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A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 235 records · Page 13Linked to original sources
PubMed1994

The basal midbrain as a region modulating the level of alerting in the toad, Bufo paracnemis.

Reversible thiopental blockade of sites located in the basal midbrain of conscious toads bearing chronically implanted cannulae induced a response in which the animal withdrew to the bottom of the experimental box with flexed head and forelegs. Partial or total eyelid closure, myosis, and reduced ventilatory movements also occurred. No significant changes in arterial pressure levels or heart rate occurred and the reflex wiping response to the application of a painful stimulus (acid) to the skin was also unaffected. However, the somatic and visceral responses to nonpainful stimuli were reduced. There was a decrease, but not abolition, of forebrain waves in the 11 Hz range grouped in spindles, perhaps due to the reduced ventilatory drive. On the basis of these findings and of previous data from our laboratory and others on other nonmammalian groups, we postulate the existence of neurons involved in the modulation of behavioral and visceral alerting in the basal midbrain.

Animals↗
PubMed1994

Carbohydrate structures of beta-trace protein from human cerebrospinal fluid: evidence for "brain-type" N-glycosylation.

The carbohydrate structures of beta-trace protein from human cerebrospinal fluid have been elucidated. This protein carries exclusively N-linked oligosaccharides at two sites (Asn29 and Asn56). Enzymatically released N-glycans were studied by compositional and methylation analyses, high-pH anion-exchange chromatography, and liquid secondary ion mass spectrometry. All glycans were found to be of the complex type, and most (90%) of them were biantennary with no (40%), one (40%), or two (20%) N-acetylneuraminic acid residues. The rest were triantennary chains or biantennary chains with intact or truncated lactosamine repeats. The innermost N-acetylglucosamine residues of nearly all structures were found to be alpha 1,6-fucosylated. Peripheral fucose (about 20% alpha 1,3-linked to N-acetylglucosamine) was also detected. Seventy percent of the oligosaccharides contained a bisecting N-acetylglucosamine. Especially in the neutral, but also in the monosialylated oligosaccharide fractions, many incomplete antennae consisting of N-acetylglucosamine only were present. At least 20 different N-glycans were identified. Analysis of the site-specific glycosylation patterns at Asn29 and Asn56 revealed only minor differences. According to the structural features (a high degree of fucosylation, high amounts of bisecting N-acetylglucosamine, as well as terminal N-acetylglucosamine and galactose residues, and significant amounts of N-acetylneuraminic acid in alpha 2,3 linkage), this protein can be classified as "brain-type" glycosylated.

Acetylglucosamine↗
PubMed1994

Restriction fragment length polymorphism analysis of reverse transcription-PCR products reveals the existence of two major strain groups of beet necrotic yellow vein virus.

Beet necrotic yellow vein virus (BNYVV)-infected sugarbeets were obtained from many parts of Europe and also from some sites in Asia and the U.S.A. Reverse transcription (RT)-PCR products of more than 1 kbp were obtained for four different regions of the viral genome which may be particularly important with respect to the pathogenic properties of the virus, i.e. for the coat protein and the 42K protein-encoding regions on RNA 2 and for major parts of RNAs 3 and 4. Restriction fragment length polymorphism (RFLP) patterns obtained with these PCR products revealed the existence of two major strain groups of BNYVV, named type A and type B. The A type was detected in Greece, the former Yugoslavia, Slovakia, parts of Austria, Italy, Spain, parts of France, Belgium, The Netherlands and England as well as in Asia (Turkey, Kazachstan, China and Japan) and the U.S.A. The B type occurs in Germany and parts of France. Mixed infections were detected at the borderline regions between areas of the A and B types. Comparisons of published and newly determined nucleotide sequences of the respective parts of the BNYVV genome indicate that the percentage of nucleotide differences between the A and the B type is approximately 3% for the respective regions of RNAs 2 and 3 and approximately 1.5% for RNA 4. Nucleotide sequences appear to be remarkably stable within each of the two strain groups. The majority of the nucleotide differences between the A and B types occur in the third triplet position. The amino acid changes in the coat protein area are outside the four previously determined antigenic regions that are accessible on the surface of the virus particles and are involved in the formation of continuous and presumably also discontinuous epitopes. This may explain why serological differences between the two strain groups have not been found.

Base Sequence↗
PubMed1994

Development of enzyme immunoassays specific for keratan sulphate- and core-protein-epitopes of the large aggregating proteoglycan from human articular cartilage.

