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S Ritter

Publications and source records attributed to S Ritter.

At least 19 recordsLinked to original sources

Glucose homeostasis and sympathoadrenal activity in mercaptoacetate-treated rats.

The effect of the fatty acid oxidation inhibitor, sodium mercaptoacetate (MA, 600 mumol/kg) on peripheral energy substrate metabolism was investigated in rats with permanent heart catheters. Rats were either fed, 48-h food deprived, or exercising for 30 min. Before and after intravenous MA injection, stress-free blood samples were taken for measurement of blood glucose, plasma free fatty acids (FFA), insulin, epinephrine (E), and norepinephrine (NE) concentrations. In fed animals, MA increased blood glucose, plasma FFA, and NE and decreased insulin concentrations. Plasma E levels did not change. In 48-h-deprived animals, MA elevated low baseline glucose concentrations to levels observed in MA-treated fed animals. Plasma insulin concentrations decreased to almost undetectable levels. Plasma catecholamines and FFA were increased compared to fed rats. In exercising rats, MA caused an exaggerated increase of blood glucose and a pronounced reduction of plasma insulin without affecting exercise-induced FFA and catecholamine responses. The data revealed that the mechanisms that regulate blood glucose concentrations during MA treatment are dependent on the nutritional state and ambient energy expenditure.

Adrenal Glands

Induction of Fos-like immunoreactivity (Fos-li) and stimulation of feeding by 2,5-anhydro-D-mannitol (2,5-AM) require the vagus nerve.

The antimetabolic fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), stimulates feeding. Selective hepatic branch vagotomy has been shown to block feeding induced by low 2,5-AM doses. However, hepatic vagal fibers are not the sole mediators of 2,5-AM-induced feeding, since hepatic branch vagotomy does not impair feeding induced by higher doses of 2,5-AM. To further evaluate the role of the vagus in the response to 2,5-AM, we examined the effect of total subdiaphragmatic vagotomy on feeding induced by a high 2,5-AM dose (500 mg/kg). In addition, we assessed the ability of 2,5-AM (300 and 500 mg/kg) to induce Fos-like immunoreactivity (Fos-li) in the brain in sham-operated (SHAM), hepatic branch vagotomized (HBV) and total subdiaphragmatic vagotomized (TSDV) rats. Both doses of 2,5-AM, but not control solutions, induced Fos-li in the area postrema (AP), nucleus of the solitary tract (NTS) and lateral parabrachial nucleus (1PBN). Very weak immunoreactivity was present in the central nucleus of the amygdala and none was observed in the locus coeruleus or paraventricular nucleus of the hypothalamus. The effect of the lower 2,5-AM dose on Fos-li was blocked by HBV. The high dose effect was blocked by TSDV but not by HBV. Feeding induced by the high dose of 2,5-AM was also blocked by TSDV. Results are consistent with the hypothesis that stimulation of feeding by 2,5-AM is dependent on the vagus nerve. Hepatic branch fibers may have the lowest threshold for activation, but fibers in other vagal branches independently mediate induction of c-fos and stimulate food intake at higher doses of the analogue.

Animals

2-Mercaptoacetate and 2-deoxy-D-glucose induce Fos-like immunoreactivity in rat brain.

2-Deoxy-D-glucose (2-DG) and 2-mercaptoacetate (MA) are antimetabolic drugs that selectively antagonize glucose and fatty acid utilization, respectively, and stimulate feeding. Fos immunohistochemistry was employed to identify brain neurons activated by these drugs and to assess the role of the vagus nerve in the drug effects. Remote intravenous infusions of both MA and 2-DG induced Fos-like immunoreactivity (Fos-li) in specific brain sites, but the pattern was different for the two drugs. Mercaptoacetate induced Fos-li in the nucleus of the solitary tract (NTS), the central subnucleus of the lateral parabrachial nucleus (1PBN), the central nucleus of the amygdala (CNA, lateral part) and the dorsal motor nucleus of the vagus (DMV). Induction of Fos-li in the brain by MA was totally abolished by vagotomy. 2-Deoxy-D-glucose also induced Fos-li in the NTS, CNA (lateral part) and DMV, as well as in the external 1PBN subnucleus, locus coeruleus, paraventricular and supraoptic hypothalamic nuclei, and in scattered cells throughout the diencephalon. Induction of Fos-li by 2-DG was not blocked by vagotomy. Results suggest that 2-DG's effects on Fos-li are mediated by a direct central action, whereas MA's effects are mediated by peripheral sensory neurons. Thus, availability of glucose and fatty acids influences the activity of specific brain sites by different neural mechanisms. The correlation of Fos-immunoreactive sites with sites where lesions have been shown to cause deficits in MA- and 2-DG-induced feeding indicates that c-fos expression defines in part the central pathways involved in the metabolic control of feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Differential effects of infused nutrients on 2-deoxy-D-glucose- and 2-mercaptoacetate-induced feeding.

