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To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BA1-p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.

The whale shark Rhincodon typus is the world's largest fish and it occurs in tropical, subtropical and warm temperate waters. Here, the northernmost record of R. typus is reported, when it was found in the Sea of Okhotsk for the first time. This occurrence can be explained by the unusually high sea surface temperature during the summer of 2012.

BACKGROUND We studied the relationship between the recurrence rate of primary superficial bladder cancer and random biopsy. METHODS We performed transurethral resection of primary superficial bladder cancer in 144 patients, and in 55 of those cases a random biopsy was also performed. The non-recurrence rate was examined in many recurrence facters. RESULTS The non-recurrence rate in the group with random biopsy was not significantly different from that observed in the group (100 patients) without random biopsy (chi 2 test, Generalized Wilcoxon test and multivariate analysis). Because the intravesical instillation therapy is an important inhibition factor in the recurrence rate of the primary superficial bladder cancer, we further analysed the recurrence rate in two non treated groups with or without random biopsy (13 and 35 patients respectively). No significant difference in the rate of recurrence between the two groups was observed. However, we noted recurrence of bladder cancer at biopsy positions in 8/13 patients. CONCLUSION It appears that random biopsy may have an effect on the recurrence or the implantation of tumor cells. Further studies are needed to clarify whether random biopsy is a risk factor in the recurrence rate of primary superficial bladder cancer.

We evaluated the damage to the gastric epithelium produced by local ischemia-reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric ischemia was induced by clamping the left gastric artery. Use of radioactive microsphere technique revealed a significant reduction in blood flow induced only in the corpus (67% reduction). Because no measurable gross lesion was observed in this model, the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. In the absence of exogenous acid, the histological damage was minimum and could not be quantified. However, a significant increase in 51Cr-EDTA clearance was observed shortly after reperfusion in a manner that depended on the duration of ischemia. This increase in clearance reached a maximum approximately 10 min after reperfusion and returned rapidly toward control levels within 40-50 min after reperfusion. In the presence of exogenous acid, EDTA clearance increased significantly during ischemia, increased further during reperfusion, and did not recover for at least 60 min after reperfusion. The acid infused after reperfusion (no acid before reperfusion) did not significantly aggravate the mucosal damage that followed reperfusion. However, the acid infused before reperfusion (no acid after reperfusion) showed an effect on EDTA clearance similar to that induced by continuous acid perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

An MR-pathologic correlation of nine intrathoracic neurogenic tumors (three neurofibromas, four schwannomas, and two ganglioneuromas) was performed to characterize their MR appearances. The three types of intrathoracic neurogenic tumor were found to have characteristic appearances on MR images that should be helpful when establishing the differential diagnosis of posterior mediastinal tumors. The MR and histologic features of these tumors are illustrated and described in this essay.

We present additional evidence that plasma from patients with deep-seated mycoses contains (1-->3)-beta-D-glucan. Digestion of such samples with endo-(1-->3)-beta-D-glucanase completely abolished the ability of the plasma to activate factor-G, a horseshoe crab coagulation enzyme that is extremely sensitive to this polysaccharide. Measurement of plasma (1-->3)-beta-D-glucan is a promising method for the diagnosis of deep-seated mycoses and for monitoring the response of these infections to antifungal therapy.

Cyclopiazonic acid (CPA), a novel specific inhibitor of Ca(2+)-ATPase in muscle sarcoplasmic reticulum, shortened the Ca(2+)-dependent after-hyperpolarization (AHP) following a spike in the rat superior cervical ganglion. This inhibitory effect was reversible and dependent on concentrations between 1 and 5 microM. The AHP in the presence of 5 microM CPA was not depressed further by ryanodine, nor was it affected by repetitive stimulation. These results suggest that CPA inhibits the intracellular Ca2+ release, probably due to the depletion of Ca2+ stores induced by inhibition of the ATP-dependent Ca2+ pump.

The spike after-hyperpolarization (AH), which is linked to the Ca-activated K conductance system, in the rat superior cervical ganglion was examined by means of intracellular recording. The AH was shortened during repetitive stimulation of the cell at 1 Hz and reached a steady state within 10 sec. These changes in the AH disappeared after a part of the AH was depressed by 5 microM ryanodine. The steady state of AHs was dependent on the frequency of stimulation ranging from 0.005 Hz and 2 Hz: half depression was observed at 0.53 Hz. Half recovery time from the depression induced by conditioning stimuli at 2 Hz was approximately 14 sec. Caffeine (1 mM) or TEA (3 mM) enlarged the AH at low stimulation frequencies. Caffeine slightly shifted the frequency depressing the AH toward high frequencies, and TEA did not cause significant changes. These results suggest that the repetitive firing of cells decreases the intracellular Ca release by contributing to the generation of the AH, rather than by accelerating the loading of Ca to its storage sites.

Thoracic aortic injury caused by blunt chest trauma is often fatal. Although aortography had been inevitable for thoracic surgery until recently, image of computed tomography (CT) is often superior to aortogram nowadays. We present a case of 64-yaer-old man with blunt chest trauma by traffic accident, who was successfully diagnosed and operated without invasive aortography. Thoracic aortic rupture was suspected by plain chest X-ray. His enhanced CT showed the localized leakage of contrast media near the arterial ligament of aortic arch. Because his condition was critically ill, operation was performed immediately without aortography. There found Y-shaped tear at the distal aortic arch, and was replaced with a prosthetic graft. Operation was performed under left heart bypass using heparin-coated circuit and centrifugal pump. We would stress that the enhanced chest CT is sufficiently diagnostic in thoracic aortic trauma like the present case.

An asynptomatic 58-year-old male was admitted to the hospital because of an abnormal nodule in the left lung field on screening chest X-ray. Chest computed tomography (CT) showed a tumor shadow mass in the left lower lobe. Open biopsy was performed to diagnose the mass. The cytological diagnosis was low-grade malignant adenocarcinoma, underwent left lower lobectomy. The histological diagnosis was pulmonary adenocarcinoma of the fetal lung type which was one of pulmonary blastoma (PB). Recently, the concept of pulmonary blastoma has changed. It will be useful to investigate the old PB's case reports to classify new concept.

