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In this work we study conjugated polyelectrolyte (CPE) films based on polyamidoamine (PAMAM) dendrimers of generations G1 and G3. These fractal macromolecules are compared to branched polyethylenimine (b-PEI) polymer using methanol as the solvent. All of these materials present a high density of amino groups, which protonated by methoxide counter-anions create strong dipolar interfaces. The vacuum level shift associated to these films on n-type silicon was 0.93 eV for b-PEI, 0.72 eV for PAMAM G1 and 1.07 eV for PAMAM G3. These surface potentials were enough to overcome Fermi level pinning, which is a typical limitation of aluminium contacts on n-type silicon. A specific contact resistance as low as 20 mΩ·cm2was achieved with PAMAM G3, in agreement with the higher surface potential of this material. Good electron transport properties were also obtained for the other materials. Proof-of-concept silicon solar cells combining vanadium oxide as a hole-selective contact with these new electron transport layers have been fabricated and compared. The solar cell with PAMAM G3 surpassed 15% conversion efficiency with an overall increase of all the photovoltaic parameters. The performance of these devices correlates with compositional and nanostructural studies of the different CPE films. Particularly, a figure-of-merit (Vσ) for CPE films that considers the number of protonated amino groups per macromolecule has been introduced. The fractal geometry of dendrimers leads to a geometric increase in the number of amino groups per generation. Thus, investigation of dendrimer macromolecules seems a very good strategy to design CPE films with enhanced charge-carrier selectivity.

Omalizumab therapy is effective and safe in patients with chronic spontaneous urticaria (CSU) resistant to nonsedating histamine1(H1) antihistamines (nsAHs).

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

Infliximab, an IgG1 monoclonal chimeric antibody against tumor necrosis factor (TNF)-α, represents the main biological drug employed for the treatment of several immuno-mediated inflammatory disorders. Infliximab infusion can be complicated by clinically heterogeneous adverse reactions, potentially interfering with the course of treatment. We analysed the adverse events recorded in 49 patients affected by different chronic inflammatory disorders (rheumatoid arthritis, seronegative spondiloarthritis, Behçet's disease, Wegener's granulomatosis, Churg-Strauss' syndrome, Cogan's disease) who were receiving a total of 709 infliximab infusions, in order to correlate the development of infliximab reactions and their features to some potential risk factors. We displayed a lower frequency of infusion reactions (1.5%; 11 out of 709 infusions) than those previously reported. However, patients suffering from rheumatoid arthritis and/or patients who underwent re-treatment after a long period, showed a higher prevalence of infliximab-related reactions. In conclusion, in our experience infliximab treatment is rarely complicated by adverse reactions which are, more importantly, almost always mild. Some good clinical practices, such as the low rate of infusion, pre-treatment with anti-histamine and prednisone in all patients, chronic immunosuppressive therapy and avoidance of long intervals between infusions may represent a combined useful strategy to reduce the frequency of infliximab reactions and to increase safety.

OBJECTIVE: To evaluate the T cell receptor β chain variable region (TCRBV) gene usage ex vivo in CSF cells and peripheral blood mononuclear cells (PBMCs) collected from patients with autoimmune and inflammatory diseases of the nervous system. METHODS: A novel sensitive seminestedpolymerase chain reaction coupled with heteroduplex analysis was developed. RESULTS: Under these experimental conditions, the minimal number of cells required for the analysis of the whole T cell repertoire was established at 2.5×10⁴--sufficient to evaluate most of the samples collected during diagnostic lumbar punctures. In the 21 patients examined, restrictions in TCRBV gene family usage were not seen. However, using heteroduplex analysis, oligoclonal T cell expansions were found in the CSF of 13 patients and monoclonal expansions in five patients. The T cell abnormalities found did not correlate with intrathecal IgG production or with any clinical variable considered. CONCLUSION: T cell clonal expansions, useful for further characterisation of pathogenetic T cells, can be found during the course of nervous system inflammations, but this abnormality is probably not disease specific.

