Search PubMed⌕ Search

Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 703 records · Page 39Linked to original sources
PubMed1989

Carbohydrate structure of recombinant human uterine tissue plasminogen activator expressed in mouse epithelial cells.

Recombinant human uterine tissue plasminogen activator (tPA), in part metabolically labeled with [6-3H]glucosamine or [35S]sulfate, was isolated from mouse epithelial cells (C127). Oligosaccharides present were liberated by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F and fractionated by high-performance liquid chromatography. The glycans were characterized by digestion with exoglycosidases, methylation analysis and, in part, by acetolysis and 1H-NMR spectroscopy. Glycopeptides comprising individual glycosylation sites were identified by N-terminal amino acid sequencing. The results demonstrate that recombinant tPA from C127 cells carries at Asn117 oligomannosidic glycans with 5-8 mannose residues as well as small amounts of hybrid-type species. Asn184 is only partially glycosylated and substituted by fucosylated triantennary and small amounts of diantennary N-acetyllactosaminic glycans. Likewise, Asn448 carries predominantly fucosylated triantennary species, in addition to, small amounts of diantennary and tetraantennary oligosaccharides. As a characteristic feature, part of the triantennary glycans at Asn184 and Asn448 contain additional Gal(alpha 1-3) substituents and/or sulfate groups linked to position six of beta-galactosyl residues forming NeuAc(alpha 2-3)[HO3S-6]Gal(beta 1-4) units. Oligosaccharides attached to Asn448 are almost completely substituted by (alpha 2-3)- or (alpha 2-6)-linked sialic acid residues and carry the majority of sulfate groups present. Glycans at Asn184 were found to be less sialylated and sulfated.

Amino Acid Sequence↗
PubMed1989

Early infant mortality in West Germany before and after Chernobyl.

Early infant mortality rates in West Germany were plotted for regions with different radioactive burdens following the Chernobyl nuclear reactor explosion in April, 1986. In all regions, the logarithms of the mortality rates fitted a linear model between 1975 and 1985, but from May, 1986, immediately after the accident, there was a striking deviation from the model in areas with greatest radioactive fallout.

Accidents↗
PubMed1989

Molecular basis for the regulation of cell fate by the lethal (2) giant larvae tumour suppressor gene of Drosophila melanogaster.

Tumour suppressor genes act as recessive determinants of cancer. Their function is required for normal cell growth and differentiation during development. When both alleles of these developmental genes are inactivated, cell growth becomes unrestricted. In Drosophila, a series of genes have been identified which when mutated produce tissue-specific tumours. Of these the lethal(2)giant larvae (l(2)gl) gene is the best studied. Homozygous l(2)gl mutations cause the development of malignant tumours in the brain and the imaginal discs. Genomic DNA from the l(2)gl locus has been cloned, introduced back into l(2)gl mutant animals by P-element-mediated transformation and shown to restore normal development. The nucleotide sequence of the l(2)gl gene (13.1 kb) has been determined, as well as the sequences of the two classes of transcripts. These transcripts encode two polypeptides of 127 kDa and 78 kDa, respectively. Both proteins have been immunologically identified. Analyses of the spatial distribution of both l(2)gl transcripts and proteins revealed that during early embryogenesis the l(2)gl gene is uniformly expressed in all cells and tissues. In late embryos, the l(2)gl expression becomes gradually restricted to tissues presenting no morphological or neoplastic alteration in the mutant animals. Further mosaic experiments pointed out that the critical period for the establishment of tumorigenesis is limited to early embryogenesis at a time when the l(2)gl expression is most intense in all cells.

Animals↗
PubMed1989

Monitoring theophylline levels in serum and saliva using fluorescence polarization immunoassay and Seralyzer.

