Search PubMed⌕ Search

Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 217 records · Page 12Linked to original sources
PubMed1996

Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease.

Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils. Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1-positive cells from cytotoxicity directed at viral antigens.

Base Sequence↗
PubMed1996

Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis.

Gene amplification or structural alteration of different erbB genes exerts a transforming effect in a variety of human neoplasms. Overexpression of the EGF receptor is associated with tumor initiation and progression of renal cell carcinoma (RCC). However, the role of erbB-2 in these processes remains unknown. We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters. No amplification of both genes has been observed. However, high expression of the EGF receptor protein and p185erbB2 was frequent in RCC and statistically significantly related to higher tumor grades. We could demonstrate a close correlation of p185erbB2 overexpression with high EGF receptor levels. Co-overexpression of both receptor types was significantly associated with metastatic disease. Our results suggest a synergistic involvement of both EGF receptor and p185erbB2 in the progression of RCC.

Blotting, Southern↗
PubMed1996

[Impingement syndrome following direct injuries of the shoulder joint].

Impingement is the most common cause of pain and limitation of movement in the shoulder, with painful arc syndrome its major clinical sign. It usually becomes manifest at between 70 degrees-120 degrees of abduction, but in severe cases, this may be reduced to only 50 degrees-70 degrees. We studied 22 patients who had developed shoulder impingement following direct injuries and who had been treated by anterior acromioplasty and decompression, with an average follow-up of 32 months. 5 had sustained fractures of the greater tuberosity of the humerus at the time of injury, 14 had tears of the rotator cuff of various sizes (1 in both shoulders) and 3 had developed fibrotic scars of the subacromial bursa. Excellent or good results were achieved in 86.6%. Healing time was shorter, and there was return of full range of shoulder movement in those with subacromial scars, undisplaced fractures of the greater tuberosity, or those with a small tear of the rotator cuff. Recovery took longer in those with larger tears of the rotator cuff and in those with displaced fractures of the greater tuberosity. Recovery time was proportional to the size of the rotator cuff tear. It is concluded that direct trauma to the shoulder bears a direct relationship to the development of impingement syndrome, and that at surgery a concomitant tear in the rotator cuff is seen more than 2/3. Because of the high rate of success in surgical treatment of this syndrome, operation is indicated when a few months of physical therapy and analgesics fail to provide relief. In the presence of fractures, decompression surgery should be postponed until the fracture has united.

Acromion↗
PubMed1996

An immunohistochemical study of TAL-1 protein expression in leukaemias and lymphomas with a novel monoclonal antibody, 2TL 242.

Fifty formalin fixed, paraffin-embedded cases of T-acute lymphoblastic leukaemia (T-ALL) from 12 bone marrow trephines and 38 lymph nodes were stained with a new monoclonal antibody, 2TL 242, raised against recombinant TAL1 protein. The antibody recognizes TAL-1 polypeptides of molecular weight 39 and 41 kD (full length). In addition, a variety of other leukaemias and lymphomas were also stained with 2TL 242. Twenty-four of the 50 cases of T-ALL showed nuclear positivity, ranging from 10 to 90 per cent of leukaemic cells. A positive staining reaction was nuclear and stippled in pattern. Nuclear staining was not seen in any other type of leukaemia or lymphoma. Five cases of follicular lymphoma showed diffuse cytoplasmic staining of variable intensity. Although some background staining is obtained with this antibody, positive nuclear staining is easily distinguishable. This monoclonal antibody has a potential role in primary diagnosis and in the detection of minimal residual disease in T-ALL.

Antibodies, Monoclonal↗
PubMed1996

Phenotypic modulation of Hodgkin and Reed-Sternberg cells by Epstein-Barr virus.

Expression of the Epstein-Barr virus (EBV) gene product LMP1 is found in tumour cells in varying proportions of Hodgkin's disease (HD) cases. It is not clear which cellular genes are influenced by EBV in HD. A total of 387 HD cases were tested for differences among LMP1-positive and -negative cases with respect to age, sex, histotype and immunophenotypic parameters (CD2, CD3, CD4, CD15, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD43, CD45RA, CD45R0, CD70, HLA-DR, T-cell receptor beta-chain, and p53 expression). Comparison of patient age and sex as well as distribution of histotype and tumour cell immunophenotype with published data suggests that the cases in this study are representative of the spectrum of HD in developed countries. LMP1 expression was found in 131/387 HD cases (36.4 per cent) with non-homogeneous distribution among HD histotypes, the mixed cellularity type (HDmc) being most frequently EBV-associated (71/129 cases, 55 percent). No relationship was found to age and sex. Significant phenotypic differences were restricted to the HDmc histotype, where the tumour cells expressed the activation marker CD30 in a larger proportion, and CD20 in a smaller proportion, when harbouring EBV. These results suggest that EBV may influence the tumour cell phenotype in HD.

