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H Kreipe

Publications and source records attributed to H Kreipe.

At least 55 records · Page 3Linked to original sources
PubMed1996

bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma.

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1-S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas (n = 40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.

Base Sequence↗
PubMed1996

Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors.

The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.

Adolescent↗
PubMed1996

Expression of bcl-2--protein in small cell lung cancer.

The expression of the proto-oncogene bcl-2, whose main function appears to be an inhibition of apoptosis, was investigated in 164 cases of primary small cell lung cancer by means of immunohistochemistry in a retrospective analysis. One-hundred twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference in serum LDH levels and proliferative activity between the two groups. An analysis revealed a median survival time of 12 months for patients with bcl-2 positive tumors compared to 9.5 months for patients with bcl-2 negative tumors. Although statistical significance is not achieved, there is a trend towards longer survival in patients whose tumors express bcl-2. This tendency is also reflected by a higher rate of complete remission after chemotherapy: 40% in patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In multivariate analysis, tumor stage followed by Karnofsky index were the most valuable predictors for complete remission. LDH and tumor stage were most predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may reflect a less aggressive mechanism of transformation and a higher susceptibility to cytostatic treatment.

Adult↗
PubMed1995

Modulation of fibroblast activity in histiocytosis X by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibrosis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidence of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B-chain of PDGF) expression was measured by gene hybridization revealing an upregulated c-sis transcript in the group of histiocytosis X and patients, whereas no c-sis expression was detectable in the control group. The alveolar macrophage supernatants from histiocytosis X patients and from the control group were incubated with a human lung fibroblast cell line (WI-38). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen III peptide concentration in fibroblast supernatants. Tritiated thymidine uptake was increased 1.6 times in histiocytosis X compared with the control group (p < 0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants from histiocytosis X were elevated 2.5 times compared with the control group (p < 0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (AA- and BB-chain) resulting in an 80% decrease of tritiated thymidine uptake and procollagen-III-peptide production in the group of histiocytosis X patients compared with native supernatants. No significant change in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T-lymphocyte marker did not show significant differences in both groups excluding unspecific antibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen production.

Adult↗
PubMed1995

Proliferation-associated nuclear antigen Ki-S1 is identical with topoisomerase II alpha. Delineation of a carboxy-terminal epitope with peptide antibodies.

Proliferation-linked expression of the nuclear Ki-S1 antigen is a significant prognostic indicator in mammary carcinomas. Here, we show staining of a protein of 170 kd by Ki-S1 antibody in immunoblots of Saccharomyces cerevisiae expressing human topoisomerase II alpha but not in the parental strain. In HL-60 cells containing both isoforms of human topoisomerase II, Ki-S1 antibody binds selectively to the 170-kd isoenzyme in a similar fashion as peptide-antibodies directed against amino acid residues 1 to 15 or 1512 to 1530 of human topoisomerase II alpha. Conversely, antibodies directed against carboxyl-terminal sequences of human topoisomerase II beta selectively stain a 180-kd protein. The immunoreactive pattern of V8 endoproteinase restriction digests of human topoisomerase II alpha was identical for Ki-S1-antibody and peptide-antibodies directed against residues 1512 to 1530 but different for peptide-antibodies directed against residues 1 to 15. The Rf values of the smallest fragment commonly recognized by Ki-S1 antibody and the carboxy terminus-specific peptide-antibody place the Ki-S1 epitope within the last 495 carboxyl-terminal amino acid residues of topoisomerase II alpha.

Animals↗
PubMed1994

Ki-S1 and PCNA expression in erythroid precursors and megakaryocytes--a comparative study on proliferative and endoreduplicative activity in reactive and neoplastic bone marrow lesions.

