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Biomedical subjects

F Müller

Publications and source records attributed to F Müller.

At least 289 records · Page 16Linked to original sources

Reduced oxidative burst responses in monocytes and monocyte-derived macrophages from HIV-infected subjects.

Oxidative burst responses of monocytes and monocyte-derived macrophages (MDM) were studied in 40 subjects with HIV infection of different clinical stages. Oxidative burst was assessed as reduction of nitroblue tetrazolium (NBT) with or without stimulants. Results were determined as oxidative burst responses per cell and as a stimulatory ratio between stimulated and unstimulated NBT reduction. Cells from 12 HIV-seronegative homosexual men and 38 blood donors served as control groups. In patients with asymptomatic HIV infection, monocyte oxidative burst responses were reduced compared with the blood donors. In MDM from the same patients, stimulatory ratios were reduced. In AIDS patients, stimulatory ratios of both monocytes and MDM were reduced compared with controls. In contrast to the progressive deterioration of CD4+ lymphocyte counts as well as other immune functions in HIV infection, monocyte oxidative burst responses are impaired already in the asymptomatic phase of the infection, almost to the same extent as in patients with AIDS.

Adult↗

Actions of excitatory amino acids on brisk ganglion cells in the cat retina.

1. Retinal ganglion cell activity was recorded extracellularly in the intact cat eye. We examined the effects of iontophoretically applied glutamate (GLU), aspartate (ASP), and the specific agonists kainate (KA), quisqualate (QQ), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), and N-methyl-D-aspartate (NMDA) on the spontaneous and light-driven activity of ganglion cells. 2. ASP and GLU increased the spontaneous as well as the light-driven activity of all brisk cell types. The effects of the two drugs were very similar. The activity of most cells remained at a constant increased level during prolonged application of these drugs. 3. KA also excited all brisk ganglion cell classes and caused effects very similar to those of GLU and ASP but was effective at a much lower concentration. In general, brisk ganglion cells responded most vigorously to KA application. 4. QQ excited approximately 50% of all ON-X and OFF-X cells encountered, the other 50% of the X cells and all Y cells were inhibited during QQ-application. This inhibition was quite likely due to the stimulation of glycinergic and GABAergic interneurons, because it was reduced or abolished during application of the respective antagonists strychnine and bicuculline. All ganglion cells apparently received either direct or indirect excitatory input from QQ receptors, which can be revealed by blocking the inhibitory interneurons. 5. The major actions of QQ on the discharge rate of ganglion cells are mimicked by AMPA. Hence, the actions of QQ are likely to be mediated by the "classical" QQ-receptor, ion-channel complex rather than by the recently described type of QQ-receptor that is coupled to a second messenger system. 6. NMDA excited ON-X, OFF-X, and OFF-Y cells but inhibited ON-Y cells. Excitatory and inhibitory NMDA effects could be blocked by the specific NMDA-receptor antagonists D(-)-2-amino-7-phosphono-heptanoate (AP-7) or 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). If the GABAergic transmission was blocked by bicuculline, the NMDA-induced inhibition of ON-Y cells was abolished. We conclude that NMDA activates GABAergic interneurons that in turn reduce the activity of ON-Y cells.

Amino Acids↗

Mechanisms contributing to the virus persistence in Aleutian disease.

In this review published results and further studies concerning the persistence of Aleutian disease virus (ADV) isolate SL3 are presented. By Southern blot and in situ hybridization with strand-specific RNA probes focal replication of ADV-DNA was demonstrated in spleen, mesenteric lymph nodes, sporadically in mononuclear cells of the peripheral blood and bone marrow cells. These findings further support the concept of the lymphotropism of ADV. All cell culture-adapted ADV strains appear to have a ts-defect. Our in vitro studies indicate that the ADV isolate G(orham) induced the synthesis of comparable amounts of viral replicative DNA and viral proteins VP1 and VP2 at the non-permissive temperature of 37 degrees C. However, the viral progeny DNA synthesis was about threefold less at 37 degrees C compared to the permissive temperature of 32 degrees C. These findings suggest that the reduced level of viral progeny DNA at 37 degrees C accounts for the reduced production of infectious ADV. Finally, we provided experimental evidence that the apparent lack of neutralizing antibodies in AD is due to the masking of critical viral epitopes by cellular phospholipids.

