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Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 379 records · Page 21Linked to original sources

Expression of the intestinal T-lymphocyte associated molecule HML-1: analysis of 75 non-Hodgkin's lymphomas and description of the first HML-1 positive T-lymphoblastic tumour.

The expression of the gut intra-epithelial T-cell associated molecule HML-1, a trimeric protein of 150, 125, 105 kD, was studied in 75 T-cell lymphomas of different subtypes: 20 T-lymphoblastic lymphomas/leukaemias; 50 nodal peripheral T-cell lymphomas; and five intestinal T-cell lymphomas. Our results confirm: (i) the usefulness of the HML-1 monoclonal antibody as an immunohistochemical marker for intestinal T-cell lymphomas: and (ii) the lack of reactivity of HML-1 with nodal peripheral T-cell lymphomas. Moreover, expression of the HML-1 molecule was found for the first time in a case of T-lymphoblastic lymphoma/leukaemia. The patient presented with a mediastinal mass which consisted of HML-1 + neoplastic cells displaying a phenotypic profile consistent with early thymocytes. Genes coding for the alpha, beta, gamma and delta chains of the T-cell receptor were in a germline configuration. The neoplastic cells could have been derived from the small subset of HML-1 + thymocytes detectable in the cortex of normal human thymus.

Adolescent↗

Effect of perinatal anti-TCR2 treatment and thymectomy on serum immunoglobulin levels in the chicken.

Treatment of chickens as embryos and in the first six days after hatching with mg amounts of anti-TCR2 (alpha beta T cell antigen receptor) antibody plus thymectomy 6 to 8 days after hatching suppressed by more than 90% the TCR2 and TCR1 (TCR gamma delta) subpopulations in the blood. Thymectomy alone resulted only in a profound reduction (greater than 90%) of the absolute number of TCR1 cells, while the absolute number of TCR2 cells was reduced only by 65%. We were interested in the regulation of the immunoglobulin synthesis in these T cell deficient chickens. We determined serum IgG, IgM and IgA levels and found a profound selective reduction (by about 90% on average) of the serum IgA level in anti-TCR2 antibody treated plus thymectomized chickens. In chickens which had been thymectomized only, the serum IgA level was reduced on average only by about 60%. Serum IgG and IgM levels were not reduced in any group. Thus, there was a positive correlation of the serum IgA level and the absolute number of TCR2 cells in all groups. These results indicate that T cells which play a role in IgA specific isotype switching or in IgA B cell differentiation belong to the TCR2 subpopulation.

Animals↗

Evaluation of endosonography in TN staging of oesophageal cancer.

Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis. Resection, the only curative treatment, is confined to early tumour stages. Tumours with local infiltration are usually unresectable and require palliative treatment. Computed tomography has been widely used for preoperative staging but often fails to define this correctly. Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours. In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement. Thirty seven of these patients underwent operation, resection, or dissection and entered the study. The intraoperative findings or the histopathological assessment, or both, were taken as a reference. For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test). This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.

Adult↗

Identification of different laminin binding proteins in basolateral cell membranes of human colorectal carcinomas and normal colonic mucosa.

The adhesive properties of tumour cells to laminin, the major glycoprotein of basement membranes, play a crucial part in the complex process of tumour invasion and metastasis. We therefore investigated the expression of laminin binding proteins in isolated basolateral cell membranes of human colorectal carcinomas and the adjacent normal colonic mucosa. Cell membrane binding assays and immunoblotting experiments showed appreciable quantitative and qualitative differences in the expression of these proteins in neoplastic and normal tissue. Epithelial basolateral cell membranes of colorectal carcinomas bound five to eight times more radioactive labelled laminin than basolateral cell membranes of the adjacent normal colonic epithelium. The expression of laminin binding proteins with Mr 66,000-69,000 daltons corresponding to the so called 'Mr 67,000 dalton laminin receptor' was three to four times higher in colorectal carcinomas than in normal colonic epithelium. In addition, laminin binding proteins with higher molecular weights, which may be related to the family of integrins, were also increased in colorectal carcinomas. In particular, laminin binding proteins with Mr 180,000 daltons were exclusively expressed on neoplastic epithelial cells of human colorectal carcinomas. Our data suggest that certain classes of laminin binding proteins may be selectively expressed on colonic tumour cells, leading to an increased capacity for migration, invasion, and metastasis.

