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L Weiss

Publications and source records attributed to L Weiss.

At least 55 records · Page 3Linked to original sources
PubMed2000

Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.

Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4-7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44-hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.

Animals↗
PubMed2000

Variation in microdeletions of the cyclic AMP-responsive element-binding protein gene at chromosome band 16p13.3 in the Rubinstein-Taybi syndrome.

Most reported microdeletions of the CREB-binding protein (CBP) gene in the Rubinstein-Taybi syndrome (RTS) were detected by fluorescence in situ hybridization (FISH) with a single cosmid probe specific to the 3' region of the gene. In order to test the hypothesis that the rate of microdeletion-positive cases would be greater if the entire gene was evaluated, we performed FISH on 66 patients with an established diagnosis of RTS, using a panel of five cosmids that span the CBP gene. Five of 66 patients had deletions by FISH (9%), consistent with those rates reported in various series that ranged between 3-25%. Among our cases, different deletions were observed; one was deleted for the 5' but not the 3' region of the CBP gene (case 055). Other deletions included a total CBP deletion extending from the 5' through the 3' region (case 017), a deletion of all but the 5' region (cases 006 and 060), and an interstitial deletion in the 3' region (case 028). Fine breakpoint mapping with additional cosmid and yeast artificial chromosome (YAC) constructs was performed on these patients. The findings of a partial 5' deletion and of interstitial deletions of the CBP gene add to the known spectrum of mutations of this gene in RTS and demonstrate the need for evaluation of the entire CBP gene region for deletions rather than only the 3' region in RTS patients. These results further suggest that the true rate of microdeletion across the CBP gene detectable by FISH has yet to be established firmly. No phenotypic differences between partial deletion, complete deletion, and nondeletion patients were observed, supporting a haploinsufficiency model for RSTS.

Chromosomes, Human, Pair 16↗
PubMed2000

Regulation of c-Jun NH(2)-terminal kinase (Jnk) gene expression during T cell activation.

The c-Jun NH(2)-terminal kinases (JNKs) are a group of mitogen-activated protein (MAP) kinases that participate in signal transduction events mediating specific cellular functions. Activation of JNK is regulated by phosphorylation in response to cellular stress and inflammatory cytokines. Here, we demonstrate that JNK is regulated by a second, novel mechanism. Induction of Jnk gene expression is required in specific tissues before activation of this signaling pathway. The in vivo and in vitro ligation of the T cell receptor (TCR) leads to induction of JNK gene and protein expression. TCR signals are sufficient to induce JNK expression, whereas JNK phosphorylation also requires CD28-mediated costimulatory signals. Therefore, both expression and activation contribute to the regulation of the JNK pathway to ensure proper control during the course of an immune response.

Animals↗
PubMed2000

CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit phenotypic and functional dendritic cell-like characteristics.

We previously reported an increased percentage of CD14+CD16++ monocytes in the peripheral blood of HIV-infected patients but the physiopathological role of this monocyte subset remains unclear. Cells with a CD14+CD16++ phenotype may be obtained in vitro by culturing human peripheral blood monocytes in the presence of GM-CSF, IL-4 and IL-10. In the present study, we compared the phenotypic and functional characteristics of monocytes-derived CD14+CD16++ cells with those of macrophages and dendritic cells. We show that the CD14+CD16++ cells express dendritic cell markers: CD40, CD80, CD86, HLA-DR, CD11b, CD11c, CD18, CD1a, and CD83. Using RNase protection assay, we demonstrate that CD14+CD16++ cell subset expresses a low ratio of IL-1beta/IL-1ra mRNA and expresses IL-6, MIP-1alpha, MIP-1beta, MCP-1, IL-8, RANTES and I-309 transcripts, similar to dendritic cells. CD14+CD16++ cells produce IL-12, MCP-1 and IL-8, as assessed by flow cytometry. Moreover, CD14+CD16++ cells pulsed with different recall antigens induce a potent autologous T cell proliferation. Altogether, these results provide evidence that CD14+CD16++ cells differentiated in vitro from peripheral blood monocytes exhibit dendritic cell characteristics.

Antigen Presentation↗
PubMed2000

[Tracheobronchial foreign bodies].

Forty cases of children with an inhaled foreign body (FB) are reviewed over a three-year period. Clinical data, radiologic findings and complications are detailed. The nature and size of FBs are also reported. Diagnosis and management are discussed according to the most recent studies in the literature. Diagnostic flexible bronchoscopy is a useful first step when the diagnosis is unclear (i.e., choking history, unexplained respiratory symptoms), but FB removal is usually not possible during this procedure. Extraction is performed via the rigid bronchoscope under general anesthesia. However, FB could be removed with the flexible bronchoscope in five children in our study. Diagnosis and removal of an inhaled FB are required as quickly as possible in order to prevent respiratory sequelae (bronchiectasis). Prevention is based upon information to be given to families, but to the medical community as well, which often minimizes the seriousness of inhalation hazards.