We examined the effects of glucose, lipid, or fructose infusion on 2-deoxy-D-glucose (2DG)- and 2-mercaptoacetate (MA)-induced feeding. Rats with chronic intra-atrial catheters were infused for 15 min with one of the above nutrients and then injected with 2DG or MA. The nutrient infusion continued for the next 2 h and food intake was simultaneously measured. For control conditions, equitonic saline was infused, and 2DG, MA, or saline was injected. We found that glucose was the only nutrient source capable of significantly reducing 2DG-induced feeding. Equicaloric infusions of lipid or fructose did not significantly reduce 2DG-induced feeding. However, feeding induced by MA was similarly and significantly reduced by glucose, lipid, and fructose. These results suggest that 2DG-induced feeding is mediated by receptor cells that are selectively responsive to glucose availability, and MA-induced feeding is mediated by receptor cells that are responsive to a wider range of metabolic fuels.

Animals

Cell cycle delays induced by heavy ion irradiation of synchronous mammalian cells.

Cell cycle delays in V79 Chinese hamster cells induced by heavy ion exposure have been investigated using flow cytometry. Synchronous cell populations in G1, S and late-S G2/M phase were used, which were prepared by centrifugal elutriation. Cells were irradiated with particles from Z = 10 (neon) up to 96 (uranium) in the energy range from 2.4 to 17.4 MeV/u and the LET range from 415 to 16,225 keV/micron at the UNILAC at GSI, Darmstadt. For comparison, experiments with 250 kV X-rays were performed. For light particles like neon, cell cycle perturbations comparable with those after X-ray irradiation were found, and with increasing LET an increasing delay per particle traversal was observed. For the highest LET values extended delavy in G1, S and G2/M phase were detected immediately after irradiation. A large fraction of the cells remained in S or G2/M phase up to 48 h or longer after irradiation: they probably died in interphase. The prolongation of delays with increasing LET is in contrast with inactivation cross section measurements, where cross sections reach a plateau at LET values > 500 keV/micron. No significant cell age dependence of cycle delays was detected for the very high LET values. In addition to cell cycle delays, two effects related to the DNA content as determined by flow cytometry were found after irradiation with very high LET particles, that were attributed to cell fusion and drastic morphological changes of the cells. Estimations based on the dose deposited by a single particle hit in the cell nucleus and the actual number of hits show that the basic trend of the experimental results can be explained by the stochastic properties of particle radiation.

Animals

Influence of radiation quality on the expression of chromosomal damage.

The amount of chromosomal damage induced in synchronous V79 cells by either 250 kV X-rays or 4.6 MeV/u Ar ions (LET: 1850 keV/microns) was determined at five successive sampling times. The experiments show that the time course of the appearance of damaged cells is strongly influenced by radiation-induced cell cycle perturbations and mitotic delay and depends on radiation quality and dose. The yield of chromosomal damage was found to increase with sampling time, but this increase was more pronounced for Ar ions. Because of the observed differences in the yield time profiles induced by sparsely and densely ionizing radiation the contribution of each sample to the overall damage was considered, i.e. the total (time integrated) amount of damage was determined. The obtained data are interpreted in terms of differences in the spatial energy deposition by sparsely and densely ionizing radiation.

Animals

Contaminated collection media as a cause of pseudoinfection.

Following the appearance of positive Gram's stains from sterile surgical cases, an investigation was begun. Nonviable but stainable bacteria were found in the gel-based transport media. The use of a cause-and-effect diagram helped to show the numerous items that affected the problem.

Bacteria

Hemolysis and autoantibodies to triosephosphate isomerase in a patient with acute hepatitis A virus infection.