The monoclonal antibody Ki-S1 reacts with a cell proliferation-associated nuclear antigen which is expressed in the G1 through G2/M phases of the cell cycle and is resistant to formalin fixation. We have studied Ki-S1 and PCNA (PC10) immunostaining of erythroid precursors (proliferative activity) and megakaryocytes (endoreduplicative activity) in bone marrow trephine biopsies in a variety of reactive and neoplastic lesions using double immunohistochemistry to identify both cell lineages. A significant increase in Ki-S1 labelling compared with PCNA positivity was found in all conditions studied. In particular, specimens derived from secondary polycythaemia (SP), polycythaemia vera (P. vera), and primary osteomyelofibrosis (OMF), and from splenic tissue with myeloid metaplasia (MM), revealed a disproportionally high labelling index of erythropoiesis, which was not present in chronic myelogenous leukaemia (CML), AIDS, and autoimmune (idiopathic) thrombocytopenia (ITP). Enhancement of Ki-S1 (PCNA) staining in SP and P. vera is in keeping with the relevant increase in erythroid precursor proliferation, but in OMF and MM there is overexpression of both proliferation markers, possibly due to secondary folic acid deficiency, which is known to cause a block in the S-phase of the cell cycle. A significant correlation was observed between the sizes of megakaryocytes and their nuclei with Ki-S1 (and also PCNA) staining. Ki-S1 (and PCNA) labelling of predominantly smaller elements of this lineage supports a hypothesis that the phases of the cell cycle have different durations in the various steps of polyploidization, with a prolongation of G1/G2 at higher ploidy levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1994

The impact of EBV, proliferation rate, and Bcl-2 expression in Hodgkin's disease in childhood.

The role of Epstein-Barr virus (EBV) in the pathogenesis of Hodgkin's disease (HD) has not yet been clarified. Using RNA in situ hybridization (ISH) and immunohistochemistry (IHC), the occurrence of small Epstein-Barr virus encoded RNA (EBER) and latent membrane protein-1 (LMP-1) was studied in 22 tissue samples from 21 patients between 4 and 17 years of age with Hodgkin's disease. EBER was detected in eight of 21 patients (38%) in Hodgkin and Reed-Sternberg cells and reactive lymphocytes irrespective of initial clinical stage and histological subtype, whereas LMP-1, positive in ten of 21 patients (48%), was restricted to neoplastic cells. All cases positive for EBER expressed LMP-1 as well. Additionally, oncoprotein Bcl-2 was identified in nine of 21 patients (43%), indicating, besides immortalization of HD cells by EBV, a further growth advantage due to apoptosis prevention by overexpression of this protein. Proliferation-associated antigens Ki-S1 and Ki-S5 were highly expressed in Hodgkin and Reed-Sternberg cells. CD 30 antigen was found in most cases, using two different antibodies (90% and 80%). The presence of this protein, which belongs to the family of nerve growth factor receptor (NGFR), is related to high expression of Ki-67 protein, detected by Ki-S5. CD 20 antigen was detectable in only three of 21 patients (14%). If we compare results of ISH and IHC with clinical data, the occurrence of EBV genome in children with HD seems to have no adverse effect on the final outcome of these patients.

Adolescent↗
PubMed1994

Ki-S1 and proliferating cell nuclear antigen expression of bone marrow macrophages. Immunohistochemical and morphometric study including reactive (inflammatory) myelitis, secondary aplastic anemia, AIDS, myelodysplastic syndromes and primary (idiopathic) osteomyelofibrosis.

There is general agreement on the fact that bone marrow macrophages present a non-proliferating cell population. Using a sequential double-immunostaining technique, a morphometric analysis was performed on routinely processed bone marrow biopsies derived from 70 patients. The purpose of this study was, firstly, to determine the frequency of bone marrow macrophages in a variety of lesions and, secondly, to elucidate whether there is any proliferative activity detectable by immunohistochemical markers. Bone marrow pathology included reactive myelitis (RM), secondary aplastic anaemia (AP), AIDS-related myelopathy, primary (idiopathic) osteomyelofibrosis (OMF) and myelodysplastic syndromes (MDS). The monoclonal antibody PG-M1 which recognizes a formalin-resistant epitope on macrophages and PC10 raised against proliferating cell nuclear antigen (PCNA) were employed. For comparison with the PCNA-labelling index, the newly developed monoclonal antibody Ki-S1, which is associated with cell proliferation, was applied. In comparison with normal bone marrow, morphometric evaluation revealed a significant increase in macrophages in MDS, OMF, RM and especially in HIV-infected patients. Moreover, a positive immunostaining of single macrophages with PC10 was noted very infrequently. This rather inconspicuous PCNA labelling increased in AIDS. By contrast, Ki-S1 expression was found in none of the other pathologies studied. The prevalence of the macrophage population in certain disorders may have a multifactorial origin, such as inflammatory changes like intercurrent infections in AIDS and enhanced cell turnover in MDS as well as involvement of the complex pathomechanisms generating bone marrow fibrosis. In keeping with previous studies, the insignificant PCNA expression of macrophages should not be related to cell proliferation, but to unscheduled DNA strand repair which may be generated in the course of viral infection in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Proliferative activity and defective replication in breast cancer].