Bronchi↗
PubMed2000

The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models.

Fludarabine phosphate, a purine analogue currently used in the therapy of hematological malignancies, is known to cause immunosuppression and long-lasting T cell lymphopenia. In this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across major and minor histocompatibility barriers was evaluated. Survival of (BALB/c x C57BL/6)F1 mice irradiated and transplanted across the major histocompatibility barrier with C57BL/6 spleen cells, and subsequently treated with fludarabine was significantly longer than that of the control animals (P < 0.0001). On the other hand, fludarabine had no effect on the graft-versus-host disease and survival of CBA mice transplanted by B10.BR and of BALB/c mice transplanted by B10.D2 spleen cells across the minor histocompatability barrier. The results indicate that in certain murine models, particularly a major mismatch, fludarabine has the potential to induce bilateral tolerance and stable chimerism after marrow transplantation. Bone Marrow Transplantation (2000) 25, 263-266.

Animals↗
PubMed2000

Conference highlight: do T cells care about the mitogen-activated protein kinase signalling pathways?

Mitogen-activated protein (MAP) kinases, which include the extracellular response kinases, p38 and c-Jun amino terminal kinases (JNK), play a significant role in mediating signals triggered by cytokines, growth factors and environmental stress. The JNK and p38 MAP kinases have been involved in growth, differentiation and cell death in different cell types. In the present paper, we describe how the JNK and p38 MAP kinase signalling pathways are regulated and their role during thymocyte development and the activation and differentiation of T cells in the peripheral immune system. The results from these studies demonstrate that the JNK and p38 MAP kinase signalling pathways regulate different aspects of T-cell mediated immune responses.

Animals↗
PubMed2000

Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene determines the concentration of ACE in serum and local tissues. The role of this polymorphism in progressive chronic renal disease is still not fully clear. METHODS: We analysed the impact of the D/D polymorphism on the rate of decline in renal function in patients with non-diabetic, chronic progressive renal insufficiency. Seventy non-diabetic patients, aged 21-69 years at baseline, with moderately advanced renal insufficiency due to primary chronic renal disease were followed for an average of 3 years with repeated measurements of their glomerular filtration rate (GFR). Their mean GFR at baseline was 41 ml/min/1.73 m(2) body surface area (BSA). The polymerase chain reaction (PCR) amplification method was used to detect the I/D polymorphism of the ACE gene. GFR was measured as the clearance of (51)Cr-EDTA and the individual rate of progression was calculated using linear regression. RESULTS: The distributions of the genotypes were: D/D 30%, I/D 49%, and I/I 21%. The rates of progression in the three ACE genotype groups were an annual decline in renal function of -4.2 (SD 4.6) ml/minx1.73 m(2) BSA in the D/D group, -2.7 (SD 3. 4) in the I/D group and -1.7 (SD 3.4) in the I/I group (ANOVA P=0. 12). In patients with proteinuria below 3.5 g/24 h, the D/D group had a significantly higher rate of progression than patients with the I allele. The same was found in a separate analysis when only patients with normal apoliprotein B (below 155 mg/dl) levels were analysed. Furthermore, the D/D genotype was a significant predictor of a more rapid decline in renal function in male, but not female, patients. CONCLUSION: The results in this study in non-diabetic patients with chronic renal disease indicate that the presence of the D allele in the ACE genotype may be of particular importance as a predictor of a high rate of progression in male patients who otherwise do not have a major burden of documented and important prognostic factors for progressive renal insufficiency.

Adult↗
PubMed2000

Assessing body composition and changes in body composition. Another look at dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry (DXA) is selected with increasing frequency as a method for both assessing body composition and measuring the changes in body composition. Issues have been raised about hydration, software version, hardware (fan beam vs. pencil beam), and the subject population in relation to the validity of DXA-derived estimates of body composition. This paper reviews validation studies of DXA to assess the impact of recent developments in its technology. Studies by Prior et al., Kohrt et al., Salamone et al., Going et al., and Pietrobelli et al. demonstrate the effectiveness of DXA estimates of changes in body composition. By contrast, Clasey et al., Nelson et al., and Friedl et al. found limitations in DXA estimates of body composition and its changes. These contradictory conclusions were explored for threats to internal validity in each research study. From this analysis, two validation guidelines are recommended for use when evaluating estimates of body composition. When multicomponent models are used, it is essential that estimates of body water as a fraction of fat-free mass fall in the expected range (71 to 75%) and have a relatively small standard deviation (2 to 3%). For measuring changes in body composition, DXA estimates of total body mass must accurately reflect both baseline and posttreatment scale body weight estimates. Failure to meet these guidelines threatens the internal validity of the study and raises the likelihood of methodological discrepancies. Applying these criteria to DXA studies of body composition under review accounts for much of the contradictory conclusions among investigations.