Adolescent↗
PubMed1996

Monokine expression in Langerhans' cell histiocytosis and sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Langerhans' cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells (LC) showing histologically an abundant reactive infiltrate composed of macrophages and lymphocytes, as well as eosinophilic and neutrophilic granulocytes. Rosai-Dorfman disease (RDD) shows a sinusoidal accumulation of large histiocytic cells with an immunophenotype similar to LC of LCH. The histological picture of LCH is reminiscent of an inflammatory disorder and LC may produce cytokines and are influenced by these soluble factors. This study set out to establish the monokine expression pattern in LCH in comparison with those of RDD; dermatopathic lymphadenopathy, which also shows a proliferation of S100-positive dendritic cells; and LC in normal skin specimens. Isotopic in situ hybridization was used for the detection of transcripts of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, in some cases combined with immunohistology for the S100 protein or CD68. In all 11 tissue samples from eight patients, LC of LCH expressed TNF-alpha; in two cases IL-1 beta transcripts were additionally noted in some LC, whereas IL-6 was found in reactive cells. Large histiocytic cells of RDD expressed all three monokines, whereas minimal or no expression of these cytokines could be detected in interdigitating reticulum cells in dermatopathic lymphadenopathy. In two out of five normal skin samples, only TNF-alpha specific signals were observed in LC. These data suggest that histologically different lesions of the histiocytic/dendritic cell system display distinct cytokine profiles. The expression of monokines, which have been demonstrated to influence various functions of epidermal LC, may play a role in the pathogenesis of LCH. Systemic symptoms in RDD may be related to enhanced production of monokines in these lesions.

Child↗
PubMed1996

Intestinal T-cell lymphoma: a reassessment of cytomorphological and phenotypic features in relation to patterns of small bowel remodelling.

Intestinal T-cell lymphoma (ITCL) is an uncommon entity among primary gastrointestinal lymphomas. In this study we evaluated tumours from 20 patients presenting with (n = 8) or without (n = 12) a history of coeliac disease (CD). Neoplastic lesions were composed of predominantly small (n = 4), small-to-medium (n = 2), medium/mixed-to-large (n = 7) or large and anaplastic (n = 7) cells. Different patterns of tumour growth and remodelling of the small bowel wall were observed. Pattern a (n = 4) was characterized by an intramucosal spread of small tumour cells with a small growth fraction. This pattern resembles mucosal inflammation in CD. In pattern b (n = 2), ulcerated solitary or multiple tumours composed of small to medium-sized cells were observed. The adjacent or distant mucosa showed a nearly normal architecture. In pattern c (n = 7), ulcerated lesions were composed of medium-sized to large cells. Mucosal flattening occurred in all segments infiltrated by lymphoma. In pattern d (n = 7), bowel remodelling was observed along the small intestine even at sites not affected by lymphoma. The main neoplastic lesions were composed of pleomorphic large or anaplastic cells frequently expressing the CD30 molecule. Intramucosal spread of a small epitheliotropic T-cell population was observed in the vicinity or even at distant segments of the small bowel. The demonstration of clonal rearrangements of T-cell receptor genes helped to trace widespread occurrence of this small intraepithelial neoplastic component. We suggest that different features of tumour cells such as the expression of activation antigens may contribute to the remodelling of small bowel mucosa. The addition of immunophenotyping data to macroscopic and microscopic features of specimens provided evidence that this uncommon lymphoma exhibits a spectrum in cytological composition and growth patterns. However, despite the considerable heterogeneity of the cases analysed, most of them shared a characteristic immunohistochemical profile (CD3+, CD8+/-, CD103+), further substantiating the view that ITCL is the neoplastic equivalent of an intraepithelial T-cell subset of the small intestine. This phenotype and the intraepithelial accumulation of lymphoma cells observed in the surviving mucosa are clues to the diagnosis of this clinicopathological lymphoma entity characterized by a broad range of morphological expressions.

Adult↗
PubMed1996

[Rare variants of cutaneous T-cell lymphomas].

