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Biomedical subjects

J Schuh

Publications and source records attributed to J Schuh.

At least 19 recordsLinked to original sources

RANK is essential for osteoclast and lymph node development.

The physiological role of the TNF receptor (TNFR) family member, RANK, was investigated by generating RANK-deficient mice. RANK(-/-) mice were characterized by profound osteopetrosis resulting from an apparent block in osteoclast differentiation. RANK expression was not required for the commitment, differentiation, and functional maturation of macrophages and dendritic cells from their myeloid precursors but provided a necessary and specific signal for the differentiation of myeloid-derived osteoclasts. RANK(-/-) mice also exhibited a marked deficiency of B cells in the spleen. RANK(-/-) mice retained mucosal-associated lymphoid tissues including Peyer's patches but completely lacked all other peripheral lymph nodes, highlighting an additional major role for RANK in lymph node formation. These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.

Animals↗

Deletion monitoring in skin tumors by interphase-FISH using band-specific DNA probes.

Thin sections from archival paraffin blocks of various skin tumors (26 melanomas, 15 squamous cell carcinomas, 5 keratoacanthomas, 5 basal cell carcinomas) were subjected to interphase-FISH (I-FISH) with DNA probes which are specific for chromosomal regions often involved in deletions in human cancer. These were probes for chromosome 3p21, the p53 gene on chromosome 17p13, and, in a few selected cases, a probe for chromosome 9p21. It was demonstrated that deletions of these regions could be reliably detected and related to tumor type and histology, i.e. grading. The most common deletion was that of 3p21 which was found in all studied squamous cell carcinomas (SCC) of low differentiation, in 60% of the Bowen carcinomas, in 70% of the metastatic melanomas less than 1.5 mm thick, and in over 55% of those which thickness over 2 mm. In contrast, FISH-detected p53 deletion was a rare finding in the investigated tumors. However, this gene was even found in an increased copy number in 60% of the poorly differentiated SCCs (grade 4) and in 50% of the non-metastatic melanomas less than 1.5 mm thick. Deletion of 9p21 was detected in 13 of the 14 tumors on which pertinent examinations could be performed. I-FISH was shown to be a reliable technique for the rapid detection of chromosome band specific deletions in archival material of human skin tumors.

Adult↗

Investigations of the rhythmic function of heart rate, blood pressure and temperature in neonates.

Over a period of 24-30 h in 10 min intervals, the systolic diastolic and mean arterial blood pressure, heart rate, rectal and skin temperature were measured simultaneously in 17 full-term babies on the 2nd day of life, and in 11 of them again at the age of 4 weeks. Each profile was analysed individually by the Cosinor method. On the 2nd day of life, a statistically significant circadian rhythm could be detected in 12 of the 17 neonates for systolic blood pressure and heart rate, in 16 for skin temperature and in all 17 neonates for rectal temperature. Summarizing the data of the 17 newborns the circadian rhythm was the most frequent component in all functions. A high portion of ultradian rhythms was observed as well. With increasing postnatal age, the variance of acrophases decreased, particularly for the temperature rhythms. This means that synchronization with the environment is beginning. Furthermore, we found an increase in the mesor of heart rate and blood pressure and an increase in amplitude of temperature.

Blood Pressure↗

[Flunarizine and sabeluzole improves behavior disorders caused by cold-induced cortical lesions in mice].

The present paper reports two experiments is which an effect of sabeluzole and flunarizine upon behavioural consequences reflecting ischemic damage following cortical freezing lesions was evaluated in NMRI female mice. The parietal lesion was performed by applying a flat (2 mm in diameter) of a metal probe cooled to -75 degrees C on the exposed skull for 5 s. Flunarizine (15 mg/kg) was administered sc 1 hr before and 4 hr after performing the lesion and then, 1 mg/kg p.o. once daily for 14 days. Sabeluzole (5 mg/kg) was administered p.o. 1 hr before and 5 hr after performing the lesion and then, 5 mg/kg p.o. once daily for 14 days. Hole--board method was used to evaluate the exploratory head-dips activity of an animal in 5 sessions separated by 24 hr intervals during the postlesion testing from the 20th to the 24th day, i.e. from day 6 to 10 after finishing the treatment. The session lasted 5 min. In both experiments, the mean number of exploratory hole visits in lesioned female mice was significantly increased. Both flunarizine and sabeluzole reduced high hole exploration of lesioned mice to levels corresponding to those of the controls. Neither flunarizine nor sabeluzole affected significantly exploratory hole visit of control animals. Results showed that flunarizine as well as sabeluzole ameliorated behavioural disturbances reflecting the brain impairment induced through cortical freezing lesion. This effect is most probably related to the protective effect of both drugs against hypoxia induced in laboratory animals by several experimental procedures. The hole--board method seems to be suitable for the screening of compounds considered as cerebroprotective drugs.

Animals↗

A synthetic linear decapeptide binds to the atrial natriuretic peptide receptors and demonstrates cyclase activation and vasorelaxant activity.