In the course of chronic inflammatory and degenerative joint diseases proteoglycans are degraded by the action of proteases and oxygen radicals. Therefore, proteoglycan fragments, released from cartilage into the peripheral blood, might be useful markers of cartilage degradation. Sensitive enzyme immunoassays are useful for the detection of these proteoglycan fragments in serum. We therefore developed specific monoclonal antibodies against the large aggregating proteoglycan (aggrecan), which has been isolated and purified from human articular cartilage. Two monoclonal antibodies which recognize a novel cartilage-specific epitope on the keratan sulphate chain of aggrecan (mAb 4B3/D10) and an epitope of the core-protein of aggrecan (4G4/A10) were selected for the development of competitive enzyme-immunoassays. These assays allow the sensitive and specific detection of cartilage-derived proteoglycan fragments, not only in synovial fluid but also in serum. They can now be used for the study of inflammatory and degenerative joint diseases.

Adolescent↗
PubMed1994

Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects.

The objective of the presented two-way randomized crossover study was to investigate whether repeated doses of grapefruit juice (200 ml at 0, 2, 4, 8 and 12 h) enhanced bioavailability of diltiazem (120 mg, orally) in nine healthy male subjects. Grapefruit juice did not alter AUC or cmax of diltiazem, whereas the half life experienced a slight, but statistically significant, increase (4.1 +/- = 1.2 vs 5.1 +/- 0.7 h). The N-demethyldiltiazem/diltiazem and deacetyldiltiazem/diltiazem ratios were not affected by grapefruit juice intake, which indicates that these metabolic pathways are not inhibited. Whereas bioavailability of some calcium channel antagonists of the dihydropyridine type metabolized via the same cytochrome P450 has been shown to be dramatically increased by grapefruit juice intake, the bioavailability of the benzothiazepine calcium channel antagonist diltiazem remained unchanged. This suggests that factors other than biotransformation may contribute to the clear effect of grapefruit juice on the bioavailability of those substances.

Adult↗
PubMed1994

Participation of the periaqueductal gray matter in the modulation of tonic immobility in the guinea pig.

Unilateral microinjection of carbachol (CCh, 1 microgram/0.2 microliter) into the specific sites in the ventral and ventrolateral portions of the periaqueductal gray (PAG) matter, which is known to be involved in analgesia, increases the duration of restraint-induced tonic immobility (TI) episodes induced in 23 adult male guinea pigs (Cavia porcellus). Mean duration of TI episodes was 107 +/- 16.38 s in the control group and increased to 220.7 +/- 40.24 s in the group microinjected with CCh. The potentiating effect of carbachol on TI duration was blocked by pretreatment with atropine (7.6 micrograms/0.4 microliter). These data suggest that PAG and the cholinergic system are involved in the modulation of the motor inhibition characteristic of TI which may be activated by the same stimuli that induce defensive analgesia.

Animals↗
PubMed1994

Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation.

The objective of this study was to investigate in a twoway randomized crossover whether repeated uptake of grapefruit juice (200 ml at 0, 2, 4, 8 and 12 h enhances bioavailability of a nifedipine (1) slow release formulation (20 mg) in ten healthy volunteers. Grapefruit juice increased the AUC and cmax of 1 statistically significantly by 103 (SD 73, range 48 to 265)% and 94 (SD 83, range -23 to 259)%, respectively. AUC of dehydronifedipine (2) was also higher during grapefruit phase, but to a lesser extent (mean increase 66, SD 106, range -30 to 236)%. Half lives of neither 1 nor 2 were altered by grapefruit juice. Because 2/1-ratio was not lowered by grapefruit juice in comparison to control, a selective inhibition of cytochrome P450 3A based on the presented in vivo data is not very likely. In the light of other reports concerning grapefruit juice induced increase in bioavailability our data contradict the assumption of a selective inhibition of only one cytochrome P450 subfamily. The observed effect could be clinically significant, especially if other factors affecting the elimination of 1 occur.

Adult↗
PubMed1994

Alteration of the motor response to an acute painful stimulus during tonic immobility.

The motor responses caused by liminal (1.0 and 3.0 mA, applied for 3 s) and subliminal electrical stimuli (40% below the liminal value) applied to the dental pulp of the upper incisors of adult guinea pigs (N = 41) are more intense during tonic immobility (TI) than in control situations. Tonic immobility is a temporary state of profound motor inhibition elicited by some form of physical restraint in our experiment induced by maneuvers of lateral postural inversion and movement restraint. This suggests the occurrence of hyperalgesia in the trigeminal territory in situations of direct confrontation with a predator, as in the case for tonic immobility. This hyperalgesia may protect in a reflex manner vital regions of the head and neck from fatal bites inflicted by the predator, but without interrupting the state of immobility, since in our experiments the electric stimuli had no disruptive effect on TI episodes.

Animals↗
PubMed1993

The parabrachial region as a possible region modulating simultaneously pain and tonic immobility.

