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H Stein

Publications and source records attributed to H Stein.

At least 289 records · Page 16Linked to original sources
PubMed1994

Renin inhibitors: C-terminal oxetanes as potent transition-state mimics.

A novel transition-state mimic containing a C-terminal oxetane has been developed. Renin inhibitors incorporating this fragment exhibit enhanced potency against human plasma renin at physiological pH. The binding affinity of this new species has allowed size reductions at other sites.

Dipeptides↗
PubMed1994

High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS.

OBJECTIVE: To determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS. METHODS: sCD30 values were determined by an enzyme-linked immunosorbent assay (ELISA) on serum samples collected at the time of the first evidence of HIV-1 infection in 110 individuals with a median follow-up of 56 months (range, 12-88 months), at the A1 (74 cases) or A2 (36 cases) stages of the 1993 revised Centers for Disease Control and Prevention classification. The data were evaluated using established clinical and immunological parameters, including circulating CD4+ T-cell count. The controls were 110 blood donors and 51 HIV-1-negative subjects belonging to groups at risk for HIV-1 infection. RESULTS: Elevated sCD30 levels (> 20 U/ml) were found in 83.6% of HIV-1-infected cases and in 47% of at-risk seronegatives. Data analysis revealed that HIV-1-infected patients with higher sCD30 levels (> 35 U/ml) experienced faster disease progression (P = 0.0002). This was also the case in patients at the earliest stage (A1) of HIV infection (P = 0.0027). In these latter cases the predictive value of sCD30 was independent of the initial absolute number of circulating CD4+ lymphocytes. CONCLUSIONS: Serum levels of sCD30 are increased in the large majority of patients in the early phase of HIV-1 infection and represent an indicator of progression to AIDS independent of other prognostic parameters.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Frequent presence of latent Epstein-Barr virus infection in lymphoepithelioid cell lymphoma (Lennert's lymphoma).

This study deals with the investigation of the biological significance of an Epstein-Barr virus (EBV) infection in lymphoepithelioid cell lymphoma. A selection of EBV-detection techniques was applied to 15 cases, including polymerase chain reaction (PCR) for the detection of EBV-DNA, in situ hybridization (ISH) for the cellular localization of EBV-encoded small nuclear (EBER 1 and EBER 2) and immediate-early (BHLF) RNAs, and immunohistology for the detection of EBV-encoded latent membrane protein (LMP) expression. PCR and EBER-ISH produced congruent results in those cases with amplifiable DNA, leading to an EBV presence in 11/15 lymphoepithelioid cell lymphoma cases (73%). EBER-ISH combined with immunohistology localized the virus predominantly in several B immunoblasts and small B lymphocytes in eight of the EBV-positive cases, five of which also contained single infected lymphocytes expressing T-cell characteristic antigens. LMP was detected using immunohistology in only a proportion of immunoblasts in four of these cases. The remaining three EBV-positive lymphoepithelioid cell lymphoma cases contained only single EBER-positive small B lymphocytes without LMP expression. No case contained BHLF-RNA expressing cells. These data imply that, although latently EBV-infected cells are frequently present in lymphoepithelioid cell lymphoma cases, the virus is probably not directly involved in the pathogenesis of this entity.

Antibodies, Monoclonal↗
PubMed1993

Recombinant human interleukin-4 inhibits growth of some human lung tumor cell lines in vitro and in vivo.

