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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 451 records · Page 25Linked to original sources

Successful treatment of severe Rh iso-immunization with immunosuppression and plasmapheresis.

Nine patients with severe Rh iso-immunization were treated by plasma exchange combined with immunosuppression. Apart from 3 abortions, previous pregnancy losses consisted of 7 intra-uterine and 5 neonatal deaths. Only 2 patients had had no previous pregnancy loss. Differences in the optical density of the amniotic fluid of 8 patients fell into the upper Liley zone. There was one intra-uterine death due to abruptio placentae but no neonatal deaths. When the outcome of the pregnancy immediately preceding the treatment pregnancy was compared to the treatment pregnancy, the fetal loss was reduced from 6 to 1. No adverse fetal effects were encountered.

Adult↗

Interaction of selenoprotein PA and the thioredoxin system, components of the NADPH-dependent reduction of glycine in Eubacterium acidaminophilum and Clostridium litorale [corrected].

Purification of protein PA of the glycine reductase complex from Eubacterium acidaminophilum and Clostridium litorale [corrected] was monitored by a new spectrophotometric assay. The procedure depended on a specific two- to threefold stimulation of a dihydrolipoamide dehydrogenase activity that is elicited by the interaction of a thioredoxin reductase-like flavoprotein and thioredoxin from both organisms. Protein PA isolated from E. acidaminophilum by 75Se labeling and monitoring of the dithioerythritol-dependent glycine reductase activity was identical in its biochemical, structural, and immunological properties to the protein isolated by using the stimulation assay. Proteins PA from both organisms were glycoproteins of Mr about 18,500 and exhibited very similar N-terminal amino acid sequences. Depletion of thioredoxin from crude extracts of E. acidaminophilum totally diminished the NADPH-dependent but not the dithioerythritol-dependent glycine reduction. The former activity could be fully restored by adding thioredoxin. Antibodies raised against the thioredoxin reductase-like flavoprotein or thioredoxin inhibited to a high extent NADPH-dependent but not dithioerythritol-dependent glycine reductase activity. These results indicate the involvement of the thioredoxin system in the electron flow from reduced pyridine nucleotides to glycine reductase.

Amino Acid Sequence↗

Thioredoxin elicits a new dihydrolipoamide dehydrogenase activity by interaction with the electron-transferring flavoprotein in Clostridium litoralis and Eubacterium acidaminophilum.

The glycine-utilizing bacterium Clostridium litoralis contained two enzyme systems for oxidizing dihydrolipoamide. The first one was found to be a genuine dihydrolipoamide dehydrogenase, present only in low amounts. This enzyme had the typical dimeric structure with a subunit molecular mass of about 53 kDa; however, it reacted with both NADP (Km 0.11 mM) and NAD (Km 0.5 mM). The reduction of pyridine nucleotides by dihydrolipoamide was the strongly preferred reaction. A second dihydrolipoamide-oxidizing enzyme system consisted of the interaction of two proteins, the previously described NADP(H)-dependent electron-transferring flavoprotein (D. Dietrichs, M. Meyer, B. Schmidt, and J. R. Andreesen, J. Bacteriol. 172:2088-2095, 1990) and a thioredoxin. This enzyme system was responsible for most of the dihydrolipoamide dehydrogenase activity in cell extracts. The thioredoxin did not bind to DEAE, was heat stable, and had a molecular mass of about 15 kDa. N-terminal amino acid analysis of the first 38 amino acid residues resulted in 38% homology to Escherichia coli thioredoxin and about 76% homology to a corresponding protein isolated from the physiologically close related Eubacterium acidaminophilum. The protein of the latter organism had a molecular mass of about 14 kDa and stimulated the low dihydrolipoamide dehydrogenase activity of the corresponding flavoprotein. By this interaction with NADPH-dependent flavoproteins, a new assay system for thioredoxin was established. A function of thioredoxin in glycine metabolism of some anaerobic bacteria is proposed.

Amino Acid Sequence↗

Closures and mergers of VNA home care agencies: a model for the study of causal factors.

Recent closures and mergers of visiting nurses associations (VNAs) raise some potentially serious questions regarding access to home care for the elderly Medicare and Medicaid populations. While VNAs comprise less than 10 percent of the nation's certified home health agencies, they provide approximately 31 percent of all medicare home care (HCFA, 1989). In March of 1986 there were 524 visiting nurses associations nationally whereas today there remain only 495 (HCFA, 1990). A model identifying potential causes of VNA mortality is presented along with some preliminary results. VNA mortality is defined and measured by the date that Medicare certification is terminated as a result of VNA closure or merger.

Aged↗

Cell-type-specific regulation of nerve growth factor (NGF) synthesis in non-neuronal cells: comparison of Schwann cells with other cell types.

