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Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

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

Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study.

Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.

Alleles↗
PubMed1996

[Video endoscopy-assisted saphenous vein occlusion--minimal invasive concept for treatment of varicose veins].

Videoendoscopy-assisted saphena occlusion (VASO) is an minimally invasive technique for the treatment of varicosis with crossectomy, dissection of perforating veins and occlusion of the saphena by endoscopic control. The advantages are lower level of pain, remobilisation without problems, and fewer complications of wound healing. Early results correspond to stripping.

Endoscopes↗
PubMed1995

Risk modifiers in carriers of BRCA1 mutations.

The majority of, but not all, women with mutations in the BRCA1 gene will be affected with breast or ovarian cancer by the age of 70. To establish whether known risk factors modify susceptibility to cancer in these women, we have studied the reproductive histories of 333 North American women who were found by haplotype analysis to carry BRCA1 mutations. An increased risk for breast cancer was associated with low parity and with recent birth cohort. The risk of ovarian cancer decreased with increasing age at last childbirth; however, in contrast to the case for sporadic cancer, the risk of ovarian cancer in BRCA1 carriers was found to increase significantly with increasing parity.

Adult↗
PubMed1995

A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening.

OBJECTIVES: To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations. DESIGN: Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples. PARTICIPANTS: A total of 1086 women with either breast or ovarian cancer. MAIN OUTCOME MEASURE: The detection of sequence variation in patients' DNA samples that is not found in sets of control samples. RESULTS: BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening. CONCLUSIONS: The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations.

Adult↗
PubMed1995

Microdissection and microcloning of chromosomal alterations in human breast cancer.

The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1-4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5-8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band- or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10-13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.

Breast Neoplasms↗
PubMed1995

Evaluation of plasma 5-fluorouracil nucleoside levels in patients with metastatic breast cancer: relationships with toxicities.

This paper describes the relationship between 5-fluorouracil (FUra)-derived toxicities and plasma levels of the FUra anabolites 5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd) monitored in patients receiving continuous infusions of FUra (1000 mg/m2 per 24 h) over 5 days preceded by the administration of cisplatin (100 mg/m2). A total of 63 courses of this treatment were given as second-line chemotherapy to 17 patients with metastatic breast cancer. The active FUra anabolites FUrd and FdUrd were monitored twice daily in the plasma by high-performance liquid chromatography. Data were analyzed using multiple analysis of variance (ANOVA). Only a low proportion of patients exhibited measurable plasmatic levels of FUrd (43%) and FdUrd (70%). The areas under the plasma concentration-time curves (AUC) determined over 120 h for FUrd (AUCFUrd) and for FdUrd (AUCFdUrd) were found to be statistically significantly different for chemotherapy cycles with and those without myelosuppression. Chemotherapy cycles without neutropenia were associated with low AUCFUrd values (mean +/- SEM, 2.9 +/- 0.7 micrograms ml-1 h) and high AUCFdUrd values (14.1 +/- 2.7 micrograms ml-1 h), respectively, whereas courses with myelosuppression (WHO grades 2-4) showed inverse profiles with high AUCFUrd values (16.3 +/- 2.3 micrograms ml-1 h) and low AUCFdUrd values (3.1 +/- 1.0 micrograms ml-1 h), respectively. A statistically significant difference in AUCFdUrd values was also observed between cycles with and those without mucositis (P = 0.0027), with AUCFdUrd values being 22.6 +/- 5.6 and 7.8 +/- 1.9 micrograms ml-1 h, respectively. Whereas hematotoxicity could be correlated with both AUCFUrd and AUCFdUrd values, mucositis was associated with high AUCFdUrd levels. Moreover, a negative correlation was found between the AUCs determined for FUrd and FdUrd (P = 0.002), indicating that activation of FUra via FUrd or via FdUrd may involve competitive processes. Therefore, to follow the development of the major FUra-derived toxicities, measurement of FUrd and FdUrd plasma levels appeared very attractive.

Adult↗
PubMed1995

[Effect of hypnosis and autogenic training on acral circulation and coping with the illness in patients with progressive scleroderma].

