all p < 0.05). rMSSD (the square root of the mean of the squared differences between adjacent normal RR intervals over the entire ECG recording) and pNN50 (percentage of differences between adjacent normal RR intervals that are greater than 50 ms computed over the entire ECG recording) were also higher in Group A patients, with borderline significance. All measurements of total frequency and low-frequency and high-frequency components tended to be higher in Group A than Group B, but this was only significant for total frequency amplitude (22.9 +/- 13.4 ms vs 10.9 +/- 6.1 ms, p < 0.05). Dopamine but not dobutamine treatment seems to restore the depressed circadian change in frequency-domain HRV classically seen in patients with CHF. The HRV change during head-up tilting did not differ between the two groups. Three patients in Group B showed non-sustained ventricular tachycardia on ambulatory ECG during the treatment period., Conclusions: Dopamine and dobutamine have comparable therapeutic effects in patients with CHF, but low-dose dopamine more favorably affects cardiac autonomic function.

In this paper, the local minima-free conditions of the outer-supervised feedforward neural networks (FNN) based on batch-style learning are studied by means of the embedded subspace method. It is proven that only if the rendition that the number of the hidden neurons is not less than that of the training samples, which is sufficient but not necessary, is satisfied, the network will necessarily converge to the global minima with null cost, and that the condition that the range space of the outer-supervised signal matrix is included in the range space of the hidden output matrix Is sufficient and necessary condition for the local minima-free in the error surface. In addition, under the condition of the number of the hidden neurons being less than that of the training samples and greater than the number of the output neurons, it is demonstrated that there will also only exist the global minima with null cost in the error surface if the first layer weights are adequately selected.

The mechanism with which the immune system of an immunocompetent host responds to Cryptosporidium parvum infection is still poorly understood. We have therefore investigated the immune response of adult immunocompetent C57BL/6 mice at Days 6 and 10 to postinfection during a self-limiting C. parvum infection. We evaluated the immune changes at the levels of intestinal intraepithelium and lamina propria as well as mesenteric lymph nodes. At Day 6 postinfection, there was a decrease in the production of IFN-gamma, IL-5, IL-6, and IL-10 by in vitro mitogen-stimulated intraepithelial lymphocytes. Moreover, an increase in the number of gammadelta-TCR+, CD8+, and cytoplasmic IgE+ cells in intestinal lamina propria was found. Concomitantly, a significant decrease in the number of cytoplasmic IgA+ and IgG+ cells was observed. These phenotypic changes may be associated with the cytokine-producing profile (decreased IL-4, IFN-gamma, and IL-10) by lamina propria lymphocytes. At Days 6 and 10 postinfection cytoplasmic IgA+ and IgG+ cell numbers remained. Nevertheless, the production of IL-5 and IL-10 by intraepithelial lymphocytes was higher than the noninfected control values; these changes may be associated with the decreased CD4+ cell numbers. In mesenteric lymphocytes IgG and IgA production in vitro was elevated while no changes were observed in cytokine production except for a significant decrease in IL-5. In conclusion, our results demonstrate that an immunocompetent defense mechanism leading to a successful recovery from C. parvum infection involved changes of T(H1)- or T(H2)-type cytokine production as well as alterations of the lymphocyte subpopulation at mucosal-associated lymphoid tissues.

Mouse hepatitis virus (MHV) is a pervasive pathogen that causes morbidity and mortality in mouse colonies worldwide. Although it is not a major cause of mortality in immunocompetent mice, infections from MHV strains of lower virulence can be fatal to athymic nude mice. The histopathologic features and alterations of serum biochemical parameters resulting from infection with a low-virulence MHV strain in severe combined immunodeficiency (scid) mice has not been well described. Thus we recently studied the disease caused by MHV-S in scid mice after intranasal inoculation. Mouse hepatitis virus infection in scid mice, which have severe defects of B and T cells, may be highly lethal, resulting in immediate mortality. However, our results indicate that scid mice survived for an average of 12 to 14 days after infection with doses of MHV up to 10(7) PFU/mouse. The virus caused a significant increase in serum enzyme activities and bilirubin concentration associated with histologically demonstrable hepatocellular injury at postinoculation days 3, 4, and 8. Furthermore, virus was detected in mouse liver homogenates and nasal and bronchial lavage specimens. These results provide valuable information regarding the histopathologic and biochemical consequences of MHV-S infection in scid mice.