Human CD4 T helper lymphocytes can be subdivided into at least three distinct functional subsets on the basis of their cytokine secretion profiles. One type of CD4+ lymphocyte, T helper 1 (Th1), produces interferon (IFN)-γ and tumour necrosis factor β, a second type (Th2) produces interleukin (IL)-4 and IL-5 and a third type (Th0) produces both Th1 and Th2 cytokines. The apparent paradox that embryos are not rejected by the maternal immune system despite the presence of paternal MHC histocompatibility antigens has been explained in mice by a Th2 switch at the level of the materno-fetal interface. We showed that some hormones enhanced during pregnancy can affect the development of Th1 and Th2 responses. Indeed, we found that progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-γ by T-cells. In addition, we showed that leukaemia inhibitory factor (LIF), which is essential for embryo implantation, associates with Th2 cells and is upregulated by IL-4 and progesterone. We also showed that LIF is down-regulated by Th1 inducers [IL-12, IFN-γ and IFN-α]. Further-more, we found a decreased production of LIF, IL-4 and IL-10 by decidual T-cells in women with unexplained recurrent abortions in comparison with women with normal gestation at the moment of voluntary abortion. The decreased production of LIF, IL-4 and IL-10 was not found in peripheral-blood T-cells. These results suggest that the local production of LIF and/or Th2 cytokines may contribute to the maintenance of pregnancy.

Primary CD30+ cutaneous T-cell lymphomas (CTCLs) represent a spectrum of non-Hodgkin’s lymphomas (NHLs) that have been well defined at the clinical, histologic, and immunologic level. This group, which includes 2 main entities (large cell lymphoma and lymphomatoid papulosis [LyP]) and borderline cases, is characterized by the expression of CD30 antigen by neoplastic large cells at presentation, possible spontaneous regression of the skin lesions, and generally favorable clinical course. Although the functional relevance of CD30 and its natural ligand (CD30L) expression in most cases of NHL is presently undefined, previous studies indicate that CD30L is likely to mediate reduction of proliferation in CD30+ anaplastic large-cell NHL. No information is currently available concerning the expression of CD30L in primary CD30+ CTCLs. In this study, we investigated the immunophenotypic and genotypic expression of CD30 and CD30L in different developmental phases of skin lesions (growing v spontaneously regressing). By immunohistochemistry, CD30L expression was detected in regressing lesions only; by molecular analysis, the expression of CD30L was clearly higher in regressing lesions than in growing ones. CD30L, while expressed by some small lymphocytes, was most often coexpressed by CD30+neoplastic large cells, as demonstrated by 2-color immunofluorescence and by immunohistochemistry on paraffin sections. Taken together, these data suggest that CD30-CD30L interaction may play a role in the pathobiology of primary cutaneous CD30+lymphoproliferative disorders. In particular, CD30L (over)expression might have a major role in the mechanism of self-regression of skin lesions, the most distinctive clinical feature of this cutaneous lymphoma subtype.

Kaposi’s sarcoma (KS) lesions are characterized by a prominent leukocyte infiltrate composed of mononuclear phagocytes and T cells. KS-associated CD4+ and CD8+ cells showed predominantly a type II cytokine profile. The CC chemokine viral macrophage inflammatory protein-II (vMIP-II) encoded by the KS-associated herpes virus 8 was a selective chemoattractant for T helper 2 (Th2 cells) and for monocytes, whereas it was inactive on other leukocytes, including Th1 cells, dendritic cells, and natural killer (NK) cells. vMIP-II was an agonist for CCR8, a chemokine receptor selectively expressed on CD4+ and CD8+ cells with a type II cytokine profile. Hence, vMIP-II has agonist activity for a chemokine receptor (CCR8), which is preferentially expressed on polarized Th2 cells. The capacity of vMIP-II to attract type II T cells selectively is likely to be a component of the virus strategy to subvert the host immune response.