We have previously shown that after peripheral nerve lesion the synthesis of NGF is induced in cells of the nerve sheath (Heumann et al., 1987a). Further analysis led to the identification of growth factors and intracellular mechanisms responsible for this induction in sciatic fibroblasts (Lindholm et al., 1988; Hengerer et al., 1990). The present work aimed at the elucidation of the regulation of NGF synthesis in Schwann cells. A variety of cytokines and peptide growth factors, including interleukin-1 (IL-1) and platelet-derived growth factor (PDGF), which are known to increase NGF-mRNA in fibroblasts and astrocytes, failed to do so in Schwann cell cultures. Forskolin (FK), an activator of adenylate cyclase, increased the level of NGF-mRNA eightfold within 3 hr of incubation. The effect of FK on NGF-mRNA was mimicked by analogs of cAMP but not by dideoxyforskolin, an FK derivative not activating adenylate cyclase. Application of norepinephrine and isoproterenol also augmented the NGF-mRNA content. Pretreatment of Schwann cells with N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-8), an inhibitor of cyclic-nucleotide-dependent protein kinases, decreased both basal and elevated levels of NGF-mRNA. Ionomycin, a Ca2+ ionophore, and phorbol 12-myristate 13-acetate (TPA), an activator of protein kinase C, potentiated the effect of FK in an H-8-sensitive manner. We show that the action of FK is independent of changes in mRNA stability and of protein synthesis. Thus, in cultured Schwann cells upregulation of NGF-mRNA expression seems to be mainly achieved by a cAMP-triggered transcriptional activation of the NGF gene. Another striking difference between various glial cell types was revealed by application of transforming growth factor beta-1 (TGF-beta 1), which is the strongest inducer of NGF-mRNA in cultured astrocytes (Lindholm et al., 1990). Schwann cells responded to TGF-beta 1 by decreasing basal as well as FK-induced NGF-mRNA levels. Together with previously published work, our results show that cell-type-specific mechanisms not only account for the different control of NGF expression in neurons as compared to glial cells, but also reveal a surprising specificity of regulatory mechanisms in different non-neuronal cell types, even those derived from the same tissue such as fibroblasts and Schwann cells of peripheral nerves.

Animals↗

Algorithm to predict triple-vessel/left main coronary artery disease in patients without myocardial infarction. An international cross validation.

Logistic regression was applied to the clinical, risk factor, and exercise data of consecutive angiographic referrals without prior myocardial infarction to determine an algorithm predicting the probability of triple-vessel/left main coronary artery disease. These data were obtained from a total of 1,074 such subjects from patient populations at four centers (Cleveland Clinic Foundation, Cleveland, Ohio; Hungarian Institute of Cardiology, Budapest, Hungary; the university hospitals, Zurich and Basel, Switzerland; and the Veterans Administration Medical Center, Long Beach, Calif.) and used to derive four separate probability algorithms. Each algorithm is based on patient data from study samples at three of the four centers and consists of 272 logistic functions, which are related to linear combinations of 13 variables (age, sex, type of chest pain, systolic blood pressure, resting electrocardiogram, serum cholesterol, fasting blood sugar, achieved exercise work load, achieved heart rate, exercise-induced angina and hypotension, heart rate-adjusted resting ST depression, and exercise ST slope). The four algorithms were cross validated by testing them on the populations not involved in their derivation. The resulting probabilities in the four test groups were then compared with the angiographic findings of triple-vessel/left main coronary artery disease. The discriminatory power of all the algorithms was fair to good (area under receiver operating characteristic curve, 0.68, 0.75, 0.82, 0.85) in the test groups. The algorithm did not significantly underestimate or overestimate disease probability except in one center (Long Beach).(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Enzyme-linked immunosorbent assay compared with gas chromatography/mass spectrometry for the determination of triazine herbicides in water.

An enzyme-linked immunosorbent assay (ELISA) was compared to a gas chromatography/mass spectrometry (GC/MS) procedure for the analysis of triazine herbicides and their metabolites in surface water and groundwater. Apparent recoveries from natural water and spiked water by both methods were comparable at 0.2-2 micrograms/L. Solid-phase extraction (SPE) was examined also, and recoveries were determined for a suite of triazine herbicides. A significant correlation was obtained between the ELISA and GC/MS method for natural water samples that were extracted by SPE. Because ELISA was developed with an atrazine-like compound as the hapten with conjugation at the 2-position, it was selective for triazines that contained both ethyl and isopropyl side chains. Concentrations for 50% inhibition (IC50) were as follows: atrazine, 0.4 microgram/L; ametryne, 0.45 microgram/L; prometryn and propazine, 0.5 microgram/L; prometon, 0.7 microgram/L; simazine and terbutryn, 2.5 micrograms/L; hydroxyatrazine, 28 micrograms/L; deethylatrazine and deisopropylatrazine, 30 micrograms/L; cyanazine, 40 micrograms/L; didealkylatrazine had no response. The combination of screening analysis by ELISA, which requires no sample preparation and works on 160 microL of sample, and confirmation by GC/MS was designed for rapid, inexpensive analysis of triazine herbicides in water.