Aleutian Mink Disease↗

The human vertebral column at the end of the embryonic period proper. 4. The sacrococcygeal region.

The sacral and coccygeal vertebrae at 8 postovulatory weeks (the end of the embryonic period proper) have been studied by means of graphic reconstructions. The cartilaginous sacrum is now a definitive unit composed of five separable vertebrae, each of which consists of a future centrum and bilateral neural processes. The base of each neural process consists of an anterolateral or alar element, not present in the lumbar region, and a posterolateral part, which includes costal and transverse elements. The usual illustrations, in which the costal component is placed in the alar element, are incorrect. The future dorsal foramina (containing dorsal rami) face laterally in the embryo and are in line with the thoracicolumbar intervertebral foramina. Considerable differential growth is required to change the dorsal openings from a lateral to a dorsal positions. The intervertebral foramina transmit ventral rami, but pelvic foramina are not yet present. The lumbosacral plexus is completed by S.N.1-3; S.N.4, 5 and Co.N.1 form the pelvic plexus. The inferior hypogastric plexus and the hypogastric nerves are present. The sacrum takes part in the spina bifida occulta that characterises the entire length of the embryonic vertebral column. The coccygeal vertebrae, which are variable, were 4-6 in number in the present series. The first is the best developed. The ventriculus terminalis ends usually at the level of Co.V.1 and the spinal cord generally at Co.V.5. The coccygeal notochord ends commonly in bifurcation or trifurcation. 'Haemal arches' were not observed.

Anthropometry↗

The human vertebral column at the end of the embryonic period proper. 3. The thoracicolumbar region.

The present study of the thoracicolumbar region continues an investigation of the vertebral column at 8 postovulartory weeks (the end of the embryonic period proper) by means of graphic reconstructions. The cartilaginous vertebrae have short neural processes associated with the normal spina bifida occulta present at this time. The separate cartilaginous centres that several authors believe to exist in the cervical and lumbar costal elements, but which have not been observed by the present authors, have been thought to be the forerunners of extrathoracic ribs. A distinction needs to be made, however, between such centres and ribs. Similarly, in the fetal period, ossific loci in the costal elements of CV 7 are very frequent, whereas cervical ribs in the adult are relatively rare. The neurocentral joints, and hence the boundaries between neural arches and centra, are unclear before ossification has begun and has progressed during the fetal period. The sternal bands are almost completely united and the scapula is high in position. Neural relationships aid in the determination of homologous parts within the vertebral column, but clarification of corresponding parts has not previously been possible within the embryonic period. Areas ventral to the dorsal rami are ribs in the thoracic region and costal elements in other regions. Areas underlying the dorsal rami are transverse processes in the thoracic region and minute 'true' transverse elements in the cervical and lumbar regions. Thus, the descriptive lumbar transverse processes correspond to the true transverse processes and the ribs in the thoracic region. The dorsal rami of the thoracic nerves pass between the transverse processes and the tubercles of the ribs and then divide. The ventral rami of lumbar Nerves 1 and 2 resemble the thoracic in their course, whereas those of Nerves 3-5 are similar to the sacral. The thoracic dorsal roots are sloping and, associated with the greater height of the lumbar centra, the lumbar roots even more so. The directions of the various dorsal roots reflect differences in growth gradients between vertebral column and spinal cord. The thoracic and lumbar portions of the column change little in proportion during the embryonic period proper.

Anthropometry↗

[Serologic studies in the diagnosis of pneumonia].