Purified T lymphocytes (E rosetting cells) isolated from the involved lymphoid organs (lymph nodes and spleen) of five patients with Hodgkin's disease (HD) were cloned under culture conditions (phytohemagglutinin plus interleukin-2) that allow clonal expansion of most T lymphocytes. A total number of 104 CD4+ T cell clones so obtained were tested for their ability to proliferate in response to autologous mitomycin-treated non-T cells. About half of these clones but none of 234 CD4+ T cell clones derived from normal lymphoid tissues or peripheral blood displayed a proliferative response to autologous stimulators. When clones proliferating in autologous mixed lymphocyte reaction (AMLR) were assessed for their ability to respond in allogeneic MLR (allo-MLR), most of them were found to exhibit consistent proliferation in response to more than one haplotype. Both the AMLR and the allo-MLR by HD clones were inhibited by adding monoclonal antibodies (MoAbs) reactive with monomorphic determinants of major histocompatibility complex (MHC) class II (DR) antigens to the cultures, whereas MoAbs reactive with MHC class I antigens were without effect. These studies suggest that lymphoid organs involved by HD contain high proportions of CD4 T cells showing abnormal recognition of DR antigens. These unusual cells may play an important role in the pathogenetic mechanisms occurring in HD.

Human bone marrow (BM) cells lacking T- and B-cell markers expressed RNA encoding interleukin (IL) 4 and secreted detectable amounts of IL-4 in supernatants in response to Fc epsilon or Fc gamma receptor (Fc epsilon R or Fc gamma R) cross-linking. In some experiments, IL-5 RNA expression in response to Fc epsilon R cross-linkage could also be detected. In contrast, RNA transcripts for, and secretion of, IL-2, IL-6, and interferon gamma were never observed. The presence of IL-3 in the cultures was essential for IL-4 production by non-B, non-T BM cells in response to Fc gamma R cross-linking and enhanced IL-4 RNA expression in response to Fc epsilon R cross-linking. Under the same experimental conditions, BM T and B lymphocytes, as well as peripheral blood T, B, and non-B, non-T cells, did not express IL-4 RNA. Prolonged incubation of non-B, non-T cells in IgE-free medium followed by extensive washing did not inhibit IL-4 production induced by anti-IgE antibodies, suggesting that the Fc epsilon R involved in the response has the characteristics of a high-affinity receptor. The Fc epsilon R+ cells were separated from the Fc epsilon R- cells by sorting non-B, non-T BM cell suspensions with fluorescein isothiocyanate-conjugated IgE and then assessed for both IL-4 RNA expression and alcian blue staining. Both IL-4-producing and alcian blue-positive cells segregated with the Fc epsilon R+ fraction. These data suggest that human BM cells, probably belonging to the mast cell and/or basophil lineage, are capable of producing IL-4 in response to Fc epsilon R or Fc gamma R cross-linkage.

Two separate studies were performed: in the first study four healthy male volunteers received three single oral doses (150, 250 and 400 mg) of 5-methylpyrazine carboxylic acid 4-oxide (acipimox) according to a randomized sequence. Plasma levels of the drug were determined by RIA and urinary excretion by HPLC.In the second trial the effect of food on the drug bioavailability and pharmacokinetics during repeated administration was investigated in six volunteers. The RIA method was adopted to measure plasma and urine levels.Acipimox was rapidly and almost completely absorbed after the three single doses.About 90% of the administered dose was recovered as unchanged drug in urine collected up to 24 h. Peak plasma levels, area under plasma level curves and urinary excretion were linearly related to the administered dose.The presence of food in the gastro-intestinal tract did not adversely affect the bioavailability of the drug. No significant changes were noted in the rate of elimination after 6 days of treatment with 250 mg t.i.d. Plasma levels determined after the 19th dose were in good agreement with those predicted on the assumption of linear pharmacokinetics and a one-compartment open model, with a half-life of about 2 h.

