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Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 397 records · Page 22Linked to original sources
PubMed1991

Diffuse lymphocyte-predominant Hodgkin's disease (diffuse paragranuloma). A variant of the B-cell-derived nodular type.

Lymph node sections from 10 cases of mixed nodular/diffuse and 10 cases of completely diffuse lymphocyte-predominant Hodgkin's disease (LPHD) were immunophenotyped. The results obtained were compared with those of nodular LPHD (nodular paragranuloma). In conventional stains, nodular/diffuse LPHD differed from diffuse LPHD in the presence of nodularity, which can be best demonstrated with silver impregnation. Immunohistologic analysis showed a correlation of the difference in nodularity with the presence or absence and pattern of follicular dendritic cell (FDC) meshwork, ie, a relatively sharply defined and large spherical meshwork was present in nodular areas of nodular/diffuse LPHD, whereas FDCs were either absent or present in a diffuse, ill-defined meshwork, usually of small size, in the diffuse zones of nodular/diffuse LPHD and in diffuse LPHD. The amount of FDC meshwork corresponded roughly to the number of reactive B cells and T cells, meaning that in diffuse areas significantly fewer B cells and more T cells were observed than in nodular areas. The immunohistologic analysis also showed that the antigen profile (positivity with the monoclonal B-cell marker L26 in the majority [14/20] of cases and negativity for CD15 in all but one of 20 cases) of the tumor cells in both nodular/diffuse LPHD and diffuse LPHD were comparable while it was different from the antigen profile (L26- and CD15+) in most cases of nodular sclerosis and mixed cellularity types of HD. This suggests that the considered subtypes of LPHD differ mainly in FDC pattern, but not in origin and nature of the tumor cells. This further justifies assignment of the above-mentioned LPHD subtypes to the category paragranuloma (LPHD).

B-Lymphocytes↗
PubMed1991

The surgical treatment of severe comminuted intraarticular fractures of the distal radius with the small AO external fixation device. A prospective three-and-one-half-year follow-up study.

Although fractures of the distal radius are very common, an optimal treatment has not been clearly delineated. This is a prospective study of 40 patients, mainly young and active adults, with comminuted and unstable intraarticular fractures of the distal radius. The end results of closed reduction and rigid fixation with the small AO external fixator includes 36 patients (90%) with excellent and good results. Roentgenograms of 33 of these patients showed accurate alignment of the healed fractures. Four patients (10%) had a fair functional result, with a partial restriction of the range of movement, although roentgenograms demonstrated good alignment of the healed fractures. The small AO external fixator is both a useful and convenient method for the reconstruction and treatment of comminuted intraarticular fractures of the distal radius.

Adult↗
PubMed1990

Differential expression of homing-associated adhesion molecules by T cell subsets in man.

The ability of lymphocyte populations to recognize and bind high endothelial venules during homing into lymphoid tissues and sites of chronic inflammation is critically dependent on their expression of certain homing-associated adhesion molecules known as homing receptors (HR). In animal models, certain lymphocyte populations, particularly subsets of memory or previously activated lymphocytes, demonstrate tissue-selective homing behavior, and it has been hypothesized that differential expression of HR accounts for this selective migration. In this study, we analyzed expression of human HR--the Dreg 56/Leu 8-defined peripheral lymph node (PLN) HR (also known as LECAM-1), H-CAM (CD44), and alpha 4-integrins (CD49d; VLA-4)--among subsets of thymocytes and peripheral blood T cells to identify populations with differential homing potential. In the thymus, these three HR classes are differentially regulated relative to phenotypically defined maturational stages, but are all expressed on the mature, surface CD3high subset. In the peripheral blood, virgin T cells (LFA-3/CD58low) show uniform high expression of the PLN HR, uniform relatively low expression of H-CAM and alpha 4-integrin, and lack markers of tissue association--the mucosal and cutaneous lymphocyte associated Ag (MLA and CLA Ags) defined by mAb Ber ACT8 and HECA-452, respectively. In contrast, circulating memory T cells (LFA-3/CD58high) are bimodal with respect to PLN HR expression, show uniform high expression of H-CAM and alpha 4-integrin, and contain essentially all the CLA and MLA Ag-bearing T cells. The circulating skin-associated T cell subset (CLA Ag+; 10 to 15% of total T cells) is predominantly PLN HR+, and shows high levels of both the alpha 4- and beta 1-integrin chains. The distinct mucosa-associated T cell subset (MLA Ag+; 1 to 3% of peripheral blood T cells) is predominantly PLN HR-; and is alpha 4high, but beta 1low. These findings indicate the independent regulation of homing-associated adhesion molecules among populations of memory/previously activated T cells, and suggest that the expression patterns of these molecules contribute to, or perhaps determine, the tissue distribution of these subsets.

