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H Stein

Publications and source records attributed to H Stein.

At least 235 records · Page 13Linked to original sources
PubMed1996

Interleukin-8 in Hodgkin's disease. Preferential expression by reactive cells and association with neutrophil density.

Hodgkin's disease (HD) shows rare neoplastic Hodgkin and Reed-Sternberg cells embedded in an abundant reactive infiltrate containing, among other cell types, neutrophilic granulocytes. Interleukin (IL)-8 is chemotactic for neutrophils. The expression of IL-8 was tested by in situ hybridization with 35S-labeled IL-8-specific RNA probes on 38 cases of HD. Reactive lesions, non-Hodgkin's lymphomas of B and T phenotype, and Langerhans cell histiocytosis served as controls. IL-8 expression was observed in Hodgkin and Reed-Sternberg cells in 3 of 33 cases of classical HD and in reactive cells in 20 of 33 HD cases as evidenced by combined isotopic in situ hybridization and immunohistology for the demonstration of cell-type-characteristic antigens or enzyme histochemistry for chloroacetate esterase. IL-8-positive cells were more numerous in cases of nodular sclerosing HD as compared with the mixed cellularity histotype (P = 0.01). The number of IL-8-positive cells and the density of neutrophils were positively correlated (P < 0. 01). In 5 cases of lymphocyte-predominant HD, IL-8 expression was not displayed. Non-Hodgkin's lymphoma cases contained IL-8 transcripts only in 1 of 23 cases in sparse reactive cells. In 4 of 7 cases of Langerhans cell histiocytosis, IL-8-specific signals were displayed in S100-negative cells. In conclusion, IL-8 expression in HD is largely confined to reactive cells and associated with infiltration by neutrophils. Elaboration of other cytokines by Hodgkin and Reed-Sternberg cells and reactive cells may explain the frequent expression of this cytokine in HD, particularly in the nodular sclerosing type.

Cell Count↗
PubMed1996

Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. German Low-Grade Lymphoma Study Group.

The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic (CB-CC (Kiel-classification)) or follicle center lymphoma (FCL (REAL classification)) and centrocytic (CC) or mantle-cell-lymphoma (MCL) were randomized for therapy with either PmM or COP and are fully evaluable for response and toxicity. PmM consisted of prednimustine 100 mg/m2/day on days 1-5 and mitoxantrone 8 mg/m2 /day days 1 and 2, while COP comprised cyclophosphamide 400 mg/m2/day on days 1-5, vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1-5. Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second randomization for interferon alpha maintenance vs observation only. Overall response rates were comparable with 83% complete and partial remissions after COP and 84% remissions after PmM. PmM revealed a significantly higher rate of complete remissions (36 vs 18%, P < 0.006), the majority being achieved after four courses. The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM resulted in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months, respectively (P=0.04). Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL (16 vs 30%, P=0.12, NS) while overall response rates were in a similar range (81 vs 85%). In both subtypes, PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP. Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP (43 vs 31 %, P < 0.0001). This difference was clinically irrelevant, however, since serious infectious complications were encountered in less than 3% of cycles after both regimens. COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia (31 vs 2%) as well as of peripheral neurotoxicity (23 vs 2%). These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin's lymphoma. PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects. A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha.

Adult↗
PubMed1996

Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell lymphoproliferations.

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.

DNA, Viral↗
PubMed1996

[Perimesencephalic subarachnoid hemorrhage--an independent clinical picture of non-aneurysmatic subarachnoid hemorrhage with a benign course].