Carrier Proteins↗

Ber-MAC3: new monoclonal antibody that defines human monocyte/macrophage differentiation antigen.

A new monoclonal antibody Ber-MAC3 is reported. It recognises a formol sensitive epitope of a not yet clustered monocyte/macrophage specific 140 kilodalton glycoprotein that is expressed on the cell surface and in the cytoplasm. In 30 cases of acute and chronic leukaemia, Ber-MAC3 staining was restricted to 15 myeloid leukaemias of M4 and M5 types. The tumour cells of two cases of true histiocytic malignancies were Ber-MAC3 positive, whereas those of all 280 malignancies of lymphocytic origin were negative. The latter included 52 cases of Hodgkin's disease and 41 cases of Ki-1 positive anaplastic large cell lymphomas which had previously been classified as true histiocytic lymphomas. Ber-MAC3 therefore seems to be of considerable value for selective identification of monocytes and macrophages at a certain stage of differentiation and seems to be suitable for diagnosing myelomonocytic or monocytic leukaemia and neoplasms of true histiocytic origin.

Antibodies, Monoclonal↗

Ber-ACT8: new monoclonal antibody to the mucosa lymphocyte antigen.

Using a newly established HTLV-1 positive T cell line as an immunogen, a new monoclonal antibody, Ber-ACT8, was produced. It reacts with in vitro activated T cells and a small subset of normal resting T cells, but not with resting B cells or any of the 29 established human permanent cell lines tested. Immunohistological analysis of a wide spectrum of human tissues showed that Ber-ACT8 reactivity is restricted to a few T cells in the peripheral blood, the extrafollicular areas of lymph nodes and tonsils, and splenic red pulp. In the gut Ber-ACT8 labelled most intraepithelial T cells and up to 50% of lamina propria T cells. The antibody also immunostained T cells present in the oral and bronchial mucosa. Double labelling on splenic cells, fresh blood lymphocytes, and in vitro activated T cells showed that most Ber-ACT8 positive cells coexpressed CD8. Ber-ACT8 did not react with any of the 14 Hodgkin's lymphomas nor any of the 172 non-Hodgkin's lymphomas tested, with the exception of 10 cases of T cell lymphomas, five of which were located in the jejunum and associated with coeliac disease, and one B cell lymphoma, and most cases of hairy cell leukaemia tested. Parallel immunostainings with Ber-ACT8, anti-TCR-beta (beta F1), and anti-TCR-delta showed that most Ber-ACT8 positive T cells carry the TCR of alpha beta type. Comparison of Ber-ACT8 with HML-1, B-ly7, and LF61 showed essentially the same reactivity and an identical molecular target. The molecular structure recognised seems to be a trimeric molecule with components of 150, 125 and 105 kilodaltons, with the Ber-ACT8 epitope localised on the 150 kilodalton chain. The 150 kilodalton molecule contains an 0-linked carbohydrate moiety of about 10 kilodaltons. Because of its very selective distribution, the trimeric antigen is a powerful reagent for the diagnosis of gut T cell-derived T cell lymphomas and other extranodal T cell lymphomas, as well as hairy cell leukaemia.

Animals↗

Cardiovascular effects of SKF 104078 in lambs.

We studied the effects of SKF 104078 in anesthetized, newborn lambs and compared it to nonspecific alpha-receptor blockade by tolazoline. SKF 104078 infusion decreased pulmonary and systemic arterial pressures in newborn lambs when infused during normoxic ventilation. When infused during hypoxia, SKF 104078 decreased cardiac output and systemic blood pressure without affecting pulmonary pressure. Due to the predominance of systemic effects, the usefulness of SKF 104078 in states of hypoxic pulmonary vasoconstriction is limited.