Adult↗
PubMed1990

The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity.

Tp103 is a 103-kDa T cell activation molecule that defines an alternative activation signal for human T lymphocytes. It is absent from or present in only low amounts on resting T cells but is expressed strongly after activation. Cross-linking of Tp103 via a mAb CB.1 leads to triggering of functional activities in preactivated CD3+ T lymphocytes. By using mAb CB.1 in immunohistology we found that Tp103 is expressed in epithelial cells of various tissues, such as kidney, prostate, epidermis and on endothelia of liver, spleen, lungs, and most vessels, and in bile duct canaliculi in the liver. We found a carcinoma cell line expressing Tp103 and could precipitate a 110-kDa molecule from the surface of these cells. We considered several known molecules of similar distribution and molecular mass for identity with Tp103 and show here that Tp103 is probably identical to the proteolytic enzyme dipeptidyl aminopeptidase IV. When we purified Tp103 by affinity chromatography, typical dipeptidyl aminopeptidase IV activity copurified with Tp103. On activated T cells the enzymatic activity associated with Tp103 is expressed on the outside of the cell. We show that mAb CB.1 recognizes the same molecule as the anti-CD26 mAb anti-Ta1. The anti-Ta1 mAb was found to have T cell-activating activity too, but to differ in its requirements for triggering of T lymphocytes.

Antibodies, Monoclonal↗
PubMed1990

The HML-1 antigen of intestinal lymphocytes is an activation antigen.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.

Antibodies, Monoclonal↗
PubMed1990

Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease.

Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy.

Antibodies, Monoclonal↗
PubMed1990

Steroid receptors and proliferative activity in non-neoplastic and neoplastic endometria.

In the glands of cyclic endometria, proliferative activity (PA), as revealed by expression of the Ki-67 antigen, is highest in the proliferative phase (P) and early secretory phase (S1). The PA decreases in the middle secretory phase (S2). In the stroma the PA is low during the whole cycle. In P and S1, the oestrogen receptor (ER) and the progesterone receptor (PR) are strongly expressed in glands and stroma. The number of positive cells and the staining intensity decreases in S2, particularly in the glands. In atrophic endometria, fibro-glandular polyps and in endometria with arrested secretion the PA is low in both glands and stroma. ER and PR can be detected in glands and stroma. The PA in atypical hyperplasias is only slightly higher than in cyclic endometria and endometria with simple hyperplasia. The ER and PR levels are comparable to those in proliferative endometria. The PA of endometrial adenocarcinomas is positively and the ER and PR negatively correlated with the degree of de-differentiation. No ER-negative carcinoma displays the PR. Immunohistologically, non-neoplastic receptor positive tissue can be seen in many ER- and PR-negative carcinomas. These structures may falsify the biochemical receptor analysis.

Adult↗
PubMed1990

Megakaryocyte precursors (pro- and megakaryoblasts) in bone marrow tissue from patients with reactive thrombocytosis, polycythemia vera and primary (essential) thrombocythemia. An immunomorphometric study.

