PubMed Health⌕ Search

Biomedical subjects

K Hell

Publications and source records attributed to K Hell.

At least 37 records · Page 2Linked to original sources

Bcs1p, an AAA-family member, is a chaperone for the assembly of the cytochrome bc(1) complex.

Bcs1p, a mitochondrial protein and member of the conserved AAA protein family, is involved in the biogenesis of the cytochrome bc(1) complex. We demonstrate here that Bcs1p is directly required for the assembly of the Rieske FeS and Qcr10p proteins into the cytochrome bc(1) complex. Bcs1p binds to a precomplex in the assembly pathway of the cytochrome bc(1) complex. Binding of Bcs1p to and release from this assembly intermediate is driven by ATP hydrolysis. We propose that Bcs1p acts as an ATP-dependent chaperone, maintaining the precomplex in a competent state for the subsequent assembly of the Rieske FeS and Qcr10p proteins.

Adenosine Triphosphate↗

Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428.

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.

Animals↗

Oxa1p, an essential component of the N-tail protein export machinery in mitochondria.

A number of nuclear encoded inner membrane proteins of mitochondria span the membrane in such a manner that their N termini are located in the intermembrane space. Many of these proteins attain this membrane orientation by undergoing an export step from the matrix across the inner membrane. This export process, which resembles bacterial N-tail export from energetic and topogenic signal requirements, is facilitated by Oxa1p, a protein that has homologues throughout prokaryotes and eukaryotes. Oxa1p, as we have previously shown, is required to export the N and C termini of the mitochondrially encoded pCoxII to the intermembrane space. We demonstrate here that imported nuclear encoded proteins physically interact with Oxa1p and depend on Oxa1p for efficient export of their N termini to the intermembrane space. Furthermore, Oxa1p interacts with nascent polypeptide chains synthesized in mitochondria, including the fully synthesized pCoxII and CoxIII species. Thus, Oxa1p represents a component of a general export machinery of the mitochondrial inner membrane.

Cross-Linking Reagents↗

[Antibiotic prophylaxis in cholecystectomy--necessary and cost saving?].

The effectiveness of antimicrobial prophylaxis was evaluated on the basis of data collected in a study on quality management carried out in 28 East German hospitals, involving 4477 laparoscopic and conventional cholecystectomies (197 of which with revision of the common bile duct). In 3128 patients a laparoscopic procedure (with consecutive conversion to an open cholecystectomy in 236 cases) and in 1349 patients a primarily conventional open cholecystectomy had been performed (a total of 2217 cases with and 2260 cases without antibiotic cover). The results obtained were significantly better in the group receiving prophylaxis than in patients not under antimicrobial cover. This applied to septic wound healing disorders, general and specific postoperative complications, postoperative chest infections, re-operations and postoperative lethality. On the basis of these results, it is strongly recommended that, in the future, neither laparoscopic nor open conventional cholecystectomy should be carried out without proper perioperative antimicrobial prophylaxis-this all the more so since such measures also result in a shorter hospital stay and thus reduced costs.

Adult↗

Leiomyosarcomas of the female genital tract: a clinical and histopathological study.

INTRODUCTION: Leiomyosarcomas are malignant tumours showing smooth muscle differentiation. They represent approximately 25% of all uterine sarcomas and slightly over 1% of all uterine malignancies. The purpose of the present retrospective review is to relate clinical and pathological findings of leiomyosarcomas of the female genital tract to prognosis. MATERIAL AND METHODS: During 1972-1992 eleven patients had diagnosed uterine leiomyosarcomas treated at the Department of Gynecology of the University of Saarland. The hospital records of all patients were reviewed and complete primary treatment had been performed at this center. RESULTS: The mean age was 46.92 years (SD: +/-13.85). Atypical uterine bleeding and pelvic discomfort were the most common presenting complaints (72.7%). The mean follow-up time was 59.60 months (20-96 months). Overall 2-year survival was 70% and overall 5-year survival 30%. The overall survival of patients in FIGO-stage I was 57.14%, in FIGO-stage II 100%, in FIGO-stage III 0% and in FIGO-stage IV 0%. CONCLUSION: The primary therapy should consist of an operation as radical as possible. Treatment with organ preserving seems to be reasonable if the patient desires children. Also, chemotherapy might provide a hopeful sign in the improvement of survival rates.