Two hundred seventy-three Patients with acute SAH were treated within the last 46 months (1.4.1991 to 31.1.1995). Diagnosis was made upon visible SAH on CT-scans or bloody spinal tap regardless of a negative CT-scan. These patients harbored 194 aneurysms, 25 AVM and cavernomas. Within the same time-period we treated 27 Patients without SAH but harboring vascular malformations (17 aneurysms, 10 AVM and cavernomas). In 30 patients (11%) no bleeding source was detectable. Fourteen of these patients (5.1%) had blood concentrated within the perimesencephalic cisterns on the CT-scans. On admission all of these 14 patients (8 men, 6 female, aged 30 to 63 years) were awake and without mentionable neurological deficit, equalling Hunt & Hess grade 1 (11 patients) and 2 (3 patients). Neither the initial nor control angiography revealed a vascular malformation as a bleeding source. MRI-scans performed for 11 patients did not reveal further etiological clues. During a follow-up interval of 3 to 48 months, none of these patients suffered a rebleeding. Vasospasm was not or only slightly present, no ischemia leading to neurological deficit. GOS reached 5 and Karnofsky-scale was 100 for all of these patients. We conclude that the perimesencephalic SAH is a homogeneous entity with a different natural course than the common aneurysmatic SAH. Probably leakage within the capillary or venous circulation causes this form of SAH with a benign clinical course. Further experience is required to determine whether control angiography is mandatory in these patents with a distinct CT appearance.

Adult↗
PubMed1996

Presence of clonal T-cell receptor gene rearrangements provides evidence of widespread intramucosal intestinal T-cell lymphoma.

Intestinal T-cell lymphoma (ITCL) is a rare type of extranodal lymphoma derived from intraepithelial T-cells and generally exhibits macroscopically evident ulcerated lesions of the bowel wall composed of pleomorphic tumor cells. We report immunophenotypic and molecular genetic findings in an unusual small-sized intramucosal type of ITCL observed in a 74-year-old man presenting with enteropathy. Biopsies obtained from duodenum and jejunum showed a conspicuous accumulation of small-sized lymphoid cells forming intraepithelial clusters. The predominantly intraepithelial spread was accompanied by a spilling over to the lamina propria but not to deeper layers of the duodenal and jejunal wall, thus resulting in a purely intramucosal manifestation. This growth pattern and the immunophenotypic profile (CD3+, CD4-, CD8+, CD103+) suggested that the lesion may fall in the spectrum of ITCL. However, since the lymphoid cells cytomorphologically lacked neoplastic features and showed a small growth fraction. a reliable diagnosis of malignant lymphoma could not be established by histological and immunohistochemical methods. In this case a tissue-based polymerase chain reaction (PCR) analysis of T-cell receptor (TCR) beta and gamma gene rearrangements proofed to be essential in confidently distinguishing multifocal monoclonal intramucosal T-cell lymphocytosis from an intense reactive inflammatory infiltrate in celiac disease (CD). Our observation highlights that detection of clonal rearrangements of TCR genes is particularly useful in detecting ITCL composed of cytomorphologically innocuous T-cells because histologic diagnosis in such cases is at best presumptive.

Aged↗
PubMed1996

[Primary traumatic midbrain syndrome--follow-up and prognosis of acute primary brain stem damage].

Within 27 months 122 patients with severe head injury were treated at our clinic. Of these patients twelve (9.8%) were categorized as having a primary brain stem lesion (9 male and 3 female, mean age 28.3 years (17 to 73 years). Their injuries were caused primarily by traffic accidents. Initial and follow-up CT ruled out mass lesions or other causes for transtentorial herniation, supporting the diagnosis of primary brain stem lesion. Respiratory insufficiency and control of vegetative function demanded artificial ventilation and analog-sedation for up to 32 days (mean 18 days) on our Intensive Care Unit. In all patients we performed initial and follow-up CT scans, ICP monitoring, evoked potentials (AEP, SSEP) and TCD. MRI was carried out in four patients. One patient died during the acute hospital phase, 7 were transferred in poor and four in good condition. During rehabilitation one patient died, two, one in a vegetative state and one in poor condition were transferred to a caring facility. Eight patients with a good or moderate recovery were dismissed home, subsequently regaining their prior social function. The primary traumatic brain stem lesion presents as a dramatic clinical picture. As shown in our series the prognosis is good independent of the duration of coma. The important prognostic factors were the primary neurological state according to the Gerstenbrand and Luecking classification, the degree of the brain stem lesion in CT scan and MRI, and normal evoked potentials, indicating a favourable outcome.

Adolescent↗
PubMed1996

Regenerating synovial lining of the normal rabbit knee: a scanning electron microscopy study.

