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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 163 records · Page 9Linked to original sources
PubMed1996

Neurosensory hearing loss in secondary adhalinopathy.

We report mild-to-moderate neurosensory hearing loss and severe childhood autosomal recessive muscular dystrophy with adhalin-deficiency in two siblings from a Bulgarian sibship of Turkish origin. Microsatellite analysis excluded linkage to the adhalin gene, mutations of which cause limb girdle muscular dystrophy (LGMD) 2D, but was compatible with linkage to the gene locus of LGMD 2C on chromosome 13q12. Compound heterozygosity of the affected siblings was detected in this chromosomal region. A severe autosomal recessive form of neurosensory deafness has been linked to the same region (locus NSRD1) which is now contained in a 7 Mb YAC contig. Using polymorphic markers and STS PCR primers mapping in this contig, we did not find evidence for major rearrangements in the suspected region. These preliminary findings are not in favor of, but do not completely exclude a contiguous gene syndrome in these cases. Therefore, we consider a potential role of the putative 13q12 gene product and/or adhalin in neurosensory hearing.

Alleles↗
PubMed1996

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Germline mutations in the BRCA1 gene have been associated with familial breast/ ovarian cancer in large families showing high penetrance of the disease. Little is known, however, about the contribution of BRCA1 mutations to breast/ovarian cancer in small families with few affected members or in isolated early onset cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age. Using the protein truncation test, we were able to identify three unique BRCA1 germline mutations (4.8%). Two of the probands had only one affected first degree and several second degree relatives and the third had three affected first degree relatives including two sisters who, when tested, were also found to carry the mutation. There was no family history of ovarian cancer in any of the three families.

Adult↗
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

[Bioequivalence of nifedipine sustained-release formulations in comparison to standard preparations in solid state].

The bioavailability of a nifedipine extended release capsule-formulation (CAS 21829-25-4, Aprical retard) was investigated in comparison to a standard retard tablet. The design of the study was two-way cross-over with 24 male volunteers in the steady state after 4 days saturation with doses of 20 mg nifedipine b.i.d. The relative bioavailability of the test preparation amounted to 98.5% for AUCSS and 82.7% for Cmax with respect to the standard preparation. Statistical test procedures decide on equivalence. Typical characteristics for extended release preparations as peak-trough fluctuation (%PTF) and half-value duration (HVD50%) resulted in quotients of 67.3% and 145.1%, respectively. These data indicate the well balanced retardation of nifedipine in the test preparation.

Adult↗
PubMed1996

[Possibilities and prospects in gene therapy in cancer patients].

The many different oncological concepts of gene therapy can be classified into three major groups. These include immunopotentiation, compensation of oncogene and tumor suppressor gene alterations, and suicide gene strategies. Gene marker studies and the transfer of drug resistance genes to normal cells have also shown to be of some importance in oncology. Although there is no clear demonstration of the efficacy of gene therapy so far, it will most likely become part of the therapeutic armamentarium of oncologists within the next two to three decades.

Adjuvants, Immunologic↗
PubMed1995

[Adjuvant treatment of colonic carcinoma].

After many years of negative trials of adjuvant chemotherapy in colon cancer, two studies in the years 1989 and 1990 of the NCCTG and the Intergroup Trial, respectively showed a significant reduction of relapse and improved survival in patients treated with 5-FU and levamisole in an adjuvant setting. The absolute and relative reductions in 5-year-relapse and death rates were approximately 35% and 17%, respectively. Intraportal perfusion of the liver in an adjuvant perioperative setting seems to be of similar benefit. Preliminary data of the adjuvant therapy with 5-FU and folinic acid also show that this combination seems to have at least the same efficacy as the current standard 5-FU/levamisole in the adjuvant therapy of colon cancer. At the current time, patients with colon cancer of Dukes stage C should be offered adjuvant chemotherapy with 5-FU/levamisole outside of clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

X-linked dilated cardiomyopathy. Novel mutation of the dystrophin gene.

