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Biomedical subjects

F Kaiser

Publications and source records attributed to F Kaiser.

At least 19 recordsLinked to original sources
PubMed1997

Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents.

Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

Administration, Intranasal↗
PubMed1997

Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone.

A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > -0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

Adult↗
PubMed1997

[Carving in comparison with ski technique of the skiing athlete (competitive skier) and the leisure and comfort level skier].

In skiing there is principally no difference between the operating mechanism of a ski-racer and a skier who masters the technic of carving. Both try to ski with as less sliding as possible. The pressure distribution on the ski in a curve is very important. Near the end of the curve the pressure on the edge of the ski must be increased through various methods, on the one hand to avoid sliding and on the other hand to prepare the next curve correctly. In mastering the necessary mechanism of movements, the carving with the more wasted skis will be easier, because it is not necessary to put as much pressure on the last section of the ski, as it is necessary with the original skies to have the same result. Therefore even the holiday-skier has the possibility with carving-skis to master the ski-technic of the ski-racer and to have the pleasure of carving instead of sliding.

Acceleration↗
PubMed1996

Long-term clinical evaluation of endodontically treated teeth by Nd:YAG lasers.

It was possible for the patients to avoid surgical intervention in a number of complicated periapical endodontic situations by means of Nd:YAG laser-assisted sterilization. A WSR has only very good primary results and the long-term successes are very limited. Once a lesions has healed in the manner explained in this study, in other words, with regeneration of the periapical anatomy, there is a very good long-term prognosis. Laser technology is an instrument whose overall effects represent a decisive improvement in the efficiency of conservative endodontic treatment in fields that were previously outside our sphere of influence.

Bacteria↗
PubMed1995

Model for external influences on cellular signal transduction pathways including cytosolic calcium oscillations.

Experiments on the effects of extremely-low-frequency (ELF) electric and magnetic fields on cells of the immune system, T-lymphocytes in particular, suggest that the external field interacts with the cell at the level of intracellular signal transduction pathways. These are directly connected with changes in the calcium-signaling processes of the cell. Based on these findings, a theoretical model for receptor-controlled cytosolic calcium oscillations and for external influences on the signal transduction pathway is presented. We discuss the possibility that the external field acts on the kinetics of the signal transduction between the activated receptors at the cell membrane and the G-proteins. It is shown that, depending on the specific combination of cell internal biochemical and external physical parameters, entirely different responses of the cell can occur. We compare the effects of a coherent (periodic) modulation and of incoherent perturbations (noise). The model and the calculations are based on the theory of self-sustained, nonlinear oscillators. It is argued that these systems form an ideal basis for information-encoding processes in biological systems.

Algorithms↗
PubMed1995

Unchanged balance between levels of mRNA encoding AMPA glutamate receptor subtypes following global cerebral ischemia in the rat.

Transient global ischemia leads to glutamate mediated delayed neuronal death in the CA1 but not in the CA3 region of the rat hippocampus, and changes in AMPA receptor subunit composition has been proposed to cause a difference in excitatory input to the CA1 and CA3 regions. In situ hybridization with riboprobes for AMPA receptor subtype GluR1-4 mRNA was performed on sections from the brain of sham operated and ischemic rats in two models (neck cuff and 4-vessel occlusion combined with hypotension) with identical results: the content of the GluR1-3 mRNA species was down regulated in the hippocampal regions CA1 and CA3 but only weak changes were observed in the dentate gyrus. The down regulation observed in CA1 was non-selective among GluR1-3, i.e. all GluR mRNA species showed approximately the same degree of down regulation. A change in calcium permeability of the AMPA channels mediated by a shift in channel sub-unit composition and corroborating an increased calcium influx is thus not supported by these findings.

Animals↗
PubMed1994

[Pneumothorax during laparoscopic cholecystectomy].

One patient developed pneumothorax during laparoscopic cholecystectomy. The pneumothorax was immediately drained with an intercostal canula. A diaphragmatic lesion caused by the electrocoagulator was identified and closed, surgery was completed, and the patient was not seriously affected by the complication. Laparoscopic cholecystectomy has gained enormous popularity. Pneumothorax is a rare, but potentially fatal complication. Immediate treatment is essential and easy. This report should make anaesthetists and surgeons aware of the possibility of gas insufflated during laparoscopy producing a pneumothorax, particularly with the increased use of the technique for major upper abdominal procedures.

Cholecystectomy, Laparoscopic↗
PubMed1994

Changes in metabotropic glutamate receptor mRNA levels following global ischemia: increase of a putative presynaptic subtype (mGluR4) in highly vulnerable rat brain areas.

Metabotropic glutamate receptors mediate their intracellular response by coupling to G proteins and may be divided into three subfamilies: mGluR1 and mGluR5, which stimulate phosphatidylinositol hydrolysis; mGluR2 and mGluR3, which are negatively coupled to cyclic AMP formation; and mGluR4 and mGluR6, which also inhibit forskolin-stimulated cyclic AMP formation. The mGluR4 subtypes may represent L-2-amino-4-phosphonobutyrate-sensitive presynaptic autoreceptors, and two alternatively spliced variants of the mGluR4 coding for two receptors with different C termini have been identified. Using in situ hybridization, we measured the levels of mGluR1-mGluR5 mRNA in regions of the rat brain 24 h after transient global ischemia, a time point when no neuronal damage can yet be observed morphologically. In the hippocampus, the mRNA levels for mGluR1, mGluR2, and mGluR5 were decreased, mGluR3 mRNA levels were unchanged, and the mGluR4 mRNA levels were strongly increased. The strongest increase appeared to be in the mRNA encoding mGluR4b. The mGluR4 mRNA was also increased in the parietal cortex, whereas the ventral posteromedial thalamic nucleus showed a small decrease in its mRNA content. These results suggest that vulnerable neurons react to an increased extracellular glutamate concentration by differential regulation of the mRNA for pre- and postsynaptically located metabotropic glutamate receptors.