Adrenergic alpha-Antagonists↗

Thyroid volume and goitre prevalence in the elderly as determined by ultrasound and their relationships to laboratory indices.

In 569 unselected elderly subjects over 60 years from the general population of an iodine-deficient area, a palpation and an ultrasound investigation of the thyroid were performed. Additionally, thyroid hormone values were determined in 466 of the 569 subjects (81.9%) and urinary iodine excretion in 491 subjects (86.3%). By palpation, no thyroid enlargement was noticed in 302 subjects (54.2%), goitre Ia in 98 (17.6%), goitre Ib in 94 (16.9%), goitre II in 53 (9.5%), and goitre III in 10 (1.8%). The thyroid volumes (medians) by ultrasound were 18.6 ml in the entire group, in women (N = 489) 19.2 ml, and in men (N = 80) 16.6 ml. One hundred and one subjects had a thyroid nodule (17.6%), 43 persons cystic lesions (7.6%). If, according to the literature, a goitre is defined as a thyroid enlargement of more than 18 ml in women and more than 25 ml in males, a goitre prevalence of 54.2% in females and of 22.5% in males was obtained. The goitre prevalence in the entire group was calculated as 49.7%. Thyroid hormone measurements showed in subjects with goitre a significant lower TSH value (p less than 0.001) and a higher thyroglobulin value (p less than 0.001). In summary, the study shows a high prevalence of goitre in elderly subjects, a high prevalence of nodules in these thyroids, a negative correlation of goitre volume with TSH, and a positive correlation of goitre volume with the thyroglobulin concentration.

Aged↗

[Proliferation of Reed-Sternberg cells in 5 Hodgkin's cell lines].

Using the monoclonal antibody Ki-67 that detects a cell proliferation-associated human nuclear antigen, incorporations of bromodeoxyuridine (Brud) and 3H-Thymidine, we studied the proliferative capacity of Reed-Sternberg (RS) cells in Hodgkin's cell lines L428, KM-H2, Holden, L540 and L591. The results revealed that in all cell lines, except L591, more than 55% of RS cells were found positive for Ki-67, and over 50% of them had Brud incorporation 5 days after cultivation. The positive score for 3H-Thymidine incorporation was low, and it is assumed that the time taken for 3H-Thymidine in cultivation was short. It shows that at least half of RS cells in these cell lines have proliferation-associated nuclear antigen or can synthesize DNA, and so they are proliferative.

Antibodies, Monoclonal↗

[Immunohistochemistry and morphometry of bone marrow in acquired immunodeficiency syndrome with special emphasis on megakaryopoiesis and macrophages].

An immunomorphometric study was performed on formalin-fixed and paraffin-embedded bone marrow biopsies in 20 patients with AIDS (18 males, 2 females-stage IV A-D). In comparison with a control group megakaryocytes (CD61-Y2/51) revealed not only a significant hyperplasia, but remarkably irregular shapes of cells and nuclei, together with a disturbance of the nuclear-cytoplasmic ratio. No predominance of micromegakaryocytes as in myelodysplastic syndromes was observable. Contrasting idiopathic (immune)-thrombocytopenia, HIV-infected patients with a pronounced depression of the platelet count did not show a significant elevation of the number of promegakaryoblasts. This feature is in keeping with findings of a severe impairment of progenitor cell proliferation and differentiation in AIDS. There was a pronounced increase in the macrophage population (PG-M1). This alteration may be related to inflammatory lesions accompanying this disorder as well as to an enforced and premature destruction of hematopoietic cell elements in the myeloid stroma.

Acquired Immunodeficiency Syndrome↗

[Expression of latent membrane proteins (LMP) of Epstein-Barr virus in malignant lymphomas].

The presence of Epstein-Barr virus (EBV) DNA and antigens was assessed by polymerase chain reaction and immunohistology, respectively, in a total of 92 cases of Hodgkin's disease, angioimmunoblastic lymphadenopathy, CD30-positive anaplastic large cell (ALC) lymphomas, and AIDS-associated atypical lymphoproliferations (ALP). Proportions of the EBV DNA-positive lesions showed latent membrane protein (LMP) expression; some of the LMP-positive ALC lymphomas and ALP cases also displayed EBNA2 immunostaining. BZLF1-protein and gp250/350 immunoreactivity were absent in all instances indicating latent EBV infection. Since the LMP gene has transforming potential, our findings support the concept of a pathoetiological role for EBV in these lymphoproliferative lesions.