Unilateral microinjection of carbachol (1 microgram) into the dorsal parabrachial region (PBR) of conscious guinea pigs produced a 100% increase in the duration of restraint-induced tonic immobility (TI) episodes. In another group of animals with a subcutaneous electrode introduced into the thigh region, microinjections of equivalent doses of the same drug in similar sites also significantly reduced the motor defense and vocalization responses elicited by the application of a noxious electrical stimulus to the skin. Both effects were blocked by pretreatment with atropine. The possible simultaneous activation of mechanisms modulating TI and the response to a noxious stimulus may be of adaptive importance since analgesia may reinforce immobility to permit the use of other defense mechanisms in a situation of prey/predator confrontation.

Amygdala↗
PubMed1993

Bacteriorhodopsin expressed in Schizosaccharomyces pombe pumps protons through the plasma membrane.

Bacterioopsin (bO) from Halobacterium salinarium ("Halobacterium halobium") has been functionally expressed in a heterologous system, the fission yeast Schizosaccharomyces pombe. Regeneration of bO to bacteriorhodopsin (bR) in S. pombe has been achieved in vivo by addition of the chromophore retinal to the culture medium, as shown for a retinal-negative mutant of H. salinarium (JW5). Western blot analysis revealed that bR is more stable than bO against proteolysis in fission yeast and also in JW5. The light-driven proton pump is expressed in the eukaryotic organism and incorporated into the plasma membrane. Illumination of intact yeast cells leads to acidification of the external medium due to the translocation of H+ from inside to outside of the cell, indicating the same orientation of bR in the yeast plasma membrane as in H. salinarium. The kinetics of proton release into the water phase was observed with the optical pH indicator pyranine. Time-resolved absorbance changes of isolated plasma membrane measured by flash spectroscopy showed rise and decay of the M intermediate during the photocycle similar to those in the homologous system. Photocurrents and photovoltages were recorded with yeast plasma membrane attached to a planar lipid membrane and to a polytetrafluoroethylene (Teflon) film, respectively. Stationary currents measured in the presence of a protonophore showed continuous pumping activity of bR. The action spectrum of the photocurrent and the kinetics of the photovoltage were analyzed and compared with signals obtained from purple membranes. From all these different investigations we conclude that the integral membrane protein bR is correctly folded in vivo into the cytoplasmic membrane of the fission yeast S. pombe.

Bacteriorhodopsins↗
PubMed1993

[Benefits of cardiac rehabilitation--a controversy].

Cardiac rehabilitation is a comprehensive process of continuing care which takes place at different levels. Individual office-based care, out-patient group activities and in-patient programmes in specialized centres may be complementary or alternatively used according to the needs of individual patients. In Switzerland organized cardiac rehabilitation is available for 6000 patients per year. Formal rehabilitation programmes exert their beneficial effects mainly through exercise training, instruction in relaxation techniques as well as dietary and occupational counseling. These benefits are documented as an overall reduction of cardiovascular mortality by 20%, a slowing of disease progression, an improvement of physical work capacity, the modification of serum lipid fractions, and possibly improved psychosocial adjustment. Patients should be helped to accept coronary disease as a chronic disease, to maintain lifestyle changes in order to halt progression and to avoid complications while enjoying a meaningful life. Future improvements in Switzerland will include the careful selection of patients for the different forms and phases of rehabilitation, more extensive psychosocial counseling, continuity of care and the involvement of family members.

Diet↗
PubMed1993

Unique TATA-binding protein-containing complexes and cofactors involved in transcription by RNA polymerases II and III.

Two multisubunit complexes containing the TATA-binding protein (TBP) were isolated from HeLa cells constitutively expressing the FLAG epitope-tagged TBP using antibody affinity and peptide elution methods. One of the complexes (f:TFIID), isolated from the P11 0.85 M KCl fraction, contains at least 13 specific TBP-associated factors (TAFs) and can mediate activator-dependent transcription by RNA polymerase II. Importantly, activator function through the highly purified f:TFIID complex still requires a general cofactor fraction containing upstream factor stimulatory activity (USA). As previously observed with partially purified activator-competent natural TFIID, f:TFIID generates extended TATA-dependent footprints on the intrinsically strong adenovirus major late promoter (MLP) but only restricted footprints on the weak adenovirus E1b and E4 and HIV (core) promoters. Along with previous demonstrations of activator-induced downstream TFIID interactions on the E4 promoter, these results argue for a relationship between downstream interactions and overall promoter strength. Initiator-like sequences appear not to be essential for downstream interactions since they have no effect on downstream MLP interactions when mutated, do not effect downstream interactions on the HIV promoter and are not present on the inducible E4 promoter. The other multisubunit complex (f:TFIIIB), isolated from the P11 0.30 M KCl fraction, contains four specific TAFs and can substitute for one of the fractions (TFIIIB) required for RNA polymerase III (pol III) transcription. Neither f:TFIID nor TBP could substitute for this pol III TBP-containing fraction. This plus the fact that f:TFIIIB failed to generate a footprint on the MLP underscores the importance of TAFs in determining promoter specificity by different RNA polymerases.

