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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 379 records · Page 21Linked to original sources
PubMed1988

Development of Trypanosoma congolense, T vivax and T brucei in the skin reaction induced in goats by infected Glossina morsitans centralis: a light and electron microscopical study.

The development and distribution of Trypanosoma congolense, T vivax and T brucei in the skin of goats was examined after the animals were bitten by infected Glossina morsitans centralis. Following the tsetse bite, the trypanosomes in the skin multiplied, reaching maximum numbers when the skin reaction (chancre) of the host attained its maximum size. In goats infected with T vivax and T brucei, trypanosomes were observed circulating in the blood before the peak of the chancre, while in T congolense-infected goats microscopically detectable parasites were found in blood only during the decline of the chancre. In contrast to T vivax, large numbers of T congolense and T brucei parasites were found in the skin following tsetse-transmitted infection. Ultrastructural differences were observed in T congolense and T brucei indicating an intracutaneous transformation from metacyclic to blood stream forms. T congolense forms in the skin reactions had a well developed secretory reticulum, small mitochondria and lacked large lipid inclusions compared to metacyclic and blood stream forms. The intracutaneous forms of T brucei had smaller mitochondria, the glycosomes were of more uniform size and the rough endoplasmic reticulum was less developed than in metacyclic or blood stream forms.

Animals↗
PubMed1987

Acetylcholine in the interpeduncular nucleus of the rat: normal distribution and effects of deafferentation.

We studied the cholinergic projection to the interpeduncular nucleus (IPN) by examining localization of choline acetyltransferase (ChAT) in the habenula, fasciculus retroflexus (FR) and among the subnuclei of the IPN of the rat, using and antibody raised against ChAT. ChAT-containing neurons were present in the ventral portion of the medial habenula, ChAT-stained axons were present in the FR and ChAT-stained axons and terminals were present in the rostral, central and intermediate subnuclei of the IPN. No ChAT staining was seen in the lateral or dorsal subnuclei. The pattern of ChAT localization was thus complementary to the pattern of the habenular substance P projection to the IPN. Lesions of the FR eliminated all ChAT from the IPN while lesions of the stria medullaris produced a modest decrease. Unilateral FR lesions indicated that the FR projection to the central and rostral subnuclei is largely bilateral and symmetrical and that to the intermediate subnuclei is largely ipsilateral. We found no evidence of lesion-induced plasticity, i.e. replacement of ChAT immunoreactivity, by surviving FR axons in these adult brains.

Acetylcholine↗
PubMed1987

Norepinephrine in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation.

We used correlative biochemical and histochemical methods to examine (1) the norepinephrine (NE) projection from the paired locus coeruleus (LC) to the midline interpeduncular nucleus (IPN) of the adult rat and (2) the ability of the LC to respond to denervation of their target following removal of noradrenergic afferents (6-hydroxydopamine lesions of the LC) or non-noradrenergic afferents (lesion of the paired fasciculi retroflexi(FR]. Histofluorescence revealed that the NE innervation from the two LC to the IPN is symmetric and overlapping. This projection is confined to rostral, central, and intermediate subnuclei and is absent from lateral and dorsal subnuclei. We found no evidence for homotypic collateral sprouting of undamaged LC neurons into the IPN following unilateral LC lesion. Bilateral LC lesions also did not induce sprouting by NE-containing neurons from other systems (e.g. the superior cervical ganglion or the lateral tegmental group) or from those LC neurons that survived the 6-hydroxydopamine lesion. Histofluorescence following bilateral FR lesions confirmed an earlier observation that apparent hyperinnervation of the IPN by LC afferents is elicited following removal of non-noradrenergic afferents. Measurements of the turnover rate of NE in the IPN of control animals and those that received bilateral FR lesions indicate an increased NE content and increased turnover rate of NE in the IPN of lesioned animals. Taken together these results suggest an increased number of NE terminals and an increase in the activity of tyrosine hydroxylase. No change in NE content or turnover rate was seen in the frontal cortex from these same animals. This is consistent with a target-dependent regulation of heterotypic collateral sprouting.