Animals↗
PubMed1994

Confirmation of association between the e4 allele of apolipoprotein E and Alzheimer's disease.

The Apo E genotype of 86 patients with Alzheimer's disease (AD) and 77 age matched controls was determined by digestion of Apo E PCR products with the restriction enzyme CfoI. The frequency of the e4 allele was significantly increased in the patient group (0.33) as compared with controls (0.12). This effect was seen in patients with a family history and in sporadic cases. The odds ratio in homozygotes for the e4 allele was 11.24 (95% confidence interval 2.45-51.50). There was no relationship between age of onset and Apo E genotype. There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.

Age of Onset↗
PubMed1993

Amyloid precursor protein mRNA levels in the mononuclear blood cells of Alzheimer's and Down's patients.

Amyloid precursor protein (APP) is expressed by many non-neural tissues and it is possible that over-expression of the APP gene in non-neural tissue is responsible for the deposition of amyloid beta-protein in the brain and elsewhere. One possible source of beta-protein is circulating mononuclear blood cells which have previously been shown to express APP. To test this hypothesis, RNA was isolated from the mononuclear blood cells of patients suffering from Alzheimer's disease (n = 27), Down's syndrome (n = 13), senile dementia non-Alzheimer type (n = 14) and from normal individuals (n = 48). The relative abundance of mRNA coding for different splicing variants of the amyloid precursor protein (APP) mRNA was measured using multiprobe oligonucleotide solution hybridisation (MOSH). There was no significant difference in APP mRNA levels between any of the groups. This indicates that Alzheimer's disease is not characterised by an increase in production of APP in circulating mononuclear blood cells.

Adult↗
PubMed1993

Model for receptor-controlled cytosolic calcium oscillations and for external influences on the signal pathway.

The external stimulation of many cells by a hormone, for example, often leads to an oscillating cytosolic calcium concentration. This periodic behavior is now designated the cytosolic calcium oscillator. A theoretical model is presented that describes this behavior on the basis of inositol(1,4,5)trisphosphate-induced calcium oscillations. In contrast to other models only a single positive feedback loop is taken into account to obtain oscillations. The model includes important innovations compared to other approaches. It includes the contribution of extracellular calcium and its modification after the stimulation of the cell. Furthermore, the signal pathway that leads to cytosolic calcium oscillations is described in more detail than in other models. This enables investigations on the influence of additional parameters like external electromagnetic fields on the signal transduction pathway. The model and the calculations are based on the theory of nonlinear self-sustained oscillators.

Biophysical Phenomena↗
PubMed1992

Mechanisms of electromagnetic interaction with cellular systems.

The question of how electromagnetic fields--static or low to high frequency--interact with biological systems is of great interest. The current discussion among biologists, chemists, and physicists emphasizes aspects of experimental verification and of defining microscopic and macroscopic mechanisms. Both aspects are reviewed here. We emphasize that in certain situations nonthermal interactions of electromagnetic fields occur with cellular systems.

Animals↗
PubMed1992

Reaction time in cancer patients receiving peripherally acting analgesics alone or in combination with opioids.

Continuous Reaction Time (CRT) was measured in cancer patients receiving peripherally acting analgesics either alone (n = 16) or in combination with opioids (n = 16). Comparison was performed matching the patients from each group for age and performance status. Statistically significant prolongations of CRT and higher sedation scores were seen in the opioid group, while performance status did not have any influence on CRT.

Acetaminophen↗
PubMed1986

Center-specific variations of thyroid hormone serum levels in hemodialysis patients.

Thyroid hormone (free and total thyroxine, total 3,5,3'- and 3,3'5'-triiodothyronine, thyroxine-binding globulin, thyrotropin) serum concentrations were measured in 107 uremic patients of 4 hemodialysis centers, in order to study the prevalence of hypothyroidism in hemodialysis patients. In accordance with the clinical impression there was no laboratory evidence of thyroid dysfunction. In spite of the fact that all patients had the expected low-T3 syndrome, there were highly significant differences between the mean thyroid hormone concentrations of the 4 different centers. The center with the highest thyroid hormone levels (all normal except for borderline low 3,5,3'-triiodothyronine) also had the lowest urea levels, indicating the relatively best metabolic control. One center had significantly lower hormone levels than the other 3 centers (all hormones except free thyroxine were below normal) with urea levels that did not differ significantly from one of these centers. A retrospective analysis of patients and of the techniques of dialysis of 3 centers excluded factors like heparin or the length of time on dialysis to be the reason for the low values of this center. Finally, only the significantly higher proportion of unsuccessfully transplanted patients and some technical differences (lack of water treatment, regenerated cellulose as dialyser membrane, and low magnesium content in the dialysate) unique for this center remained as possible factors that may speculatively explain the observed low thyroid hormone values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Nonlinear polarisationoscillations in a biophysical model system II: external dynamics.

To describe a metastable electric dipole state in a biological system, Fröhlich suggested a nonlinear model potential. In this paper we investigate a system of two nonlinear dipoles, which are coupled by a dipole-dipole interaction. We apply an external field and add linear damping terms. The external drive leads to a phase-locking of the dipoles. Mathematically, the system corresponds to an externally driven anharmonic oscillator with damping. We investigate the system of coupled oscillators and look for the stable and metastable solutions as a function of the internal and external parameters.

Mathematics↗