Acquired Immunodeficiency Syndrome↗

[Lymphoid tissues and AIDS: role of lymphocytes and follicular dendritic cells (FDC)].

Currently discussed models of AIDS pathogenesis attribute a pivotal role to HIV-variants developing in T cells during the course of the disease resulting in an increasingly rapid depletion of the infected T cells. Such models do not however explain the morphological findings observed in AIDS lymphadenopathy. To clarify the significance of the hyperplasia and subsequent destruction of the lymphoid follicles in HIV-related lymphadenopathy, we used in situ hybridization in combination with immunohistological labelling techniques to identify the phenotype of HIV-infected cells in lymph nodes. In addition to few T helper cells, mainly in germinal centres, large amounts of HIV-RNA were found in CD4-negative follicular dendritic cells (FDC) rather than in macrophages or other cells. This finding is well in accordance with the recent observations made by other authors suggesting that purified FDC can be infected with HIV in vitro. Furthermore, TNF alpha expression is localized mainly in centroblasts (activated B cells) of germinal centres. TNF alpha, released by antigen-activated B cells in vitro, has been shown to induce HIV replication in latently infected T cells. On the basis of these observations we propose that latently infected CD4+ T cells, having entered germinal centres, start HIV replication under the influence of cytokines present in this microcompartment of all lymphoreticular tissues. Here the T cells infect FDC which, in turn, pass on the virus to new healthy T helper cells. This model may explain both peculiarities of the lymphadenopathy syndrome as well as the long latency period of HIV-infection, ultimately leading to AIDS.

Acquired Immunodeficiency Syndrome↗

Risk factors for infection in fracture war wounds (1973 and 1982 wars, Israel)

The development of post-surgical wound infection was compared in two groups of soldiers who sustained fractures or amputations on the battlefield during the first month of the 1982 and 1973 wars. Risk factors for the development of post-surgical wound infection were sought. In the 1982 group, numbering 184, the four variables independently associated with infection were multiple operations during the follow-up period; drains inserted in the first operation; extensive tissue loss; and blood transfusion during the first operation. For the 1973 group, numbering 130, the significant variables were multiple operations; amputations (highly correlated with extensive tissue loss); injury involving other body systems in addition to the fracture; and open drains. The high risk associated with open drains in both wars raises doubt about their usefulness. The main distinction between injuries of the two wars was the high prevalence (72.3%) of multi-system injuries in 1973 versus low prevalence (29.2%) in 1982. Overall infection rates were similar (30.5% and 31.5%), but infections at the site of the fracture were twice as high in 1982. Pseudomonas was the most common single species of bacteria isolated from infected wounds (26% in 1982, 33.6% in 1973). It appeared in the wounds relatively late, 10-14 days after admission.

Adult↗

Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease.

Transforming growth factor (TGF) beta 1 has been implicated in the control of hepatocyte growth and stimulation of extracellular matrix synthesis in acute and chronic liver disease. The cellular localization of transforming growth factor (TGF) beta 1 and beta 2 RNA transcripts was determined in normal and fibrotic liver by in situ hybridization with [35S]-labeled RNA probes in combination with immunostaining for cell type characteristic markers. Fibrotic specimens were from patients with hepatitis B virus infection or alcohol abuse and rats with fibrosis secondary to bile duct ligation and scission. In normal liver, low levels of TGF beta 1 transcripts were found in some portal tract stromal cells, and TGF beta 2 RNA was not detectable. In fibrotic liver, high TGF beta 1 RNA levels were present in most mesenchymal liver cells, in most inflammatory cells, and in few bile duct epithelial cells. Hepatocytes did not express this cytokine with the exception of few limiting plate hepatocytes in cases of human cirrhosis with high activity. TGF beta 2 transcripts were detected at high levels in proliferating bile ducts of fibrotic livers, but were absent in all other cell types. TGF beta 1 expression in the liver is thus a function predominantly of mononuclear and mesenchymal cells as well as of some hepatocytes, whereas TGF beta 2 expression is a specific property of bile duct epithelial cells that may be related to the formation of specialized periductular connective tissue during bile duct proliferation.

