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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

518 records · Page 29Linked to original sources

Blockade of NMDA receptors in the amygdala prevents latent inhibition of fear-conditioning.

The association between a conditioned stimulus (CS) and an unconditioned stimulus (US) in fear-conditioning depends on N-methyl-D-aspartate (NMDA) receptors in the basolateral amygdala complex (BLA). Latent inhibition (LI) is the retardation in learning due to nonreinforced presentation of the prospective CS before conditioning. Disruption of LI in rats is an animal model of schizophrenia, reflecting the deficits of schizophrenic patients in neglecting irrelevant information. We investigated whether the BLA is involved in LI of fear-potentiated startle. Infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5; 12.5 nmoles) into the BLA before preexposure of rats to the neutral stimulus prevent LI of fear-conditioning. We also demonstrated by the same method that a complex of thalamic nuclei, comprising the medial part of the medial geniculate nucleus, the posterior intralaminar nucleus, and the suprageniculate nucleus, is involved in fear-conditioning, but not in LI. This suggests that the presentation of an innocuous stimulus during preexposure leads to an NMDA receptor-dependent change of neurotransmission in the BLA, but not in the thalamus. Our data show that the BLA but not the thalamus regulates in LI of fear-potentiated startle. Furthermore, it supports the hypothesis that the inability of schizophrenic patients to ignore irrelevant stimuli may be caused by hypofunction of the glutamatergic transmission in the brain and suggests an involvement of the amygdala in the neuropathology of schizophrenia.

2-Amino-5-phosphonovalerate↗

A low molecular weight peptide from snow mold with epitopic homology to the winter flounder antifreeze protein.

Evidence for a small size protein (ca. 3500 kDa) exhibiting epitopic homology to the Atlantic winter flounder antifreeze protein (AFP) is found in the snow molds Coprinus psychromorbidus, Myriosclerotinia borealis, and Typhula incarnata. The protein shows strong cross-reactivity with antisera specific for the flounder AFP. Preliminary studies suggest that the protein is synthesized in response to lowering the culture temperature, and that it is membrane associated and, therefore, may function in an analogous capacity to the fish AFP. Also, the protein is shown to have antifreeze properties as determined by nuclear magnetic resonance microimaging experiments.

Agaricales↗

Cloning and analysis of a murine PIAS family member, PIASgamma, in developing skin and neurons.

Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that become activated in response to stimulation by various cytokines. Recently a new family of five structurally related proteins, called PIAS (Protein Inhibitor of Activated STAT) has been identified as potentially important downregulators of this pathway. Members of the PIAS family of STAT inhibitors may play a prominent role in the downregulation of STAT-mediated signaling processes. In this article we describe the isolation of the cDNA and expression of the gene for the murine homologue of the human STAT inhibitor family member PIASgamma. The cDNA for mPIASgamma encodes a protein of 507 amino acids that is highly homologous to the human protein and is expressed in the mouse as early as d 7.5 of gestation. In situ hybridizations of staged mouse embryos localized the transcript for the PIASgamma gene to the limbs, neuroepithelium, and the inner root sheath of the hair follicle, suggesting a role in the development of these structures. Immunostaining studies with a polyclonal antibody (PAb) recognizing human PIASgamma localized the protein in the hair follicle of human scalp hair and in monkey neuronal cells. Thus PIASgamma exhibits a highly selective pattern of expression, suggesting that it modulates the response of cells to developmental cues.

Amino Acid Sequence↗

How can adaptive behavioural plasticity be implemented in the mammalian brain?

The adaptive control of behaviour requires brain mechanisms for the selection (i.e. activation and suppression) of responses, as well as mechanisms for the modulation of the response vigour. The concept of motivation postulates the existence of brain centres that regulate the selection and strength of behavioural responses. The present paper provides examples from the behavioural neurosciences for brain mechanisms that lead to adaptive changes of an organisms responsiveness to external stimuli. The mammalian startle response is a simple defensive behaviour which is mediated by an oligosynaptic pathway located in the lower brainstem. The startle response is enhanced by aversive states (fear, anxiety) and attenuated by appetitive states (pleasure), which can be regarded as an example of motivational priming. Furthermore, the startle response is inhibited by a weak sensory stimulus presented shortly before the startling stimulus. The suppression of startle by a prepulse is an example of sensorimotor gating, a principle that is important for the hierarchical organisation of behaviour. This paper describes the neuronal mechanisms underlying the modulation (prepulse inhibition and fear potentiation) of the startle response in rats, and discusses the possible adaptive significance of these different phenomena of behavioural plasticity.

Acclimatization↗

Pharmaceutical container/closure integrity. V: An evaluation of the WILCO "LFC" method for leak testing pharmaceutical glass-stoppered vials.