Absorptiometry, Photon↗
PubMed2000

Labeling effects of a controversial psychiatric diagnosis: a vignette experiment of late luteal phase dysphoric disorder.

During the 1990s debate arose about the inclusion of Late Luteal Phase Dysphoric Disorder in the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual. Opponents argued that the inclusion of this category would increase stigma and be used as a legal defense for child abuse and other violent crimes. Proponents argued that it would decrease stigma and enhance treatment seeking. Using an experimental vignette design, we tested these propositions in a study of 307 men and women living in Putnam County, New York. In general, the results do not indicate a pervasive negative impact of this label. On the other hand, labeling the disorder a "psychiatric condition" did increase recommendations for psychiatric help.

Adolescent↗
PubMed2000

Non-Hodgkin's lymphoma: an analysis of the Metropolitan Detroit SEER database.

We evaluated incidence and survival trends of non-Hodgkin's lymphoma (NHL) in a large population-based cancer registry. Data regarding demographics, histology, incidence, and survival were obtained on all patients with NHL registered in the Metropolitan Detroit Cancer Surveillance System, a participant in the Surveillance Epidemiology and End Results (SEER) Program of the National Cancer Institute. Incidence and survival trends from 1973 through 1995 were evaluated and stratified based on age at diagnosis, sex, race, and tumor grade. There were 11,978 patients diagnosed with NHL and recorded in the Metropolitan Detroit SEER registry from 1973 to 1995. The age-adjusted incidence rate increased from 8.6 to 15.8 per 100,000, leading to an overall increase in incidence of 83% and an average annual increase of 3.2% per year. Incidence increased significantly (p < 0.05) over time in all age groups except the youngest (ages 0-19) and in all demographic groups studied. Incidence was highest in white men and lowest in black women. The incidence of both low-grade and intermediate/high-grade NHL increased significantly for each age group (p < 0.05) except the youngest (ages 0-19). In the oldest patients (70+ years), the incidence of intermediate/high-grade NHL was almost double that of low-grade NHL. Five-year relative survival increased from 64% (1973-1983) to 68% (1984-1991) for patients with low-grade NHL and from 40% to 44% for those with intermediate/high-grade NHL. The increase in relative survival was only seen in whites, however, with 5-year relative survival in blacks decreased from 53% (1973-1983) to 45% (1984-1991). In metropolitan Detroit, the current NHL epidemic affects all age groups except the very young (ages 0-19), both sexes, and both whites and blacks and is due to increases in the incidence of both low-grade and intermediate/high-grade NHL. Five-year survival rates have increased for whites but not for blacks.

Adolescent↗
PubMed2000

Survival of patients with synchronous brain metastases: an epidemiological study in southeastern Michigan.

OBJECT: It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring more than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents. METHODS: Data obtained in 2682 patients with synchronous brain metastases treated between 1973 and 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 population increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median length of survival was 3.2 months. There was no significant difference in the median survival of patients with primary lung/bronchus and those with an unknown primary site (3.3 months and 3.2 months, respectively). CONCLUSIONS: Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in more than 90% of cases, is related to systemic disease; however, despite poor median survival times, certain patients will experience prolonged survival.

Adolescent↗
PubMed2000

An experimental evaluation of theory-based mother and mother-child programs for children of divorce.

This study evaluated the efficacy of 2 theory-based preventive interventions for divorced families: a program for mothers and a dual component mother-child program. The mother program targeted mother-child relationship quality, discipline, interparental conflict, and the father-child relationship. The child program targeted active coping, avoidant coping, appraisals of divorce stressors, and mother-child relationship quality. Families with a 9- to 12-year-old child (N = 240) were randomly assigned to the mother, dual-component, or self-study program. Postintervention comparisons showed significant positive program effects of the mother program versus self-study condition on relationship quality, discipline, attitude toward father-child contact, and adjustment problems. For several outcomes, more positive effects occurred in families with poorer initial functioning. Program effects on externalizing problems were maintained at 6-month follow-up. A few additive effects of the dual-component program occurred for the putative mediators; none occurred for adjustment problems.

Adaptation, Psychological↗
PubMed1999

Efficacy of a five-drug combination including ritonavir, saquinavir and efavirenz in patients who failed on a conventional triple-drug regimen: phenotypic resistance to protease inhibitors predicts outcome of therapy.