A 60-year-old man had sudden chest pain and right lower extremity pain. A diagnosis of acute aortic dissection (Stanford type A) with right lower extremity ischemia was made. An emergency ascending aortic and total arch replacement, right axillo-femoral bypass, and coronary artery bypass grafting was performed for acute aortic dissection, acute right iliac arterial occlusion, and acute myocardial infarction. Myonephropathic metabolic syndrome (MNMS) occurred 2 days after operation. The serum creatine kinase value increased over 68,000 U/l, hemodiafiltration was started on the 2nd postoperative day (POD). The patient fell into anuric state and hemodiafiltration was performed 3 times a week. Urination was obtained over 1,000 ml/day from the 25th POD and hemodiafiltration was not necessary any more. We emphasize that prompt operation including revascularization of ischemic leg should be performed in acute aortic dissection with extremity ischemia and also prompt hemodiafiltration to improve the prognosis of these disastrous lesion.

An extensive outbreak of staphylococcal food poisoning occurred in Kansai district in Japan. As many as 13,420 cases frequently ingested dairy products manufactured by a factory in Osaka City. The main ingredient of these dairy products was powdered skim milk manufactured by a factory in Hokkaido. Staphylococcal enterotoxin A (SEA) (< or = 0.38 ng/ml) was detected in low-fat milk and approx. 3.7 ng/g in powdered skim milk. The total intake of SEA per capita was estimated mostly at approx. 20-100 ng. The assumed attack rate was considerably lower than those reported in previous outbreaks. SEA exposed at least twice to pasteurization at 130 degrees C for 4 or 2 s retained both immunological and biological activities, although it had been partially inactivated. The present outbreak was unusual in that the thermal processes had destroyed staphylococci in milk but SEA had retained enough activity to cause intoxication.

Case 1. A 69-year-old male, who had undergone coronary artery bypass grafting with saphenous vein graft for acute myocardial infarction 16 years previously, was admitted into our hospital for heart failure and recurrent angina. Coronary angiography showed occlusion of the graft and 75% stenosis in the proximal circumflex artery. Left ventriculography showed end-diastolic volume of 216 ml and ejection fraction of 24%. Dor operation combined with redo coronary artery bypass grafting was performed. Postoperatively, the ejection fraction improved to 53% and the cardiac index improved from 1.8 to 2.2 l/min/m2. Case 2. A 67-year-old male, who had undergone double coronary artery bypass grafting using saphenous vein grafts for acute myocardial infarction 8 years previously, was admitted into our hospital for heart failure and recurrent angina. Coronary angiography showed occlusion of the 2 grafts and 99% stenosis of the proximal left anterior descending artery. Although the left ventricle was slightly dilated, echocardiography demonstrated a thrombus in the left ventricle. Dor operation was performed concomitantly with removing of the thrombus and redo coronary artery bypass grafting. Postoperatively, the ejection fraction improved to 68% and the cardiac index improved from 1.6 to 2.3 l/min/m2. When the patients underwent coronary artery bypass surgery with saphenous vein grafts for acute myocardial infarction, they could be susceptible to left ventricular asynergy and graft failure on the long run. Therefore, the patients who need redo coronary revascularization may be potential candidates for Dor operation, and they require close examination regarding the myocardial viability, volume and shape of the left ventricle.

Allergic airway eosinophilia is suppressed by cysteinyl leukotriene (CysLT) receptor (CysLT1 receptor) antagonists in several species including humans and guinea-pigs, suggesting that CysLTs are directly or indirectly involved in induction of the response.We examined the effect of CysLT antagonists (pranlukast and MCI-826) on antigen inhalation-induced eosinophilia in peripheral blood and lung, and on IL-5 activity in serum during late increase of airway resistance (late asthmatic response, LAR) in sensitized guinea-pigs.Guinea-pigs inhaled ovalbumin (OVA) + Al(OH)3 and OVA mists alternately for sensitization and challenge, respectively, once every 2 weeks. At the fifth challenge, the effects of CysLT antagonists and an anti-IL-5 antibody (TRFK-5) on the occurrence of LAR, and blood and lung eosinophilia, which appeared at 5 h after challenge, were examined. The time-course of IL-5 activity in the serum after the challenge was evaluated by measuring in vitro 'eosinophil survival prolongation activity'. The influence of CysLT antagonists on IL-5 activity was assessed.CysLT antagonists and TRFK-5 completely abolished blood and lung eosinophilia. LAR was suppressed by both MCI-826 and TRFK-5 by 40-50%. Sera obtained from sensitized, challenged animals 3 h and 4 h after challenge induced an obvious prolongation of eosinophil survival. The activity of the sera was completely neutralized by prior exposure to TRFK-5, suggesting that it reflected IL-5 activity. Increased IL-5 activity in the serum was inhibited by both pranlukast and MCI-826 by over 90%.CysLTs produced after antigen provocation sequentially induced IL-5 production from some immune component cells via CysLT1 receptor activation. Thus, it is likely that CysLTs indirectly cause antigen-induced eosinophilia through IL-5 production.

In surgical reconstruction for left ventricular asynergy after myocardial infarction, the conventional linear closure technique second to simple resection and endoventricular circular patch plasty, which is the so-called Dor technique, are commonly utilized. We assessed these techniques using an abnormally contracting segment (ACS) in the left ventriculogram.We reviewed 10 and 15 patients who underwent the linear technique (group L) and the Dor technique (group D), respectively. %ACS was determined as the percent ratio of both akinetic and dyskinetic chords among the total chords in the centerline method of regional wall motion analysis. A difference between preoperative and postoperative ejection fraction (EF) was generated by preoperative EF and this percentage ratio was determined as %EF.Postoperative EF improved from 31% to 41% in group L and from 33% to 49% in group D (p0.05). Postoperative EF in group D was higher than in group L (p0.05). %ACS decreased from 41% to 34% in group L and from 41% to 19% in group D (p0.05). Postoperative %ACS was lower in group D than in group L (p0.05). The significant correlation between preoperative %ACS and %EF was negative in group L and positive in group D (p0.05).The Dor technique is more effective for the postoperative systolic function than the linear technique because more extensive reduction in %ACS is possible with the Dor technique than with the linear technique. Dor technique becomes more crucial to the postoperative systolic function as the preoperative %ACS becomes larger.