In 12 patients with systemic sclerosis the influence of hypnosis and autogenic training on the acral blood circulation and the coping with the disease was investigated in a pilot study. In the first step significant increases in the skin temperature of the finger (mean +/- SD: 3.9 +/- 1.2 degrees C) could be found after relaxation hypnosis. In the second step six patients (study group) gained experience with autogenic training. The other six patients served as control group. In the study group, the skin temperature of the fingers (short-term effect) was significantly higher than in the control group (1.9 +/- 1.0 degrees C). Long-term effects of the autogenic training (mean acral rewarning time, duration and course of the Raynaud attacks, acral lesions of the hands, psychosomatic status of complaints, type of relation to the disease as precondition for coping with the disease) were not found within the relatively short follow-up period of 4 months. Two patients, however, reported that they could shorten the duration of Raynaud attacks by autogenic training. In our patients heterogenicity and an increased score of multiple psychosomatic complaints were registered at the outset. As far as the type of relation to the disease is concerned, the patients could be assessed as almost adapted. Hypnosis and autogenic training can be recommended as complementary therapy in systemic sclerosis.

Adaptation, Psychological↗
PubMed1995

[Substance P and vasoactive intestinal peptide in patients with progressive scleroderma. Determination of plasma level before and after autogenic training].

In 12 patients suffering from systemic sclerosis (SSc) the influence of autogenic training on the plasma level of the neuropeptides substance P and vasoactive intestinal peptide (VIP) was studied. Compared with healthy controls the SSc patients exhibited significantly elevated levels of substance P (mean +/- SD: 7.1 +/- 3.2 pmol/l vs 1.6 +/- 1.6 pmol/l). Apart from variations the VIP plasma concentration did not significantly differ from that in healthy controls (mean +/- SD 10.7 +/- 7.1 pmol/l versus 12.0 +/- 5.3 pmol/l). Autogenic training did not bring about any significant changes in the plasma levels of neuropeptides.

Adolescent↗
PubMed1995

Evaluation of the reliability of 6 current anti-HIV-1/HIV-2 enzyme immunoassays.

The sensitivity for early detection of HIV antibodies and specificity of 6 anti-HIV-1/HIV-2 screening enzyme immunoassays (ELISAs) currently on the market were investigated by testing a panel of 249 well-characterized serum samples. The panel included sera from AIDS patients or children with congenital HIV infection, high-risk individuals and patients with conditions unrelated to AIDS. 'Tricky' sera (repeatedly positive results by ELISA and negative or indeterminate results by Western blot; n = 69) were also used in this evaluation along with 6 seroconversion panels. One second-generation assay (Biotest) and two third-generation assays (Abbott and Murex) showed the highest sensitivity for early detection of HIV-1 antibodies in seroconversion panels. A high specificity was achieved with the Cambridge Biotech (100%) and Ortho ELISA (99.4%). A relatively high rate of false-positive results was obtained with the Biotest (n = 10) and the Pasteur assays (n = 8) by testing 'tricky' sera and samples from high-risk individuals and from patients with other acute viral infections. In conclusion, it remains difficult to combine high specificity with an accurate detection of early seroconversion for anti-HIV-1/HIV-2 screening enzyme immunoassays.

Acquired Immunodeficiency Syndrome↗
PubMed1995

In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate.

Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100-fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.

Antigens, Viral↗
PubMed1995

Coping with employment discrimination against diabetics: trends in social medicine and social psychology.

In many European countries, social-medical aspects in the management of diabetes mellitus are not satisfactorily respected. Our contribution reports a study addressing the impact of diabetes on the patient's career and daily work, in order to determine the extent to which diabetics are being discriminated against at work. Type I diabetics were questioned about their experience, and not on the objective burden. A questionnaire was developed to evaluate patients' social and employment problems. Few elements of an education program for Type I diabetes optimizing social skills (social competence) are demonstrated. In a group of 6-8 patients, assertive behavior in the work place is modelled (e.g., for hypoglycaemia, social phobia) by applying psychological methods (behavior modification role-playing). These methods can help diabetic patients to master their discrimination. They learn assertive behavior in social situations with superiors and colleagues and develop self-confidence (self-efficacy). This special education program supports Type I diabetics in coping with employment discrimination.

Adaptation, Psychological↗
PubMed1995

Dorso-ventral and rostro-caudal sequential expression of M-twist in the postimplantation murine embryo.

M-twist is the murine homolog of the Drosophila twist gene which is a zygotic target for maternal genes that establish embryonic dorso-ventral polarity and is necessary for mesoderm formation. We recently showed that before gastrulation, M-twist transcripts are detected in morulae and blastocysts, then in extra-embryonic tissues of early implanted mouse embryos before the onset of gastrulation, and we suggested that M-twist might be involved in embryonic polarity (Stoetzel et al., submitted). Here, using in situ hybridization on whole mount embryos, we present the expression pattern of M-twist from primitive streak stage up to 10.5 days p.c. In implanted embryos, M-twist is first expressed in extra-embryonic tissues, then in embryo proper around egg cylinder stage within some embryonic ectodermal cells of the primitive streak. Slightly later, scattered cells within the amniotic cavity apparently detached from the primitive streak also express the gene. Then, M-twist transcripts accumulate in head mesenchyme, the first aortic arches, somites and lateral mesoderm and, as development proceeds, successively the second, third and fourth branchial arches, the anterior limb buds and, finally, the posterior limb buds. Thus M-twist expression in implanted embryos occurs first along a dorso-ventral gradient pattern until the headfold stage, then it is gradually observed along the rostro-caudal axis of the embryos as development procedes in the mesodermal cell layer and in neural crest cell derivatives. In addition, we show the existence of some previously undescribed subsets of scattered cells that express M-twist and thus might participate in murine embryo development.