Adult↗

[Antibiotic prophylaxis in appendectomy. Often neglected--but necessary!].

For several decades it has been proven that adequate antimicrobial prophylaxis is effective in reducing postoperative septic complications also in appendectomy. The rational for this approach--including laparoscopic procedures--is discussed and national and international recommendations for antibiotic prophylaxis in appendectomy are cited. Unfortunately, in spite of all the evidence, less than 50% of all appendectomies in 1996 in Germany had been carried out under antibiotic cover--with serious consequences for many patients and increased costs for prolonged hospital stay and treatment due to the higher incidence of infectious postoperative complications. Surgeons are encouraged not to neglect facts and benefits concerning the use of appropriate prophylactic antimicrobials in all appendectomies.

Antibiotic Prophylaxis↗

Oxa1p mediates the export of the N- and C-termini of pCoxII from the mitochondrial matrix to the intermembrane space.

Oxa1p is a mitochondrial protein reported to be involved in the assembly of the cytochrome oxidase complex. In the absence of a functional Oxa1p, subunit II of the cytochrome oxidase accumulates as its precursor form (pCoxII). Using mitochondria isolated from a yeast strain bearing a temperature sensitive mutation in the Oxa1p, pet ts1402, we have analyzed the function of the Oxa1p protein. We demonstrate that the accumulation of pCoxII in the pet ts1402 mitochondria does not reflect a compromised Imp1p activity in this mutant. Furthermore, measurement of the membrane potential has shown it to be sufficient to support the export of CoxII from the matrix. Rather, we found that newly synthesized pCoxII accumulates in the matrix of the pet ts1402 mitochondria, because export across the inner membrane is inhibited in the pet ts1402 mitochondria. In conclusion, Oxa1p mediates the export of the N- and C-termini of the mitochondrially encoded subunit II of cytochrome oxidase from the matrix to the intermembrane space.

Biological Transport↗

[Hodgkin cells are clonal B-cells in various stages of differentiation].

Hodgkin's disease, especially its biology and pathogenesis, has been under discussion for more than 160 years. Numerous investigations have focused on the nature and clonality of Hodgkin cells, but so far no definitive answer have been yielded by immunohistochemistry, Southern blotting and PCR. However, the use of single-cell PCR has now made it possible to answer the question of the derivation of Hodgkin cells. Using a micromanipulator, Hodgkin cells can be picked out of histological sections and B-cell specific gene rearrangements (VDJ) can be amplified. With this technique it has proved possible to demonstrate the B-cell derivation of Hodgkin cells and their clonality. Mutated immunoglobulin genes in lymphocyte-predominant Hodgkin's disease indicate a germinal center cell origin of Hodgkin cells of this type. These findings, however, do not exclude cases of Hodgkin's disease with Hodgkin cells with a T-cell genotype.

Antigens, CD↗

Reactive versus neoplastic monocytoid B-cell proliferations. In situ hybridization study of immunoglobulin light chain mRNA.