The third ossification mode, known as transchondroid bone formation, is displayed chiefly in the bone morphogenetic protein (BMP)-induced heterotopic bone formation model. This paper describes the results of histopathological, histochemical, immunohistochemical, and in situ hybridization examinations of BMP-induced heterotopic bone in mice. The research focuses on the localization of typical matrix proteins (peptide and its mRNA) of cartilage and bone — type-I and type-II collagen, osteocalcin and osteopontin — in the chondroid bone matrix.

Gastric pit cells express mitogen oxidase1 (Mox1) and essential components for the phagocyte NADPH oxidase (p67-, p47-, p40-, and p22-phoxes). Helicobacter pylori (Hp) lipopolysaccharide (LPS) is a potent up-regulator of the Mox 1 oxidase. In this study, we examined the expression levels of several key members of the Toll-like receptor (TLR) family in primary cultures of guinea pig gastric pit cells. These cells expressed the TLR4 mRNA. Immunoblot analysis and immunofluorescence histochemistry with an anti-TLR4 antibody showed that gastric pit cells possessed significant amounts of TLR4 protein preferentially on the plasma membrane. In contrast, the cells did not express the TLR2 and TLR9 transcripts and did not contain detectable amounts of TLR2 protein. Neither peptidoglycan from Staphylococcus aureus nor Hp DNA with the CpG motif up-regulated Mox1 oxidase activity. Hp LPS activated nuclear factor-kappa B in association with the expression of cyclooxygenase II and tumor necrosis factor alpha transcripts. These findings suggest that TLR4 may play a crucial role in the initiation of inflammatory responses of gastric pit cells against Hp infection.

Sclerosing encapsulating peritonitis (SEP) is recognized as a serious complication of peritoneal dialysis. However, recovery is possible if an appropriate diagnosis and treatment are made. The term SEP is used most often, but is inaccurate, particularly the reference to peritonitis. A more accurate description would be "encapsulating peritoneal sclerosis" (EPS). From the therapeutic perspective, the diagnosis should be established before EPS develops. Early diagnosis is important. Furthermore, it is also important to determine the therapeutic tactics for EPS according to the disease stage. Most cases of EPS develop with manifestations of fever, increased levels of C-reactive protein (CRP), and slight ileus symptoms, accompanied by increased ascites ("inflammatory stage"). Following precise identification of the inflammatory stage, steroid administration should be initiated immediately with the onset of EPS. Methylprednisolone pulse therapy is recommended during the early stage. If the EPS is not relieved, or if it recurs within 1 month, the steroid dose should be decreased and the patient should be managed by total parenteral nutrition (TPN) ("encapsulating stage"). If ileus symptoms remain despite the absence of inflammatory findings and decreased ascites, laparotomy and enterolysis should be considered within 6 months ("ileus stage"). However, it is important that the enterolysis be performed without damaging the capsule-covered intestine. To date, we have successfully treated EPS in 18 of 19 patients using these options. In 3 patients, EPS was relieved by steroid administration. In 15 patients, EPS was relieved by total intestinal enterolysis. Enterolysis patients had satisfactory operative outcomes and eventually returned to their previous social activities. One patient experienced perforation of the small intestine and pan-peritonitis, and died of sepsis. In summary, EPS is not an incurable disease. It can be completely overcome by active diagnosis and treatment.

Pancreatic cancer remains one of the most formidable tumors defying early detection and effective treatment. Long-term survivors, however, do exist after resection. We investigated the clinicopathologic features of patients with pancreatic cancer who survived more than 5 years to draw out some suggestions concerning the indication of surgical treatment.We studied the clinicopathologic features of 13 patients with pancreatic cancer who survived more than 5 years after resection. We reviewed their clinical records to investigate preoperative symptoms, serum tumor markers, operative findings, postoperative adjuvant therapy, and modes of recurrence and survival periods. Information on the location, size, histology and spread of the primary tumors were mainly obtained from pathology reports.Histologic types of the long survivors included ductal adenocarcinoma of common type in 4 patients, mucinous noncystic adenocarcinoma in 2, intraductal papillary-mucinous carcinoma (invasive) in 4, undifferentiated carcinoma in 1, endocrine tumor (islet cell carcinoma) in 1 and acinar cell carcinoma in 1. All 4 cases of ductal adenocarcinoma of the common type showed a moderate invasion either to the retroperitoneum, the portal vein or the duodenum. Two patients with mucinous noncystic carcinoma attained a long survival despite extensive invasion of the pancreatic stroma, although one died of peritoneal carcinomatosis. Two of 4 patients with intraductal papillary-mucinous cancer (invasive) died of peritoneal dissemination 6 and 11 years after resection, respectively. Three patients with cancer of other special histologic types, i.e., undifferentiated, well-differentiated endocrine carcinoma and acinar cell carcinoma, showed invasion of the portal vein and splenic artery, involvement of the retroperitoneum and a metastatic tumor in the liver, respectively.Whereas special histologic types including ductal variants tended to predispose to long-term survival, ductal adenocarcinoma of the common type had some chance of long survival even with invasion of the surrounding tissues.