The reliability and predictive value of salivary theophylline levels was investigated in 58 children who were treated with oral sustained-release theophylline preparations for bronchial asthma. Serum and saliva levels were assessed by fluorescence polarization immunoassay (FPIA), and Seralyzer (reagent strip reflectance photometer method). Forty-six paired serum and saliva samples from 28 patients (Group 1) were used to develop a linear regression formula. This formula was tested on 130 paired serum and saliva samples from 32 patients (Group 2). When saliva theophylline levels were assayed using FPIA, 95% of serum levels were predicted within 30% of the measured value. Using Seralyzer, 95% of serum levels were predicted within 45% of the measured value. For patients with three and more paired serum and saliva specimens, individual regression formulas were determined showing considerable variation. This study indicates that salivary theophylline levels provide for an estimation of serum levels if FPIA is used. The Seralyzer technique is only useful for serum theophylline measurements. Using a special device it is now easier to obtain saliva samples than by conventional methods.

Adolescent↗
PubMed1989

Recombinant human interleukin-1 beta decreases serum carboxypeptidase N and modifies serum amino acid concentrations in rats.

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on various serum constituents were studied following subcutaneous injection (12.5 or 125 micrograms/kg) in female Wistar rats. Protein electrophoresis and the determination of the serum concentrations of carboxypeptidase N (CPN), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, aldolase, total proteins, iron, urea, creatinine, and several amino acids were performed 12, 24, and 72 hr after injection. With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration. Iron and CPN were still low after 24 hr but returned to normal levels after 72 hr. With the higher dose of rhIL-1 beta, only alanine and phenylalanine levels were increased after 12 and 72 hr, taurine after 12 hr, and methionine after 24 hr. There were no biochemical or histological signs of hepatotoxicity. The findings indicate that rhIL-1 beta produces a reversible alteration of various biochemical plasma constituents without any apparent signs of cytotoxicity. Moreover, the decrease in CPN observed may influence the degradation of inflammatory peptides.

Amino Acids↗
PubMed1989

Differential cleavage rates and sex determination in bovine embryos.

The purpose of this study was to determine whether a correlation between embryonic cleavage rates and sex ratios in dairy cattle could be substantiated. Embryos were collected at Day 7 after estrus following superovulation and artificial insemination. Embryos from flushings where at least two different developmental stages within the same flushing could be identified were examined. A total of 476 such embryos was transferred to recipients and 110 calves were born. The sex effect was only demonstrable in flushings yielding embryos of at least three different developmental stages. The sex ratios from this group were 32%, 58% and 62% in the slow, intermediate and fast developing groups of embryos, respectively. The deviations were not significant (P = 0.084). Only 23% of the flushings provided embryos that fell into this cathegory, which limits the use of differential cleavage rates as a sexing method, unless additional embryo culture is introduced to the technique.

Journal Article↗
PubMed1989

CHOP-VP16 chemotherapy and involved field irradiation for high grade non-Hodgkin's lymphomas: a phase II multicentre study.

Sixty previously untreated patients with high grade non-Hodgkin's lymphomas stages II-IV received cyclophosphamide 750 mg m2 i.v., doxorubicin 50 mg m2 i.v., and vincristine 2 mg i.v. on day 1, prednisolone 100 mg p.o. on days 1-5 and etoposide 100 mg m2 i.v. on days 3-5 (CHOP-VP16). After four courses an involved field irradiation with a total dose of 25 Gy was employed and followed by two additional courses of CHOP-VP16. The overall response rate was 93%, with 49 patients (82%) achieving a complete remission (CR). Seven patients had a partial response and four patients showed no response. During a median follow-up period of 55 months, 22 of the 49 patients with CR relapsed, seven of them achieving a second complete remission with the same drug regimen. A maintained complete remission of up to 68 months was seen in 55% of all patients initially achieving CR. The median survival is 43 months. Mean side-effects of this drug regimen were alopecia (89%), nausea/vomiting (76%) and leukopenia (61%). No therapy-related deaths were seen. The results of this study demonstrate that this combined modality treatment produces high complete remission rates and that more than half of these patients achieve long-term disease-free survival.

Adolescent↗
PubMed1989

Urinary excretion of guanosine 3':5'-cyclic monophosphate during sleep in obstructive sleep apnoea patients with and without nasal continuous positive airway pressure treatment.

