Monoamine oxidase inhibitors in tetrahydrobiopterin deficiency.
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Biopterins↗
Biomedical subjects
A Schuler
Publications and source records attributed to A Schuler.
Nucleotide-specific PCR for molecular virus typing.
Nucleotide sequence studies detected a double-point mutation in the genomic RNA segment 4 (nt 871 and 872) of the persistent variant C/AA-pi of influenza C/Ann Arbor/1/50 virus. The 3'-end-points of two distinct PCR primers were positioned exactly at this genome location and thereby adjusted the priming determinant complementary to the varied strain or to its wild-type counterpart. Consequently, positive RT-PCR products strictly referred to one of the two viruses examined, in both cases, using either virion or infected-cell RNA templates. Artificial virus mixtures could easily be distinguished by this method in a subsequent qualitative gel analysis. PCR annealing conditions and control reactions were optimized, for the monitoring of influenza virus isolates throughout multifold passages. Thus, sequence diversity in just two neighbouring nucleotides is sufficient to determine whether or not successful PCR amplification takes place, and this method can be used as a reliable means of virus strain differentiation.
Animals↗
Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome.
Maternal phenylketonuria (PKU) has adverse effects on the offspring including microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Maternal non-PKU mild hyperphenylalaninaemia (MHP) is believed to be benign, but whether there may be long-term consequences to offspring is unclear. In an international survey we have obtained information about 86 mothers with MHP (blood phenylalanine 167-715 mumol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital heart disease (2.3% of offspring), and severe non-cardiac anomalies (2.9% of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percentile was the 50th but that for birth head circumference was the 25th. Median z-scores for birth length and head circumference were significantly lower for offspring of mothers with phenylalanine concentrations above 400 mumol/L than for those whose mothers had lower values (p = 0.05 and p = 0.005, respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100 for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylalaninaemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r = 0.53, p < 0.001) than with maternal phenylalanine concentration (r = 0.45, p = 0.02). Maternal MHP does not seem to have serious consequences for the fetus. A maternal phenylalanine concentration of less than 400 mumol/L does not warrant intervention. Nevertheless, maternal blood phenylalanine above this value is associated with slightly lower birth measurements and offspring IQ than lower maternal blood phenylalanine concentrations.
Adolescent↗
Cognitive development related to metabolic phenotype and mutation genotype in 25 Hungarian patients with phenylketonuria.
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Adolescent↗
Productive and non-productive phases during long-term persistence of influenza C virus.
Persistent infection with a variant of influenza C/Ann Arbor/1/50 virus in MDCK cells has been previously reported. However, the precise molecular mechanism of persistence is still unknown. We show that the release of active progeny virus, as tested for by haemagglutination and acetylesterase profiles, does not take place in freshly seeded MDCK cells. Productive virus replication occurs simultaneously with massive production of structural proteins as shown by immunoprecipitation and immunofluorescence. PCR for the HEF structural protein-encoding segment 4 revealed that positive-sense RNA is present only during virus multiplication whereas negative-sense RNA appears to be constantly detectable. In this study we give initial evidence that influenza C virus can persist in the form of its genomic minus strand RNA, and plus strand transcription, protein synthesis and virus replication remain restricted to productive phases.
Animals↗
Rat brain glyceraldehyde-3-phosphate dehydrogenase interacts with the recombinant cytoplasmic domain of Alzheimer's beta-amyloid precursor protein.
Abundant senile plaques are a histological hallmark in the brain of Alzheimer's disease patients. Such plaques consist of, among many other constituents, aggregated beta A4 amyloid peptide. This peptide is derived from an amyloid precursor protein (APP) by irregular proteolytic processing and is considered to be involved in the development of Alzheimer's disease. To study possible interactions of brain proteins with beta A4 amyloid or other fragments of APP, beta A4 amyloid and beta A4 amyloid extended to the C-terminus of APP were recombinantly produced as fusion proteins termed "Amy" and "AmyC," respectively. Using Amy and AmyC affinity chromatography, a 35-kDa protein from rat brain was isolated that bound tightly to AmyC but not to Amy, thus indicating an interaction of the protein with the C-terminus of APP. This 35-kDa protein was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Binding of GAPDH to AmyC but not to Amy was confirmed by gel filtration. Although AmyC slightly reduced the Vmax of GAPDH, the same reduction was observed in the presence of Amy. These findings suggest that the interaction of the cytoplasmic domain of APP with GAPDH is unlikely to influence directly the rate of glycolysis but may serve another function.