Development of mixed chimerism by donor bone marrow transplantation (DBMT) has led to long-term tolerance of solid organ allografts in nonhuman primates. As an initial attempt to extend this approach to cellular transplant, islet transplant from the same donor was attempted in the recipient previously made tolerant to a kidney allograft.After the conditioning with ATG, total body irradiation, thymic irradiation, and splenectomy, DBMT was performed followed by 4 weeks of cyclosporine. Kidney transplantation and native nephrectomies were subsequently performed on day 89. After 2.8 years of DBMT, diabetes was induced by streptozocin (STZ) and islets from bone marrow and kidney donor were transplanted without immunosuppression.After DBMT, the recipient developed chimerism and no evidence of kidney rejection for more than 1000 days. STZ induced diabetes was reversed after the islet transplantation. Islet biopsies demonstrated insulin staining without rejection. Although the recipient became diabetic 300 days after islet transplantation, viable transplanted islets were found in the liver and under the kidney capsule without any evidence of rejection.Tolerance with a nonmyeloablative conditioning can allow successful pancreatic islet transplantation without immunosuppression. Because no histological evidence of rejection was identified, recurrent diabetes is presumed to be inadequate islet mass.

In November, 1999, U.S. Food and Drug Administration approved a highly sensitive CRP(hs-CRP) assay that could assist medical doctors to predict the risk of cardiovascular accidents. Many doctors are now interested in the assay and trying to elucidate the relationship between serum CRP levels and cardiovascular diseases. In the past, it was difficult to establish a valid reference interval of serum CRP because of the poor analytical sensitivity and difficulty in sampling reference individuals. We have established a reference interval of serum CRP for the hs-CRP assay(Dade Behring). The study population consisted of 7,224 individuals(21-81 years old) who received a regular medical check-up. Potentially abnormal samples were excluded, depending on the results of other laboratory tests related to serum CRP variation. The upper limit of the reference interval was 0.15 mg/dl. The serum CRP was higher in smokers than in non-smokers, especially in men.

Pleomorphic carcinoma of the pancreas is a rare tumor with an extremely poor prognosis. The mean survival time is reported to be approx 3 mo.A 56-yr-old Japanese man presenting with general fatigue, loss of weight, and high fever was found to have a large hypervascular mass in the body of the pancreas with regional lymph node metastases. Laboratory investigation revealed leukocytosis, elevated erythrocyte sedimentation rate (ESR), and high serum C-reactive protein (CRP). In addition to distal pancreatectomy, splenectomy and lymph node dissection were performed. Histology showed the presence of pleomorphic large cells with bizarre mono- or multinuclei, growing in sarcomatoid pattern without mutual cohesiveness. Another noticeable finding was massive lymphocytic infiltration of the stroma of the neoplasm. Immunohistochemically, the infiltrating lymphocytes consisted of cytotoxic type of T cells. In addition, in situ hybridization for Epstein-Barr virus-encoded RNA (EBAR-1) was not seen in the tumor cells or in lymphocytes. After surgery the patient did not undergo chemotherapy or radiotherapy. He has been well without recurrence for 8 yr.We report a case of pleomorphic carcinoma, possibly lymphoepithelioma-like carcinoma, of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection. Cytokine responses and cellular immunoreactivity may have contributed to a long-term survival, which is unusual in the common type of pleomorphic carcinoma of the pancreas.

Nonmyeloablative T cell depletion followed by donor bone marrow infusion has proved to be an effective approach to induction of mixed chimerism and tolerance of organ allografts in non-human primates. To help define the mechanisms involved we have compared T cell depletion with ATG versus anti-CD2 monoclonal antibody with respect to establishment of mixed chimerism and induction of tolerance.Both nonmyeloablative regimens included low dose total body irradiation (1.5 Gy x 2), thymic irradiation (7 Gy), splenectomy and kidney plus donor bone marrow transplantation, followed by a 4-week posttransplant course of cyclosporine. In addition, the ATG group (13 recipients) received antithymocyte globulin, although the LOCD2b group (10 recipients) were treated with an anti-CD2 monoclonal antibody (LOCD2b).In the ATG group, 11 of 13 monkeys developed multilineage chimerism and 9 survived for more than 100 days without kidney allograft rejection. In contrast, 0/10 monkeys in the LOCD2b group developed chimerism, 5 died of infection and 5 suffered progressive rejection; only 1 recipient survived beyond 100 days. Sequential monitoring of peripheral blood mononuclear cells revealed greater T cell (CD3+) depletion in the LOCD2b-treated animals compared to those receiving ATG. However, NK cells (CD16+CD8+) were significantly more depleted in the ATG group and NK function remained abrogated longer after ATG than LOCD2b treatment (3 weeks vs.5 days).Despite excellent T cell depletion by LoCD2b, ATG was more effective in inducing chimerism and tolerance. This difference correlated with anti-NK activity of the two reagents. These data suggest that NK cells may also resist engraftment of allogeneic bone marrow cells in this model.

Between 1991 and 1999, 23 cases underwent cardiac valve surgery concomitant with myocardial revascularization at our institution. Twelve cases (group I) had a primary valvular disease combined with coronary atherosclerosis, and other 11 cases (group II) were due to ischemic mitral insufficiency. There were 2 hospital deaths in group I (17%) and 4 in group II (36%). Three deaths in group II underwent left ventricular volume reduction surgery. On the basis of this observation, we concluded severe mitral regurgitation with ischemic cardiomyopathy was a particularly difficult management problem with disappointing clinical results. On the other hands, we considered concomitant revascularization should be done in the case of primary valvular disease when angiographically significant coronary artery stenosis was present.