Animals↗

HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit.

The monoclonal antibodies HML-1, B-ly7 and Ber-ACT8 recognize intramucosal gut T lymphocytes, activated cells, and hairy cell leukemia. The antigen on hairy cells consists of three glycoproteins (160 kappa D, 130 kappa D and 105 kappa D unreduced; 145 kappa D and 120 kappa D reduced). These peptides have biochemical features reminiscent of integrins but we have shown by immunoprecipitation that they are not known integrin subunits. We have used a newly produced antibody (BP6) to purify this molecule and shown by N-terminal sequence analysis that the smallest subunit is the product of integrin beta 7 cDNA. This molecule is thus a new member of the integrin family of leucocyte adhesion proteins. Immunoprecipitation experiments indicate that the two larger subunits are recognized by HML-1, B-ly7 and Ber-ACT8.

Amino Acid Sequence↗

Temporal and spatial patterns of proto-oncogene expression at early stages of toxic liver injury in the rat.

Sequential and transient expression of c-fos, c-jun, c-myc, c-Ha-ras and c-Ki-ras proto-oncogene RNA transcripts with zonal heterogeneity was demonstrated in virtually all hepatocytes of adult rat liver by in situ hybridization with single-stranded, [35S]-labeled cRNA probes at various time points after intraperitoneal administration of a single dose of carbon tetrachloride (CCl4). After a brief interval, elevated RNA levels of these genes were also observed in nonparenchymal cells. A second phase of proto-oncogene expression was characterized by high RNA levels in only a fraction of parenchymal cells with preference of mediolobular areas. Distribution and number of these cells were comparable tl hepatocytes expressing the proliferation-associated nuclear antigen Ki-67 72 hours after toxic injury. Oncogene expression in the nonparenchymal compartment correlated with distinct morphologic changes preceding type I procollagen gene expression by desmin-positive perisinusoidal cells, accumulating together with numerous c-fms expressing cells in the areas of hepatocellular necrosis. We conclude that zonal hepatic destruction by carbon tetrachloride induces proto-oncogene expression with distinct temporal and spatial patterns initiated by the most severely damaged hepatocytes. Proto-oncogene products thus represent valuable markers of cellular activation preceding and accompanying various aspects of tissue repair reactions.

Animals↗

[The incidence of endemic sprue/celiac disease in Berlin (West). A prospective study with short discussion of a case].

This study was carried out between June 1986 and May 1988 in Berlin (West). In cooperation with 5 Pathological Departments, we prospectively recorded every bioptical diagnosis of total/subtotal villus atrophy (group S) or of partial villus atrophy (group SV). In addition, we registered anamnestic, clinical and laboratory findings from these patients. The diagnosis of coeliac disease was considered verified if the patient showed an unequivocal improvement of his clinical conditions and laboratory findings within three months on a gluten-free diet. In total, 42 patients were registered, among them were 29 with mucosal alterations typical for coeliac disease and 13 whose biopsies showed partial villus atrophy. The diagnosis of coeliac disease could be verified in 28 patients, among them one woman with intestinal lymphoma after longstanding untreated coeliac disease. A second patient with complete villus atrophy had intestinal lymphoma but without preceeding coeliac disease. Our findings show that the incidence of coeliac disease in Berlin is 1 out of 2113 newborn children. This figure is similar to the data reported from France, yet being clearly lower than those from Western Ireland, Switzerland and Sweden. Women are affected twice as often as men. 20 out of 28 patients were children under five years of age. The most common symptoms were meteorism/flatulence, recurrent diarrhea, loss of body weight, or inappropriate growth. 70% of the patients suffered from anaemia, the D-Xylose-test was pathological in 92% of the patients.

Aged↗