During the third trimester of pregnancy umbilical artery pulsatility index was measured in 30 insulin dependent diabetic women, classes B to R, according to the White (1978) classification. A mean capillary glucose value 6.1 mmol/1 (110 mg/dl) was selected to indicate poor glucose control. The patients were divided into three groups (10 patients in each) based on mean capillary blood glucose: group I, 6.1 mmol/1 (110 mg/dl); group II, 6.1-7.2 mmol/1 (130 mg/dl); group III, 7.2 mmol/1 (130 mg/dl). Each patient had one measurement of the umbilical artery pulsatility index at 31 weeks and one at 34 weeks. No Doppler measurements were outside the normal range in group I and III. Sixteen measurements (80 per cent) were more than 1 s.d. above the mean in group II. No differences were found between mean pulsatility indices in controls, in group I and in group III. The mean pulsatility index in group II was greater than that in controls (P 0.01) and that in group I (P 0.01) and group III (P 0.01).

More than 500 CD4^+ T-cell clones (TCCs) derived from the skin of eight patients with atopic dermatitis (AD), two patients with nonatopic dermatologic disorders, two patients with allergic rhinitis, and one healthy nonatopic donor were analyzed for both their pattern of cytokine production and their antigen specificity. The proportions of TCCs from patients with AD producing interleukin-4 in response to stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody were higher, whereas the proportions of interferon-@c-producing TCCs were lower than those of control subjects. In two patients with AD, the majority of TCCs had a T"H"2/T"H"0-like phenotype, whereas in six patients with AD a T"H"1/T"H"0-like phenotype was prevalent. TCCs with a T"H"2/T"H"0-like phenotype were also isolated from the healthy skin of two patients with allergic rhinitis and one nonatopic donor. In contrast, no T"H"2-like TCCs were derived from the skin of the two patients with dermatologic disorders of nonallergic origin. No unambiguous correlation was found between the proportions of TCCs producing interleukin-4 or interferon-@c (or of TCCs with T"H"2- or T"H"1-like profile) and the level of total serum IgE, suggesting that CD4^+ T cells infiltrating the atopic skin do not play a major role in the production of serum IgE antibodies. When TCCs from five patients with AD were examined for their specificity, the proportions of allergen-specific (Dermatophagoides pteronyssinus and Lol p 1) clones were consistently 6% or lower even in patients with high titers of ryegrass- or D. pteronyssinus-specific IgE antibodies. Because similar percentages of allergen-specific TCCs were found in skin from two healthy control subjects, the role of aeroallergens in favoring and maintaining skin lesions in patients with AD remains unclear. (J ALLERGY CLIN IMMUNOL 1995;96:411-20.)

A simple, sensitive radioimmunoassay has been developed for the direct determination of glipizide in human plasma. Antisera raised in rabbits immunized with a glipizide analogue conjugated to bovine serum albumin were highly specific, the two main metabolites, 3,cis-hydroxycyclohexyl derivative and 4,trans-hydroxycyclohexyl derivative, having cross reactivities of 0.73% and 1.66%, respectively. The method can measure amounts as small as 1 ng/ml. The intra- and inter-assay coefficients of variation lay between 2.98–5.79% and 2.35–8.66%, respectively. The mean recovery of glipizide added to plasma was 99–105% over the range 1–500 ng/ml. The method was employed to determine plasma levels in six subjects after administration of a 5 mg tablet of glipizide. The results were in accordance with those found after administration of the same dose of radiolabelled glipizide to two other subjects.