The importance of serological determination procedures for the diagnosis of pathogens was investigated in 207 episodes of pneumonia. The pathogenic organisms were detected in 138 cases; in 40 cases serological analysis helped to establish the diagnosis, while in 11 cases of pneumonia, the diagnosis was possible only with serology. The organisms most commonly found by serological investigations were Cytomegalovirus (n = 10), Aspergillus fumigatus (n = 7), and the influenza B virus (n = 7). Multiple infections, usually triggered by bacterial pathogens, were found in 48% of the cases of pneumonia with serological evidence of pathogens. In 71 episodes of pneumonia, the patients were immunosuppressed; in 11 cases, the causative organism was detected serologically.

Adult↗

[Pneumonia in patients with and without immunosuppression--value of bronchoscopic biopsy technics for the detection of pathogens].

Bronchoscopic diagnosis was performed in 91 patients with 100 episodes of fresh pneumonia. In already existing immunosuppression (n = 51, Group A) pathogens were most frequently identified via bronchoalveolar lavage (70%); in patients without immunosuppression (n = 49, Group B) the identification quota in respect of the central bronchial secretion (53%) and bronchoalveolar lavage (47%) were comparable. In Group A the most frequently occurring pathogens were Pneumocysti carinii (n = 18) and Aspergillus fumigatus (n = 7), in Group B Streptococcus pneumoniae (n = 8) and Staphylococcus aureus (n = 7).

Adult↗

[The effect of L-carnitine on the energy metabolism of isolated rat heart perfused by Langendorff's method using 31P-NMR spectroscopy].

31P-NMR spectroscopy is a method for continuous, noninvasive determination of high-energy phosphates in the intact organ. On the isolated Langendorff perfused rat heart the effect of L-carnitine on concentration of cytosolic ATP and phosphocreatine was studied under influence of a single or repeated periods of 20 min ischemia. On reperfusion the carnitine-treated hearts showed higher CP/Pi values and an increase of the energy index (CP + ATP)/(C) + ATP + Pi) then did control hearts. An improved ischemia tolerance was demonstrated.

Adenosine Triphosphate↗

Cis-acting sequences from mouse rDNA promote plasmid DNA amplification and persistence in mouse cells: implication of HMG-I in their function.

Searching for amplification promoting sequences within the murine rDNA cistrons, we isolated two elements from the nontranscribed spacer region. These 370 bp and 423 bp long cis-acting elements, referred to as muNTS1 and muNTS2, are localized 4.1 kb and 4.6 kb upstream the RNA polymerase I transcriptional start site. They contain ca. 50 bp long AT-rich sequences that strongly interact with a protein from nuclear extracts. The protein could be purified and identified as HMG-I. A synthetic oligonucleotide encompassing the AT-rich stretch from muNTS1 is able to substitute for the muNTS elements. A similar sequence from the nontranscribed spacer of rat has previously been reported to be important for the function of the RNA polymerase I enhancer (1). Therefore the interaction of HMG I with the muNTS elements may play a role both in the stimulation of DNA amplification and transcription.

Amino Acid Sequence↗

Identification of an amplification promoting DNA sequence from the hypotrichous ciliate Stylonychia lemnae.

The macronucleus of the hypotrichous ciliate Stylonychia lemnae contains a 1218 bp long DNA molecule which becomes highly amplified during vegetative growth due to a continuous overreplication over a long time range. The region which is located upstream the open reading frame of the overamplified 1.2kbp Stylonychia DNA molecule enabled plasmids containing an inefficiently transcribed thymidine kinase gene to persist and amplify upon transfection into mouse L fibroblasts under selective conditions. This region contains long AT-rich stretches. The AT-rich sequences interact with a previously characterized HMG-I like protein from mouse Ehrlich ascites tumour cells. A binding activity for AT-rich stretches could also be identified in macronuclear extracts from Stylonychia lemnae. We suggest a common mechanism for overamplification in Stylonychia macronuclei during vegetative growth and amplification of plasmid DNA in heterologous mouse cells under the influence of a common element.