Besides the classical forms of cutaneous T-cell lymphoma (C-CTCL), such as mycosis fungoides and Sézary's syndrome, unique variants may be encountered. The classification of these rare cutaneous T cell lymphomas is problematic and controversial. Newer classifications of lymphoma in general, such as the Revised European-American Lymphoma (REAL) Classification, emphasize well-established clinico-pathological entities. It seems appropriate to attempt to bring greater clarity to the classification of cutaneous T-cell lymphomas using the same principles. In this review, we list and characterize the rare variants of cutaneous T-cell lymphoma, such as (1) clinical, histological and immunological variants of mycosis fungoides; (2) progressive cutaneous T-cell lymphoma (P-CTCL) including transformed classical cutaneous T-cell lymphoma (TC-CTCL) and primary progressive cutaneous T-cell lymphoma (PP-CTCL); (3) angiocentric and angioimmunoblastic cutaneous T-cell lymphomas; (4) large cell anaplastic, CD30+ cutaneous T-cell lymphoma; (5) HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL); (6) cutaneous manifestations of primary extracutaneous T-cell neoplasias; (7) unclassifiable cutaneous T-cell lymphoma.

Antigens, CD↗
PubMed1996

[2 unusual cutaneous T-cell lymphomas with extracutaneous involvement].

In this paper we present two patients with T-cell lymphomas, who presented with unique skin lesions, but later developed extracutaneous involvement. The first patient showed marked edematous infiltration of the trunk and legs as well as grouped, umbilicated red-to-blue papules limited to the body folds. The second patient had lesions reminiscent of poikiloderma vascular atrophicans, with erythema, teleangiectasia, hypo- and hyperpigmentation, and bizarre scarring, followed by development of papules and nodules. The first patient also had marked leukocytosis and lymph node enlargement. Histology, immunohistology, and immunophenotyping revealed an unclassifiable CD8+, alpha, beta +, CD10+ cutaneous T cell lymphoma with leukemic involvement. Unclassifiable cutaneous T-cell lymphoma was also diagnosed in the second patient: it was associated with a monoclonal proliferation of T-cell receptor V gamma 9, delta + large granular T lymphocytes and finally developed into frank, acute pre-T lymphatic leukemia.

Adult↗
PubMed1996

[Intracerebral hemorrhage after systemic thrombolysis in patients with occlusion of the central retinal artery. Report of 2 cases].

Pharmacological thrombolysis is a valuable therapeutic modality for embolic arterial occlusion. Nevertheless, thorough evaluation of the indications is imperative to avoid serious complications. The most frequent complication is hemorrhage. Of these, the intracerebral hemorrhages are rare, but when they do occur they are an immediate threat to life they are accompanied by very severe complications, and they have an extremely poor prognosis. Within 58 months 361 patients were treated at our neurosurgical clinic with intracerebral hematomas. In 22 patients (6.1%) the hematoma developed as a complication of systemic thrombolysis. Two of these patients had been treated for occlusion of the central retinal artery. One patient died: the other survived but was severely disabled. The latter patient experienced no benefit from the thrombolysis as for as the underlying ophthalmologic disease was concerned. These worrying examples stress the necessity for careful evaluation of risk factors and the natural history of the underlying disease for which systemic thrombolysis is indicated. Local selective (or superselective) thrombolysis is preferable to the systemic procedure, provided that the indications are equally strictly observed and are less likely to lead to severe complications.

Aged↗
PubMed1996

Surgical therapy of gastrointestinal non-Hodgkin's lymphomas.

Within a period of 13 years 39 patients underwent surgery for primary gastrointestinal non-Hodgkin's lymphoma. The stomach was the most frequent site of involvement (26 cases) followed by the small intestine (10 cases) and the large bowel (three cases). Operative procedures included: total gastrectomy (n = 19), subtotal gastrectomy (n = 5), partial gastrectomy (n = 2), small bowel resection (n = 7), right hemicolectomy (n = 5) and sigmoid resection (n = 1). According to Musshoff's modification of the Ann Arbor system, we found stage I in nine, stage II in 12, stage III in two and stage IV in 16 patients. Histological typing according to the Kiel classification showed low-grade malignancy in 11 cases and high-grade in 28. Twenty-eight patients received chemotherapy and/or radiation in accordance with the tumour staging and type of malignancy. The follow-up data were analysed by the method of Kaplan and Meier. Including five patients who died post-operatively from perforated or bleeding lymphomas, the overall 5-year survival rate was 53.8%.

Adult↗
PubMed1996

Anti-CD30 (BER=H2) immunotoxins containing the type-1 ribosome-inactivating proteins momordin and PAP-S (pokeweed antiviral protein from seeds) display powerful antitumour activity against CD30+ tumour cells in vitro and in SCID mice.