Multilineage chimerism and long-term acceptance of renal allografts has been produced in non-human primates conditioned with a nonmyeloablative regimen. Our study was undertaken to evaluate the immunological and pathological status of long-term survivors and to define the role of splenectomy and of the primarily vascularized kidney in the regimen.Monkeys were treated with the basic regimen, including: total body irradiation, thymic irradiation, antithymocyte globulin, donor bone marrow transplantation, and a 4-week course of cyclosporine after which no further immunosuppression was given. They were divided into four groups according to the timing of kidney transplantation (KTx) and splenectomy as follows; group A (n=13): KTx and splenectomy on the day of donor bone marrow transplantation (day 0); group B (n=3): KTx on day 0 without splenectomy; group C (n=7): splenectomy on day 0 but delayed KTx until 3 to 16 weeks post-donor bone marrow transplantation; group D (n=3): both splenectomy and KTx delayed until day 120 post-donor bone marrow transplantation.In group A, 11 of 13 monkeys developed chimerism and 9 monkeys achieved long-term survival of 4 to 70 months without evidence of chronic vascular rejection. Alloantibodies were detected in only one long-term survivor. In contrast, all three monkeys in group B developed alloantibodies and rejected their allografts. In group C, long-term survival without alloantibody production was observed in two of three monkeys that had developed chimerism. In group D, all three recipients were sensitized and rejected the kidney allografts rapidly after transplantation.1) Production of anti-donor antibody was prevented in most recipients that developed mixed chimerism in the regimens with splenectomy at the time of donor bone marrow transplantation. 2) If splenectomy is not included in the initial conditioning regimen, induction of B cell tolerance is less likely and the result is late onset of alloantibody production and allograft rejection. 3) Immediate transplantation of the kidney at the time of recipient conditioning is not essential for induction of donor specific hyporesponsiveness by bone marrow transplantation.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Endothelin-1 (ET-1), a 21-amino acid peptide, is a novel and long-lasting vasoconstrictor that increases pulmonary arterial pressure in both in vivo and in vitro experiments. To study the effects of HHE on ET-1 activity in the lungs, 59 male rats were subjected to the equivalent of an altitude of 5500 m for 1 to 4 weeks. In rats exposed to HHE, the mean pulmonary arterial pressure increased significantly from 15.2+/-0.3 (ground level) to 30.6+/-1.5 mm Hg (5500-m level) at 4 weeks, whereas their mean systemic arterial pressure remained normal. The levels of ET-1 mRNA and protein, measured respectively by Northern blot analysis and enzyme immunoassay, increased rapidly in the lungs on exposure to HHE. By in situ hybridization and immunohistochemistry, respectively, ET-1 mRNA and protein were detected in control rats in nonciliated bronchiolar epithelial cells and alveolar epithelial cells, as well as in the endothelial cells of pulmonary arteries, but minimally in the smooth muscle cells of pulmonary arteries. ET-1 mRNA- and protein-reactive smooth muscle cells in pulmonary arteries and ET-1 mRNA-reactive airway epithelial cells were significantly more abundant in rats exposed to HHE than in ground level controls. These results suggest the possibility that in smooth muscle cells in pulmonary arteries and airway epithelial cells, ET-1 may play an autocrine or paracrine role in the remodeling of blood vessels during the development of the pulmonary hypertension that is induced by HHE.

Multi-facility joint randomized clinical trials for cancer treatment are the most common method of current clinical study. However, the difference in the rate of participation in multi-facility randomized clinical trials may damage the resulting general validity. Therefore, we studied whether the rate of participation in randomized clinical trials is different between university hospitals and other general hospitals using a questionnaire (with anonymity preserved). There were 744 subjects from university hospitals and 339 from general hospitals participating in the study. The results showed that 10.9 percent of those from university hospitals were willing to participate, against 28.1 percent who were not. Of those from general hospitals (public hospitals in this study) 10.6 percent answered that they would participate and 27.4 percent that they would not. Little difference was found in the rate of participation in randomized clinical trials between university hospitals and other general hospitals. The focus is thus on doctors to solve the possible differences between the facilities in further multi-facility joint studies.

Emergency CABG for acute coronary syndrome (ACS) was studied. Sixty patients had CABG for medically refractory UAP, 78 patients for AMI and 8 patients for post-infarction angina (PIA). In UAP group 7 patients (12%) died postoperatively, mainly due to perioperative myocardial infarction (PMI) and operative complications. In AMI group, 26 patients (33%) died, 14 of them due to myocardial failure. The operative mortality was extremely high in shock-state patients group (48%) and cardiac pulmonary arrest state patients group (85%). Operative result was poor in those patients whose infarct-related artery was not recanalized preoperatively. Operative mortality was 13% in PIA group. It was concluded that the reduction of mortality of those patients required much refined myocardial preservation technique and powerful mechanical assist system to support the postoperative myocardial failure.

Between October 1996 and June 1988, radial artery grafts were used in 49 patients undergoing myocardial revascularization. There were three hospital deaths, none of them due to the use of radial artery. In 32 patients studied early, 33 of 34 radial artery grafts were patent (patency 97%), and 30 of 32 internal thoracic artery grafts (94%), 32 of 35 saphenous vein grafts (90%), 3 of 3 gastroepiploic artery grafts (100%) were patent respectively. The mean diameter ratio of graft and recipient coronary artery was 1.03 +/- 0.17 in radial artery, 0.92 +/- 0.16 in internal thoracic artery and 1.67 +/- 0.55 in saphenous vein graft. Our result suggest that the radial artery is an excellent conduit for myocardial revascularization, although a longer follow-up is mandatory.

Between May 1992 and December 1997, 14 parents aged 80 or older underwent CABG with cardiopulmonary bypass. (Group A: mean age 82.1 +/- 1.73). This group was compared with 127 patients aged 70s. (Group B: mean 73.3 +/- 0.70). Left main trunk stenosis was more frequent in group A (p0.05), and number of patient who had old myocardial infarction was also frequent (p0.05). Emergency operation and preoperative use of intra aortic balloon pump was frequent in group A (p0.05). While there was no significant change in the number of graft per patient and used number of internal thoracic artery between the two groups, postoperative complications such as atrial arrhythmia and respiratory failure was appeared more frequently in group A (p0.05). The hospital mortality did not differ between the groups (21.4% for group A and 14.2% for group B). In group A, 11 patients are alive without recurrence of angina. In conclusion, while there is many problems pre and post operative term, CABG in over 80 years patients of age was satisfactory result, so we should not exclude octogenarian because of age alone.