1. It has recently been shown that obstructive sleep apnoea (OSA) patients have increased urinary water and salt excretion during sleep which tends to normalize with nasal continuous positive airway pressure (CPAP) treatment. 2. To investigate the mechanisms of these changes in renal function, nocturnal urinary excretion of catecholamines and guanosine 3':5'-cyclic monophosphate (cyclic GMP), which reflects atrial natriuretic factor (ANF) release, and next-morning plasma active renin concentrations were studied in 21 OSA patients on 2 consecutive nights, either untreated or treated with nasal CPAP. 3. In keeping with previous results, fractional urine flow and fractional Na+ and Cl- excretions were higher during untreated than during CPAP-treated nights. 4. No difference in plasma active renin concentration or in urinary excretion of noradrenaline, adrenaline, free dopamine and total dopamine could be demonstrated, but cyclic GMP excretion was significantly higher during untreated than during CPAP-treated nights. 5. The data are consistent with the hypothesis that the increased water and salt excretion in OSA patients is due to increased ANF release. 6. The proposed mechanism is an atrial distension due to increased (more negative) intrathoracic pressures during ineffective inspiratory efforts against the occluded upper airways which have been found in OSA.

Adult↗
PubMed1989

Vaccination against hepatitis B: comparison of three different vaccination schedules.

Three different hepatitis B vaccination schedules employing injections at months 0, 1, 2, and 12, at months 0, 1, and 6, or at months 0, 1, and 12 were compared in 89 healthy young adults. Concentrations of antibodies to hepatitis B surface antigen (anti-HBs) after the third injection were dependent on the interval between the second and the third dose; geometric mean titers (GMTs) in the three groups were 53 IU/l, 5,846 IU/l, and 19,912 IU/l, respectively, when the third dose was given at month 2, 6, or 12. Whereas the anti-HBs responses to the third dose at month 6 or 12 were typical booster reactions, the kinetics after a third dose given at month 2 resembled those after only two doses but on a significantly higher level. A fourth dose given at month 12 to the individuals vaccinated at months 0, 1, and 2 led to a prompt anti-HBs response similar in height to the response in those vaccinated at months 0, 1, and 12. Thus, for achieving a high anti-HBs concentration guaranteeing its long-lasting persistence, vaccination at months 0, 1, and 12 seems to be preferable to vaccination at months 0, 1, and 6. For individuals at high risk of hepatitis B infection, vaccination at months 0, 1, 2, and 12 might be considered for obtaining an optimal early seroconversion as well as long-term protection.

Adult↗
PubMed1989

Renal effects of perindoprilat, an angiotensin-converting enzyme inhibitor, in the anesthetized dog.

The effects of perindoprilat on renal hemodynamics and the elimination of water and electrolytes were studied acutely in the anesthetized dog. Two groups of animals were compared, one on normal sodium and water, the other on an acutely restricted sodium and water diet. In all cases, perindoprilat injected into renal artery (0.1 and 0.5 mg/kg) reduced blood pressure. In the animals on a low sodium diet, perindoprilat increased renal blood flow from 2.2 +/- 0.3 to 2.9 +/- 0.3 ml/min/g and decreased the filtration fraction; the decrease in renal vascular resistance predominated on the efferent arteriole of the glomerule (45% decrease), preferential site for the vasoconstrictor action of angiotensin II. In the animals on a normal sodium diet, renal blood flow was also increased from 4.1 +/- 0.6 to 5.1 +/- 0.6 ml/min/g but without the filtration fraction being affected. The renal vascular resistance was decreased at both pre- and post-glomerular levels (respectively, 50 and 25% decrease). After sodium and water restriction, but not in animals on a normal sodium diet, perindoprilat increased the fractional elimination of water and electrolytes. This salidiuresis might be accounted for by the hemodynamic effect of converting enzyme inhibitor and the decrease it elicits in filtration fraction, modifying sodium and water reabsorption in the proximal tubule.

Anesthesia↗
PubMed1989

Myristoylation of budgerigar fledgling disease virus capsid protein VP2.

We present evidence that the structural protein VP2 of budgerigar fledgling disease virus, an avian polyomavirus, is specifically modified by covalent attachment of myristic acid. The fatty acid linkage is insensitive to hydroxylamine treatment and thus represents the amide type of fatty acylation of proteins.

Animals↗
PubMed1989

Inhibition of sorbitol formation in human erythrocytes by calcium dobesilate.