To distinguish reactive versus neoplastic monocytoid B-cell (MBC) proliferations, the clonality of MBC was examined in paraffin-embedded tissues by in situ hybridization (ISH) of immunoglobulin (Ig) light chain messenger RNA (mRNA) with sensitive oligonucleotide probes in 26 cases. They included 13 cases of lymphadenitis with MBC reaction and 13 cases of nodal (n = 8) and extranodal (n = 5) monocytoid B-cell lymphoma (MBCL). Two cases represented a composite lymphoma showing a centroblastic-centrocytic and MBCL component. The clonality of MBC infiltrates could be demonstrated in 16 of 26 (61.5%) cases by immunostaining for Ig light chains and in all (100%) cases by ISH. Neoplastic MBC usually expressed a faint-to-moderate light chain restriction of mRNA, whereas some MBC (10% to 30% of total MBCL population) showed a strong positivity irrespective of plasmacytoid differentiation as indicated by Ig immunostaining (present in 9 of 13 cases). Reactive MBC expressed a faint kappa and lambda light-chain mRNA positivity. Five percent to 20% of total reactive MBC showed also a strong positivity for both Ig light chain mRNA, although only a minor part of these cells (7 of 13 cases) expressed polyclonal Ig by immunohistochemistry. These results indicate that (1) both reactive and neoplastic MBC can differentiate into plasma cells; and (2) a relatively high percentage of reactive and neoplastic MBC show a detectable mRNA transcription, but not a corresponding Ig synthesis. Either the Ig detection is not sensitive enough or these cells might be in an early differentiation phase, where the Ig production has not yet started.

Adolescent↗

Combination of Hodgkin's disease and diffuse large cell lymphoma: an in situ hybridization study for immunoglobulin light chain messenger RNA.

It is not clear whether the rare combination of Hodgkin's diseases with non-Hodgkin lymphomas are true composite lymphomas or differentiation stages of one tumour cell clone. We used in situ hybridization and immunohistochemistry for the demonstration of immunoglobulin light chains in order to investigate the relationship between the two lymphoma components. In three cases of nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma the Hodgkin cells, as well as the tumour cells in the diffuse large B-cell lymphoma, showed the same messenger RNA for one light chain. Thus, using in situ hybridization in nodular lymphocyte predominance Hodgkin's disease combined with diffuse large B-cell lymphoma in a small number of cases a possible genetic relationship between the two components could be shown. In nodular sclerosis combined with diffuse large B-cell lymphoma, in situ hybridization did not support a common clonal origin of both tumour parts. However, a unique clonal derivation cannot be excluded by the techniques applied.

Hodgkin Disease↗

Hodgkin cells accumulate mRNA for bcl-2.

BACKGROUND: The bcl-2 oncogene is able to prevent cells from apoptosis. Overexpression of the bcl-2 protein seems to be important for the pathogenesis of follicular center cell lymphomas, in which both protein and mRNA usually show high levels. In addition, the expression of the Epstein-Barr virus-encoded late membrane protein up-regulates the bcl-2 protein in cell lines. The aim of the current study was to investigate the expression of the bcl-2 oncogene in Hodgkin's disease both at the protein and mRNA level in correlation with the expression of the late membrane protein. EXPERIMENTAL DESIGN: Thirteen cases of all histologic types of Hodgkin's disease, six cases of chronic nonspecific lymphadenitis, three tonsils with follicular hyperplasia, seven cases of follicular small cleaved cell lymphoma, and six cases of follicular large cell lymphoma, were analyzed. We designed a novel digoxigenin-labeled oligonucleotide probe complementary to bcl-2 mRNA for nonisotopic in situ hybridization. Bcl-2 oncoprotein and late membrane protein expression were determined by immunohistochemistry. The presence of the 14;18 translocation was analyzed by PCR for the major breakpoint region. RESULTS: The main finding was that, irrespective of subtype, the vast majority of Hodgkin cells express abundant bcl-2 mRNA. Oncoprotein expression, however, varied from case to case, with the highest prevalence in the nodular sclerosing subtype, and showed no strict correlation with the late membrane protein. In our case, no 14;18 translocation could be found in Hodgkin's disease. CONCLUSIONS: Hodgkin cells in all types of Hodgkin's disease demonstrated high levels of bcl-2 mRNA, while the bcl-2 protein expression was inhomogenous. In nodular lymphocyte predominant type, the bcl-2 mRNA and protein pattern is comparable to germinal center cells. This finding is a further argument for the germinal center cell origin of this type of Hodgkin's disease.