Cytokines play an important role in activating the immune system against malignant cells. One of these cytokines, interleukin-4 (IL-4) has entered clinical phase I trials because of its immunoregulatory potency. In the present study we report that recombinant human (rh) IL-4 has major direct antiproliferative effects on one human lung cancer cell line (CCL 185) in vitro as measured by a human tumor cloning assay (HTCA), tritiated thymidine uptake, and counting cell numbers and marginal activity in a second cell line (HTB 56) in the HTCA. This activity could be abolished by neutralizing antibody against rhIL-4. The biological response of the tumor cells to the cytokine is correlated with expression of receptors for human IL-4 on both the mRNA level and the protein level. The responsive cell line, CCL 185, secretes IL-6 after being incubated with rhIL-4. On the other hand, neutralizing antibodies against IL-6 showed no influence on the growth modulatory efficacy of rhIL-4 in this cell line. Furthermore, CCL 185 does not show detectable production of IL-1, tumor necrosis factor alpha or interferon gamma after incubation with rhIL-4. Thus, the response to rhIL-4 is not mediated through autocrine production of these cytokines triggered by rhIL-4. In a next series of experiments some of the cell lines were xenotransplanted to BALB/c nu/nu mice. Subsequently, the mice were treated for 12 days with two doses of 0.5 mg/m2 rhIL-4 or control vehicle subcutaneously per day. Treatment with rhIL-4 yielded a significant inhibition of tumor growth versus control in two of the non-small cell lung cancer cell lines being responsive in vitro (CCL 185, HTB 56). Histology of the tumors in both groups showed no marked infiltration of the tumors with murine hematopoietic and lymphocytic cells consistent with the species specificity of IL-4. In contrast, no tumor growth inhibition was found in the small cell lung cancer cell lines (HTB 119, HTB 120) being nonresponsive in vitro. We conclude that rhIL-4 has direct antiproliferative effects on the growth of some human non-small cell lung cancer cell lines in vitro and in vivo, which together with its regulatory effects on various effector cell populations makes this cytokine an interesting candidate for further investigation in experimental cancer treatment.

Animals↗
PubMed1993

Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas.

We investigated 81 cases of peripheral pleomorphic T-cell lymphoma (PMTCL) occurring in human immunodeficiency virus-negative Europeans for the presence of Epstein-Barr virus (EBV)-DNA through polymerase chain reaction (PCR) for the presence of EBV-encoded small nuclear RNAs (EBER) and immediate early mRNAs (Bam H-fragment, lower strand frame [BHLF]) by in situ hybridization (ISH) and for EBV-encoded latent membrane protein (LMP) and nuclear antigen 2 (EBNA2) by immunohistology (IH). EBER-ISH, which could be applied on all cases, showed an overall incidence of EBV-infected cells in 38 of 81 cases (47%) of PMTCL. These data could be confirmed by PCR, which produced congruent results in the cases with amplifiable DNA. By EBER-ISH, the virus was located in the tumor cells in 30 of the 38 EBV-positive cases, with the proportion of the infected cells ranging from 1% to 100%. In 18 of these cases and in the 8 cases without EBV-infected tumor cells, the virus was, respectively, either additionally or exclusively detectable in occasional nonmalignant lymphoid bystander cells. An LMP expression was observed in several of the EBER-expressing tumor cells in 18 cases, whereas EBNA2 was detectable only in one case, which also displayed signs of viral replication. Some nonmalignant EBV-infected B immunoblasts also expressed LMP in several cases. Primary cutaneous and enteropathy-associated PMTCL displayed less frequent EBV infection when compared with other extranodal or nodal manifestations.

Adult↗
PubMed1993

[Mediastinal chloroma with right heart involvement. Unusual cause of a superior vena cava syndrome].

For four months a 28-year-old man had been suffering from a sensation of pressure in his head when lying down, swelling of the face, exertional dyspnoea and weight gain of 9 kg. Biochemical tests and chest radiograph were unremarkable. Echocardiography revealed a 3 x 5 cm mass in the right atrium, extending into the superior vena cava whose lumen was narrowed to a few millimetres. Computed tomography and magnetic resonance imaging were suggestive of a malignant tumour. Bone marrow biopsy as well as transvascular and mediastinoscopically obtained biopsies failed to provide a pathological diagnosis. Exploratory thoracotomy uncovered a nonresectable chloroma surrounding both venae cavae. It had penetrated into the right and left atria, as well as the pulmonary veins. A Gore-tex bypass was placed between the innominate vein and right atrial appendage. The tumour was identified as a local manifestation of acute myeloid leukaemia. Treatment with idarubicin (12 mg/m2 daily for 3 days) and adriamycin (1.5 mg/m2 daily for 4 days) followed by radiotherapy with 35 Gy achieved partial remission and 15 months after onset of treatment the patient is in a good general condition.

Adult↗
PubMed1993

Overexpression of CD3 eta during thymic development does not alter the negative selection process.