A unique case of desmoplastic ameloblastoma is reported from the clinical, radiographic, and histologic viewpoints. The patient was a 56-year-old man who complained of a painless swelling on the buccal aspect of the left mandible. Periapical and panoramic radiographs revealed a rounded, slightly radiolucent area with blurred osteosclerotic margins. Occlusal radiograph and computed tomography images disclosed buccal bone expansion outlined by thinned cortices. Computed tomography images exhibited an enhanced area in the anterior portion of the lesion. Interestingly, the coronal computed tomography images revealed a close relationship between the periodontal membrane of the left mandibular second premolar and the enhanced area. Biopsy specimens from the anterior portion of the lesion displayed typical histologic features of the desmoplastic variant of ameloblastoma. However, those from the posterior portion disclosed a large cystic formation. Oxytalan fibers were identified in the stromal tissue of the tumor, which suggested that the tumor arose from the epithelial rests of Malassez in the periodontal membrane of the related tooth. We also reviewed previously reported 41 cases. In 36 of 38 cases in which the location was specified, the tumor was found in the anterior to premolar region of the maxilla or mandible. A radiographic description was given in only 29 previous cases, 28 of which involved multilocular lesions. No cyst as large as the one in the present case was found among the previously reported desmoplastic ameloblastomas. Although the present case deviates from the usual desmoplastic variant of ameloblastoma in terms of locus, radiologic appearance, and cyst formation, it still meets the histologic criteria for this variant in both the stromal and epithelial components.

The aim of this study was to describe the radiographic patterns of cemento-osseous dysplasia.Fifty-four patients affected with benign fibro-osseous jaw lesions that showed periapical radiopacities and/or radiolucencies in a focal or a multiplex form were studied. The clinical, radiographic, and histopathologic features of the patients with cemento-osseous dysplasia were retrospectively studied. Radiographic features of the cemento-osseous dysplasia lesions were classified according to the appearance of calcified bodies. Radiographic visibility of periodontal ligament spaces of related teeth was assessed.Forty-nine (91 %) of the 54 patients were women. The mean age of the total group was 50.8 years, and that of the male group was 64.6 years. The cemento-osseous dysplasia lesions could be classified into 6 types radiographically. Eighteen patients had at least 2 or more types of cemento-osseous dysplasia lesions. Of 147 related teeth, 142 had periodontal ligament spaces clearly visible. Six of 9 patients who had a total of 25 teeth with active hypercementosis showed concomitant occurrence of other types of cemento-osseous dysplasia lesions. Biopsy specimens showed various amounts of bonelike and cementumlike tissues.It is likely that cemento-osseous dysplasia consists of 3 variations of a single entity, all with the same unknown cause. In one variation, the entity originates from the periodontium; in another, it is of medullary bone origin; and in the third it results from the simultaneous involvement of both tissues.

The purpose of this study was to describe a radiographic variety of gross periostitis ossificans in mandibular osteomyelitis and to determine what types of gross periostitis ossificans are related to a specific form of mandibular osteomyelitis without demonstrable causes.We reviewed 20 cases of gross periostitis ossificans in patients with mandibular osteomyelitis that had been reported with illustrations in the English literature, and we reviewed our own 14 cases of gross periostitis ossificans, previously reported. The radiographic features of the 34 cases of gross periostitis ossificans were classified according to the status of original contour and the appearance of gross periostitis ossificans. Histopathologic features were studied in 12 cases.The 34 cases of gross periostitis ossificans could be classified radiographically into 4 types. Type A, showing an "onion-skin" appearance, was caused by a carious tooth or followed extraction of a tooth. Type B and type C showed a consolidation form; in the 36.8% (7/19) of these cases in which no infectious source could be identified, it was suspected that the condition was caused by a developing unerupted tooth or a dental follicle. Type D was seen in the most chronic stage. Biopsy specimens of 12 cases commonly showed proliferation of newly formed bone, loose interstitial fibrous tissue, and a low-grade inflammatory cell infiltration.Gross periostitis ossificans of type B or type C may be a specific form of mandibular osteomyelitis without demonstrable cause.

We encountered three adults with varicella and bronchial mucosal lesions. Respiratory symptoms were minimal in all three. Chest X-ray films showed bilateral, diffuse, small, nodular shadows. Small, elevated lesions with white plaque's were seen on the bronchial mucosa bronchoscopically. Transbronchial lung biopsy, bronchial mucosal biopsy, and bronchoalveolar lavage were also done. The lung-biopsy specimen showed infiltration of lymphocytes into the interstitial space: VZV antigen was found by immunohistochemical staining of the lesion in one case. Analysis of bronchoalveolar lavage fluid revealed abnormally low CD 4/8 ratios in three cases. These findings suggest a high incidence of respiratory complications, especially bronchial lesions, despite the lack of respiratory symptoms, in adults with varicella.

We report a case of oral malignant melanoma with metastasis to the cervical lymph node. The MR appearance corresponded to previously reported MR characteristics of malignant melanoma in other regions. Both the primary tumor and the nodal metastasis showed high signal intensity on T1-weighted images.