Enzyme-Linked Immunosorbent Assay↗

Platelet membrane glycoprotein Ib: genetic polymorphism detected in the intact molecule and in proteolytic fragments.

Genetic polymorphism of platelet membrane glycoprotein (GP) Ib was studied in 128 healthy German blood donors using immunoblotting with monospecific anti-glycocalicin antibodies. Only three GP Ib forms (B,C and D) were detected. In a smaller number of Vietnamese individuals analysed for comparison all four polymorphic GP Ib forms were found. The frequency distribution of GP Ib phenotypes in the German population was similar to that reported for U.S. Americans of Caucasian origin. GP Ib polymorphism was also observed in purified glycocalicin samples of single donors. Using trypsin-cleaved glycocalicin the polymorphic region could be located in the C-terminal carbohydrate-rich glycocalicin fragment (macroglycopeptide).

Asian People↗

[Peripheral neuropathy with monoclonal gammopathy].

The case is reported of a patient with IgM-kappa paraproteinemia and polyneuropathy (PN) with very slow nerve conduction velocities. The association of demyelinating PN with severely decreased nerve conduction velocities and an IgM-kappa paraprotein usually suggests the diagnosis of monoclonal gammopathy of undetermined significance (MGUS), but less often of clinically manifest macroglobulinemia. Demyelinating PN with IgG-lambda- or IgA-lambda paraproteinemia occurs often in the uncommon but readily treatable osteosclerotic myeloma. A monoclonal protein combined with peripheral neuropathy involving predominant pain, temperature and autonomic loss (small fibre neuropathy) is by and large pathognomonic for primary systemic amyloidosis or amyloidosis associated with multiple myeloma or Waldenström's macroglobulinemia. Mild sensorimotor axonal polyneuropathy is an unspecific syndrome found in all gammopathies. It is important to differentiate between paraproteinemia with clinically pure chronic sensory PN and paraneoplastic sensory polyneuropathy. Unlike amyotrophic lateral sclerosis (ALS), paraproteinemias associated with a motor neuron disease-like syndrome sometimes evolve unusually slowly and exhibit neurophysiologically subclinical lesions of sensory nerve fibers. Mononeuropathy or multifocal neuropathy with a monoclonal protein is typical of cryoglobulinemia. Demyelinating PN of osteosclerotic myelomas presenting with one or a small number of bone lesions usually regress after excision or irradiation of the plasma cell proliferations. Immunosuppressants and plasmapheresis in the treatment of the demyelinating IgM-kappa neuropathies, of paraproteinemia with the motor neuron disease-like syndrome, and of mononeuropathy or multifocal neuropathy with cryoglobulinemia, are of doubtful value.(ABSTRACT TRUNCATED AT 250 WORDS)

Demyelinating Diseases↗

Platelet membrane defects in fawn hooded bleeder rats.

An inbred strain of fawn hooded rats with a congenital platelet defect shows a marked bleeding tendency with prolonged bleeding time. This haemorrhagic disorder has been exclusively related to a deficiency of nucleotides in platelet dense granules. When tested in cell electrophoresis platelets from fawn hooded bleeder rats showed a significantly lower electrophoretic mobility than normal rat platelets. Subsequent studies on the platelet membrane protein pattern by high resolution two-dimensional gel electrophoresis revealed the deficiency of a membrane glycoprotein (apparent molecular mass 90.000, isoelectric point 5.6), which is detectable in normal rat platelets after surface labeling by periodate-tritiated sodium borohydride. It seems likely, that this glycoprotein defect contributes at least partially to the disorder of platelet function in fawn hooded bleeder rats.

Animals↗

The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator.

Hepatitis B virus (HBV) is regarded as the main aetiologic factor in the development of human hepatocellular carcinoma (HCC), one of the most frequent fatal malignancies worldwide. Detection of integrated HBV sequences in the cellular DNA of almost all HCCs studied, and the recent finding that the integrated HBV open reading frame (orf) X encodes a transactivating activity, supports the notion that integrated HBV DNA could contribute to liver carcinogenesis by activation of cellular genes in trans. But not all HCCs seem to harbour a functional orf X. We report here that 3'-truncated preS2/S sequences in integrated HBV DNA of liver cell carcinomas encode a so far unidentified transcriptional trans-activation activity. This activity is also produced by an artificially 3'-truncated preS2/S gene of the wild-type HBV genome. Besides the simian virus 40 promoter of the reporter plasmid pSV2CAT, the promoter of the human c-myc oncogene can also be activated. These results, taken together with the fact that preS/S is the only HBV gene found to be integrated in almost every HBV-related HCC analysed so far, indicate that trans-activation by integrated preS2/S sequences is a possible mechanism for HBV-associated oncogenesis.

Amino Acid Sequence↗