The anti-CD30 immunotoxin (IT) Ber-H2/saporin is effective in patients with refractory Hodgkin's disease. However, responses are short and partial, one of the main reasons being the inability to repeat IT doses because of formation of human antibodies against the murine antibody and/or the toxin. To overcome this problem, we constructed two new anti-CD30 ITs by covalently linking the mouse monoclonal antibody Ber-H2 to the type 1 ribosome-inactivating proteins (RIPs) momordin (MOM) and pokeweed antiviral protein from seeds (PAP-S), which do not cross-react with each other or with saporin. Both ITs inhibited protein synthesis by Hodgkin's disease and anaplastic large-cell lymphoma (ALCL)-derived CD30+ target cell lines with a very high efficiency (IC50 ranging from < 5 x 10(-13) M to 2.75 x 10(-11) M, as RIP). In a SCID mouse model of xenografted CD30+ human ALCL, a 3d treatment with non-toxin doses of Ber-H2/MOM (50%LD50), started 24 h after transplantation, prevented tumour development in about 40% of the animals and significantly delayed tumour growth rate in the others. Main toxicity signs in mice and rabbits were dose-related increase of serum transaminases (AST and ALT) and creatine phosphokinase (CPK). LD50 (as RIP) in Swiss mice was 7 mg/kg for Ber-H2/MOM and 0.45 mg/kg for Ber-H2/PAP-S. Sequential administration of two anti-CD30 ITs (Ber-H2/MOM and Ber-H2/saporin) was well tolerated and did not result in formation of antibodies cross-reacting and with the two plant toxins. The results presented in this paper suggest that in the future, sequential administration of anti-CD30 humanized antibodies linked to antigenically distinct type 1 RIPs (saporin, MOM, PAP-S) should be feasible.

Animals↗
PubMed1996

Inflammatory pseudotumors of lymph node origin show macrophage- derived spindle cells and lymphocyte-derived cytokine transcripts without evidence of T-cell receptor gene rearrangements. Implications for pathogenesis and classification as an idiopathic retroperitoneal fibrosis-like sclerosing immune reaction.

Sclerosing pseudotumorous immune reactions of the retroperitoneum have been shown to consist of HLA-DR-positive spindle-shaped fibroblasts and macrophages that resemble fibroblasts, and in some instances they contain clonal populations of T lymphocytes not found in granulation tissue, keloids, nodular fasciitis, or fibromatoses. In patients who are iatrogenically immunosuppressed, circulating monocytes may be induced in vitro to transform into spindle-shaped macrophages, and secrete collagen after stimulation by conditioning medium from activated T lymphocytes. The authors investigated a series of five inflammatory pseudotumors (IPT) of lymph node origin for identification of spindle-shaped macrophages, T-cell receptor gene rearrangements, and lymphocyte-derived cytokine mRNA production. All cases of IPT demonstrated spindle-shaped macrophages resembling fibroblasts or myofibroblasts characterized by vimentin, CD45 (LCA), CD68 (KP1) or HAM-56, and HLA-DR(LN3) immunoreactivity and demonstrated production of procollagen-alpha1 (I) mRNA by in situ hybridization. Clonal T-cell receptor chain gene rearrangements were undetectable by polymerase chain reaction. Strong specific lymphocyte-derived interleukin-1beta and interleukin-6 mRNA cytokine transcripts were identified. Although all patients with IPT were managed with steroids and nonsteroidal anti-inflammatory medication, some had treatment-refractory disease. Because all-trans retinoic acid has been demonstrated to inhibit the in vitro transformation of monocytes into collagen-producing spindle-shaped macrophages ("neofibroblasts"), it may be of benefit for patients with IPT.

Antigens, CD↗
PubMed1996

Ig rearrangements in isolated Reed-Sternberg cells: conclusions from four different studies.

The cellular origin and the type of proliferation of the Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of Hodgkin's disease (HD), is an issue of constant debate. Immunohistochemical and molecularbiological studies of different research groups revealed contradictory results among the different groups ranging from a complete absence to a frequent presence of B-cell or T-cell characteristic features in the HRS cells. The determination of their clonality by cytogenetic means produced no conclusive results. To unequivocally clarify these questions we and others isolated single HRS cells and amplified their immunoglobulin (Ig) rearrangements. Most groups found Ig rearrangements within the HRS cells pointing to a B-cell nature of these HD cases. Individual IgH rearrangements were found in a proportion of the HD cases whereas most cases harbor monoclonal HRS cells with or without additional polyclonal rearranged HRS cells. Further studies are needed to clarify whether the differences among the different groups are caused by the selection of the HD cases used for investigation.