Amino Acid Sequence↗

Time-resolved fluorescence spectroscopy of NADPH-cytochrome P-450 reductase: demonstration of energy transfer between the two prosthetic groups.

Fluorescence as well as fluorescence anisotropy decay parameters have been obtained from NADPH-cytochrome P-450 reductase by time-resolved fluorescence spectroscopy. The two flavins in the enzyme, FMN and FAD, are slightly fluorescent and exhibit heterogeneous fluorescence lifetimes, as observed with other flavoproteins. The time-dependent anisotropy is also multiexponential and is wavelength-dependent. The anisotropy decay is biexponential with two correlation times when the enzyme is excited at the red edge of the first absorption band (514 nm). When the enzyme is excited in the light absorption maximum (458 nm), an additional shorter correlation time is found, which contains information about the rate of energy transfer between the two flavins present in the enzyme. FMN-depleted NADPH-cytochrome P-450 reductase shows also only two correlation times, as does the enzyme in the "air-stable" semiquinone state when excited at 458 nm. Wavelength-dependent steady-state anisotropy measurements of native and FMN-depleted protein show that the former exhibits lower values than the latter in the region of the first absorption band, but when the red edge of the absorption band is reached, the anisotropy becomes equal in both preparations. A similar situation is encountered in model compounds, monomeric and dimeric flavins, immobilized in poly(methyl methacrylate). Both in the models and in the flavoprotein this can be attributed to failure of energy transfer at the red edge of the absorption band. From the results we were able to derive both geometric parameters and dynamic properties of both flavins in the NADPH-cytochrome P-450 reductase.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

The relation between the oxidative biotransformation of hexachlorobenzene and its porphyrinogenic activity.

The relation between the major toxic effect of hexachlorobenzene, hepatic porphyria, and its oxidative biotransformation was studied in vivo, by observing the effect of modulating its biotransformation on the expression of porphyria. This modulation was achieved by selective in vivo inhibition of the major cytochrome P450 isoenzyme involved in both the hydroxylation of hexachlorobenzene and its primary oxidative metabolite, pentachlorophenol. The involvement of this isoenzyme, cytochrome P450p, was established by in vitro biotransformation studies using microsomes derived from rats treated with various inducers of cytochrome P450 isoenzymes and selective in vitro inactivation of cytochrome P450p by triacetyloleandomycin (TAO), resulting in a strong inhibition of the microsomal conversion of hexachlorobenzene and pentachlorophenol. In vivo inactivation of cytochrome P450p was achieved by coadministration of hexachlorobenzene and TAO. Female rats which were treated with this diet for 10 weeks showed a strongly diminished urinary excretion of the major oxidative metabolites, pentachlorophenol and tetrachloro-1,4-hydroquinone, as compared to rats treated with hexachlorobenzene alone. The TAO coadministration was found to result in complexation of 70% of the total amount of hepatic microsomal cytochrome P450. The group treated with hexachlorobenzene alone displayed a 600-fold increase in the amount of hepatic porphyrins, whereas an almost complete absence of hepatic porphyrins was observed after administration of hexachlorobenzene together with TAO. The urinary excretion of porphyrins was also significantly lowered by cotreatment with TAO. A strong correlation was found to exist between the amount of porphyrins excreted and the amount of oxidative metabolites excreted, as a function of exposure time. Glucuronidation of pentachlorophenol was observed to an average extent of 30%. This percentage was not influenced by either TAO or phenobarbital. These results suggest that oxidative biotransformation, and thus the formation of the very reactive tetrachloro-1,4-benzoquinone, is directly related to the porphyrinogenic action of hexachlorobenzene.

Animals↗

[Visually evoked responses as follow-up parameters in multiple sclerosis].

VEP- and MRI-changes were compared in 93 patients with definite or probable multiple sclerosis. A high correlation between slowing of visual conduction time and volume of peri-ventricular white matter lesions was found. The finding suggests a retrogenicular site of the pathogenic process being frequently responsible for VEP-abnormalities. Long-standing clinical courses show better VEP/MRI-correlations even without clinical symptoms, whereas acute cases more often have related visual disabilities but no convincing correlations. VEP represent one function of those regions in the brain which are frequently impaired by the demyelinating process in multiple sclerosis. They provide an optimal parameter of clinical course.