Adenovirus E1B Proteins↗
PubMed1993

[Carotid endarterectomy in the elderly patient. Life table analysis and review of the literature based on 594 consecutive operations].

The significance of age as a prognostic factor was evaluated in patients undergoing carotid artery surgery between 12.8.86 and 31.10.92 in the Department of Vascular Surgery, Erlangen, 594 operations were performed on 546 consecutive patients using somatosensory evoked potentials as routine monitoring. Patients were divided into an older group of 139 (150 operations) with a mean age of 78.2 years and a younger group of 407 (444 operations) with a mean age of 64.4 years. There was no statistical difference in preoperative neurological status and number of risk factors, although there were different distributions of risk factors and concurrent illnesses. Thirty-day mortality rates were 1.7% for younger and 0.7% for older patients, and the incidence of postoperative stroke was 1.7% and 0.7% respectively (not statistically significant). Cumulative 5-year survival was 72.2% and 68.2% respectively. Cardiac diseases were the main cause of death in both groups, mainly fatal cardiac ischemia in younger patients and non-ischemic disease in the older patients. The 5-year stroke-free survival rate was 81% and 91.3% respectively (not significant). There was a trend towards a worse outcome for older patients with stages IIb and IV disease.

Adult↗
PubMed1993

A local education campaign on early diagnosis of malignant melanoma.

The growing incidence of all kinds of skin cancer is a worldwide phenomenon observed in the last decades. Malignant melanoma is of special concern because of its high death rate when in an advanced stage, poor therapeutic response and fast growing incidence. Malignant melanoma is primarily located on the skin and therefore well suited for early cancer detection. The "Deutsche Dermatologische Gesellschaft" carried out a highly successful information campaign in Germany. Under this roof we organised different campaigns. Following considerable success in a campaign in 1989, a total of 1467 patients were examined and advised in the course of a local initiative (Education Campaign "Black cancer") in the city of Bochum (approximately 400,000 inhabitants) in the summer of 1991. In addition to full body examinations, important data were collected concerning the degree of knowledge about skin cancer, epidemiology, and the risk of skin cancer in general. As a result of the clinical examinations, 73 patients with strongly suspected skin cancer have been treated. Within this group, 14 malignant melanomas (1.0%) as well as 34 basal cell carcinomas (1.9%) were diagnosed. These numbers highly exceed the assumed risk incidence of skin cancer in Germany. Even on the assumption that the population was selective it is to be feared that a high number of individuals with skin cancer remain undetected and untreated. The majority of persons seeking advice had been motivated by the local media. The response and results of this local campaign indicate that further preventive measures for the general population in Europe are conceivable, meaningful and urgently needed.

Adolescent↗
PubMed1993

Purification and partial sequence of proteins involved in the cholic acid transport into rat liver hepatocytes.

Two proteins, in previous work labeled by affinity markers derived from taurocholic acid, were purified and partially sequenced. Antibodies were raised against purified proteins, and cross-reactions were carefully checked. The influence of these antibodies upon taurocholic acid import into vesicles from rat liver plasma membranes was measured, and showed a distinct inhibition of transport in the case of the 54 kD protein.

Affinity Labels↗
PubMed1993

Tumors in rat kidney generated by initiation with trans-4-acetylaminostilbene and several promoting treatments.

trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or beta-cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by beta-cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical.

Adenoma, Chromophobe↗
PubMed1993

Temperature and central chemoreceptor drive to ventilation in toad (Bufo paracnemis).

The central chemoreceptor drive to ventilation was assessed in unanesthetized toads, Bufo paracnemis, exposed to three different temperatures: 15, 25 and 35 degrees C. The acid-base status of the fourth ventricle was manipulated by mock CSF perfusion. In additional experiments, arterial pH was varied by inspiration of hypercapnic gas mixtures. Ventilation was measured directly by pneumotachography and arterial blood samples were analyzed using electrodes for pH and PO2. Regardless of temperature, the ventilatory control of acid-base status was predominantly central. Moreover, an increase in temperature was accompanied by a proportional increase in the ventilatory response to chemoreceptor stimulation by either lowered mock CSF pH or hypercapnia. The alphastat hypothesis could not adequately account for the temperature effects on the ventilatory responses to hypercapnia or on air convection requirements in the toad.

Animals↗