To determine the number of megakaryocyte precursors (pro- and megakaryoblasts), an immunomorphometric study was performed on paraffin-embedded trephine biopsies of the bone marrow using a monoclonal antibody against platelet glycoprotein IIIa. Eighteen control specimens from patients with no evidence of any hematological disorder and a normal platelet count were selected and assessed together with the same number of specimens from patients with reactive thrombocytosis, polycythemia vera rubra (P. vera) or primary (essential) thrombocythemia (PTH). A strikingly proportionate increase in early megakaryocytes occurred in all patients enrolled in this study, compared with the controls. Moreover, there were no significant correlations between counts for precursors or total megakaryocytes per square millimeter of bone marrow with the corresponding values for platelets. This indicates that despite an orderly increase in immature forms in the bone marrow, the number of platelets circulating in the blood is influenced by other additional factors, such as the expanded platelet pool in the enlarged spleen. The non-disproportionate expansion of megakaryocyte precursors extends previous findings on progenitor cells of this lineage in vitro, particularly in PTH. Histological evaluation of the bone marrow of patients with P. vera and PTH indicated that megakaryopoiesis proceeded to the production of appropriate mature forms with no obvious excess of very small or blastic elements.

Antibodies, Monoclonal↗
PubMed1990

Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis.

To localize the cellular sources of the collagens excessively deposited in the liver in the course of secondary biliary fibrosis, we have analyzed by in situ hybridization the distribution of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen and albumin RNA transcripts in rat livers up to 6 wk following common bile duct ligation and scission. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen RNA were found in nonparenchymal cells, while alpha 1(IV) procollagen gene expression was at the threshold of detection. Following bile duct obstruction, increasing amounts of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen gene transcripts were observed in cells of the expanding portal tracts and in perisinusoidal cells in areas of excessive collagen deposition. Procollagen gene expressing perisinusoidal cells were colocalized with desmin-immunoreactive cells, suggesting that Ito cells and transitional cells were among the collagen-expressing cell types. Only alpha 1(IV) procollagen transcripts were found in epithelial cells of newly formed bile ducts. Neither normal nor fibrotic liver showed any hybridization signal above background over hepatocytes, indicating that hepatocytes are unlikely to be a major source of hepatic collagen.

Animals↗
PubMed1990

Hodgkin's disease followed by lymphomatoid papulosis. Immunophenotypic evidence for a close relationship between lymphomatoid papulosis and Hodgkin's disease.

The clinical association of lymphomatoid papulosis and Hodgkin's disease and the striking morphologic similarity of atypical cells in lymphomatoid papulosis to Reed-Sternberg cells in Hodgkin's disease suggest that lymphomatoid papulosis and Hodgkin's disease are related. To test this possibility we studied the antigenic profile of Reed-Sternberg cells in the lymph nodes and of atypical cells in cutaneous lesions of lymphomatoid papulosis in two patients with Hodgkin's disease and lymphomatoid papulosis. In paraffin sections both cell types expressed CD30, CD45 T cell-restricted antigens, and occasionally CD15 antigens. They were negative for CD45 B cell-restricted antigens and for lysozyme. In cutaneous lymphomatoid papulosis lesions a similar immunologic profile of the atypical cells was found; that is, they were positive for CD30, CD2, CD3, and CD25 but negative for B cell and macrophage antigens. The similarity of the immunophenotype of Reed-Sternberg cells in lymph nodes affected by Hodgkin's disease and the immunophenotype of atypical cells of lymphomatoid papulosis lesions in the same patients suggests that the malignant cells in both conditions are derived from activated T cells and that they are closely related if not identical.

Adult↗
PubMed1990

Variable expression of leucocyte-common (CD45) antigen in CD30 (Ki1)-positive anaplastic large-cell lymphoma: implications for the differential diagnosis between lymphoid and nonlymphoid malignancies.

