Medical biology最新文献

The presynaptic and postsynaptic actions of amino acid transmitters gamma-aminobutyrate, glutamate, aspartate and glycine in the central nervous system are reviewed.

The re-aggregation of dispersed islet cells from non-inbred ob/ob-mice was studied by light and electron microscopy. After 3 days of culture, spontaneously formed aggregates with more than 95% beta-cells were up to 0.5 mm in diameter and exhibited a high degree of viability on dye exclusion tests. In comparison with cultures at 1 or 3 mM D-glucose, or 1 mM D-glucose in combination with 19 mM 3-0-methyl-D-glucose, aggregates formed in 20 mM D-glucose were more closely packed, had a smoother circumference with elongated peripheral beta-cells, and exhibited well developed micro-villi in localized intercellular widenings. A stereological analysis of electron micrographs showed that beta-cells aggregated at 20 mM D-glucose exhibited the same individual profile area but a significantly lower form factor, and a significant reduction in granule volume density as compared with aggregates at 3 mM D-glucose. It is concluded that D-glucose has morphogenetic effects on both the cellular and the micro-anatomical level of pseudo-islet structure in culture.

Reinnervation and sensibility were investigated in patients previously subjected to split thickness skin transplantation after excision of skin and subcutaneous fat for treatment of malignant melanoma. All patients except one showed poor sensibility and no neurofilament positive sensory nerve fibres were detected. Most patients had heat and pain sensibility but with a higher threshold than on the control side. It is suggested that this heat pain sensibility is mediated from nerve fibres in the underlying tissue. In one patient, however, sensibility was encountered and in this patient neurofilament positive sensory nerve fibres were observed in the dermis and epidermis.

Selective neuronal loss in the hippocampus following transient forebrain ischaemia appears to be excitotoxic in origin. The early cytological changes in the rat hippocampus (1-2 hours after 10 or 30 minutes of ischaemia) have the ultrastructural appearances of an excitotoxic lesion. Focal injection of an excitatory amino acid antagonist acting competitively on the N-methyl-D-aspartate (NMDA) receptor, 2-amino-7-phosphonoheptanoic acid (2-APH) in one hippocampus protects against the early cytopathology, and, when repeated 4 and 10 hours after the ischaemia, partially protects against selective nerve cell loss. Systemic administration of 2-APH or of a non-competitive antagonist at the NMDA receptor, ketamine, also protects against neuronal loss. Blockade of excitatory transmission at the NMDA receptor may provide a therapeutic approach to the acute treatment of cerebral ischaemia.

This short review describes the benzodiazepine receptors, their interplay with GABAergic transmission and chloride ionophore, the search for endogenous ligands, and the drug responses that can be evoked through these receptors. Benzodiazepine receptors offer a unique pathway through which opposite drug actions e.g., anxiogenic and anxiolytic effects can be exerted, and these actions can be inhibited with competitive receptor antagonists. The most plausible endogenous ligand for benzodiazepine receptors discovered so far, a polypeptide DBI, exerts actions opposite to those of the benzodiazepines used in clinical therapy. This has been the stimulus for a new look at the physiological role for these receptors.

The central question in cell biology is how cells detect, interact and respond to extracellular matrix. The cell surface molecules, which mediate this recognition, consist of a lipophilic membrane domain and an ectodomain binding matrix materials. One group of this kind of molecules is the cell surface heparan sulfate proteoglycans (HSPG). This review summarizes recent information obtained on the cell surface PG of mouse mammary epithelial cells. The glycosaminoglycan containing ectodomain of this PG binds with high affinity Type I, III and V collagen fibrils and the C-terminal heparin binding domain of fibronectin. The PG is mobile on the cell surface, but can be immobilised by ligand binding. At the same time the PG associates with cytoskeleton and links the epithelial cytoskeleton to extracellular matrix. Thus the PG can mediate the changes in the matrix into changes in cellular behaviour, often seen during the regulation of cell shape, proliferation and differentiation. The cell surface PG is also released from the cell surface by cleaving the matrix-binding ectodomain from the membrane domain. Because of the binding properties of the ectodomain, this shedding may provide a means by which epithelial cells loosen their association with the matrix and with other cells, e.g., during normal epithelial development and the invasion of carcinomas.

Adenosine has emerged as an important regulator of many physiological processes. This review briefly describes the formation and inactivation of the nucleoside, its effects in different tissues and the mechanism by which these effects are executed.

Radioimmunoassays of brain extracts have shown that several peptides occur in high concentrations in the CNS. The releasing-factor peptides TRF, LRF, somatostatin, CRF and GRF have the highest concentration in the hypothalamic extracts. High levels of somatostatin, CCK octapeptide, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) are found in cortical extracts. Substance P, CCK, NPY, and enkephalins are present in high concentrations in basal ganglia and mesolimbic areas. Pharmacological doses of these peptides result in several behavioural and vegetative effects. Immunocytochemical studies show that the CNS peptides are localised in neurones and in synaptic vesicles. In vitro studies with brain tissues show that peptides are capable of modifying the ongoing classical neurotransmission. In depressive patients several neuropeptides (CCK, CRF and NPY) have been shown to have low CSF levels. Patients dying of senile dementia have low cortical levels of somatostatin, CRF and substance P. In schizophrenic patients CCK peptides have shown to improve some symptoms. At present the therapeutic potentials of peptides are poorly known. More studies are required to understand their role in neurotransmission and related pathological states.

Remarkable progress has been made during recent years in the central regulation of the hypothalamic releasing and inhibiting factors and the respective anterior pituitary hormones. There are two nearly universal inhibitory organizations: short tuberoinfundibular dopamine (TIDA) neurons and somatostatinergic system originating from the periventricular hypothalamus and terminating to the median eminence. It is now known that e.g. dopamine, noradrenaline and acetylcholine enhance while 5-hydroxytryptamine and GABA inhibit somatostatin secretion. These transmitters are also involved in the regulation of all releasing factors and pituitary hormones. Clinical applications have been developed based on the regulation of prolactin and growth hormone. Inhibitory TIDA neurons are undoubtedly the major determinants of prolactin secretion. Hyperprolactinaemia is one of the most common endocrinological side-effects of the drugs antagonizing dopaminergic transmission. Expectedly, dopaminergic drugs (bromocryptine, lergotrile, piribedil, dopamine and levodopa) are quite effective in reducing high prolactin levels regardless of the reason. The secretion of growth hormone is predominantly under dual dopaminergic control: hypothalamic stimulation and pituitary inhibition. The former masters the function of the normal gland, while the peripheral inhibitory component takes over in acromegalic gland. Hence dopaminergic drugs are able to reduce elevated growth hormone levels in 30-50% of the acromegalic patients. In normal man, dopamine agonists increase growth hormone levels. An analogous situation can be seen in Cushing's disease regarding ACTH secretion.