To elucidate the role of CD3 eta in thymic development and to determine whether CD3 eta is involved in the negative selection process, CD3 eta was overexpressed > 100 fold in transgenic (tg) mice using a Thy-1 promoter and regulatory elements. CD3 eta was readily observed in the majority of cortical thymocytes and in a fraction of medullary thymocytes in tg mice by immunohistochemical staining with an anti-CD3 eta-specific mAb. In contrast, endogenous CD3 eta levels were too low to detect in normal littermates. Flow cytometric analysis demonstrated an increased level of TCR on thymocytes with intermediate TCR density in tg animals and parallel biochemical studies showed a marked increased in TCR-associated CD3 zeta-eta heterodimers and CD3 eta-eta homodimers relative to controls. Despite this change in surface TCR phenotype, there was no significant alteration in the total numbers or proportion of CD4+CD8+ double-positive or CD4+CD8- or CD4-CD8+ single-positive thymocytes or peripheral T cells. Percentages of SP V beta 5, V beta 6, and V beta 8 thymocytes in tg animals were unaltered compared to normal littermates when backcrossed either to C57BL/6 (H-2b) or DBA/2 (H-2d) backgrounds. Furthermore, induction of DNA fragmentation with anti-CD3 epsilon mAb treatment in vivo was not significantly different for tg and normal littermates. Collectively, these data imply that CD3 eta is not a limiting component of the negative selection process.

Animals↗
PubMed1993

Expression of cytokines and growth factors in human glomerulonephritides.

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, from the various autocrine and paracrine mediators identified in vitro and in animal models, so far only a few have been demonstrated in selected human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodies (ANCA), an example of an acute form of GN, and mesangial IgA GN, usually a chronic form of GN, with immunocytochemistry, in situ hybridization and the polymerase chain reaction. Normal renal tissue from tumour nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrating mononuclear cells in glomeruli and in the interstitium expressed interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha, IL-2, interferon (IFN)-gamma, platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epithelial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cytokine and growth factor receptors TNF-R, IL-1R type II, IL-2R, IFN-gamma R and PDGF beta-R. In contrast, in mesangial IgA-GN, IL-1 beta, TNF-alpha, IFN-gamma and IL-2 were usually absent in glomeruli. Mesangial expansion in this disorder was accompanied by an increased expression of PDGF, PDGF beta-R, TGF-beta and IL-6 in mesangial areas. In both conditions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistry).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Histological features of prognostic significance in CML--an immunohistochemical and morphometric study (multivariate regression analysis) on trephine biopsies of the bone marrow.

To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph(1+)-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro- and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.

Adolescent↗
PubMed1993

Fetal endocrine and renal responses to in utero ventilation and umbilical cord occlusion.

OBJECTIVE: Fetal to neonatal transition involves a myriad of endocrine and renal adaptive changes triggered by multiple simultaneous stimuli. We examined the extent to which ventilation and umbilical cord occlusion have an impact on the many endocrine and renal function changes in fetal sheep at 133 +/- 1 day of gestation. STUDY DESIGN: Nine fetuses were chronically prepared with an endotracheal tube, vascular and bladder catheters, and an inflatable umbilical cord occluder. After a 2-hour control period fetuses were treated with commercially prepared surfactant and ventilated with 100% oxygen. One hour after the onset of stable ventilation the umbilical cord was occluded and the animals were monitored for 3-hours. RESULTS: In response to ventilation fetal arterial PO2 increased (18 +/- 1 to 86 +/- 29 mm Hg) and remained significantly above control values after cord occlusion. Fetal arterial pH, hematocrit, and mean arterial pressure and heart rate did not change during the study. Ventilation alone evoked significant increases in epinephrine and norepinephrine concentrations. Renal responses to ventilation included significant decreases in urine flow rate, fractional sodium excretion, and fractional water excretion. Neither ventilation nor cord occlusion resulted in significant changes in plasma concentrations of atrial natriuretic factor, arginine vasopressin, and angiotensin II or in glomerular filtration rate, urine osmolality, free water, and osmolar clearances. CONCLUSIONS: (1) Mechanical ventilation and oxygenation alone increase circulating fetal catecholamine levels. (2) The addition of umbilical cord ligation has minimal impact on fetal endocrine and renal adaptive responses.

Animals↗