We examined the expression of T cell markers in the peripheral blood of five immunologically normal human fetuses at 18-20 weeks of gestational age. The distribution of T cells expressing CD1, CD3, CD4, CD8, CD56, and the α/β and γ/δ receptors for antigen was comparable to that of newborns and normal adults, except for the absence of γ/δ cells expressing the δTCS-1 epitope. The Vβ repertoire, as evaluated by two-color flow cytometry using mAbs to specific Vβ families, was also comparable to that of adult samples. A significant fraction (8.9 to 16.4%) of fetal CD3⁺ T cells expressed the α chain of IL-2R (CD25) in the absence of HLA-DR; this suggests that antigenic stimuli trigger, during intrauterine life, an unusual pathway of T cell activation. Consistent with this, 7 to 27% of fetal T cells were found to express the CD45R0 marker of "memory" cells. Copyright 1994, 1999 Academic Press

CD3O is a member of the tumor necrosis factor (TNF) receptor family, originally described as a marker for Hodgkin and Reed‐Sternberg cells in Hodgkin's disease, which has been found to be preferentially expressed by T cells producing Th2‐type cytokines. The presence of CD3O expression was assessed by both immunohistochemistry and reverse transcriptase‐polymerase chain reaction in the target organs of patients with Th1‐ or Th2‐dominated disorders. CD3O expression was found in neither the gut of patients with Crohn's disease nor in the gastric antrum of Helicobacter pylori‐infected patients, where there was high interferon‐γ (IFN‐γ) expression. In contrast, high CD3O expression in the apparent absence of IFN‐γ expression was observed in the skin of patients with systemic sclerosis or chronic graft versus host disease (GVHD), which can be considered Th2‐dominated disorders. Moreover, high levels of soluble CD3O were found in the serum of both systemic sclerosis and GVHD patients but not in the serum of patients suffering from multiple sclerosis, a Th1‐dominated disorder. Thus, CD3O expression appears to be preferentially associated with Th2‐type responses not only in vitro but also in vivo. J. Leukoc. Biol.61: 539–544; 1997.

Thirteen CD4 + T cell clones (TCCs) showing autologous mixed lymphocyte reaction (AMLR) and 12 CD4 + AMLR-negative TCCs derived from involved lymph nodes (LN) of 4 untreated patients with newly-diagnosed Hodgkin's disease (HD) were analyzed for some functional activities and for T cell receptor (TCR) gamma and beta gene rearrangementThe majority of the AMLR-positive-, but only two AMLR-negative TCCs showed cytolytic potential when assayed by a lectin-dependent assay. In addition, the proportion of clones able to produce interleukin 2 (IL-2) was higher among AMLR-positive- than AMLR-negative TCCs and the amount of IL-2 synthesized by AMLR-positive TCCs was significantly greater than that of AMLR-negative TCCs. In contrast, no difference in the profile of interleukin 4 (IL-4) and interferon-gamma (IFN-γ) production between AMLR-positive- and AMLR-negative TCCs was detectedWhen AMLR-positive TCCs were analysed for their TCR beta and gamma gene rearrangements, a highly heterogeneous pattern was found. More importantly, TCCs derived from the same donor and displaying the same kind of TCR beta and gamma gene rearrangement showed different patterns of rearrangements, suggesting that CD4 + cells from LN involved by HD, displaying such an unusual functional profile, are polyclonal

We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.

We analyzed at clonal level the functional profile of circulating or skin-infiltrating T lymphocytes from two individuals infected with the human immunodeficiency virus type 1 (HIV-1), suffering from a Job's-like syndrome (eczematous dermatitis, recurrent skin and sinopulmonary infections, and hypergammaglobulinemia E) and showing virtually no circulating CD4+ T cells. Most of the CD3+ T cell clones generated from both patients were CD4- CD8+ TCR alpha beta +. The others were CD4- CD8- TCR alpha beta + which exhibited reduced mRNA expression for the CD8 molecule or no mRNA expression for either CD4 or CD8 molecules. The great majority of both CD4- CD8+ and CD4- CD8- did not produce interferon (IFN) gamma and exhibited reduced cytolytic activity. Rather, most of them produced large amounts of both interleukin (IL) 4 and IL-5 and provided B cell helper function for IgE synthesis. These data suggest that a switch of cytolytic CD8+ T cells showing a Th1-like cytokine secretion profile to cells that make Th2-type cytokines, exhibit reduced cytolytic potential, and provide B cell helper function can occur in the course of HIV-1 infection. These cells may contribute to the reduced defense against viral infections and intracellular parasites and account for the elevated IgE serum levels, eosinophilia, and the allergic-like clinical manifestations seen in a proportion of HIV-1-infected individuals.

The effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (IL-12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of IL-12 exhibited reduced ability to produce IL-4 and increased ability to produce interferon gamma (IFN-gamma), and developed into Der p I-specific CD4+ T cell clones showing a T helper type 0 (Th0)- or Th1-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-IL-12 antibody exhibited an increased ability to produce IL-4 and developed into PPD-specific CD4+ T cell clones showing a Th0-, instead of Th1-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti-IFN-gamma antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16+ cells. Thus, IL-12 and CD16+ cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Th1-like responses.

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

A large panel of CD8+ T cell clones generated from peripheral blood lymphocytes (PBL) of healthy donors or human immunodeficiency virus (HIV)-infected individuals were assessed for both cytokine secretion profile and CD30 expression and release. The great majority of CD8+ T cell clones generated from healthy individuals showed the ability to produce interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), and none of them either expressed membrane CD30 or released substantial amounts of soluble CD30 (sCD30) in their supernatant. In contrast, high numbers of CD8+ T cell clones generated from HIV-infected individuals, which produced IL-4 (and IL-5) in addition to IFN-gamma or IL-4 (and IL-5) alone, expressed membrane CD30 and released detectable amounts of sCD30 in their supernatants. Indeed, CD30 expression appeared to be positively correlated with the ability of CD8+ T cell clones to produce IL-4 and IL-5 and inversely correlated with their ability to produce IFN-gamma, whereas no correlation between CD30 expression and production of IL-10 was observed. These data suggest that CD30 is a marker for CD8+ T cells that have switched to the production of type 2 helper cytokines.

Abstract. In 142 diabetic pregnancies fetal biparietal diameter (BPD), transverse abdominal diameter (TAD) and abdominal circumference (AC) were estimated by means of serial ultrasound examinations. An accurate evaluation of fetal growth was obtained in 85% of the cases. AC was found to have the highest degree of reliability in predicting macrosomia (71%) followed by TAD (60%) and BPD (17%).Placental morphology was estimated at the last scanning before delivery in 85 of the patients. In pregnancies resulting in macrosomic infants the placental maturation seemed to be retarded.In 26 patients a third trimester amniocentesis was performed. A mature (grade III) placenta was always associated with a lecithin-sphingomyelin (L/S) ratio> 2, indicating fetal lung maturity but there was no constant relation between placental maturity and the L/S ratio.In conclusion, ultrasound examination during diabetic pregnancy offers valuable information concerning the prenatal diagnosis of macrosomia and could serve as a guidance in the determination of the optimal time and route of delivery. The grading of placental maturity might help to identify fetuses at risk, but further studies in this area are needed before final conclusions can be drawn.

We have studied the surface antigen pattern, enzymatic phenotype, and functional capacity of peripheral blood lymphocytes from a patient with Sézary syndrome (SS). The majority of these cells formed E rosettes but lacked the Fc(µ) receptor. The neoplastic cells were reactive with pan-T cell (OKT3)- and helper T cell (OKT4)-subset monoclonal antibodies; however, they lacked the 5/9 antigen, which identifies a more restricted subset of helper T cells. Most SS cells also reacted with PTF 29.12, a monoclonal antibody which recognizes DR determinants. Only 35% of the cells expressed single, focal accumulations of a-naphthyl-acid esterase activity, which is a characteristic of T.M cells, but 85% of them showed this focal staining pattern with acid phosphatase or ß-glucuronidase. Mononuclear cells from the SS patient showed poor or no proliferative response to phytohemagglutinin, pokeweed mitogen, concanavalin A, purified protein derivative, Candida, and allogeneic cells and lacked both helper and suppressor activity for pokeweed mitogen driven production of IgM and IgG immunoglobulins by normal B cells, but they were able to stimulate a marked proliferative response in mixed-lymphocyte culture. The defective expression of enzymatic and surface membrane characteristics, together with the lack of some T-cell functions, suggests that the patient cells may be immature T.M lymphocytes.