Base Sequence↗

Incidence of Epstein-Barr virus bcl-2 expression and chromosomal translocation t(14;18) in large cell lymphoma associated with paragranuloma (lymphocyte-predominant Hodgkin's disease).

Seven cases of large cell lymphoma (LCL) developing simultaneously or secondarily to lymphocyte-predominant Hodgkin's disease (nodular paragranuloma [NP]) were investigated for the presence of Epstein-Barr virus genomic material and the chromosomal translocation t(14;18) involving the major breakpoint region of the bcl-2 gene using the polymerase chain reaction on paraffin-embedded material. The translocation t(14;18) and Epstein-Barr virus could not be demonstrated in any case. The expression of the bcl-2 oncogene product was investigated using immunohistochemistry. Only in one case were the lymphocytic and histiocytic cells positively stained with the bcl-2 antibody, whereas the associated LCL demonstrated a completely negative immunoreaction. In another case the LCL had a positive immunoreaction with this antibody and the corresponding lymphocytic and histiocytic cells were completely negative. We conclude that Epstein-Barr virus infection is rare or absent in NP and in the LCLs associated with NP. The chromosomal translocation t(14;18) does not seem to be a factor in the transformation of NP into LCL.

Adult↗

Demonstration of light chain mRNA in Hodgkin's disease.

The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by immunohistochemistry is a well-known phenomenon. However, up to now, in situ hybridization techniques have failed to demonstrate light chain messenger(m) RNA in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26 cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease, mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled oligonucleotide probes for kappa and lambda light chains by in situ hybridization. In nearly half of the cases of nodular lymphocyte predominant Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one light chain could be clearly demonstrated in the lymphocytic and histiocytic cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at least some cases of Hodgkin's disease are B-cell neoplasms.

Hodgkin Disease↗

Expression of the proliferating cell nuclear antigen in the different types of Hodgkin's disease.

Thirty-eight cases of Hodgkin's disease (HD, lymphocyte-predominant, n = 10; nodular sclerosis, n = 10; mixed cellularity, n = 10; lymphocyte depletion, n = 8) were investigated with the antibody PC10 directed against the proliferating cell nuclear antigen (PCNA) with B- and T-cell markers using a double-staining technique in paraffin-embedded material. It could be shown that nearly all (95-97%) Hodgkin's and Reed-Sternberg (HRS) cells and their variants were PCNA-positive regardless of the type of HD. There was only a low number of PCNA-positive lymphocytes (2.8-3.4%) in all types mostly consisting of MT1-positive T lymphocytes. In contrast to the other types, lymphocyte-predominant type showed a relatively high percentage (5%) of Leu-7-positive lymphocytes. The high percentage of PCNA-positive HRS cells correlates with their malignant nature, and might be another example of dysregulated expression of PCNA.

Antigens, Differentiation↗

[Which are the proliferating cells in Hodgkin's disease?].

This investigation characterizes the proliferating cells in Hodgkin's disease. We used the antibody PC 10 which reacts with the proliferating cell nuclear antigen (PCNA) and works on paraffin sections in combination with B- and T-cell markers in a double-staining technique. In all 38 cases of Hodgkin's disease (lymphocyte predominant type n = 10, nodular sclerosis type n = 10, mixed cellularity type n = 10, lymphocyte depletion type n = 8) a high percentage of the Hodgkin and Sternberg-Reed cells (95%-97%) expressed PCNA. There was no statistical significance between the different types. In contrast, only a small amount of the reactive lymphocytes (2.8%-3.4%) demonstrated positivity for PCNA in the four types of Hodgkin's disease. Nearly all of these lymphocytes were T-lymphocytes.

Antigens, CD↗

[Bcl-2 in potentials precursors of nodular paragranuloma and its dedifferentiated variant (large cell B-lymphoma)].

We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas.

Adult↗