Regeneration of the synovial lining in the synovectomized rabbit knee was studied using the scanning electron microscope. The resected synovia regenerated considerably 3 weeks after synovectomy. However, 44 weeks following excision, their surface morphology was still very different from that of the normal tissue of intact animals. The regenerated synovia were characterized by three main features: the large number of various patterns, the many fields harboring fibrillation and the almost total lack of a bubble layer (the latter was formerly shown to be predominant on normal, intact synovia). The surface morphology of the non-operated (contralateral) knee differed greatly from that of normal synovia. The surface of sham-operated synovia was totally covered by the bubble layer. The appearance of vast fields harboring fibrillations indicated deficient ultrastructural regeneration. The altered surface morphology of the contralateral synovia was a novel finding. We wonder whether it would be appropriate to propose that the systemic reaction induced by synovectomy of the experimental knee initiated the synovial appearances recorded on the contralateral knee. The data reported here rule out the possibility of using the contralateral leg as an intact control.

Animals↗
PubMed1995

Insulin-like growth factor-I and its complexes in normal human articular cartilage: studies of partition and diffusion.

Insulin-like growth factor-I (IGF-I) plays a major role in cartilage homeostasis. Our objective was to study the penetration of IGF-I, both alone and bound to serum proteins, into the different zones of normal human cartilage using radioactively labeled IGF-I. The uptake of free IGF-I was higher than that predicted on the basis of excluded volume calculations and showed concentration dependence: we attributed this to reversible binding of the hormone to the tissue. Since the extent of binding was much higher than that calculated for binding to cell receptors, we concluded that IGF-I binds to matrix components. The kinetics of desorption of IGF-I from cartilage confirmed our conclusions regarding binding. The degree of uptake of IGF-I protein complexes prepared by labeling human serum with [125I]IGF-I showed that such complexes are largely excluded from normal cartilage and that the amounts present in the tissue are too low to affect proteoglycan metabolism.

Absorption↗
PubMed1995

Hodgkin's disease with monoclonal and polyclonal populations of Reed-Sternberg cells.

BACKGROUND: There is strong evidence that Reed-Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cell antigen receptors have not been demonstrable in tumor tissue from most patients with Hodgkin's disease. To elucidate this issue, we assayed single Reed-Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobulin variable-region heavy-chain (VH) genes. METHODS: We isolated single Reed-Sternberg cells from frozen sections that had been immunostained for CD30. The rearranged VH genes of these cells were amplified by the polymerase chain reaction and analyzed by gel electrophoresis and nucleotide sequencing. RESULTS: In all 12 patients, the Reed-Sternberg cells studied contained rearranged VH genes. Three patterns were observed: in three patients the rearrangements in each patient were identical, in six patients all the rearrangements were unrelated and unique, and in three patients both identical and unrelated rearrangements were detected. Apparently somatic mutations of VH genes were present in some Reed-Sternberg cells but absent in others. CONCLUSIONS: Reed-Sternberg cells with B-cell phenotypes have rearranged VH genes; therefore, these cells arise from B cells. The pattern of VH gene mutations suggests that Reed-Sternberg cells can correspond to either immunologically naive or memory B cells. In half our patients the population of Reed-Sternberg cells was polyclonal; in the other half, monoclonal or mixed cell populations were found. Correlation with the clinical stage suggests that polyclonal Hodgkin's disease can present as a widespread lymphoma.

Adolescent↗
PubMed1995

ALK gene products in anaplastic large cell lymphomas and Hodgkin's disease.

The translocation t(2;5)(p23;q35), discovered in CD30+ anaplastic large cell (ALC) lymphomas, creates a potentially oncogenic fusion gene, part of which is contributed by a novel tyrosine kinase, ALK. Absence of ALK expression from normal hematolymphoid cells provides a basis for the morphologic assessment of t(2;5). The distribution of the t(2;5) in ALC lymphomas and Hodgkin's disease (HD), as assayed by nonmorphologic methods, is controversial. We used in situ hybridization and/or immunohistology to show ALK gene products in 85 ALC lymphomas, 82 HD cases, 40 other lymphoproliferations, as well as in 6 HD- and 4 ALC lymphoma-derived cell lines. ALK gene products were restricted to t(2;5)-positive ALC lymphoma cell lines and tumor cells of 16 primary non-B cell, common-type ALC lymphomas. These were mainly from young patients with initial lymphonodal disease. ALK expression was not detectable in any other specimen, including all cases of HD and HD-like type ALC lymphoma as well as secondary ALC lymphomas. Full congruence was noted for labeling results obtained with both methods. In agreement with cytogenetic analyses, but at variance with recently published studies, ALK gene expression distinguishes a subset of ALC lymphomas from other CD30+ lymphomas, including HD. The results do not support concepts attributing a significant role to the t(2;5) in the development of HD.