Animals↗
PubMed1987

Normal development and effects of early deafferentation on choline acetyltransferase, substance P and serotonin-like immunoreactivity in the interpeduncular nucleus.

The normal postnatal development and response to neonatal fasciculus retroflexus (FR) lesions of serotonin, substance P (SP), and choline acetyltransferase (ChAT) distribution are described for the rat interpeduncular nucleus (IPN). Serotonin-, SP- and ChAT-containing axons differed in development, distribution, and response to deafferentation. Serotonergic axons and cell bodies were present at birth. SP was present in the FR and in the lateral subnuclei by 3 days of age but did not appear in the rostral or dorsal subnuclei until 7-14 days. Intrinsic SP perikarya were not seen until 17 days of age. The development of ChAT was late, appearing only during the second week of life and not reaching adult patterns and density until after 21 days of age. The pattern of development of cytochrome oxidase and Bodian silver staining are also described. Both cytochrome oxidase and Bodian staining paralleled the patterns of localization and development of ChAT staining. Bilateral neonatal FR lesions resulted in a permanent loss of ChAT and cytochrome oxidase staining throughout the IPN and of SP in the lateral and rostral subnuclei. No changes were seen in the serotonergic system. Following unilateral lesions, the pattern of SP loss and replacement paralleled that seen after adult lesions. The pattern of replacement of ChAT differed from that after adult lesions in that there was partial replacement in the ipsilateral intermediate subnucleus following neonatal lesions. This result suggests that late developing cholinergic axons can innervate the contralateral intermediate nucleus to a much greater extent following infant lesions than following adult lesions.

Age Factors↗
PubMed1987

[125I] triiodothyronine in the rat brain: evidence for neural localization and axonal transport derived from thaw-mount film autoradiography.

Previous thaw-mount light microscopic autoradiographic studies have shown that intravenously administered [125I] triiodothyronine is saturably concentrated and retained for at least 10 hours in discrete neural systems in the rat brain. To survey the brain more completely and to gain information about the time course of labeling, serial thaw-mount film autoradiograms were prepared from rat brains obtained at intervals through 48 hours after intravenous injection of high specific activity [125I] triiodothyronine. Parallel biochemical studies of whole brain homogenate extracts revealed that, at all time intervals, the label in the brain was mainly due to triiodothyronine itself (80%), or other organic iodocompounds (15%), but probably not due to free [125I] iodide (3%), which is rapidly transported out of the brain. The highly reproducible, well-defined labeling patterns seen on film indicated a widespread but selective localization of the hormone. At early times after intravenous injection of [125I] triiodothyronine, label was nonuniformly and prominently concentrated in selected regions of gray matter; evidence for saturability of hormone processing was obtained in competition studies with unlabeled triiodothyronine. Discrete labeling of fiber tracts (usually after 10 hours) left some regions of white matter conspicuously unlabeled. At 48 hours, many originally labeled gray regions showed markedly diminished or virtually complete loss of radioactivity, whereas others became newly or more prominently labeled. At that time, certain fiber tracts were also conspicuously labeled. The observed changing profiles of regional labeling over time are best explained by movement of the hormone from original sites of saturable incorporation in specific nuclei, to terminal fields, through the mechanism of axonal transport.

Amygdala↗
PubMed1987

New heterocyclic modifiers of oxidative drug metabolism--II. Steric factors in the interaction of isomeric 2-(naphthyl)methylbenzimidazoles with rat hepatic microsomal cytochrome P-450 and monooxygenase activities.