Skeletal malformations affect one out of every 500 newborn babies in Italy. Genetic counselling enables identification of women at risk for these abnormalities, and ultrasound scanning permits prenatal diagnosis. Of 49 patients studied between October 1984 and June 1988, 29 women had a greater risk of fetal skeletal abnormalities than that in the general population. With ultrasound scanning, no false positive diagnoses were made. In four women at increased risk, pathological features were found in utero by ultrasound and in two women the diagnosis was missed and made after birth. One of these was a case of hypophosphataemic rickets, diagnosed by X-ray at 10 months of age; the other was monitored for cleft lip and palate, but a cleft lip was found only at birth.

Introduction: The increase of left auricular volume (LAV) is a robust cardiovascular event predictor. Despite that echochardiography is more often used, cardiac MRI is considered more accurate. Our objetives are to validate "fast" LAV measures by MRI vs the considered gold standard (GS) and to compare Echo and MRI in a wide spectrum of patients. Methods: In a non-selected popullation with MRI study previously realized, we measured LAV by biplane method (BPMR) and by area-length in 4 chamber view (ALMR) and compared them with biplane (BPe) and discs method (MDDe) in 4 chamber view in echo. To validate MRI measurements, we measured LAV in short axis slices (Simpson Method, SM) in a group of patients and considered it the GS. Results: 186 patients were included (mean age 51 ± 17 age; 123 male; 14 in AF) with clinical indication of cardiac MRI (Philips 1,5 T). In 24 patients SM was calculated. 29% of cardiac MRI were considered normal. Mean underlying pathologies were myocardiopathy (27%), Ischemic myocardiopathy (17%), myopericarditis (10%), prior to AF ablation (4%), valvular disease (6%) and miscellaneous (7%). Excellent correlation was obtained between "fast" MRI measurements and SM in MRI (SM vs BPMR interclass correlation coefficient ICC=0.965 and SM vs ALMR, ICC=0.958; P<0.05) with low interobserver variability (ICC=0.983 for SM; ICC=0.949 for BPMR; ICC=0.931 for ALMR). "Fast" measurements by MRI showed stadistical correlation between them (CCI=0.910) (Figure). Correlation between Echo and MRI measures was only moderate. (BPRM vs BPe CCI=0,469 mean difference -30 ml; ALMR vs MDDe ICC=0,456 mean difference -24 mL). Conclusions: ‘fast’ LAV measures by MRI are comparable with the MRI GS and also between them. Echo values seem to underestimate compared to MRI, so its use may not be suitable.

The aim of any radiodiagnostic procedure is to obtain a high quality image while keeping the dose to the patients as low as practicable. Significant problems and wide variations in the current mammography practice could be avoided by performing regularly a quality control programme (QCP). The technical QCP consists of tests on the characteristics of the X ray equipment, dose, image quality, dark room, sensitometry, and viewing conditions. The judgement of the overall effectiveness of a QCP is, in general, left to a subjective evaluation and sometimes fluctuations in the results are not easily interpreted. The aim of this paper is to introduce an objective evaluation of the impact of a QCP through a statistical analysis of the results of the measurements. The proposed statistical methods are a randomisation test named Shuffling Without Replacement and the Student-t test. Another application of the statistical tests is to validate the frequency of the measurements chosen for a single parameter by a centre performing a QCP.