Adolescent↗

[Infection 1979 to 1986. Epidemiology, etiology, clinical aspects and prognosis in 691 patients].

691 patients with clinically and bacteriologically established sepsis were included in three prospective studies conducted at a university hospital with 1,300 beds in 1979, 1982 and 1986. Only 22.4% of the patients did not suffer from severe underlying diseases. There was a fairly even distribution of gram-positive and gram-negative organisms among the isolated pathogens. A marked increase was seen in the incidence of polymicrobic and mycotic infections. The most frequently isolated bacterial species were E. coli (24.9%), Staph. aureus (19.5%), Staph. epidermidis (8%), Enterococci (4.8%) and Klebsiellae (4.6%). 26.8% of the patients died. The mortality rate showed a marked decrease from 33.6% in 1979 to 22.4% in 1986.

Adult↗

Anticonvulsant and proconvulsant effects of inhibitors of GABA degradation in the amygdala-kindling model.

The effects of three drugs, namely gamma-vinyl GABA (vigabatrin), gamma-acetylenic GABA, and aminooxyacetic acid, which increase brain GABA concentrations by irreversible inhibition of GABA degradation, were studied in amygdala-kindled rats. Vigabatrin 800 or 1,200 mg/kg i.p. 4 h after its administration, caused prolongation of behavioural seizures and electrographic afterdischarges recorded from the stimulated amygdala. One to three days after administration it dose dependently reduced seizure severity, seizure duration and afterdischarge duration in most animals. Determination of GABA levels in synaptosomes isolated from 12 brain regions of kindled rats 4 or 48 h after injection of 1,200 mg/kg vigabatrin indicated that the variable effects of this drug at different times after its administration could be related to differences in the time course of nerve terminal GABA increases in selective brain regions such as amygdala and corpus striatum. In contrast to vigabatrin, gamma-acetylenic GABA, 100 mg/kg i.p., reduced seizure severity in kindled rats as early as 4 h after its administration but afterdischarge duration increased significantly on subsequent days. Similar late increases in afterdischarge duration (and limbic seizure activity) after the time of maximum anticonvulsant effect had elapsed were also observed with vigabatrin, which could suggest that the anticonvulsant effect of such drugs is followed by withdrawal hyperexcitability. Aminooxyacetic acid, 20 mg/kg i.p., exerted no significant anticonvulsant effect in kindled rats but prolonged afterdischarge duration in several of the animals studied. The data suggest that GABA-T inhibitors, such as vigabatrin, differ from most antiepileptic drugs previously tested in the kindling model in that they may produce both anticonvulsant and proconvulsant effects at the same dose in the same animal as a function of time after administration.

Alkynes↗

Distinct mouse DNA sequences enable establishment and persistence of plasmid DNA polymers in mouse cells.

Distinct elements isolated from mouse genomic DNA confer on plasmid DNA the ability to persist at high copy numbers in mouse L fibroblasts (1). Field inversion gel electrophoresis demonstrated that - in contrast to our previous assumption - the persisting plasmid DNA does not exist extrachromosomally but as clusters of tandem repeats integrated into genomic DNA. Digestion with restriction endonucleases that do not cut within the plasmid DNA results in fragments of 50-300 kb in length indicating reiteration of 10-50 plasmid DNA molecules. Restriction with several enzymes that cut once or twice within the plasmid sequences lead to fragment(s) indicative for head-to-tail tandem repeats. In situ hybridization revealed signals for a long homogeneously staining region (HSR) in one or two chromosomes per cell nucleus. Possibilities how these elements could act in the establishment and/or maintenance of the head-to-tail polymers of plasmid DNA in mouse cells are discussed.

Animals↗