The inhibitory potency of the two isomeric 2-(naphthyl)methylbenzimidazoles towards three monooxygenase activities (aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and aniline p-hydroxylase) was assessed in hepatic microsomal fractions from untreated, phenobarbitone-induced and beta-naphthoflavone-induced rats. The isomers were essentially equipotent with each other as inhibitors of the phenobarbitone-induced monooxygenases (the ratio of the I50s of the isomers was about 1.0 in each case) but differences between the isomers were noted in the inhibition potencies against three monooxygenase activities from beta-naphthoflavone-induced liver. The isomer 2-(1'-naphthyl)methylbenzimidazole was approximately twice as potent as the 2'-naphthyl isomer against 7-ethoxyresorufin O-deethylase activity, whereas the opposite was observed with respect to 7-ethoxycoumarin O-deethylase inhibition; aniline p-hydroxylase was poorly inhibited by both isomers. The binding affinity and extent of binding, assessed from double-reciprocal plots of spectral binding studies, of the 1'-isomer was much greater than that of the 2'-isomer in beta-naphthoflavone-induced microsomes. Inhibition data in untreated hepatic microsomes were more complex and the finding of principal interest was that the 1'-isomer was poorly inhibitory towards aniline p-hydroxylase activity whereas the 2'-isomer enhanced this activity. These studies suggest that the steric conformations of the isomeric naphthylmethylbenzimidazoles at the cytochrome P-450 active centre determines the extent to which the inhibitors modulate a specific monooxygenase activity, and that multiple binding sites with the capacity to interact to different extents with benzimidazole derivatives are present in P-450 in beta-naphthoflavone-induced hepatic microsomes. The apparent importance of steric conformation as a determinant of inhibition and enhancement of aniline p-hydroxylase in untreated microsomal fractions may well reflect specific interactions with multiple binding sites.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1987

The presence of enkephalin-like substances in the eyestalk and brain of the land crab Gecarcinus lateralis.

The eyestalk of the land crab, Gecarcinus lateralis, is rich in Met-enkephalin-like materials. Leu-enkephalin, if present, is at a level which is below the sensitivity of our assay. The brain (cerebral ganglion) of this organism contains both Met- and Leu-enkephalin-like materials. Material which was reactive with our Met-enkephalin antibody was also detected in a peak that migrated after Leu-enkephalin. This biochemical study confirms earlier immunohistochemical reports which indicated that opioid substances are present in crustaceans. It also strongly supports the concept that opioid mechanisms are a product of early evolution and further demonstrates that the sequence of the smaller opioid compounds has been conserved.

Animals↗
PubMed1987

Impaired androgen 16 alpha-hydroxylation in hepatic microsomes from carbon tetrachloride-cirrhotic male rats.

Hepatic cirrhosis produced by repeated inhalation of carbon tetrachloride is associated with reduced levels of microsomal cytochrome P450. In this study the C19-steroids androstenedione and testosterone were used as specific probes of the functional activity of several forms of cytochrome P450 in microsomal fractions from control and cirrhotic rat liver. The principal finding, that androstenedione 16 alpha-hydroxylation and testosterone 2 alpha-, 16 alpha-, and 17 alpha-hydroxylation were reduced to 14%-38% of control activity, strongly suggests that levels of the male sexually differentiated cytochrome P450 (P(450)16 alpha) are decreased in hepatic cirrhosis. The activity of other cytochrome P450-mediated C19-steroid hydroxylases, with the exception of androstenedione 6 beta-hydroxylase, appeared essentially unaltered in microsomes from cirrhotic rats. Cirrhosis induced by carbon tetrachloride was also associated with greatly decreased activity of the microsomal cytochrome P450-independent 17 beta-oxidoreductase, an enzyme that catalyzes the conversion of androstenedione to testosterone. Consequently, and in view of the impaired activity of cytochrome P450-mediated testosterone 17 alpha-hydroxylation, the capacity of cirrhotic microsomes to catalyze the interconversion of androstenedione and testosterone was much lower than that of control microsomes. The present data confirm and extend earlier observations that selective impairment of drug oxidation pathways occurs in hepatic cirrhosis. These changes are unrelated to the acute toxicity produced by carbon tetrachloride exposure. The available evidence supports the assertion that specific forms of cytochrome P450 are subject to altered regulation in cirrhosis.