Animals↗
PubMed1995

Effects of desferrioxamine on human cytomegalovirus replication and expression of HLA antigens and adhesion molecules in human vascular endothelial cells.

Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in cultured human endothelial cells and on the expression of several cell surface molecules, which mediate interactions of endothelial cells with other cell types in the immune system. The concentrations of DFO required for 50% reduction in the number of endothelial cells expressing HCMV late antigen, ranged for several HCMV strains from 5.2 to 8.8 microM. DFO concentrations ranging from 5 to 40 microM inhibited cellular DNA synthesis in a dose-dependent manner without any significant effects on the cell viability. DFO at 10 microM concentration suppressed expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1), while it had no significant effect on the expression of vascular cell adhesion molecule-1 (VCAM-1). Expression of HLA class I and class II was not influenced by DFO treatment. The results showed that DFO is both effective in inhibition of HCMV replication and expression of ICAM-1 and ELAM-1 in endothelial cells, a combination that warrants attention to its potential use to prevent HCMV-induced allograft rejection in transplant recipients.

Cell Adhesion Molecules↗
PubMed1995

Isolation of the myc transcription factor nucleoside diphosphate kinase and the multifunctional enzyme glyceraldehyde-3-phosphate dehydrogenase by cAMP affinity chromatography.

Cyclic AMP affinity chromatography applied to various mammalian tissue extracts yielded two proteins in addition to the regulatory subunits of protein kinase. This paper characterizes these proteins and provides a simple procedure for their preparation. The polypeptides (36 kDa and a 19 kDa/21 kDa doublet) were isolated from the cAMP matrix by sequential elution with cAMP solutions of increasing concentrations. Microsequencing was accomplished following chemical or enzymic degradation of isolated polypeptides. Partial amino acid sequences of the 36 kDa protein and analyses of its enzymic activity indicated identity with glyceraldehyde-3-phosphate dehydrogenase whilst the lower MW protein proved to be identical with mammalian nucleoside diphosphate kinase subunits. In both cases, binding to cAMP appeared to occur at the nucleotide (NAD and ATP, respectively) sites. In conclusion, we present a one step-procedure, applicable to tissue and cell extracts, which allows the simultaneous isolation of both glyceraldehyde-3-phosphate dehydrogenase and nucleoside diphosphate kinase. This procedure may help to elucidate the multiple functions of these two important enzymes.

Amino Acid Sequence↗
PubMed1995

Seroprevalence of HCV, HAV, HBV, HDV, HCMV and HIV in high risk groups/Frankfurt a.M., Germany.

During the period from August 1991 to April 1993, serum samples originating from different risk groups were tested for antibodies against hepatitis C virus (HCV), using a second-generation ELISA. The highest HCV seroprevalence levels were observed in haemophiliacs (87.0%) and intravenous drug abusers (IVDA) (78.9%). The HCV-seropositivity rates of polytransfused and organ transplant recipients were nearly identical (18.4% vs. 16.8%). Significantly lower HCV-seroprevalence rates were determined in chronic haemodialysis patients (8.1%) and homo/bisexuals (10.0%). The lowest HCV seroprevalence levels were found in the groups of female prostitutes (1.4%) and health care staff (0.8%). A strong correlation between HCV seropositivity and the presence of antibodies against HIV-1, HBc and HCMV was observed. There was also an association between HCV seropositivity and HAV. The seroprevalence of HDV and the proportion of HBsAg and HBeAg carriers was not significantly influenced by HCV serostatus. The incidence of HCV infection in renal transplant recipients was 3.9%. In 10 (6.5%) patients, anti-HCV seroconversion was observed in the immediate post-transplantation period followed by a decrease of the index value and finally, disappearance of antibodies at the end of the study. Antibodies passively acquired through intravenous immunoglobulin (IVIG) donation may account for overestimation of HCV seroprevalence in retrospective seroepidemiological surveys as established by our findings.

Adolescent↗