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Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 91 records · Page 5Linked to original sources

Lazabemide (Ro 19-6327), a reversible and highly sensitive MAO-B inhibitor: preclinical and clinical findings.

Ro 19-6327 (lazabemide, L), MDL 72974, selegiline, AGN 1135 and MDL 72145 were investigated for their MAO inhibitory effect in rat tissues in vitro. The selectivity of MAO-B inhibition of L, selegiline and MDL 72974 was also measured in vitro in human brain tissue as well as ex vivo in rat brain and liver after acute and subchronic administration. Of all compounds investigated L was the most selective for MAO-B inhibition under in vitro and ex vivo conditions. In volunteers, L completely but reversibly inhibited platelet MAO-B with a dose-dependent duration. Clinical trials with L are under way in both Alzheimer's and Parkinson's disease (PD).

Animals↗

Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: II. Different types of lymphatic vessels.

In diverse mammalian species, including (man, cow and rat) the very flat endothelial cells of lymphatic vessels of various organs, including the retothelial meshwork of sinus of lymph nodes, are connected by zonula-like plaque-bearing junctions which differ from the similarly structured junctions of blood vessel endothelia by the presence of desmoplakin or an as yet unknown but closely related plaque protein. These extended junctions, which also contain plakoglobin but none of the presently known desmogleins and desmocollins, are therefore different from the spot-like desmosomes (maculae adhaerentes) present in epithelia, myocardium and dendritic reticulum cells of lymphatic follicles, and are collectively subsumed under the new category of complexus adhaerentes, including the 'syndesmos' connecting the processes of the retothelial cells. The lymphatic endothelial cells possessing these special desmoplakin-containing junctions also contain the calcium-dependent transmembrane glycoproteins, V-cadherin and cadherin 5, of which the latter has also been partly localized to regions with desmoplakin-positive junctions. Possible functional reasons for the formation and maintenance of complexus adhaerentes are discussed as well as the potential value of reagents which allow their identification in relation to physiology and pathology.

Animals↗

Dopamine efflux during withdrawal from continuous or intermittent cocaine.

Daily, intermittent, subcutaneous cocaine injections produce sensitization, while the continuous administration of cocaine produces tolerance to the behavioral effects of subsequent cocaine injections. The present experiments examined whether these behavioral differences are related to differences in the ability of cocaine to increase extracellular dopamine. Increases in perfusate DA, in response to different concentrations of cocaine, were measured in caudate-putamen slices obtained from rats withdrawn for 7 days from a 14-day treatment of either continuous or daily subcutaneous cocaine injections. Compared to saline controls, cocaine-induced DA efflux was increased in subjects receiving daily injections and markedly decreased in subjects receiving continuous cocaine. Thus, different temporal patterns of cocaine administration produce dramatically different alterations in DA neurotransmission. Such changes in dopamine release may be related to the withdrawal symptoms experienced by human cocaine abusers.

Animals↗

Regional fat distribution and metabolism in a new mouse model (C57BL/6J) of non-insulin-dependent diabetes mellitus.

It has been suggested that a genetic predisposition and an increased total fat mass, particularly a specific increase in visceral fat, contribute to the metabolic aberrations associated with human non-insulin-dependent diabetes mellitus (NIDDM). In this study, we investigated the interactions between genetic and dietary components on fat distribution and metabolism in two mouse strains, one genetically predisposed to NIDDM (BL/6) and one not (A/J), fed either a chow diet or a high-fat, high-simple carbohydrate (HFHSC) diet for 5 months. As expected, both strains of mice fed a HFHSC diet were heavier, had more fat in both the subcutaneous (inguinal [ING] and visceral (mesenteric [MES]) regions, and had larger fat cells and higher lipoprotein lipase (LPL) activities. The results of interactions between strain and diet showed important differences in fat distribution and metabolism between strains. In comparison with A/J mice, BL/6 mice fed a HFHSC diet developed hyperglycemia, hyperinsulinemia, and hypercholesterolemia, were heavier, had more overall fat, and particularly increased their MES adipose tissue. This increase in visceral fat mass was due to an increase in fat cell number. In contrast, BL/6 mice fed a chow diet had less overall fat, a smaller MES fat pad with smaller adipocytes, and lower LPL activity than A/J controls. Significant differences between BL/6 and A/J mice fed either a HFHSC or a chow diet were not observed in ING adipose tissue. These data suggest that in BL/6 mice, changes in the metabolic characteristics of visceral fat seem to be a specific characteristic associated with the genetic predisposition for NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Expression of the P-protein of the human hepatitis B virus in a vaccinia virus system and detection of the nucleocapsid-associated P-gene product by radiolabelling at newly introduced phosphorylation sites.

Hepatitis B virus (HBV) contains a particle-associated DNA polymerase/reverse transcriptase activity encoded by the P (pol) open reading frame. Due to its low abundance, the corresponding protein has so far escaped direct detection and structural analysis. As a first step to overcome these difficulties, a series of recombinant vaccinia viruses was constructed and used for the synthesis in human hepatoma cells of both the authentic full length protein and of its functional domains. Pulse chase experiments demonstrated that the P-proteins had very short half lives in striking contrast to the viral core protein expressed in parallel with the same system. No evidence was obtained for a specific proteolytic processing of the P-protein as occurring with retroviral pol gene products. Overexpression of P-protein by recombinant vaccinia viruses was then employed to develop a highly sensitive detection method based on the in vitro phosphorylation of newly introduced target sites for protein kinase A. The usefulness of this method was demonstrated in the analysis of encapsidated P-gene products that were transiently expressed from an appropriately modified HBV genome. The results obtained indicate that the P-protein acts unprocessed, at least during the initial steps of nucleocapsid assembly and reverse transcription, and that a fraction of the P-protein molecules is linked as such to the viral DNA. Direct detection of the hepadnaviral P-protein by in vitro phosphorylation should greatly facilitate future analyses on P-protein structure and function.