Monoclonal antibodies (mAbs) directed against the leucocyte common (CD45) antigen have been proposed as a useful tool for the differential diagnosis between malignant lymphomas (CD45+) and poorly differentiated nonhemopoietic tumors (CD45-). Thanks to the availability of mAbs directed against fixative-resistant epitopes of the CD45 molecule, this distinction can now easily be made even in routinely processed tissues. However, a small percentage of morphologically poorly defined neoplasms are difficult to diagnose even with the help of immunohistochemistry. The investigators report that 63 out of 165 anaplastic large-cell (ALC) lymphomas did not show any reactivity for the CD45 antigen in paraffin sections. In routine biopsies, the lymphomatous nature of these cases, most of which had been sent for consultation, could be always unequivocally established by demonstrating negativity for cytokeratins (mAb KL1) and clear dot-like and/or surface reactivity with the Ber-H2 mAb, which is directed against a fixative-resistant epitope of the lymphoid cell activation antigen CD30. Strikingly, 54% of the CD45-cases reacted with mAbs directed against fixative-resistant epitopes of the T cell-restricted CD45RO antigen (mAb UCHL1) or the B-restricted molecules CD45RA (mAb 4KB5) and L26 (unclustered). In order to avoid confusion of ALC lymphomas with anaplastic nonlymphoid tumors, pathologists must be aware of the existence of CD30+/CD45- ALC lymphomas, as they can mimic the above-mentioned malignancies both morphologically (due to the sinusoidal growth pattern) and phenotypically (due to the expression of EMA). The investigators conclude that the combined use of mAbs directed against fixative-resistant epitopes of the CD30, CD45RO, CD45RA, and L26 antigens and cytokeratins is essential for the correct diagnosis and treatment of these equivocal cases.

Antibodies, Monoclonal↗
PubMed1990

Pro-megakaryoblasts in bone marrow tissue from patients with primary (idiopathic) osteo-myelofibrosis (agnogenic myeloid metaplasia). An immunomorphometric study on trephine biopsies.

An immunomorphometric study was performed on bone marrow biopsies from 40 patients with primary osteomyelofibrosis--OMF, (agnogenic myeloid metaplasia) by employment of a monoclonal antibody against glycoprotein IIIa (Y2/51) to determine the number of pro-megakaryoblasts. Specimens from 15 individuals without any hematological disorder served as controls. With reference to the pertinent literature on megakaryocyte precursors and following a pilot study on corresponding smears, in tissue sections pro-megakaryoblasts were characterized by a size of 42.1 +/- 2.6 microns 2 (diameter 7.5 +/- 0.3 microns). In comparison with controls, in OMF no relevant increase in the number of pro-megakaryoblasts per square and cubic millimeter bone marrow was evaluable. The relative frequency of these precursors was significantly reduced due to an increase in the total amount of conspicuously large and abnormal megakaryocytes. Statistical analysis failed to reveal any correlations between counts for pro-megakaryoblasts or the total number of Y2/51--positive megakaryocytic elements with the density of argyrophilic fibers (determined by morphometry) or the platelet values. Our findings imply that in OMF the marked increase in circulating progenitor cells of the megakaryocyte lineage may be generated by extramedullary, probably splenic hematopoiesis. Moreover, the evolution of medullary fibrosis is thought to be associated with the striking predominance of large atypical, possibly overaged and hyperpolyploid megakaryocytes and not with an increase in precursor cells.

Aged↗
PubMed1990

Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action.

Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility. This inhibitor demonstrated excellent efficacy and a long duration of action upon intravenous administration to monkeys. While activity was also observed intraduodenally, a comparison of the blood pressure responses indicated low bioavailability. Subsequent experiments in rats showed that, although the compound was absorbed from the gastrointestinal tract, extensive liver extraction severely limited bioavailability.

Animals↗
PubMed1990

So-called fibroepithelial polyps of the vagina exhibiting an unusual but uniform antigen profile characterized by expression of desmin and steroid hormone receptors but no muscle-specific actin or macrophage markers.

The nature of the atypical, often multinucleated stromal cells proliferating in the so-called fibroepithelial polyps of the vagina (FEPV) is obscure. The authors therefore investigated immunohistochemically four polyps of this type with a panel of monoclonal and polyclonal antibodies, including those directed against intermediate filaments, steroid hormone receptors, and macrophage antigens. The authors found that the atypical stromal cells of FEPV expressed vimentin, desmin, and receptors for estrogen and progesterone but lacked all the other markers studied. The homogenous antigen profile strongly suggests that FEPV form a disease entity whose characteristic cells are special hormone-sensitive stromal cells with a myoid component of differentiation. Morphologically similar stromal cells expressing steroid hormone receptors but lacking desmin were found in myxomatoid subepithelial regions of the vaginal wall and the cervix.

Actins↗
PubMed1990

Comparison of anaplastic large cell Ki-1 lymphomas and microvillous lymphomas in their immunologic and ultrastructural features.