Having returned from a holiday in Southeast Europe, a 30-year-old German woman developed acute hepatitis. Hepatitis A virus (HAV) infection was diagnosed serologically. During the course of the infection, hemolysis was found. IgM antibodies against triosephosphate isomerase (IgM anti-TPI) were detected in the patient's serum from the acute phase of the HAV infection. Affinity purified IgM anti-TPI from the serum reduced the enzyme activity in vitro and caused an increased 51Cr release from erythrocytes. IgM anti-TPI is assumed to be one of the causative agents of hemolysis in HAV infection.

Acute Disease

Z-DNA binding and inhibition by GTP of Drosophila topoisomerase II.

A Z-DNA binding protein has been isolated and characterized by biochemical means from Drosophila melanogaster tissue culture cells and embryos. This protein shares the following properties with the known, cloned Drosophila topoisomerase II: (1) expression of an ATP-dependent relaxation activity on supercoiled DNA; (2) a monomer mass of 165 kDa in SDS denaturing gels; (3) a sedimentation coefficient, S20,w, of approximately 10 S for the active enzyme; (4) cross-reactivity for the respective monoclonal and polyclonal antibodies; (5) generation of covalent enzyme-DNA intermediates at preferred cutting sites in the Drosophila HSP70 intergenic spacer region; (6) inhibition of DNA relaxation activity by antitumor drugs, e.g., the etoposide VM26, and by monospecific antibodies raised against the protein; and (7) in vitro phosphorylation by a casein kinase activity. However, we have identified new properties for our topoisomerase II preparation not previously reported for the conventionally isolated enzyme: (1) The enzyme binds to Z-DNA with an affinity 2 orders of magnitude greater than that for B-DNA. (2) The binding to Z-DNA is increased 5-10-fold by GTP or GTP-gamma-S. (3) GTP and GTP-gamma-S inhibit the catalytic activity of topoisomerase II through a proposed allosteric mechanism. (4) Z-DNA inhibits the relaxation of closed circular supercoiled DNA. (5) The preparation consists of a single polypeptide chain of 165 kDa on denaturing SDS gels with no evidence of proteolytic degradation. We postulate that the Z-DNA binding activity of undegraded topoisomerase II may be important in targeting the enzyme both to structural motifs required for chromatin organization and to sites of local supercoiling. Some of these features arise during processes such as replication and gene expression and may be more frequent during embryogenesis and early development.

Animals

Lateral parabrachial subnucleus lesions abolish feeding induced by mercaptoacetate but not by 2-deoxy-D-glucose.

Lesions of the area postrema/nucleus of the solitary tract (AP/NTS) region abolish feeding induced by mercaptoacetate (MA) and 2-deoxy-D-glucose (2DG), metabolic inhibitors that selectively impair fatty acid and glucose utilization, respectively. Because the AP/NTS region is important for both MA- and 2DG-induced feeding, the present experiment investigated the involvement of the lateral parabrachial nucleus (1PBN), which is innervated by AP/NTS neurons, in these feeding responses. Electrolytic and ibotenic acid lesions were directed at the entire parabrachial nucleus or at specific lateral parabrachial subnuclei. Rats with electrolytic lesions were tested for feeding in response to 0.9% NaCl (subcutaneous or intraperitoneal), MA (400, 600, and 800 mumol/kg ip), and 2DG (100 and 200 mg/kg sc). Ibotenate-lesioned rats were tested with NaCl and MA only. Lesions were verified either by cresyl violet staining or by glial fibrillary acidic protein immunohistochemistry. Bilateral destruction of the 1PBN severely impaired or abolished MA-induced feeding. Cell bodies important for MA-induced feeding appear to be localized in the dorsal-central 1PBN subnuclear area, because both electrolytic and cytotoxin microlesions centered in this area abolished feeding in response to MA. Fibers of passage important for MA-induced feeding appear to pass through the external and superior 1PBN because electrolytic but not cytotoxin lesions of these subnuclei disrupted the feeding response. In contrast, 2DG-induced feeding did not differ significantly from sham-lesioned controls in any of the 1PBN lesion groups. These results indicate that 2DG and MA stimulate feeding by activating separate central neural pathways and, perhaps, distinct metabolic controls of food intake.

Animals

Hypothalamic paraventricular nucleus lesions do not abolish glucoprivic or lipoprivic feeding.