A linear decapeptide, [cyclohexylalanine 106]ANP-(105-114)NH2 (1), where ANP is atrial natriuretic peptide, was prepared by solid phase synthesis and purified by reverse-phase liquid chromatography. This novel peptide was found to bind to ANP receptors in rabbit lung membranes, to stimulate cGMP production in various tissues, and to fully relax precontracted rabbit aorta in a dose-dependent fashion. The potency of 1 in the various in vitro assays varies between one-twentieth and one-eightieth of the potency of the reference peptide, the 24-mer rat ANP-(103-126). The linear decapeptide 1, which encompasses amino acid residues from the rat ANP sequence (105-114), features a cyclohexylalanine residue instead of the phenylalanine 106 residue in the hormone sequence, a free sulfhydryl function at the N-terminal cysteine 105, and a carboxamide C terminus. Its disulfide dimer 6 was active in the rabbit aorta assay while the S-methyl cysteine 7 analogue was not active in the same assay at similar concentrations. The decapeptide 1 is of particular significance because it is the shortest analogue reported to date endowed with agonistic activity at the guanylate cyclase-coupled ANP receptor. In particular, it is interesting to compare its structure to the structures of other short linear analogues of ANP which are totally devoid of the ability to stimulate particulate guanylate cyclase activity.

Adenylyl Cyclases↗

[Frequency and phase correlations of the biorhythms of metabolic indices in mice during their postnatal ontogeny].

In laboratory mice the daily rhythms of feeding, plasma insulin, blood glucose and liver glycogen were investigated beginning from an age of 1 week to 52 weeks. For all parameters circadian and ultradian rhythms changing in the course of development could be quantified. During juvenile phase and inversion of all patterns connected with temporary increasing ultradian components takes place. The beginning and the end of this inversion are specific for various parameters, to that changing frequency and phase correlations could be obtained. The lowest degree of phase correspondence is found at weaning, it reaches its maximum in adults and decreases again in older mice. The possible consequences of demonstrated phenomena for the stability of the functional system and the existence of sensitive phases during postnatal ontogeny are discussed.

Aging↗

[Ontogenetic changes in the circadian rhythm of plasma insulin and its correlation to food intake].

In experiments with laboratory mice of different age (3, 9, 13, 18, 31 and 52 weeks old) directed changes of the daily pattern of plasma insulin concentration depending on the development stage of the animals could be quantified. The circadian acrophase undergoes a negative shift from the end of dark/beginning of light period in 3-weeks-old mice to the end of light/beginning of dark period in adults. The amplitude decreases up to an age of 9 weeks, whereas the amount of ultradian components is high, and increases during further development. Similar changes could be obtained for the daily pattern of feeding activity, occurring however some weeks earlier. The result is a temporary desynchronisation. In adult animals the phase correlations are relatively stable. The plasma insulin concentration reaches its maximal value before the maximum of feeding activity, thus stimulating a high food consumption and utilisation rate.

Aging↗

Circadian rhythm of eicosanoid formation as affected by dietary linoleate.

Circadian rhythms of eicosanoid formation were investigated in linoleic acid (LA) rich (sunflower seed oil, 13.3 cal% LA) and LA deficient (hydrogenated palm kernel fat, 0.5 cal% LA) diet fed male Wistar rats adapted to an artificial lighting regimen of 12 hours light and 12 hours darkness. Over a period of 24 hours we examined at 4 hour intervals eicosanoid formation in the aorta (PGI2, PGE, PGF2 alpha), in the heart (6-keto-PGF1 alpha, PGE, PGF2 alpha, TXB2), in the kidney (PGE, PGF2 alpha) and in the brain (PGE, PGF2 alpha). Two types of circadian variation curves were observed: Low eicosanoid formation in the light period and increase in the dark cycle (PGE in aorta and heart, TXB2 in heart). The increase in eicosanoid formation in the dark cycle was diminished after an LA deficient diet. Continuous decrease (PGI2 in aorta) and increase (PGE in the brain), respectively, in the course of the day, without differences between the two dietary groups. We assume that the circadian oscillations of eicosanoid formation might be of importance for the development of the circadian time structure of the organism.

Animals↗

[Desynchronization of the circadian rhythm of plasma insulin levels and feeding schedules after inversion of periodicity].

In experiments with laboratory mice a desynchronisation of daily rhythms in plasma insulin concentration and feeding after inversion of the light-dark periodicity is documented. Whereas the feeding rhythm follows the exogenous Zeitgeber (differences concern above all the quantity of food which decrease after inversion), the acrophase of the hormone rhythm is stable in relation to astronomic time. The daily mean, however, is reduced and the main maximum is split into three components. The results support the hypothesis that rhythms of the two investigated parameters are generated by separate oscillators.

Animals↗

Bovine abortion caused by Bacillus cereus.

Bacillus cereus was identified as an infrequent abortigenic agent in cattle. Necrotizing placentitis with no or sporadic lesions in fetal tissues was seen. Bacillus cereus was isolated in pure culture from fetal tissue and/or placenta. The recent identification of a bovine abortion caused by B cereus, prompted a retrospective survey of the pathology files. Eight of 947 bovine abortions were attributed to B cereus. Bacillus cereus is often mistaken as a contaminant in bovine abortion because of the failure to identify lesions in fetal tissues compatible with bacterial invasion. A necrotizing toxin may be responsible for the placentitis, with expulsion of the fetus before bacterial colonization.

Abortion, Septic↗

Chronobiologic and metabolic characterization of rats fed low or high linoleic acid diets.

The influence of a modified endogenous prostanoid synthesis on circadian rhythmicity at different functional levels (prostanoid formation, behavioural parameters, circulatory indices, hematological parameters, energy metabolism) was investigated. The daily rhythmic changes observed for all parameters were partly modified by the variation of dietary linoleate intake.

Animals↗

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions.

Apolipoproteins↗