Androgens↗
PubMed1987

Chemical characterization of phosphoribosylamine, a substrate for newly discovered trifunctional protein containing glycineamide ribonucleotide synthetase activity.

PRA has been characterized for the first time using 13C-NMR spectroscopy. Incubation of [1-13C]ribose-5-phosphate with NH3 results in the production of 38:62 alpha:beta anomeric mixture of PRA, alpha,beta ribose-5-phosphate and variable amounts of dimeric materials. NMR studies at various pHs allowed determination of the pH independent Kequi = 0.95 +/- 0.14 M-1 for this reaction. In addition, using magnetization transfer NMR methodology the rate of conversion of alpha to beta PRA was determined to be 44 sec-1 at 37 degrees C (pH 8.0). The rates of formation (from ribose-5-phosphate and NH3) and degradation of PRA were also measured using E. coli GAR synthetase (recently cloned, overproduced and purified to homogeneity) as a trap. Determination of these rates allowed an independent and accurate measurement of Kequi = 2.7 M-1. In addition, in close agreement with early studies of Nierlich and Magasanik, the half life of PRA at 37 degrees C and pH 7.5 was determined to be 35 sec. Characterization of the chemical stability of PRA and Kequi for ribose-5-phosphate, NH3 with PRA will now allow detailed kinetic analysis of the newly discovered trifunctional protein containing GAR synthetase activity in addition to AIR synthetase and GAR transformylase activities. Comparison of the properties of the 110 kd GAR synthetase and an independently isolated 54 kd GAR synthetase are reported. Experiments are underway to investigate the possibility that unstable intermediates such as PRA are not released into solution, but that the transfer is mediated by specific protein-protein interactions between GAR synthetase and PRPP amidotransferase.

Ammonia↗
PubMed1987

Opiate binding sites in the interpeduncular nucleus of the rat: normal distribution and the effects of fasciculus retroflexus lesions.

Opiate receptors have been localized autoradiographically to many regions of the rat central nervous system. The interpeduncular nucleus has an especially high concentration of these receptors. We used [3H]naloxone and [125I] [D-Ala2,MePhe4,Glyol5]enkephalin as ligands to map the distribution of opiate receptors among the subnuclei of the interpeduncular nucleus. The rostral subnucleus contains label that is densest dorsally. More caudally, high densities of opiate binding sites are found in the lateral, rostral, and central subnuclei. The dorsal subnucleus contains a moderate density of binding sites and the intermediate subnuclei contain almost none. Opiate receptors have also been localized to the medial habenulae and the fasciculi retroflexi, which provide a major afferent input to the interpeduncular nucleus. Lesions of the fasciculi retroflexi decreased the density of opiate binding sites in the rostral and lateral subnuclei of the interpeduncular nucleus. There were no changes seen in the dorsal, intermediate or central subnuclei. These results suggest that a minority of opiate receptors in the interpeduncular nucleus are located presynaptically on fasciculi retroflexi axons. Immunocytochemical studies have demonstrated that the rat interpeduncular nucleus contains substance P, serotonin and enkephalin, and each has a distinct subnuclear distribution. Although the opiate binding sites have a wider distribution than substance P, serotonin, or enkephalin individually, the pattern of opiate binding most closely parallels substance P distribution. The combined distribution of substance P, serotonin, and enkephalin is equivalent to that of the opiate binding sites.

Animals↗
PubMed1987

Latent oculogenital infection with Chlamydia trachomatis.

Thirty patients attending a sexually transmitted disease clinic were evaluated for genital and ocular infection with chlamydia. Eight patients had positive conjunctival immunofluorescent staining. This represents an asymptomatic, latent carrier state with important epidemiologic considerations.

Chlamydia Infections↗