This experiment assessed the importance of the hypothalamic paraventricular nucleus (PVN) for feeding stimulated by blockade of glucose utilization (glucoprivic feeding) and fatty acid oxidation (lipoprivic feeding). The PVN was investigated because it is innervated by neurons residing in the area postrema and nucleus of the solitary tract (AP/NTS) region where lesions have been shown to abolish both glucoprivic and lipoprivic feeding, and because the PVN appears to be a site of action for certain feeding-stimulatory peptides and amines. Bilateral electrolytic lesions were placed in the PVN and adjacent areas. Lesioned rats were subsequently tested for feeding in response to 2-deoxy-D-glucose (2DG)-and mercaptoacetate (MA)-induced blockade of glucose and fatty acid oxidation, respectively. Results revealed that total destruction of the PVN does not impair either 2DG- or MA-induced food intake and suggest that this structure is not essential for these particular controls of feeding.

Animals

Age-related changes in capsaicin-induced degeneration in rat brain.

Previous results indicate that the pattern of capsaicin-induced degeneration in the rat central nervous system is age-related. Experiments utilizing capsaicin's selective neurodegenerative effects to study the function of central neural circuits will therefore require a detailed understanding of capsaicin's central neurotoxicity in rats of different ages. The goal of this experiment was to characterize the degeneration induced in the rat brain by systemic treatment with capsaicin at different ages (10, 15, 20, 25, 30 or 75 days, or 11 months), using a cupric silver stain to label degenerating neurons. Results revealed degenerating cell bodies in the ventromedial brainstem in capsaicin-treated rats of all age groups, though they were more numerous in adult rats than in pups. In addition, many areas contained capsaicin-induced nerve terminal degeneration both in rat pups and in adult rats. These areas were the substantia gelatinosa of the spinal cord dorsal horn; the solitary tract; the nucleus of the solitary tract, visceral portion; the area postrema; the trigeminal nerve and spinal trigeminal nucleus; the medial nucleus of the inferior olive; the rostral, dorsomedial and dorsolateral interpeduncular subnuclei and overlying interfascicular nucleus; the supramammillary area; the lateral septal nucleus; the bed nucleus of the stria terminalis, anterior medial portion; the optic nerve and tract; the suprachiasmatic nucleus, ventroposterolateral portion; the magnocellular subnucleus of the ventrolateral geniculate nucleus; the intergeniculate leaf; the medial pretectal nucleus and the olivary pretectal nucleus. In several, but not all of these areas, the apparent density of degenerating terminals was significantly less in adult rats than in pups. In other brain sites, capsaicin-induced degeneration was observed only in rats younger than 30 days of age. These areas were the lateral habenula, medial part; the sphenoid nucleus; and the stria medullaris. Still other brain sites lost their sensitivity to capsaicin sometime between 30 and 75 days of age. These areas were the bed nucleus of the stria terminalis, medial posteromedial part; the medial preoptic nucleus, central part; the septohypothalamic nucleus; the ventral reuniens area; and the ventromedial hypothalamic nucleus. Adult rats 75 days and 11 months of age did not differ detectably in their response to capsaicin. Thus, loss or attenuation of capsaicin sensitivity is not progressive throughout life. It does not occur in all capsaicin-sensitive sites. Where it does occur, loss of sensitivity occurs prior to adulthood and follows a distinct and reproducible time course that may differ for different sites.

Aging

Presence of galanin in rat vagal sensory neurons: evidence from immunohistochemistry and in situ hybridization.

Galanin (GAL), a 29 amino acid peptide originally isolated from the porcine upper small intestine, is widely distributed in the rat central nervous system, including the area postrema (AP) and nucleus of the solitary tract (NTS). Although vagal sensory neurons terminate in the AP/NTS, it is not known whether these neurons contain GAL in the rat. Therefore, we examined the presence and distribution of GAL in the rat nodose ganglia which contain the cell bodies of vagal sensory neurons. We used avidin-biotin-peroxidase immunohistochemistry and in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe. Results with both techniques revealed the presence of GAL-containing cell bodies and fibers in the nodose ganglion. GAL-like immunoreactive cell bodies, mostly between 25 and 40 microns in diameter, were unevenly scattered throughout the nodose ganglia. The distribution and cell diameter range of GAL mRNA-labeled neurons appeared similar to those of GAL-like immunoreactive cells. These findings suggest a role for GAL in the transmission of visceral sensory information by the vagus nerve in rats.

Animals