The effect of positioning on pulmonary function has been previously evaluated, and the prone position has been reported to be preferable for neonates with various respiratory diseases. Studies in healthy neonates have yielded conflicting results. Using a crying pulmonary function test, we examined the effect of positioning on pulmonary function in healthy full-term neonates. Thirty-nine infants with a mean birthweight (+/- SD) of 3,140 +/- 379 g and a mean gestational age (+/- SD) of 39.8 +/- 1.6 weeks were investigated during the first 6 hours of life. Measurements were obtained in both supine and prone positions using a computerized volume-flow system. There were statistically significant decreases in crying vital capacity (CVC) and peak expiratory flow rate (PEF) in the prone compared with the supine position. However, there were no significant differences in forced expiratory flow rate at 75% (V(75)), 50% (V(55)), and 25% (V(25)) of vital capacity between the two positions. These results suggest that prone positioning decreases lung volume and increases resistance of upper airways. We conclude that healthy neonates should be in the supine posture for optimal ventilation.

In modern China the investigation and treatment of scoliosis began in the late 1970s. The incidence of scoliosis in the Chinese population of the Sichuan province was 0.064%, and the incidence of >10 degrees for Beijing students was 1.04%. The surgical treatment of scoliosis for 2122 patients reported in the Chinese literature was reviewed by the authors. In this study, the female to male ratio was 1.3:1, the incidence of idiopathic scoliosis was 67.7%, and the incidence of congenital scoliosis was 18.1%. The overall result showed that the correction rate after surgery in the coronal plane was approximately 50% using the Harrington, Luque, Dwyer, or Cotrel-Dubousset instrumentation techniques. However, it would be increased by >60% if a partial vertebrectomy was carefully done and the soft tissue in the concave side was released completely. The postoperative complications were approximately 20% with 0.24% of major spinal cord injury. Biologic and anatomic research of the spine has been done so that the quality of surgical implants can be improved in the future.

C57BL 6 mice inoculated with the murine leukemia retrovirus mixture, LP-BM5, rapidly produce murine AIDS with many functional similarities to human AIDS. Human HIV infection has recently been shown to inhibit thymocyte maturation. Therefore, the kinetics of the proliferation of thymocytes induced by Con-canavalin A (ConA) and levels of cytokines produced by in vitro ConA-stimulated thymocytes were examined during the progression of murine AIDS. The proliferation of thymocytes induced by ConA was significantly enhanced by retrovirus infection at 4 weeks post-infection compared to control, but significantly inhibited during 8-12 weeks post-infection. Release of IL-2 by ConA-stimulated thymocytes was significantly increased by retrovirus infection during 2-5 weeks post-infection and 11-18 weeks post-infection compared to control, but significantly decreased during 7-9 weeks post-infection. Secretion of IL-4 by ConA-stimulated thymocytes was significantly enhanced by retrovirus infection from 5 to 18 weeks post-infection compared to control. The level of IL-6 produced by ConA-stimulated thymocytes was significantly inhibited by retrovirus infection at the beginning of retrovirus infection (2-9 weeks), but significantly elevated after 11 weeks post-infection compared to control. Release of IFNgamma by ConA-stimulated thymocytes, however, was significantly enhanced during the whole period of retrovirus infection compared to control, while it surged at 13 weeks post-infection. We conclude that retrovirus infection affects the thymus, producing altered T-cell differentiation via the dysregulation of thymocyte cytokine secretion.

Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we reported that autoantibodies were elevated during the initiation phases of this murine retrovirus infection and bound peptide determinants corresponding to CDR1 of several TCR V beta-chains. Therefore, we designed studies to determine whether administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation of T cell function. Administration of the TCR V beta CDR1 peptide before murine retrovirus infection significantly prevented its suppression of splenic NK cell activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk postinfection. However, delaying peptide immunization until severe suppression of T and B cell mitogenesis had occurred did not restore their functions. Immunization with TCR V beta peptide prevents development of retrovirus-induced immune dysfunction, which suggests a possible pathogenic role of autoreactive T cells as regulatory elements.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in a liquid diet, significantly restored levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which were suppressed by retrovirus infection. Retrovirus infection elevated levels of IL-6 and IL-10 produced by splenocytes, which were significantly normalized by all levels of vitamin E supplementation, respectively. Increased levels of IL-6 and tumor necrosis factor-alpha, produced by splenocytes during progression to murine AIDS, were also significantly normalized by all levels of vitamin E supplementation. Vitamin E supplementation restored retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E supplementation also alleviated the AIDS symptoms: splenomegaly and hypergammaglobulinemia. These data indicate that dietary vitamin E supplementation at extremely high levels was not immunotoxic, and can modulate cytokine release and normalize immune dysfunctions during progression to murine AIDS. It should favorably affect host resistance and thereby retard the development of AIDS.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS, which is functionally similar to human AIDS. Vitamin E effects on immune functions, cytokine production and nutritional concentrations in retrovirus-infected mice were determined. Retrovirus infection inhibited release of interleukin-2 (IL) and interferon-gamma (IFN) and some immune functions, whereas it stimulated secretion of IL-4, IL-5, IL-6 and tumor necrosis factor-alpha (TNF) and immunoglobulin (Ig) production. Furthermore, retrovirus infection induced some nutritional deficiencies in the tissues. A 15-fold increase in dietary vitamin E largely restored concentrations of some micronutrients (vitamins A and E, zinc and copper) in the liver, intestine, serum and thymus. It also partially restored production of IL-2 and IFN-gamma by splenocytes. Retrovirus-induced elevated production of IL-4, IL-5 and IL-6 by splenocytes in vitro was normalized by vitamin E. Elevated release of IL-6, TNF-alpha, IgA and IgG produced by splenocytes in vitro during murine AIDS were also completely or partially normalized by vitamin E. Vitamin E also prevented retrovirus-induced suppression of splenocyte proliferation and natural killer cell activity. These data indicate that vitamin E supplementation during murine AIDS can help to ameliorate the disorders during murine AIDS, suggesting vitamin E usefulness in treatment of AIDS in humans.