We report on a family with a severe form of X-linked dilated cardiomyopathy (DCM). Two brothers, the elder requiring heart transplantation, and a maternal cousin presented elevated creatine kinase levels, increased right ventricular diameters and electrocardiographic abnormalities. All complained of exertional cramping myalgia, but none had muscle weakness or a pathological electromyogram. Muscle biopsies of these individuals revealed a mild myopathic picture with atrophic type I and hypertrophic type II fibers. Immunofluorescence using N- and C-terminal antibodies (dys-2, dys-3) against the dystrophin protein showed preserved, but reduced intensity of staining of the sarcolemmal membranes. Using the same two antibodies, Western blot analyses revealed a dystrophin molecule of the expected molecular weight, which was quantitatively reduced by 80%. However, the dys-1 antibody, directed against the mid rod region of the dystrophin protein, did not react with dystrophin both on Western blot and immunofluorescence. Linkage analysis with polymorphic markers of the dystrophin gene revealed an identical haplotype at the 5' region in all affected individuals (two point lod score of 1.93, phi = 0). A deletion of exons 48, 45-53, 2-7 and 1 including the promoter region of the dystrophin gene, as described in rare cases with similar clinical signs could be excluded by multiplex PCR and Southern blot analyses of this DCM family. In addition, a major splice-mutation of dystrophin mRNA was excluded by RT-PCR of skeletal and heart muscle tissue. Therefore, we conclude that a novel mutation in the 5' region of the dystrophin gene phenotypically leads to this severe form of DCM. Extensive analyses of the dystrophin gene, in particular of the sequences coding for the antigenic determinants of the dys-1 antibody in the mid rod region, may identify the molecular cause of this monogenetic form of DCM.

Adult↗
PubMed1995

[Participation in multicenter studies as quality control in the therapy of Hodgkin disease: an interim report].

UNLABELLED: From 1988 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) entered 113 patients with Hodgkin's disease into three stage adapted trials (HD-4-6) from the German Hodgkin Study Group (DHSG). In an interim analysis freedom from treatment failure (FFTF) and overall survival (OS) of the SAKK patients (SAKK-pt) were compared to the remaining study population (GHSH-pt) (median follow-up: 30 months for HD-4 and HD-5, 24 months for HD-6). RESULTS: HD-4: SAKK (n = 16), DHSG (n = 241), FFTF-SAKK: 100%, FFTF-DHSG: 85%, p: ns, OS-SAKK: 100%, OS-DHSG: 99%, p: ns, HD-5: SAKK (n = 66), DHSG (n = 639), FFTF-SAKK: 90%, FFTF-DHSG: 85%, p: ns, OS-SAKK: 93%, OS-DHSG: 95%, p: ns, HD-6; SAKK (n = 31), DHSG (n = 411): FFTF-SAKK: 62%, FFTF-DHSG: 68%, p: ns, OS-SAKK: 70%, OS-DHSG: 88%, p < 0.008. The results in the SAKK patients with advanced disease are unsatisfactory. Despite the fact that the treatment was given on time with full doses, 10/30 patients achieved no complete remission (CR). Only one patient relapsed after an initial CR. 6 patients had primary progressive disease. 6 patients died despite conventional salvage chemotherapy. High dose chemotherapy/autologous bone marrow transplantation (HDC/ABMT) was only given to 3 out of 8 potential candidates. Only 2/11 patients are still alive and disease-free after relapse or initial progression. Both had received HDC/ABMT as part of their salvage regimen. This interim analysis identifies a group of patients in which treatment strategies need to be optimized.

Adult↗
PubMed1995

Expression in Escherichia coli and affinity purification of a CKS-troponin I fusion protein.