Base Sequence↗

Coexistence of bronchial atresia and bronchogenic cyst: diagnostic criteria and embryologic considerations.

We report a case in a neonate of concurrent bronchial atresia and bronchogenic cyst. An accurate, noninvasive, preoperative diagnosis of this unusual combination of anomalies was made by ultrafast computed tomography (UFCT). This case supports the hypothesis that bronchial atresia results from an event occurring in the 5th-6th week of embryological development, rather than after the 16th week as previously believed.

Bronchi↗

Intermittent and continuous cocaine administration: residual behavioral states during withdrawal.

Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either subcutaneous injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regime for 1 or 7 days and given a 20-mg/kg IP cocaine challenge (day 1) or a 0-, 10-, 20-, or 40-mg/kg IP cocaine challenge (day 7). The results indicate that rats receiving intermittent, daily injections exhibited sensitization to the behavioral effects of a cocaine challenge on days 1 and 7 of withdrawal. In contrast, rats receiving continuous cocaine exhibited tolerance to the behavioral effects of a cocaine challenge on days 1 and 7 of withdrawal. The present results support and extend previous research that indicates that the route and temporal pattern of administration influences the effects of chronic cocaine. Furthermore, the present results indicate that the continuous infusion paradigm may represent an alternative animal model of some aspects of high-dose cocaine abuse, as compared to the typical procedure of single, or multiple, daily cocaine injections.

Animals↗

Massage reduces anxiety in child and adolescent psychiatric patients.

A 30-minute back massage was given daily for a 5-day period to 52 hospitalized depressed and adjustment disorder children and adolescents. Compared with a control group who viewed relaxing videotapes, the massaged subjects were less depressed and anxious and had lower saliva cortisol levels after the massage. In addition, nurses rated the subjects as being less anxious and more cooperative on the last day of the study, and nighttime sleep increased over this period. Finally, urinary cortisol and norepinephrine levels decreased, but only for the depressed subjects.

Adjustment Disorders↗

Relaxation therapy reduces anxiety in child and adolescent psychiatric patients.

The immediate effects of relaxation therapy (RT) were assessed in 40 hospitalized children and adolescents with diagnoses of adjustment disorder and depression. These effects were assessed using a within subjects pre-test/post-test design and by comparison with a control group of 20 depressed and adjustment disorder patients who watched a 1-h relaxing videotape. The 1-h RT class consisted of yoga exercise, a brief massage and progressive muscle relaxation. Decreases were noted in both self-reported anxiety and in anxious behavior and fidgeting as well as increases in positive affect in the RT but not the video group. In addition, adjustment disorder patients and a third of the depressed patients showed decreases in cortisol levels following RT, while no changes were noted in the video group. Thus, both diagnostic groups appeared to benefit from the RT class.

Adjustment Disorders↗

Deposition of amyloid of unknown origin in articular cartilage.

Articular cartilage, obtained from the large toe during hallux valgus operations in 37 patients, was investigated for the presence of amyloid by using the Congo red staining method. Amyloid deposits were demonstrated, particularly in the superficial layer of the cartilage, in 30 cases. This amyloid did not react immunohistochemically with any of the antibodies against the known five major amyloid types (AA, A lambda, A kappa, AF, AB). From these data it is concluded that hyaline cartilage in older individuals is prone to infiltration by an amyloid of a hitherto unidentified class. From the morphological observations there seems to be no correlation between amyloid deposits and the development of osteoarthrosis.

Aging↗

Corticotropin releasing factor stimulates growth hormone secretion in neonatal rats.

Corticotropin releasing factor (CRF) both stimulates ACTH secretion from the pituitary and inhibits secretion of growth hormone (GH) in adult rats through actions in the CNS. The purpose of the present study was to evaluate these pituitary and central actions of CRF in neonatal rats, in which the hypothalamo- pituitary adrenal (HPA) axis is relatively hypo-functional. The results of this study show that central or peripheral administration of CRF evokes a marked dose-related rise in serum corticosterone in 6-day old rats. The same doses of CRF stimulate, rather than inhibit GH secretion. These results suggest that CRF has unique central actions early in ontogeny.

Animals↗

A cluster of four genes selectively expressed in the male germ line of Drosophila melanogaster.

The gene Mst87F is exclusively expressed in the male germ line and is subject to translational regulation. The Mst87F mRNA is transcribed in the primary spermatocytes, stored for three days and then subsequently translated in the post-elongation period of spermiogenesis. Here we report on the isolation of a cluster of four small genes closely related in structure and function to Mst87F. These genes are located at polytene band 84D on the right arm of chromosome three and are named Mst84Da, Mst84Db, Mst84Dc and Mst84Dd. All four genes encode putative proteins composed primarily of a repetitive motif of cysteine-glycine-proline. The genes are exclusively expressed in the male germ line. The poly(A) tail of the Mst84D mRNAs increases in length at day three of pupal development, the time at which a similar change in Mst87F mRNA and translation has been shown to begin. In addition we have identified a conserved 12 base pair element within the 5' untranslated region (UTR) of each gene which is also found at an identical position in Mst87F and which has been demonstrated to be the structural element for translational control of Mst87F expression (Schäfer et al., 1990 EMBO J. 9, 4519-4525). We have mapped the gene cluster to a small deletion associated with a rotund mutation at 84D. Although flies with a homozygous deletion of the cluster still produce motile sperm, electron microscopic examination revealed numerous malformations in the ultrastructure of the axoneme resulting in a drastic reduction of motile sperm.

Amino Acid Sequence↗