A 15-fold increase in dietary vitamin E (160 IU/liter) normalized hepatic and serum levels of vitamin E normally reduced by retrovirus infection. It also significantly retarded development of splenomegaly and hypergammaglobulinemia induced by retrovirus infection, while significantly restoring release of interleukin-2 (IL) and interferon-gamma by splenocytes which are suppressed by retrovirus infection. Retrovirus infection elevated production of IL-4 and IL-6 by splenocytes, but this elevation was inhibited by vitamin E. Increased levels of IL-6 and tumor necrosis factor-alpha produced by splenocytes during progression to murine AIDS were also inhibited by vitamin E. Vitamin E supplementation also helped restore retrovirus-suppressed splenocyte proliferation. These data indicate that vitamin E supplementation can help overcome retrovirus-induced reduction in tissue vitamin E, modulate cytokine release, and normalize immune dysfunctions during progression to murine AIDS.

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably affecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160 IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and interferon-gamma by concanavalin A (Con A)-stimulated splenocytes and interleukin-6 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleukin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin-4 and interferon-gamma production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.

Modification of the mucosa-associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber-DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber-DeCarli diet had fewer CD8+ cells/villus than the chow-fed controls. Mice that received ethanol in the drinking water had fewer IgA-containing cells and CD8+ cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol-treated mice and their respective controls. Nevertheless, chow-fed control mice had more cells than those fed the Lieber-DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM-1+, and LECAM-1+ CD4+ cells, there was a decrease in the percentage of LECAM-1+ CD8+ cells in ethanol-fed mice when compared with their Lieber-DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber-DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber-DeCarli-fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4- CD8+ cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+ and IgA+ cells in the intestinal lamina propria, important in mucosal immune defenses.

Prolonged consumption of ethanol (ETOH) results in alterations of host defense via immune modulation, increasing susceptibility to infection. In the present study, effects of chronic dietary ETOH on cytokine production by splenocytes and thymocytes, splenocyte and thymocyte proliferation induced by mitogens, splenic natural killer cell activity, and antibody production (IgA and IgG) were examined. C57BL/6 mice were fed 5% ETOH v/v in the Lieber-DeCarli liquid diet for 11 weeks. Release of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon (IFN)-gamma produced by concanavalin A (Con A) stimulated splenocytes was significantly decreased, whereas secretion of IL-4 was slightly decreased by chronic dietary ETOH compared with controls. Production of tumor necrosis factor-alpha and IL-6 by lipopolysaccharide-stimulated splenocytes was significantly and slightly decreased by ETOH compared with controls, respectively. Splenocyte and thymocyte proliferation induced by Con A was significantly inhibited by ETOH, whereas splenocyte proliferation induced by lipopolysaccharide was not affected. Natural killer cell activity was significantly inhibited by ETOH compared with controls. The production of IgA and IgG by splenocytes were also significantly decreased by ETOH compared with controls. The levels of IL-2, IL-4, and IL-6 produced by Con A-stimulated thymocytes were significantly reduced by dietary ETOH compared with control, whereas production of IFN-gamma by thymocytes was not affected. Our results suggest that chronic dietary ETOH alters the cytokine release, thereby impairing immune response and T-cell maturation, which increase host susceptibility to infection.