Activin Receptors↗
PubMed1995

CD79a: a novel marker for B-cell neoplasms in routinely processed tissue samples.

The CD79 molecule, comprising two polypeptide chains, mb-1 (CD79a) and B29 (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and may, therefore, be considered the B cell equivalent of CD3. It appears before the pre-B-cell stage, and the mb-1 (CD79a) chain can still be present at the plasma cell stage. In this report, we describe a new anti-CD79a monoclonal antibody, JCB117, which reacts with human B cells in paraffin embedded tissue sections, including decalcified bone marrow trephines. When tested on a total of 454 paraffin embedded tissue biopsies, gathered from a number of different institutions, it reacted with the great majority (97%) of B-cell neoplasms, covering the full range of B-cell maturation, including 10 of 20 cases of myeloma/plasmacytoma. It is of interest that the antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it the most reliable B-cell marker detectable in paraffin-embedded specimens in this disorder. All neoplasms of T cell or nonlymphoid origin were negative, indicating that antibody JCB117 may be of value to diagnostic histopathologists for the identification of B-cell neoplasms of all maturation stages.

Antibodies, Monoclonal↗
PubMed1995

Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of atypical T cells, B cells including B immunoblasts, and plasma cells, as well as eosinophilic granulocytes accompanied by proliferated high endothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely believed to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [35S]-labeled cytokine-specific RNA probes in seven cases subsequent to immunohistology for cell type characteristic antigens. Expression of all four cytokines was strongly enhanced in AILD-TCL when compared with the control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were present in atypical T cells and in a variable proportion of B immunoblasts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcripts were mainly found in nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for cytokine transcripts. It became evident that expression of LT and TNF by EBV-infected cells was largely restricted to B immunoblasts, which were only infrequently present in most AILD-TCL cases, whereas the expression of IL-6 was very rare, and IL-1 beta was not found in EBV-infected cells. These data suggest that expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expression by EBV-infected cells does not, in most cases, contribute significantly to the overall cytokine expression. Because it has been shown that LT is an autocrine growth factor for EBV-infected B cells, expression of this cytokine could contribute to the proliferation of EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphomas.

Cytokines↗
PubMed1995

Recombinant human interleukin 4 has antiproliferative activity on human tumor cell lines derived from epithelial and nonepithelial histologies.

Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study we report that rhIL-4 has an antiproliferative effect on five of nine cell lines derived from human colon tumors, head and neck tumors, and glioblastomas as measured by a decrease of colony formation in human tumor cloning assays. All of the cell lines with in vitro responsiveness express at least 100 high-affinity receptors for human interleukin 4 per cell on their cell surface, whereas the nonresponsive tumor cell lines lack expression of high-affinity receptors for human interleukin 4 on their cell surface. In the next series of experiments we have xenotransplanted some of the responsive cell lines into athymic nude mice. Subsequently, the animals were treated s.c. twice daily with 0.5 mg/m2 rhIL-4 or control vehicle for at least 12 days. There was a clear growth inhibition of these xenotransplanted tumors in the mice treated with rhIL-4. Histology of the tumors in both groups revealed no marked infiltration with murine hematopoietic and lymphocytic cells as evaluated by staining with a rat anti-mouse CD45 antibody. We conclude that rhIL-4 has a direct therapeutic activity on the growth of some human epithelial and nonepithelial tumor cell lines which, along with its regulatory function on hematolymphopoietic cells, makes this cytokine an interesting candidate for experimental tumor therapy.

Animals↗
PubMed1995

Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus.

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

Adolescent↗