Gene Rearrangement↗
PubMed1996

Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma.

Since lymphocyte predominant Hodgkin's disease (LPHD) may comprise more than one entity, diagnostic criteria, clinical features, and treatment strategies are still being controversially discussed. Thus, in December 1994 a multinational project on lymphocyte predominant Hodgkin's disease was initiated by the European Task Force on Lymphoma. This project is aimed at clarifying the clinical and histopathological spectrum of LPHD, as well as its relation to T-cell- rich B-cell lymphoma and classical types of HD. 525 paraffin blocks and clinical data of 478 patients from 16 international centres were submitted. At the Third International Symposium on Hodgkin's Lymphoma in Cologne, 232 of these cases were discussed by an expert panel. The preliminary results are presented here. Most cases of LPHD were reclassified into nodular paragranuloma (NP) and lymphocyte rich classical HD. In both groups, a considerable number of cases with atypical features was observed. Few cases of NHL were found among the cohort. LPHD was generally treated according to common standards for HD. The whole group of LPHD did not have a better prognosis than NS; whereas early stage NP did perform better than early stage NS (data from the German Hodgkin's Lymphoma Study Group). There is however a striking discrepancy between good survival and the frequent relapses observed in NP which needs to be elucidated.

Hodgkin Disease↗
PubMed1996

[Pruritometer 1: Portable measuring system for quantifying scratching as an objective measure of cholestatic pruritus].

Objective assessment of subjective symptoms such as pruritus always presents problems, which can often be resolved only indirectly. The objectification of pruritus was necessitated by a study on the efficacy of a serotonin antagonist used as treatment of cholestatic pruritus. In the present paper, a portable measuring system for the indirect objective assessment of pruritus via the quantification of scratching is described. A piezoelectric scratch-vibration sensor for attachment to the middle finger of the patient's dominant hand was developed. A sensor interface detects the scratching signals and generates pulses that are then summed in an adapted sports watch. The entire system-Pruritometer 1- is worn by the patient like a wrist watch, and is characterized by ease of handling. Acceptance by the patient is reported to be good. A statistically good correlation between measured (Pruritometer) and visually counted scratches was demonstrated. Pruritometer 2, which will enable scratch frequency and intensity distribution over time to be determined, is presently being developed.

Cholestasis, Intrahepatic↗
PubMed1996

Monoclonal antibodies PG-B6a and PG-B6p recognize, respectively, a highly conserved and a formol-resistant epitope on the human BCL-6 protein amino-terminal region.

The human BCL-6 gene, which is rearranged in approximately 30% of diffuse large B cell lymphomas, encodes a 706-amino-acid nuclear protein of the Kruppel-type zinc finger transcription factors mainly expressed in normal germinal center B cells and related lymphomas. Four monoclonal antibodies (PG-B6, PG-B6a, PG-B6p, and PG-B6m), specifically directed against the human BCL-6 protein, were generated by immunizing BALB/c mice with a recombinant protein corresponding to the BCL-6 amino-terminal region (amino acids 3 to 484). The PG-B6 monoclonal antibody reacted with a BCL-6 epitope sensitive to fixatives and preserved in all mammalian species. PG-B6a (a is for avian) recognized the most evolutionarily conserved BCL-6 epitope (expressed in all animal species including avian). PG-B6p (p is for paraffin) recognized a fixative-resistant epitope of BCL-6 that was detectable on paraffin sections after microwave heating in 1 mmol/L EDTA buffer. PG-B6m (m is for mantle) was the least specific monoclonal antibody as, in addition to BCL-6, it reacted with a yet undefined antigen selectively located in the cytoplasm of mantle and marginal zone B cells. All monoclonal antibodies detected strong nuclear expression of BCL-6 in follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and nodular, lymphocyte-predominance Hodgkin's disease. In diffuse large B cell lymphomas, BCL-6 expression was independent of BCL-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. BCL-6 was not expressed in B-CLL, hairy cell leukemia, mantle-cell- and marginal-zone-derived lymphomas. Labeling of paraffin sections with PG-B6p proved useful for differentiating proliferation centers in B-CLL (BCl-2+/BCL-6-) from trapped germinal centers in mantle cell lymphomas (BCL-2-/BCL-6+) and for identifying neoplastic cells in cases of nodular, lymphocyte-predominance Hodgkin's disease. Because of their high specificity, wide reactivity in humans and animal species including avians (PG-B6a), and suitability for labeling routine paraffin sections (PG-B6p), the reagents described in this paper should prove valuable in both research and diagnostics.

Amino Acid Sequence↗