Alzheimer Disease↗
[The color Doppler-guided compression therapy of a large false aneurysm of the femoral artery following left heart catheterization].
A ventrally located false aneurysm (7 x 5.2 x 3.4 cm) of the right common femoral artery occurred, after left-heart catheterization by the Judkins technique via this artery, in an 83-year-old woman with aortic valve stenosis. Colour Doppler sonography demonstrated a puncture canal (neck of the aneurysm) filling in both systole and diastole, as well as turbulent flow within the aneurysm. Flow into the aneurysm was considerably reduced when the transducer head compressed the aneurysm, while flow continued in the femoral artery and vein. This compression, maintained for 25 min, completely thrombosed the puncture canal and aneurysm so that no vascular surgery was required.
Aged↗
In vivo latex phagocytosis primes the Kupffer cells and hepatic neutrophils to generate superoxide anion.
Activation of liver macrophages during clearance of endotoxins, bacteria, or other particulate materials may be accompanied by the migration of polymorphonuclear neutrophils (PMNs) into the liver and priming of the hepatic phagocytes to release toxic oxygen metabolites. In the present study we investigated the effect of in vivo administration of latex particles on the hepatic sequestration of PMNs and the release of superoxide anion (O2-) by the in situ perfused rat liver and isolated hepatic phagocytes. One hour after an intravenous injection of latex beads, a significant amount of O2- (0.7 nmol/min/g) was produced by the in situ perfused liver. Administration of latex particles into the perfused liver also elicited O2- production. Hepatic phagocytes from latex-treated rats generated large amounts of O2- (2-14 nmol/60 min/10(6) cells) when these cells were stimulated in vitro with opsonized zymosan or phorbol myristate acetate (PMA), whereas phagocytes from saline-treated rats released less than 0.8 nmol O2-. Intravenous infusion of superoxide dismutase or ibuprofen did not prevent the immigration of PMNs to the liver. However, ibuprofen inhibited the production of O2- by the perfused liver. Also, after addition of ibuprofen in vitro to isolated cells, there was more than 50% inhibition of O2- generation by Kupffer cells and hepatic PMNs treated with either zymosan or PMA. These observations suggest that arachidonic acid metabolites play a role in O2- release under these conditions. Thus, activation of the reticuloendothelial system by latex phagocytosis induces the migration of PMNs into the liver and enhances the production of toxic oxygen-derived radicals by these cells and the resident Kupffer cells. The toxic oxygen radicals may also contribute to hepatic injury.
Animals↗
In vivo metabolic response of hepatic nonparenchymal cells and leukocytes to granulocyte-macrophage colony-stimulating factor.
This study investigates the in vivo glucose utilization of various immune-competent cells after an intra-arterial injection of a nonlethal dose (30 micrograms/kg body weight) of murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Injection of GM-CSF resulted in a rapid but transient reduction in the number of circulating neutrophils. After 20 min the number of neutrophils returned to normal values, and by 4 h it was about 80% greater than in time-matched saline-injected controls. One hour after the treatment, neutrophils were accumulated in the livers of GM-CSF-injected animals but not in control livers. In vivo glucose utilization by circulating neutrophils and mononuclear cells and various liver cell types was investigated by combining the 2-deoxyglucose tracer technique with cell isolation procedures. GM-CSF increased the in vivo glucose utilization of circulating and infiltrating neutrophils by more than 200%. Glucose utilization by circulating mononuclear cells was also doubled. After GM-CSF injection, glucose utilization by Kupffer cells was increased by 130% and by hepatic endothelial cells was increased by 60%. Indomethacin pretreatment blunted the hyperglycemia caused by GM-CSF injection; however, it did not inhibit the increased glucose utilization by immune-competent cells. This suggests that the effect of GM-CSF on glucose utilization by these cells is not mediated by prostanoids and is at least partially independent of the mass action of elevated glucose concentration. These findings indicate that GM-CSF may be an important member of the cytokine cascade that mediates the acute in vivo metabolic response of immune-competent cells in sepsis or endotoxemia.