The human cardiac troponin I gene was subcloned and expressed at high levels in Escherichia coli as a fusion protein to CMP-KDO synthetase (CKS). Expression levels of the CKS-troponin I fusion were 8% of total cellular protein 4 h after induction with IPTG. The fusion was expressed primarily as an insoluble protein as shown by SDS-PAGE analysis. Expressed CKS-troponin I fusion from a crude lysate was antigenic against anti-CKS and anti-troponin I monoclonal antibodies in Western blots. The fusion was affinity-purified over a TnC affinity column using a urea-solubilized extract of a crude cell lysate. Serial dilutions of crude soluble extracts of the troponin I fusion were assayed in several microparticle enzyme immunoassays and found to exhibit similar immunogenic responses relative to cardiac troponin I isolated from human heart tissue.

Biomarkers↗
PubMed1995

Effects of omega-3 fatty acids on intravascular lipolysis of very-low-density lipoproteins in humans.

Very-low-density lipoproteins (VLDLs) are the major carriers of fasting plasma triglyceride (TG). TG-enriched VLDLs become cholesterol (C)-enriched low-density lipoproteins (LDLs) through hydrolysis facilitated by lipoprotein lipase (LPL). Omega-3 fatty acid (n-3 FA) supplementation may increase LDL-C while decreasing plasma TG in hypertriglyceridemic patients. It has been proposed that n-3 FAs increase LDL-C by promoting production of TG-poor VLDL and accelerating conversion of VLDL to LDL. To study the effects of n-3 FA supplementation on in vivo lipolysis of VLDL directly, we treated 11 hypertriglyceridemic subjects with n-3 FA (3.3 g/d). Each participant was studied three times: at baseline, after a 1-month period of run-in olive oil placebo, and after 1 more month of n-3 FA supplementation. Lipolysis was induced by intravenous infusion of heparin for 2 hours. Plasma samples were obtained every 30 minutes for determination of lipids and apoproteins (apos), separation of individual lipoproteins by fast protein liquid chromatography (FPLC), and measurement of LPL and hepatic TG lipase (HTGL) levels. n-3 FA supplementation decreased fasting plasma TG (2.51 +/- 0.23 v 3.97 +/- 0.46 mmol/L), VLDL-TG (1.08 +/- 0.18 v 2.35 +/- 0.35 mmol/L), and VLDL-C (0.39 +/- 0.05 v 0.72 +/- 0.13 mmol/L) while increasing LDL-C (3.59 +/- 0.21 v 3.00 +/- 0.23 mmol/L) and plasma apo B (3.31 +/- 0.19 v 2.90 +/- 0.17 mmol/L). The absolute rate of TG lipolysis correlated with fasting TG (r = .74, P < .005) and was lower after n-3 FA supplementation (0.11 +/- 0.01 mmol/mL/min) as compared with placebo (0.19 +/- 0.01, P < .01), whereas percent decreases from baseline TG levels were similar at entry onto the study (57.4% +/- 2.5%), after placebo (58.8% +/- 2.7%), and after n-3 FA (52% +/- 3.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Positive cooperativity among insecticidal scorpion neurotoxins.

The insecticidal activity of scorpion neurotoxic polypeptides increased 5-10-fold with no apparent increase in mammalian toxicity when a combination of two toxins was injected. Synergistic combinations could be predicted from binding studies and competitive displacement assays. Our results indicate that simultaneous expression in baculovirus or other transgenic organisms of the synergistic combinations of insecticidal toxins may result in more potent insect-selective biopesticides.

Animals↗
PubMed1995

Direct effects of recombinant nuclear polyhedrosis viruses on selected nontarget organisms.