The sensitivity, reliability, reproducibility and ease of use of the WILCO LFC package integrity test method was evaluated by preparing and testing a series of rubber-stoppered glass vials which were modified by affixing a glass micropipette through the vial side wall. The test units contained water, 50% aqueous ethanol, 20% lithium chloride or 20% aqueous glycerol. Leakage measurement obtained by LFC testing were compared to helium leak rate measurements. The LFC methods detected all leak > 0.0014 standard cubic centimeters per second (sccs), which represents a sensitivity about fourteen-fold greater than standard vacuum decay methods. The minimum detectable leak corresponded to a nominal micropipette internal diameter of between 1 and 2 microns. The effective detection range corresponded to a leak size associated with a 40 to 100% probability of microbial ingress based on a previously reported logistical regression model between helium leak rate and microbial immersion. The sensitivity did not vary with solvent or testing duration in range of 5 to 10 seconds. The coefficient of variation was about 3%. The LFC operation was rapid and without apparent mechanical or electronic problems over the two day testing period used in these studies.

Drug Packaging↗

[Insulin antibodies: methodology and clinical implications].

Anti-insulin antibodies detection is based on the demonstration of a specific and saturable binding to insulin either radiolabelled with 125 I (Radiobinding assay or RBA) or coated on a solid phase (Enzyme linked immunosorbent assay or EIA). The 2 assays are remarkably different by their sensitivity to the affinity of the antigen antibody reaction. In addition, RBA may be biased by the presence of the iodine atom on the radioiodinated insulin whereas, at least on theoretical grounds. EIA could be biased because of denaturation or non availability of some epitopes when insulin is coated. Anti-insulin antibodies may be induced by insulin therapy. When they "spontaneously" appear, they are called autoantibodies. Insulin autoantibodies may be detected in the normal population, in type 1 diabetic patients before any administration of exogenous insulin and in patients suffering from the autoimmune hypoglycemic syndrome. In some patients, this syndrome may be associated with administration of a thiol containing drug. In some cases, insulin antibodies may appear several years after a transient insulin therapy, possibly as a consequence of a disturbance of the immunologic memory. The properties of antibodies and autoantibodies (concentration, affinity, number and nature of epitopes, heavy and light chain composition and ability to form aggregates) are relatively characteristic of the disease with which they are associated and determine their potential effects on insulin bioavailability and plasma glucose homeostasis.

Autoantibodies↗

The natural history of diverticular disease of the colon: a role for antibiotics in preventing complications? A retrospective study.

Medical and surgical treatment of diverticular disease has to be set against a background of incomplete knowledge of the natural history and geographical differences of the disease, and difficulties in its definition and classification. This clinical retrospective study was performed to answer the following questions: 1) what was the clinical course after an episode of acute diverticulitis, obliging to an hospital admission? 2) what was the role of cyclic course of antibiotics, if any, in reducing the risk of complications? We examined all admissions to the surgical ward from 1967 to 1991 for a complication of diverticular disease: we looked for occlusion, perforation, fistula, or bleeding. Patients not operated with diverticular disease have been divided in 2 groups, that is patients with a medical prescription at the end of hospital period, and patients admitted without a drug prescription. All patients have been prescribed bulk agents. The medical prescription included monthly cycles of 1 week of oral antibiotics (Neomycin associated with Bacitracin, Paromomycin, or 1989 Rifaximin). We looked for the natural history of the disease in the 2 groups (the "drug" group and the "no drug" group) after the first admission, that is the development of new complications of the diverticular disease and the reason for readmissions, calculating the Absolute Risk Reduction (the difference in event rates between the treatment and control groups) and the Relative Risk Reduction (the difference in event rates between the treated and control groups, divided by the event rate in the control groups). The total number of admitted patients in the period 1967-1991 was 505. A statistically significant trend in favour of a risk reduction of new admissions in the group given antibiotics seems evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Dietary fiber in internal medicine].

The suggestion that dietary fibre is of particular importance in our diet is a relatively recent concept. Much of the initial emphasis for increased dietary fibre began with the pioneering work of Burkitt and Trowell in the 1960s who observed that traditional African populations consumed diets high in plant fibre and that these populations experienced very low incidences of non-communicable diseases including cardio-vascular disease, diabetes mellitus and non-infectious bowel diseases, including cancer. Although it is difficult to predict from the chemical structure how dietary fibres will behave physiologically, generally dietary fibre sources can be grouped into two major types: (a) soluble, viscous, fermentable and (b) insoluble, non-viscous, slowly fermentable. As detailed below, these sources of fibres appear to have quite different physiological effects.

Blood Glucose↗