Animals↗
Characterization of a new 120 kDa microtubule-associated protein (MAP) of rat brain.
A novel protein was identified in rat brain microtubules using a monoclonal antibody. The immunoreactive protein is a microtubule-associated protein (MAP) by the criteria of co-purification with tubulin through repeated cycles of microtubule polymerisation in vitro. It belongs to the class of thermostable MAPs and runs as a closely spaced polypeptide doublet of 120 kDa on SDS-PAGE gels. MAP-120 kDa is brain- and neuron-specific and is localized predominantly in Purkinje cell bodies and dendrites in the cerebellum and in dendritic compartments of pyramidal and granule neurons in the hippocampus and dentate gyrus. During postnatal brain development, MAP-120 kD levels increase about 3 to 4-fold.
Animals↗
Tumor necrosis factor increases in vivo glucose uptake in hepatic nonparenchymal cells.
This study aims to elucidate the in vivo metabolic response of different liver cells following a short-term (30 min) infusion of a nonlethal dose of human recombinant tumor necrosis factor (TNF). In vivo glucose uptake of different tissues and isolated liver cells was determined by a sequential double-labeling version of the tracer 2-deoxyglucose technique. Following TNF administration glucose uptake was increased in the liver, lung, spleen, and skin while it was not changed in muscle and testis. In response to TNF infusion neutropenia developed which was sustained for 40 min. The number of lymphocytes in the blood was also decreased after the termination of TNF infusion. This short-term infusion of TNF, however, was not accompanied by marked sequestration of leukocytes into the liver. In vivo glucose uptake in response to TNF was doubled in the Kupffer cells and increased by 56% in hepatic endothelial cells. Glucose uptake of parenchymal cells was not significantly affected. The prompt increase of glucose uptake in the reticuloendothelial cells of the liver, primarily in the Kupffer cells, following TNF administration suggests that a similar metabolic response of these cells to sepsis may be mediated at least in part by TNF. It is suggested that the increased glucose uptake by the hepatic nonparenchymal cells is a reflection of the immunomodulatory effect of TNF.
Animals↗
Upregulation of glucose metabolism by granulocyte-monocyte colony-stimulating factor.
Alterations of glucose metabolism were investigated for 6 hours following an intraarterial injection of murine recombinant granulocyte-monocyte colony-stimulating factor (GM-CSF) (30 micrograms/kg body weight). GM-CSF resulted in a transient elevation of plasma glucose. The rate of whole body glucose appearance, as measured by infusion of [6-3H] glucose, was increased by about 10% between 0.5 and 3 hours following GM-CSF injection. In vivo glucose utilization of individual tissues was investigated by the tracer 2-deoxyglucose technique. At 30 min, GM-CSF increased glucose utilization by 80-90% in liver and lung, and 50-60% in skin and spleen. At 3 and 6 hours, glucose utilization by these tissues returned toward control levels except for lung. There was a 40-50% increase in glucose utilization by skeletal muscle 30 min after GM-CSF which was sustained for 6 hours. Glucose utilization of testis, ileum and kidney did not change significantly. Plasma concentrations of insulin, glucagon and tumor necrosis factor were not altered in response to GM-CSF. These findings indicate that some of the acute metabolic effects of a short-term administration of GM-CSF are observed in macrophage-rich tissues, and suggest that GM-CSF may be involved in the metabolic upregulation of immunologically active tissues.
Analysis of Variance↗
Tumor necrosis factor-alpha stimulates superoxide anion generation by perfused rat liver and Kupffer cells.
