Medical biology最新文献

Bombesin-like peptides are a group of brain-gut peptides found in several neuronal groups in the central nervous system and in peripheral intrinsic gut neurons and sensory neurons. The SIF cells (small intensely fluorescent cells) of the sympathetic ganglia also contain immunoreactivity for these peptides. These peptides are present in some pulmonary endocrine cells and tumors originating from these cells. Chromatographic studies suggest that several different peptides, possibly originating from at least two different precursors, are present in mammalian tissues. Authentic amphibian peptide bombesin does not appear to be found in mammalian tissues. Functional studies indicate that these peptides may be involved in many important functions, including sensory transmission, regulation of central autonomic pathways, thermoregulation, secretion of pituitary hormones, gastric and pancreatic secretion, food intake and satiety.

Several transmitters and modulators have been found to exist in the superior cervical ganglion of the rat. It has been shown that noradrenaline is present in the principal neurons and dopamine is the main catecholamine in the small intensely fluorescent cells. 5-hydroxytryptamine and histamine have been investigated immunohistochemically and found to be present only in the small intensely fluorescent cells of an adult rat, in the same cells which are also immunoreactive to tyrosine hydroxylase. On the other hand, enkephalins which were studied using highly specific antibodies against methionine-enkephalin-arginine-phenylalanine and methionine-enkephalin-arginine-glycine-leucine were found in the principal neurons and nerve fibres. Ligation studies showed that enkephalins in the superior cervical ganglion of the rat are both of intrinsic and extrinsic origin. It is evident that the transmission in the sympathetic ganglion is complex. The possible function of the transmitter and modulator candidates is discussed.

A potent gonadotropin releasing hormone (GnRH) agonist, D(Nal2)6 GnRH (Nafarelin) has been administered to two groups of normal men for 16 weeks by two routes in order to assess its effectiveness in suppressing spermatogenesis. In this report 400 micrograms of the GnRH agonist was given daily by constant subcutaneous infusion and the results compared to an earlier study in which 200 micrograms of the same agonist was given as a single daily subcutaneous injection. All subjects in both groups received an intramuscular injection of testosterone enanthate (200 mg) every two weeks to prevent symptoms of androgen deficiency. The higher dose infusion regimen was much more effective in suppressing spermatogenesis than the single daily injection. With infusion treatment, 3 of 7 subjects were azoospermic, a fourth subject had less than 1 million sperm per ml of semen and 5 of 7 subjects had sperm counts less than 5 million per ml. Because of the differences in GnRH dose it is unclear if the enhanced effect seen in the infusion group is the result of the route or dose of drug. Data from experimental animals and short term comparative studies with two routes and two doses suggest that both mechanisms may be operative. In either case, the results are the most promising to date and raise the possibility that constant delivery of a higher dosage of agonist could produce azoospermia in most or all subjects.

The effect of systemic administration of the parkinsonism-inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its metabolite MPP+ (1-methyl-4-phenylpyridine) on sympathetic adrenergic nerves in mouse iris and atrium has been investigated employing histo- and neurochemical techniques. The results indicate that MPTP does not have any potent neurotoxic effects on sympathetic adrenergic nerves. The effects of MPTP noted appear mainly to be restricted to a noradrenaline (NA) -depleting action and an acutely transient impairment of the NA uptake mechanism. This latter effect could be counteracted by monoamine oxidase inhibition. MPP+ was found to have more potent neurotoxic actions than MPTP as reflected i.e. by a patchy loss of histochemically demonstrable adrenergic nerves in iris which persisted for at least 7 days. Pretreatment with the NA uptake blocker desipramine antagonised the effects of MPP+, indicating that neurotoxicity is mediated via the NA uptake mechanism. The difference in neurotoxic potency of MPTP between sympathetic adrenergic nerves and central catecholamine neurons might be related to differences in metabolism of MPTP in the CNS and the periphery and/or due to the sympathetic adrenergic nerves being more resistant towards the cytotoxic actions following MPTP administration.

The effects of guanethidine, chloroquine and quinacrine on noradrenergic nerves have been compared in vitro using the isolated expansor secundariorum muscle of chicks. The effect of chloroquine on alpha-methyl-noradrenaline uptake by noradrenergic nerve terminals in various tissues were studied. The inhibitory action of guanethidine and quinacrine on noradrenergic nerves appeared to be mediated intraneuronally. The inhibitory action of chloroquine was readily reversible and unaffected by dexamphetamine. Chloroquine caused supersensitivity of the expansor muscle to noradrenaline by blocking its neuronal reuptake since the supersensitivity caused by denervation was not further increased by chloroquine. This was confirmed by the finding that chloroquine inhibited alpha-methylnoradrenaline uptake (Uptake1). Quinacrine did not cause supersensitivity to noradrenaline, possibly due to its direct depressant action on the expansor secundariorum muscle.