The highly proliferating phenotype of mammary carcinoma is known to be associated with a particularly aggressive clinical course. We have been interested in the underlying molecular causes that give rise to the increased proliferative activity Proliferative activity was determined immunohistochemically by the detection of topoisomerase II-alpha (Ki-S1). The subgroup of highly proliferating tumors with a Ki-S1 index exceeding 30% was characterized by a high frequency of c-myc amplification and aberrant p53 expression, whereas tumors, with a low mitotic activity rarely exhibited gene amplification or an altered p53 expression. We conclude, that the highly proliferating phenotype is not capable of regular replication and tends to develop gene amplifications. One of the causes might be a defective cell cycle control by p53.

Breast Neoplasms↗
PubMed1993

Amplification of c-myc but not of c-erbB-2 is associated with high proliferative capacity in breast cancer.

Proliferative capacity provides an independent prognostic marker of progression in breast cancer. Little is known about the molecular mechanisms influencing the cell division rate in mammary carcinomas. In order to address this issue, the copy numbers of c-erbB-2 (HER/neu) and c-myc protooncogenes that have been shown to be amplified in aggressive types of cancers were determined in 60 mammary carcinomas and related to the proliferation rate. The proliferative activity was determined by labeling of the proliferation-associated nuclear antigen which is defined by the recently described monoclonal antibody Ki-S1. Approximately one-third of samples under investigation displayed a Ki-S1 labeling index exceeding 30%. In this subgroup, amplification of c-myc was found in 52.6%, whereas in the remaining cases, 26.1% exhibited an enhanced copy number of c-myc (P < 0.025). By contrast, c-erbB-2 amplification was not found to be associated with a higher proliferation index. Except for one case of invasive lobular carcinoma, both protooncogenes exhibited regular copy numbers in the low proliferation subgroup (< 20%; P < 0.03). We conclude from our findings that c-myc amplification may be one of the molecular causes underlying the highly proliferating phenotype of mammary carcinoma, known to be associated with an unfavorable clinical course.

Base Sequence↗
PubMed1993

Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (iii) examined in a flow cytometric study Ki-S1 staining in archival, clinical breast carcinoma samples. In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis. Ki-S1 staining intensity mirrored the changes in proliferative activity of ZR75 cells during serum deprivation and refeeding. In a small series of human breast carcinoma, Ki-S1 staining intensity correlated with S-phase fraction (SPF) derived from DNA profiles. The antigen labelled by Ki-S1 is extremely robust, resisting degradation by fixation and by an aggressive enzymic tissue disaggregation method. Ki-S1 warrants further investigation as a proliferation-related marker, particularly for routine clinical application.

Animals↗
PubMed1993

[Determination of proliferation activity of prostate cancers by means of nuclear proliferation-associated formalin resistant Ki-S5 antigens].

In order to evaluate the growth fraction in normal, hyperplastic and neoplastic prostatic tissue, we examined paraffin sections of 55 cases of prostatic cancer containing areas of benign (BPH) and atypical hyperplasia (AH). Cellular proliferation was assessed by nuclear staining with the monoclonal antibody Ki-S5 directed against a formalin-resistant epitope of the Ki67 antigen. The proliferation rate was minimal in normal glands and BPH (mean 0.35%), rather low in AH and grade I carcinoma (0.5 to 15% compared to grade II carcinoma (1 to 40%) and peaking to near 80% labeled cells in grade III carcinoma. In the majority of the tumors, foci of increased cell growth could be detected by this method. Ki-S5 labeling indices correlated significantly with the histopathologic grading established by Dhom. Correlation with the clinical outcome will be the subject of subsequent retrospective studies.

Antigens, Neoplasm↗
PubMed1993

Determination of the growth fraction in non-Hodgkin's lymphomas by monoclonal antibody Ki-S5 directed against a formalin-resistant epitope of the Ki-67 antigen.