Anaplastic large cell Ki-1 malignant lymphomas (MLs) resemble microvillous lymphoma in having a pleomorphic infiltrate with a prominent sinus growth pattern. Ultrastructural features of anaplastic large cell Ki-1 MLs and their immunologic relationship to the microvillous MLs have not been thoroughly evaluated. We have studied 23 anaplastic large cell Ki-1 MLs immunologically as well as 14 cases ultrastructurally, and compared them with 7 cases of microvillous MLs. Anaplastic large cell Ki-1 MLs were predominantly T-cell in type (13 cases) with three cases marking as B; in seven cases the immunophenotype was not clearly defined. Six microvillous MLs expressed monotypic cytoplasmic or surface immunoglobin and the remaining case had a probable B-cell phenotype (LN-1+, UCHL1-). All microvillous MLs were Ki-1/Ber-H2 (CD30) negative. Epithelial membrane antigen (EMA) marked most anaplastic large cell Ki-1 MLs, except those of B-cell type, whereas all microvillous MLs were EMA negative. By electron microscopy, both lymphomas had features of transformed lymphocytes although anaplastic large cell Ki-1 MLs generally had more nuclear irregularity and variability from cell to cell. Numerous cytoplasmic processes were present in three anaplastic large cell MLs and in all microvillous MLs. The ultrastructural features of the cytoplasmic projections were not sufficiently distinctive to differentiate these two lymphomas. It is apparent that at least two forms of MLs may have a sinus growth pattern and that these MLs cannot be differentiated by morphology alone. Full characterization requires a battery of immunological markers and ultrastructural studies; even then there is overlap of these MLs. The majority of microvillous MLs, are Ki-1-, EMA-, and have a B-cell phenotype, but a small population (21% in this study) of Ki-1+ MLs have numerous cytoplasmic processes. The biological and clinical significance of cytoplasmic projections in these lymphomas are unknown.

Antigens, Differentiation↗
PubMed1990

Complete infraclavicular brachial plexus palsy with occlusion of axillary vessels following anterior dislocation of the shoulder joint.

Two cases of complete infraclavicular brachial plexus palsy after anterior dislocation of the shoulder joint are reported. Both patients had transient motor brachial plexus paralysis and extensive anesthesia of the whole upper limb. Additionally, one of them had occlusion of the axillary vessels. Vascular recovery occurred immediately after manipulation and reduction of the affected shoulder joint. Neurological recovery occurred 9 to 12 months later in both cases without surgery, other than closed reductions. Such neurological and vascular complications after anterior dislocation of the shoulder joint are unique.

Axillary Artery↗
PubMed1990

Serum levels of soluble CD30 molecule (Ki-1 antigen) in Hodgkin's disease: relationship with disease activity and clinical stage.

In all cases of Hodgkin's disease (HD) Reed-Sternberg (RS) cells express the CD30 antigen. It has been recently demonstrated that this molecule can be released from the cell membrane of CD30+ neoplastic cells in a soluble form (sCD30), detectable in culture supernatants and body fluids. In this paper we investigated by an immunoassay the serum levels of sCD30 in 58 patients with HD, in order to define the possible relationship of this molecule to the clinical and pathological findings. sCD30 molecule was found at detectable levels in 24 out of 50 patients (48%) with active disease, whereas it was always absent in control sera and in cases in complete remission. Among the patients with active HD, the incidence and mean values of detectable levels (+/- SEM) of sCD30 were higher in cases with progressive or relapsing disease (61.5%, mean 458 +/- 190 U/ml) as compared to those at presentation (43.2%, mean 116 +/- 33 U/ml). Among the cases at presentation, detectable levels were observed more often in patients with advanced stages (III + IV: 61%) and constitutional symptoms ('B': 61.5%) than in early stages (I + II: 26%) and without symptoms ('A': 33.3%). In addition, higher mean values were found in stages III + IV (182 +/- 60 U/ml) and in 'B' cases (208 +/- 73 U/ml) than in stages I + II (65 +/- 30 U/ml) or 'A' patients (64 +/- 26 U/ml). The above findings suggest a possible role for the sCD30 as a tumour marker in HD.

Adolescent↗