Different research areas might gain from the use of cultured endothelial cells. An understanding of how endothelial cells interact with hormones, plasma constituents and drugs, could make a fresh contribution to knowledge of the functional and pharmacological responses of different organs. In vitro cultures of EC are an easy tool for these studies. The culture medium can be artificially modified and the biological responses monitored. This technique, however, still presents limitations. These are: the relatively few cells that can be obtained; the limited number of vascular districts that can be used as cell sources; and the functional modifications of the cells when kept in tissue culture.

Faecal suspensions from healthy humans, conventional (CV), germ-free (GF) and intestine-decontaminated (ID) rats were tested for the in vitro hydrolysis of 125I-labelled iodothyronine sulphates and 3,3',5-triiodothyronine glucuronide (T3G). Whereas 20-fold diluted human and CV rat faecal suspensions hydrolyzed up to 90% of the sulphates, no hydrolysis was observed in 5 times diluted faecal suspensions of GF and ID rats. These results add further weight to the assumption that intestinal iodothyronine sulphatase activity is of bacterial origin. Twenty times diluted human and CV rat faecal suspensions hydrolyzed approximately 80% of the T3G. In the 5 times diluted faecal suspensions of GF and ID rats up to 15% hydrolysis of T3G was still observed. It was concluded that the major part of the gastrointestinal iodothyronine glucuronidase activity is produced by bacteria. The remaining activity presumably originates from gastrointestinal mucosal cells.

Prominent glycogen accumulations have been found in the floor plate radial glial cells of the human spinal cord and brain stem during the 6th to 13th week of intrauterine life. These glycogen-rich cells are totally negative to indirect immunoperoxidase staining with an antibody to glial fibrillary acidic protein, a protein that is strongly expressed in the remaining radial glial cells that border the central canal of the spinal cord. The glycogen-rich floor plate radial glial cells are, on the other hand, heavily stained by a monoclonal antibody against a vimentin-related protein. The neighbouring lateral radial glial cells do not express this protein. These and other distinctive features of the floor plate radial glial cells indicate an organoid specialisation of the floor plate during limited periods of intrauterine life. The function(s) of this specialised tissue remains obscure, but it may be related to cortico-spinal fibres crossing the midline through the floor plate, or to the transport of substances in both directions between blood vessels and the central canal.

The cellular localisation of caligulin-like immunoreactivity (caligulin-LI) in rat central and peripheral tissues was studied using antibodies against bovine brain caligulin raised in rabbits. Both immunofluorescence and immunoperoxidase techniques were used to demonstrate caligulin-LI in paraformaldehyde fixed tissues. Certain neurons in the cerebral cortex, basal ganglia and brain stem contained caligulin-LI. In the cerebellum a majority of Purkinje cells were labelled with immunoreactive material localised to dendrites, perikarya and axons. In the gastrointestinal tract some neurons in Auerbach's and Meissner's plexa contained caligulin-LI. Ligation of the sciatic nerve caused accumulation of immunoreactive material both proximal and distal to the crush. A non-neuronal localisation of caligulin-LI could also be demonstrated, e.g., in parts of the renal tubular system, in the islets of Langerhans and in certain enteroendocrine cells. The specific localisation of caligulin-LI in some but not all neurons of the rat brain and gastrointestinal tract suggests a specific function of caligulin in central and peripheral nervous mechanisms.

The expression of the DNA of hepatitis B virus (HBV) was analysed in three cell lines (PLC/PRF/5, Hep 3B, L6EC3) which contain the HBV DNA integrated in their genome and release the viral surface antigen (HBsAg) in relation to cell growth. Using the in situ hybridisation technique and a cloned DNA probe specific for hepatitis B virus (PTKH9), the intracellular viral RNA localisation showed that for the three cell lines, HBV RNA are present in the different cell compartments according to the age of the culture. The nucleolar and nuclear localisation are visible in the early stages of the cell growth, whereas in the later stages viral RNA are found in the cytoplasm corresponding to the maximal production of the HBsAg. These observations suggest that the nucleolus is implicated in the expression of the integrated form of HBV genetic information, the regulation of which is linked to cell growth.