Tumor necrosis factor (TNF) has been implicated as one of the mediators of the immunologic and metabolic changes in endotoxemia. Under adverse conditions, TNF can also be cytotoxic, and its effects can ultimately contribute to organ failure. This study shows that a 30-min infusion of a nonlethal dose of TNF induced the release of superoxide anion (0.9 nmol.min-1.g-1) by the in situ perfused rat liver. TNF also primed the liver to generate more superoxide anion (2.0 nmol.min-1.g-1) in response to an in vitro challenge with phorbol 12-myristate 13-acetate (PMA). Kupffer cells are most likely responsible for the superoxide anion production under these conditions, because the isolated Kupffer cells from TNF-infused rats produced increased quantities of superoxide anion (4-8 nmol/10(6) cells) when subsequently treated in vitro with either PMA or opsonized zymosan (control less than 1 nmol/10(6) cells). Thus, under these experimental conditions, TNF in vivo primed the Kupffer cells, but not the hepatocytes, endothelial cells, and the blood or hepatic neutrophils, to release more superoxide anion. These studies indicate that during a short-term nonlethal TNF infusion, Kupffer cells are a major target of TNF action, leading to the release of toxic-oxygen metabolites that may contribute to organ failure.
Animals↗
Defective V-to-J recombination of T cell receptor gamma chain genes in scid mice.
The status of T cell receptor gamma chain genes (TcR gamma) in 11 spontaneous T cell lymphomas from mice with severe combined immune deficiency (scid) was analyzed. We found that as a result of large abnormal deletions accompanying attempted site-specific V-to-J recombinations, 36 of 47 rearranged TcR gamma genes lacked the variable (V) and/or joining (J) region gene segment involved in this attempted recombination. No such deletions were found in T cell lymphomas from normal mice. We interpret our data as indicating a defective V-to-J recombination in scid lymphocytes consistent with our earlier observation of faulty D-to-J recombination in transformed scid lymphocytes (Schuler et al., Cell 1986. 46: 963). The present results further support the hypothesis that the scid mutation affects a component of the VDJ-recombinase system used in common by B and T cells to assemble antigen receptor genes.
Animals↗
[Surgical correction of bronchial stenosis: increased somatic development following elimination of the stenosis].
A 5 year old girl suffered from nearly total stenosis of the bronchus intermedius and exspiratory collaps of both main bronchi. Because of preterm birth she was postnatally intubated and mechanically ventilated for 6 weeks. Her somatic development was significantly retarded in comparison with the monozygotic twin, and pulmonary impairment increased again in the last preoperative year. By the combination of latest surgical technics (pericardial patch, interposition of a costal segment, fibrine glue) the bronchial abnormalities could be corrected successfully. In the first year after surgery catch-up growth was observed in the girl.
Aprotinin↗
[Prenatal toxoplasmosis: diagnosis and prevention].
Sera of six children, clinically suspected of having congenital toxoplasmosis, and of their mothers were examined for specific antibodies. In four, prenatal infection was established shortly after birth by significant titre differences between the neonatal and maternal sera. In three neonates, toxoplasma-specific IgM antibodies were demonstrated. In two children, aged seven and 16 months, postnatal infection could not be absolutely excluded, although both they and their mothers had high toxoplasma antibody titres.
Animals↗
Transcription of unrearranged antigen receptor genes in scid mice.
The scid mouse mutant is severely deficient in lymphocytes; cells of the B or T lymphocyte lineage cannot be detected by either serological or functional assays. However, as shown here, germ-line transcripts of B cell immunoglobulin (Ig) constant and variable region genes and of T cell receptor (TCR) genes are detectable in lymphopoietic tissues of scid mice, as well as B and T lineage-specific lambda 5 and T3 delta transcripts. We conclude that B and T lineage-committed cells do arise in scid mice and that their Ig and TCR genes are accessible to enzymes involved in their recombination. This suggests that scid impairs lymphopoiesis at the stage at which antigen receptor genes normally undergo rearrangement.
Animals↗
[Simultaneous occurrence of malignant thymoma and congenital adrenal hyperplasia].
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Adrenal Hyperplasia, Congenital↗