A limitation to effective field use of naturally occurring nuclear polyhedrosis viruses (NPVs) is the slow rate at which they kill their host. In making NPVs a more attractive pest management tool, this problem has been addressed by modifying NPVs genetically to express insecticidal proteins resulting in substantial increases in their speed of action. One concern associated with these recombinant NPVs, however, is their effects on nontarget insects associated with pests targeted for control by applications of NPVs. Our studies evaluated the direct effects of wild-type Autographa californica NPV (AcNPV) and a recombinant AcNPV (AcAaIT) on three insects beneficial to production agriculture. The recombinant NPV expresses an insect-selective neurotoxin, AaIT, which was isolated from the scorpion, Androctonus australis Hector. Two generalist predators, Chysoperla carnea Stephens and Orius insidiosus (Say), were not adversely affected by feeding on larvae of Heliothis virescens (F.) infected with AcAaIT. Similarly, no adverse effects were detected in the honey bee, Apis mellifera L., when injected with wild-type or recombinant NPVs. Results from this study may provide a foundation upon which potential risks associated with genetically engineered NPVs may be evaluated on a limited scale in greenhouse or field experiments.

Animals↗
PubMed1995

Evidence for a mutual regulation of p53 and c-myc expression in human colorectal cancer metastases.

BACKGROUND: Alterations of the c-myc and the p53 genes occur in a majority of human colorectal cancers, and functional interaction between these two genes has recently been suggested. PATIENTS AND METHODS: We analyzed p53 sequence and c-myc and p53 mRNA expression in 26 metastases and 4 advanced primaries of human colorectal cancer. RESULTS: Twenty-one of 30 tumors (=70%) carried mutations of the p53 gene. In these samples, c-myc and p53 were overexpressed in 70% (15/21) and 71% (14/20) of evaluable cases, respectively, while in tumors carrying only wild-type p53, overexpression of c-myc and p53 was observed in only 33% (3/9; p < 0.05) and 22% (2/9; p < 0.01), respectively. Expression of p53 and c-myc were positively correlated (p = 0.014; r = 0.563) in tumors carrying a p53 mutation, but not in those with only wild-type p53. CONCLUSION: We conclude that c-myc might induce p53 expression in human colorectal cancer and that wild-type but not mutant p53 might be involved in a negative feedback regulation of c-myc expression. The abrogation of this normal control mechanism seems to be an essential step during colorectal tumorigenesis and metastatic progression.

Colorectal Neoplasms↗
PubMed1995

The proline-rich P65 protein of Mycoplasma pneumoniae is a component of the Triton X-100-insoluble fraction and exhibits size polymorphism in the strains M129 and FH.

Previously, we described the identification of a novel Mycoplasma pneumoniae M129 protein, named P65 because of its apparent molecular mass of 65 kDa estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (T. Proft and R. Herrmann, Mol. Microbiol. 13:337-348, 1994). DNA sequence analysis of the P65 open reading frame (orfp65), however, revealed an ORF encoding a protein with a molecular weight of 47,034. This discrepancy can be explained by the unusual amino acid composition of this protein. According to the deduced amino acid sequence, the N-terminal half of P65 contains several penta- and hexapeptides (DPNAY and DPNQAY) forming a proline-rich acidic domain. Secondary-structure predictions indicated beta-sheets and turns within that region, suggesting an extended and rigid conformation. Near the C terminus of P65 the tripeptide Arg-Gly-Asp (RGD) was found. This motif is known to play an important role in binding of extracellular matrix proteins to integrins. P65 could be located exclusively to the Triton X-100-insoluble cell fraction. The results of immunofluorescence microscopy and of immunoadsorption experiments indicated that P65 carries surface-exposed regions. Mild treatment of whole cells with proteases resulted in cleavage of a limited amount of P65 molecules, suggesting either that only a small percentage of P65 molecules are exposed on the surface or that protease cleavage is hampered by a compact protein conformation or by binding of an unknown component to P65. P65 exhibits size polymorphism in M. pneumoniae M129 and FH. This is caused by an intragenetic duplication of a 54-bp sequence within the FH orfp65. As a consequence, the number of DPNAY pentapeptides increased from 9 to 12 repeats in the FH strain.

Amino Acid Sequence↗