Optimizing therapeutic monoclonal antibody (mAb) depends on the incorporation of the necessary effector functions and the development of hypoantigenic "humanized" antibodies by genetic engineering, which then need to be tested in appropriate preclinical trials.Constructs of humanized OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and the framework and constant regions of human light (kappa) and heavy chains (IgG1 and IgG4) were prepared and tested in cynomolgus monkeys who received a renal allograft. A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/ hIgG4, either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1 mg/kg for 12 days) was given, and the effects on graft survival, immunohistology, circulating cells, and lymph node cells were assessed.The IgG1 isotype induced coating of T cells, modulation of surface CD4 molecules, and profound depletion of CD4+ lymphocytes in peripheral blood, which persisted as long as the animals were followed (up to 7 weeks). The IgG4 isotype induced only cell coating without cell clearance or modulation. In lymph nodes, coating of lymphocytes (approximately 60%) was seen with both isotypes in the earliest sample (6 hr). After 2 days, significant depletion of lymph node CD4 cells was evident, with a decrease in the CD4 to CD8 ratio in the IgG1-treated group; no depletion occurred in the IgG4 group. The emigration of CD4+ cells into the allograft was significantly delayed in the CDR-OKT4A/hIgG1-treated animals when compared with the CDR-OKT4A/hIgG4 group as judged by immunocytochemistry (23.8+/-13.2 days vs. 7.4+/-1.5 days, P0.001) or interleukin-2-promoted T-cell outgrowth from allograft biopsies (22.2+/-11.0 days vs. 6.3+/-0.5 days, P0.01).This study demonstrates that the in vivo effects of CDR-grafted OKT4A are dependent on its isotype. The depleting mAb CDR-OKT4A/hIgG1 significantly delays the entry of CD4+ cells into the graft, inhibiting the early phase of rejection. However, graft rejection occurs when CD4+ cells eventually infiltrate the graft, even in the presence of depressed levels of circulating CD4+ cells. Both isotypes demonstrated therapeutic efficacy: graft survival was prolonged over controls. In the case of CDR-OKT4A/hIgG4, neither lymphocyte depletion, antigenic modulation, nor prevention of infiltration is necessary for a beneficial effect, which indicates that this mAb blocks CD4 function or renders the CD4+ cell less responsive. The lack of depletion is a feature of potential clinical advantage in minimizing the risk of excessive immunosuppression.

Sairei-to has been reported to inhibit granulation and fibroblast proliferation. We administered Sairei-to (9.0 g/day) to two 77-year-old men with repeated urethral stenosis after transurethral resection of prostate (TUR-P) and examined its clinical effects. Urethral stricture did not recur in these patients for 7 to 8 months. There were no side effects in these patients. Sairei-to is suggested to be useful to prevent recurrence of urethral stricture after a transurethral procedure.

Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay.Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay.Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation.Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.

Platelet-derived growth factor (PDGF) is synthesized and secreted by mesenchymal cells. We used immunohistochemistry and in situ hybridization to determine whether immunoreactivity for PDGF and PDGF receptor (PDGF-R) might be a prognostic indicator in lung carcinoma. We compared these results with those of immunohistochemistry for anti-proliferating cell nuclear antigen (anti-PCNA). Indirect immunohistochemistry and in situ hybridization were performed for PDGF B-chain, PDGF-R beta and PCNA antibodies, and PDGF B mRNA on frozen, paraffin-embedded sections of 92 surgically resected lung carcinomas (39 squamous cell carcinomas, 47 adenocarcinomas, 2 large-cell carcinomas, 2 adenosquamous carcinomas, and 2 double carcinomas). Clinicopathologic data (sex, age, stage, survival period, histologic type, and degree of cell differentiation) were evaluated using a statistical analysis system. PDGF reactivity was positive in tumor cell cytoplasm in some cases of squamous cell carcinoma (64%) and adenocarcinoma (55%) and in all cases of large-cell carcinoma, adenosquamous carcinoma, and double carcinoma. PDGF-R reactivity was detected only in tumor stroma. Positive PDGF staining was associated with a poor prognosis in patients with lung carcinoma, independent of age, sex, stage, and degree of cell differentiation (risk ratio = 2.53, p = 0.03). PDGF B mRNA was detected in 100% of PDGF-positive squamous cell carcinomas and in 85% of adenocarcinomas. There was no correlation between PDGF expression and PCNA index in lung carcinomas. Together, these results suggest that immunohistochemistry for PDGF B-chain may predict the outcome for lung carcinoma patients.

We demonstrated previously that a nonmyeloablative preparative regimen can induce mixed chimerism and allograft tolerance in cynomolgus monkeys.The current studies were designed to clarify the importance and toxicity of various elements of the allotolerance conditioning regimen by: fractionating or reducing the whole-body irradiation (WBI) dosage; adding deoxyspergualine; or deleting donor bone marrow, cyclosporine, irradiation, or splenectomy.Monkeys treated without donor bone marrow, cyclosporine, or irradiation did not develop chimerism or long-term allograft survival. One of three monkeys treated without splenectomy developed chimerism but died of a surgical complication. The other two did not develop chimerism and rejected by day 117. Six of six monkeys treated with 300 cGy of fractionated WBI developed chimerism. Five of these recipients had long-term graft survival. Only two of four monkeys treated with 250 cGy developed chimerism, so a 2-week course of deoxyspergualine was added. This led to chimerism in two monkeys, but one died of ureteral stenosis and the other died of allograft rejection. An unanticipated high incidence of ureteral complications felt to be secondary to rejection episodes and ischemic injury was observed in the long-term surviving animals.All parameters of the original preparative regimen seem to be essential for consistent success. The degree of lymphocyte depletion was proportional to the WBI dose. Long-term graft survival was observed only in recipients achieving lymphocyte chimerism of1.5%. In this model, lymphocyte depletion seems to be the best predictor of chimerism, and significant lymphocyte chimerism seems to be important in achieving tolerance.

To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the cystatin C levels in the serum and urine of 33 healthy volunteers as well as in the serum and urine of 35 patients with various renal diseases and compared them with those of creatinine. In addition, we evaluated this substance as an indicator of removal rate of low molecular weight protein with high flux membranes in 6 hemodialysis (HD) patients.Serum and urinary cystatin C levels were measured by using an enzyme-linked immunosorbent assay (ELISA) method, 24-hour creatinine clearance was used as an indicator of GFR.Reference intervals with 95% ranges are 0.47-1.03 mg/l in the serum from healthy volunteers. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.936, p0.001) in the patients with various renal diseases. Serum cystatin C and creatinine inversely and logarithmically correlated to creatinine clearance as shown in the following equations: log cystatin C = -0.564 x log creatinine clearance + 1.216 (r = -0.850), log creatinine = -0.678 x log creatinine clearance + 1.449 (r = -0.904). In these equations l/day is the unit used for creatinine clearance, mg/l is the unit used for serum cystatin C. The range for cystatin C is 0.67-6.15 mg/l, 0.66-7.23 mg/dl for creatinine and 8.9-186.3 l/day (6.2-129.4 ml/min) for creatinine clearance. Serum cystatin C levels started to increase over normal range when creatinine clearance fell below 135.9 l/day (94.4 ml/min), while serum creatinine remained within normal ranges. The daily urinary excretion of cystatin C was increased significantly in the group in which creatinine clearance was below 30 l/day (20.8 ml/min) compared to that in which creatinine clearance was higher than in 70 l/day (48.6 ml/min). Fractional clearance of cystatin C increased proportionally and markedly to the decrease of creatinine clearance. In a regular HD condition with high flux membrane, the cystatin C removal rate was 38.7 +/- 1.7%.These data suggest that combined measurement of cystatin C in the serum and urine is useful to estimate GFR, especially to detect the mild reduction of GFR. Cystatin C measurement can also be used as an indicator of removal rate of low molecular weight protein with different types of high flux membranes in hemodialysis.