OBJECTIVE: to assess the safety and efficacy of a combination of ritonavir, efavirenz and two recycled nucleosides in patients who failed on a conventional triple-drug regimen including indinavir or ritonavir. METHODS: An open label study of ritonavir (100 mg twice daily), saquinavir (1000 mg twice daily), efavirenz (600 mg per day) and nucleoside analogues in 32 saquinavir- and efavirenz-naive protease inhibitor-experienced patients. Patients were included on the basis of plasma levels of HIV RNA above 5000 copies/ml while on conventional antiretroviral therapy. Phenotypic resistance and genotypic resistance mutations to saquinavir were assessed at baseline. Peak and trough plasma levels of saquinavir were monitored throughout the study. RESULTS: Median CD4 cell counts and median plasma HIV RNA at baseline were 258 x 10(6)/l and 4.31 log10 copies/ml, respectively. The plasma viral load decreased by a median of 1.20 log10 copies/ml and the CD4 cell count increased by a median 60 x 10(6) cells/l at week 24 of therapy. Seventy-one per cent of the patients achieved a plasma viral load < 500 copies/ml and 45% achieved a viral load < 50 copies/ml. Patients exhibiting phenotypic resistance to saquinavir at baseline experienced a median decrease in HIV RNA of 0.91 log10 copies/ml at week 24 of therapy, as compared with a decrease of 1.52 log10 copies/ml in those exhibiting sensitive viral strains (P = 0.03). Genotypic resistance to saquinavir was not predictive of virologic failure. CONCLUSION: Our results indicate that the combination of ritonavir, saquinavir and efavirenz is safe and effective at 24 weeks in over two-thirds of patients who previously failed on highly active antiretroviral therapy, and that the determination of phenotypic resistance may be of greater value than the detection of resistance mutations to predict the outcome of salvage therapy in this setting.

Adult↗
PubMed1999

A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution.

OBJECTIVE: Body fat redistribution ('lipodystrophy'), with gain in abdominal and trunk fat, and decline in facial and limb fat, is a newly recognized problem in patients with HIV infection that has been linked to use of HIV-1 protease inhibitors. Increased abdominal fat may predispose these patients to hypertension, diabetes, and coronary artery disease. At this time no effective treatment is available. We examined whether exercise training could reduce trunk fat in men with fat redistribution. DESIGN: Open-label pilot study. METHODS: Ten men with increasing abdominal girth participated in a 16 week pilot study of progressive resistance training with an aerobic component. They trained in a community health club three times per week. Total body lean and fat mass, and trunk fat mass, were assessed by dual-energy x-ray absorptiometry (DXA). RESULTS: After 16 weeks of exercise, strength increased for three of the four exercises tested (leg press + 13% [p < 0.02], leg extension + 19% [p < 0.03], seated row + 7% [p < 0.13], chest press + 18% [p < 0.0051). There was a significant decline in total body fat by 1.5 kg (= 2.1 percentage points, p < 0.01); most of the decline in body fat occurred in trunk fat, which decreased by 1.1 kg (p < 0.03). Weight, lean mass (+ 1.1 + 2.6 kg, p = 0.23), and bone mineral density measured by DXA did not change. No adverse effects were seen from the training. CONCLUSIONS: Exercise training may reduce trunk fat mass in HIV-positive men with fat redistribution. Controls trials of this approach are warranted.

Abdomen↗
PubMed1999

Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group.

BACKGROUND: Intermittent interleukin-2 therapy for HIV-1 by continuous intravenous infusion leads to sustained increase of CD4 T cells. This method of administration is, however, inconvenient and has limiting toxic effects. We did a randomised study to compare safety and efficacy of antiviral treatment alone or combined with various interleukin-2 regimens in HIV-1-infected patients. METHODS: 94 symptom-free patients, naïve to antiretroviral treatment, with CD4-T-cell counts of 250-550 cells/microL at baseline were randomly assigned zidovudine and didanosine alone (n=26) or combined with interleukin-2 administered intravenously (12 million IU/day, n=22) or subcutaneously (3 million IU/m2 twice daily, n=24) for 5 days, or were given polyethylene-glycol-modified (PEG) interleukin-2 (2 million IU/m2 intravenous bolus, n=22) administered every 2 months from week 2 to week 50 (seven cycles). Safety and immunological and virological results were monitored until week 56. FINDINGS: CD4-T-cell count increased to higher than baseline by a mean of 564 cells/microL (subcutaneous group), 676 cells/microL (intravenous group), 105 cells/microL (PEG group), and 55 cells/microL (antiretroviral-therapy group, p=0.0001). 68% and 77% of patients in the subcutaneous and intravenous groups, respectively, achieved an 80% increase of CD4 T cells (p<0.001). In these two groups, 50% of patients restored a CD4/CD8-T-cell ratio of more than 1. The groups did not differ significantly for changes in plasma HIV-1 RNA loads throughout the study. The duration of common side-effects of interleukin-2 was shorter in the subcutaneous group, which enabled outpatient treatment. Naïve and memory CD4 T cells, CD28 expression on CD4 and CD8 T cells, and restoration of in-vitro proliferative response to mitogens and recall antigens increased in the intravenous and subcutaneous groups. INTERPRETATION: Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit.

Adult↗