Relevant prognostic information can be added to the histological classification of non-Hodgkin's lymphoma (NHL) by the determination of the growth fraction. In unfixed fresh tissue samples the Ki-67 antigen has proven its utility as an operational marker of proliferative activity in NHL. We have generated a monoclonal antibody directed against a formalin-resistant epitope of the Ki-67 antigen, designated Ki-S5. The immunoreactivity of Ki-S5 is confined to the nuclei of proliferating cells and, unlike Ki-67, no cross-reactivity with cytoplasmic antigens of epithelial cells occurs. In 100 cases of different NHL types, parallel staining of Ki-67 and Ki-S5 antigen yielded almost identical results in fresh tissues and fixed tissues, respectively (P < 0.00001; r = 0.95). In some cases, the Ki-S5 labeling index exceeded that of Ki-67, most probably due to a partial degradation of the epitope recognized by Ki-67 in frozen stored tissue samples. Significant differences in the median Ki-S5 labeling index could be demonstrated between high grade (> 50%) and low grade malignant NHL (< or = 30%), although the proliferative activity varied to a considerable range within identical histological categories (P < 0.001). We conclude that Ki-S5 provides a reliable means to assess proliferation in paraffin-embedded NHL specimens. Retrospective studies relating the proliferative activity to clinical outcome are thus rendered possible using archival routinely processed tissue samples.

Aged↗
PubMed1993

A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1.

A monoclonal antibody (Ki-S1) has been raised that reacts with the nuclei of proliferating cells. The antigen recognized is resistant to formalin fixation and can be detected in frozen tissues as well as in routinely processed specimens. In immunohistochemistry, nuclear staining can be seen in those tissues and cellular compartments known to be actively proliferating. Peripheral blood lymphocytes are negative but show a strong increase in antigen expression after mitogen stimulation. Flow cytometric determination of DNA content and antigen expression revealed negativity of G0 cells and positivity of G1 to G2/M cells. A cytoplasmic co-reactivity, not associated with proliferation, was confined to Langerhans islands of the pancreas. The nuclear localized antigen has a molecular mass of 160 kd and therefore seems to be different from all other known immunohistochemical markers of proliferating cells. We conclude that the monoclonal antibody Ki-S1 might provide a useful tool for studying cell proliferation in situ under normal and pathological circumstances.

Animals↗
PubMed1993

Prognostic significance of a formalin-resistant nuclear proliferation antigen in mammary carcinomas as determined by the monoclonal antibody Ki-S1.

Proliferative activity is a potential prognostic indicator of neoplastic cell growth. Usually the assessment of the tumor growth fraction requires specially processed or frozen tissue. We have raised a monoclonal antibody, Ki-S1, suitable for the detection of proliferating cells in routinely processed and paraffin-embedded tissue specimens. A retrospective study was conducted on 83 mammary carcinoma patients with a median follow-up of 45.6 months. Ki-S1 positivity was significantly (P < 0.0001) correlated with the S-phase fraction. A high proliferative activity of more than 30% of tumor cells being Ki-S1-positive was significantly correlated with recurrence (P < 0.001). Cumulative survival was significantly reduced in the high Ki-S1 expressing subgroup. In a multivariate model including Ki-S1, lymph node metastases, tumor size, and progesterone receptor positivity, independent significant information was provided by Ki-S1. We conclude that in mammary carcinomas, Ki-S1-determined growth fraction represents a significant and independent prognostic predictor.

Adult↗
PubMed1992

Isolation of monocytic serine esterase and evaluation of its proteolytic activity.

Monocytes are characterized by high activity of alpha-naphthyl acetate esterase (ANAE), distinguishing them from all other blood cells. The physiological function of this monocyte marker enzyme has not yet been elucidated. In this study ANAE's potential proteolytic activity was analyzed because serine esterases/proteases can function as effector molecules in cell-mediated cytotoxicity and because monocytes-macrophages are known to exert cytotoxic effects on tumor cells. This enzyme was purified from the monocytic cell line U-937 by preparative isoelectric focusing and a three-step high-performance liquid chromatography that conserved its catalytic activity. It has a molecular mass of 60 kd, and partial amino acid sequence revealed that the enzyme is not identical to known serine esterases/proteases. The purified enzyme failed to digest a couple of peptides, indicating lack of protease activity. In addition, the esterolytic activity of ANAE was not inhibited by protease inhibitors. The isolation and purification of ANAE enable further studies concerning its function in monocytes-macrophages and its relation to monocytic cytotoxicity.

Amino Acid Sequence↗