To study the relevance of anti-donor antibody (ADA) to chronic rejection in kidney transplantation, we retrospectively examined the long-term kinetics of ADA by flow cytometric analysis. Among 537 recipients who underwent living-donor kidney transplantation between 1986 and 1994, 29 patients with chronic rejection (CR group) and 33 patients with stable graft function (ST group) were randomly selected for analysis. Patient serum taken 1 or 2 days before transplantation, serum taken 1 month after transplantation, and the most current serum were analyzed for the presence of ADA to donor T and B cells. In the CR group, IgG antibody to donor B cells of the most current serum was positive in 25 of 29 patients, whereas it was positive in only 5 patients in the ST group P0.001. The mean fluorescent intensity of the antibody was also significantly higher in the CR group than that in ST group P0.01. In contrast, IgG antibody to donor T cells of the most current serum was positive in only five patients in the CR group. No significant difference was observed in the pretransplant and 1-month posttransplant sera between the CR and ST groups. We conclude that the posttransplant production of IgG antibody to donor B cells seemed to be highly relevant to chronic rejection.

A 42-year-old man was hospitalized for evaluation of hypoxemia. Laboratory findings were consistent with diffuse intravascular coagulation, and the level of carcinoembryonic antigen in serum was high. Despite intensive treatment, the patient died due to hypoxemia 20 hours after admission. An autopsy revealed gastric cancer in the antrum with metastases due to the lymph nodes, liver, and bone marrow. No metastases were found in the lung parenchyma but the pulmonary microvasculature was occluded by tumor-cell microemboli. Pulmonary tumor embolism must be suspected in patients who present with hypoxemia but without parenchymal opacities on chest roentgenograms, even if there are no history of malignancy.

Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells. CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests. It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.

Two kinds of presealed vascular prostheses were started to use for the thoracic aortic surgery at May 1991. The Gelseal graft was implanted in 13 patients and the Hemashield graft in 31 patients. Each cases was performed enhanced computed tomographic scan periodically to determine the extent of postoperative dilatation of both grafts. These showed that the Gelseal graft is significant more dilated than the Hemashield graft (51.2 +/- 8.1% vs 10.2 +/- 5.8%: p0.001). The dilatation was almost completed within one month and no addition later on both grafts. Because of more dilatation and possibility of serous discharge, the Gelseal graft is not good prosthesis for the patients who require postoperative anticoagulant therapy. If the Gelseal graft is used, smaller size should be selected for its dilatation. As the result of this study, the Hemashield graft is more suitable for thoracic aortic lesions than the Gelseal graft.

Acetaldehyde is suspected to be the ultimate carcinogen in alcohol-related carcinogenesis. The atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have higher blood concentrations of free acetaldehyde after drinking alcohol. We measured levels of acetaldehyde reversibly bound to hemoglobin (HbAA) after drinking 0.4 ml/kg ethanol using fluorigenic high performance liquid chromatography method in volunteers with the two major ALDH2 genotypes. In the ALDH2*1/*1 genotype with high ALDH2 activity, the increase of HbAA was small. By contrast, in the ALDH2*1/*2 genotype with low ALDH2 activity, HbAA increased considerably at 1-6 h after the drink, and the elevated levels persisted up to 48 h. We also measured HbAA in 81 male workers. Although HbAA levels were significantly correlated with alcohol consumption levels in both of the ALDH2 genotypes, the slope was significantly steeper in the ALDH2*1/*2 genotype than in the ALDH2*1/*1 genotype. In summary, we demonstrated for the first time a significant difference in the increase of HbAA levels after drinking alcohol, depending on the ALDH2 genotype. The HbAA levels are not only a good biomarker for increased internal exposure levels to acetaldehyde but may also be a predictive biomarker for acetaldehyde-mediated carcinogenesis.

In several types of carcinoma, angiogenesis is associated with metastasis and might be a prognostic indicator. Platelet-derived growth factor (PDGF) is one of several growth factors known; it is involved in the regulation of cell migration and proliferation. There have been few reports, however, dealing with the expression of PDGF B-chain mRNA and angiogenesis in transitional cell carcinoma. We evaluated both the expression of PDGF B-chain mRNA and angiogenesis in transitional cell carcinoma of the upper urinary tract and examined their interrelation with metastasis, patient prognosis, and other established clinicopathologic parameters. For this purpose, formalin-fixed, paraffin-embedded tumor tissues from 91 patients with invasive tumors were analyzed with in situ hybridization for PDGF B-chain mRNA and immunohistochemical staining of Factor VIII-related antigen to assess angiogenesis. The expression of PDGF B-chain mRNA was positive in 59 (66%) of the 91 patients. Microvessel density was significantly increased in positive PDGF B-chain mRNA cases (P.0001). There was no significance, however, in any relationship between the expression of PDGF B-chain mRNA or between the microvessel density and the clinicopathologic findings, metastasis, or prognosis. Assessment of the expression of PDGF B-chain mRNA and microvessel density seems to be of no real value in predicting either the risk of metastasis or the prognosis in transitional cell carcinoma of the upper urinary tract.