The effects of calcium dobesilate (Doxium, a drug already known to prevent or reverse the retinal microvascular lesions of diabetes mellitus) on sorbitol formation in human erythrocytes was studied, and compared with the effects of tetramethylene glutaric acid (TMGA), a specific aldose reductase inhibitor. Both compounds inhibited sorbitol formation. In a 29 mmol/l glucose medium, calcium dobesilate in concentrations of 2 and 10 mmol/l caused, 50 and 100% inhibition of sorbitol formation, respectively, whereas TMGA completely inhibited sorbitol formation at a concentration of 0.1 mmol/l. These results suggest that calcium dobesilate may exert, at least in part, its beneficial effect on diabetic microangiopathy by inhibiting the formation of sorbitol. The inhibition of sorbitol synthesis may be mediated by an inhibitory action of calcium dobesilate on aldose reductase.

Aldehyde Reductase↗
PubMed1989

Arthrography with iotrolan: double-blind comparison between nonionic, monomeric (iohexol 300) and nonionic, dimeric (iotrolan 300) contrast media.

Arthrography of the shoulder and knee joints is optimized by the new nonionic, dimer contrast medium iotrolan 300 in comparison to the nonionic, monomer iohexol 300. Detail recognition increases and is longer lasting. The contrast density remains good for more than 40 minutes, thus making repeated examinations due to diagnostic uncertainty superfluous.

Arthrography↗
PubMed1989

Modulation of arachidonic acid metabolism has limited effects on the development of type I diabetes in animal models.

The therapeutic potential of modulators of arachidonic acid metabolism was probed in two animal models of type I (insulin-dependent) diabetes. Sulphasalazine treatment (50 and 400 mg/kg) did not affect diabetes development in the low dose streptozotocin model in male CD-1 mice nor in diabetes prone BB/WorD rats (100 mg/kg). Administration of acetyl salicylic acid (50 mg/kg) or BW755C (60 mg/kg) caused partial suppression of hyperglycaemia in male C57BL/6 mice after low dose streptozotocin. Twice daily treatment of BB rats with acetyl salicylic acid (5 mg/kg) did not significantly alter the course of diabetes development. We conclude that modulation of arachidonic acid metabolism has limited effects on immune-mediated diabetes.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Sex determination of bovine embryos based on embryonic cleavage rates.

Bovine embryos (n = 64) collected at day-6 from 10 superovulated and inseminated donors were evaluated upon recovery and again after incubation for approx. 12 hrs. According to cleavage rate they could be divided into a fast, an intermediate and a slow developing group, respectively. This grouping was correlated to embryonic sex determined by karyotyping (n = 29). From the fast developing group we found 7 males and 2 females (male ratios 78%), from the intermediate group 3 males and 8 females (male ratio 27%) and from the slow group 1 male and 8 females (male ratio 11%). From this preliminary study it is concluded that the rate of embryonic development may be used as a sex discriminator.

Animals↗
PubMed1989

Sex determination of bovine embryos using H-Y antibodies.

6 days old bovine embryos (n = 126) were obtained from 8 superovulated cows or heifers by flushing the uteri and oviducts either non-surgically or after slaughter. Part of the embryos (n = 72) (morula stages) were placed in Ham's F-10 or PBS supplemented with 10% fetal calf serum (FCS) diluted 1:1 with supernatant from the H-Y antibody producing clone and cultured at 38 degrees C, in 5% CO2/95% air and 100% humidity. Control embryos (n = 54) were cultured in H-Y antibody free medium. After culture the embryos could be separated into a blastocyst--and a morula group. A subsequent colchemid and hypotonic treatment and fixation and Giemsa staining allowed a precise karyotyping, and thus sex determination for 36 H-Y antibody treated embryos and 22 control embryos. The limiting factor for proper karyotyping was lack of metaphases, incomplete methaphases or poor preparation. Among the H-Y antibody treated embryos we found 7 males and 15 females in the blastocyst and 14 males and 0 females in the morula group. A statistical analysis of these proportions led to the conclusion that the H-Y antibody had a significant influence on the sex ratio.

Animals↗