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A Shum

Publications and source records attributed to A Shum.

At least 19 recordsLinked to original sources

Selective expansion of Vgamma2-Vdelta7 TCR gammadelta cells in C57BL/6 mice is postnatal and extrathymic.

Previous studies have shown that TCR-gammadelta cells expressing Vgamma2 region elements are selectively expanded in vivo in C57BL/6 (B6), but not DBA/2, mice. Genetic analysis demonstrated that the expansion of Vgamma2+ was linked to the TCR alphadelta loci, suggesting that a particular Vgamma-Vdelta pair may be necessary for the expansion. In the studies presented here, we find that the expanding TCR gammadelta cells in B6 mice express a Vgamma2+/Vdelta7+ TCR. The Vgamma2-Jgamma and Vdelta7-Ddelta-Jdelta junctional amino acid sequences of these cells display wide variation in length, suggesting that expansion is based on variable region usage and not junctional diversity. The kinetics and dynamics of Vgamma2+/Vdelta7+ T cell expression were studied to determine the biological basis of clonal expansion. Although expression of the Vgamma2+ cells in B6 and DBA/2 neonates was similar, Vgamma2+ cells in the B6 mice expanded fourfold by 4 wk of age, while the expression in DBA/2 mice remained constant. In addition, expansion of the Vgamma2+ cells occurred in athymic nude mice, suggesting that expansion was driven by extrathymic stimuli. Finally, B6 mice housed under germfree conditions expressed expanded levels of Vgamma2+ gammadelta T cells similar to their normally housed counterparts. Thus, expansion and diversification of Vgamma2+/Vdelta7+ T cells are postnatal extrathymic events that do not require microbial antigenic exposure.

Animals↗

Evaluation of intestinal protozoan morphology in polyvinyl alcohol preservative: comparison of zinc sulfate- and mercuric chloride-based compounds for use in Schaudinn's fixative.

As a result of disposal problems related to the use of mercury compounds, many laboratories have considered switching from mercuric chloride-based Schaudinn's and polyvinyl alcohol (PVA) stool preservatives to other non-mercury-based preservatives. The primary use for PVA-preserved specimens is the permanent stained smear, the most important technique in the routine ova and parasite examination for the identification and confirmation of intestinal protozoa. A comparison of organism recovery and morphology of the intestinal protozoa was undertaken with PVA containing either a zinc sulfate base or the "gold standard" mercuric chloride base. Paired positive fecal specimens (106 from 64 patients) were collected and examined microscopically by the trichrome stain technique. There were 161 instances in which organism trophozoite and/or cyst stages were identified and 3 in which human cells were identified. Morphology, clarity of nuclear and cytoplasmic detail, overall color differences, and the ease or difficulty in detecting intestinal protozoa in fecal debris, as well as the number of patients with a missed diagnosis, were assessed from the permanent stained smear. Overall organism morphology of the intestinal protozoa preserved in zinc sulfate-PVA was not always equal in nuclear and cytoplasmic detail or range of color after permanent staining to that seen with mercuric chloride-PVA. However, the same organisms were usually identified in both specimens, with the exception of situations in which organism numbers were characterized as rare (no organisms per 10 oil immersion fields at x1,000 magnification but at least one organism in the smear) [9 of 161 (5.6%)] or the organism was missed because of poor morphologic detail [12 of 161 (7.5%)]. In only six of these cases [6 of 161 (3.7%)] did the results involve pathogens. The patient diagnosis was missed in four cases of amebiasis and two cases of giardiasis; in both situations the organism numbers were rare. There were no discrepant results with Dientamoeba fragilis. Overall agreement between the two PVA-based results was 87.0% (140 of 161); when the instances of rare organisms were disregarded, the overall agreement was 92.5% (149 of 161). On the basis of these findings, zinc-PVA is viable substitute for mercuric chloride-PVA used for trichrome permanent stained smears.

Animals↗

Acute lymphoid changes and ongoing immune activation in SIV infection.

Two features of simian immunodeficiency virus (SIV) infection are emphasized: a transitory decrease in CD4 T cells in the first 2 weeks of infection followed by CD8 T-cell rise, and immune cell activation occurring by 4 weeks and persisting throughout the illness. The short-term changes included a fall in CD4 T cells by 2 weeks with partial recovery by 4 weeks and a CD8 rise that starts at 2 weeks. Subsequent characterization of CD4 T cells showed reduced expression of HLA-DR and CD25 (IL-2 receptor alpha chain) antigens later in SIV infection. Immune cell activation is evident in increased serum levels of neopterin and soluble CD8 antigen. Serum beta 2-microglobulin changes are less marked. Activation of CD8 T cells is reflected by increased percentages of cells expressing HLA-DR antigen. The B-cell numbers increased late in the course of SIV infection. Increased expression of the CD78 (Leu 21) activation phenotype was also seen in some monkeys. The immune activation changes (serum neopterin levels) induced by SIV infection in rhesus macaques appear to be associated with duration of illness, although the number of monkeys observed until death were too few for conclusive data. Thus, immune activation as well as T-cell deficiency may reflect significant immunopathogenic processes in SIV-induced disease.

Animals↗

Prolactin increases the activity of tuberoinfundibular and nigroneostriatal dopamine neurons: prolactin antiserum inhibits the haloperidol-induced increases in dopamine synthesis rates in median eminence and striatum of rats.

The role of PRL in mediating the haloperidol-induced increase in tuberoinfundibular dopamine synthesis rate was assessed by studying the effects of administration of PRL antiserum. Antiserum to PRL generated in rabbits and not cross-reacting with other anterior pituitary hormones was administered IV to adult, male rats which received haloperidol 2.5 mg/kg or tartaric acid vehicle SC 22 hr and 12 hr before measurement of dopamine turnover. Comparable groups of haloperidol or vehicle-treated animals received normal rabbit serum as control. Dopamine synthesis or turnover rate was estimated by measurement of accumulation of L-dihydroxyphenylalanine following inhibition of L-aromatic amino acid decarboxylase with m-hydroxybenzylhydrazine. Haloperidol increased median eminence dopamine synthesis rate, and PRL antiserum completely prevented this effect, supporting the thesis that the haloperidol-induced increase in tuberoinfundibular dopamine turnover is mediated by PRL. PRL antiserum did not alter basal median eminence dopamine synthesis rate in male rats. In addition to its effect in median eminence, PRL antiserum blunted the haloperidol-induced increase in striatal dopamine synthesis rate, suggesting that the haloperidol-induced increase in nigroneostriatal dopamine turnover is mediated in part by PRL. Neither haloperidol nor PRL antiserum altered serotonin synthesis rate in mediobasal hypothalamus or striatum. The data provide further support for a mechanism by which PRL can regulate its own secretion. They also suggest that prolactin alters the activity not only of tuberoinfundibular but also of nigroneostriatal neurons.

Animals↗

Simultaneous measurement of 5-hydroxytryptophan and L-dihydroxyphenylalanine by high-performance liquid chromatography with electrochemical detection. Measurement of serotonin and catecholamine turnover in discrete brain regions.

A sensitive method, using reversed-phase high-performance liquid chromatography with electrochemical detection, which allows the measurement of both 5-hydroxytryptophan and L-dihydroxyphenylalanine is described. This method, used in conjunction with the administration in vivo of an L-aromatic amino acid decarboxylase inhibitor, allows the simultaneous measurement of serotonin and catecholamine synthesis rates in small discrete brain regions.

5-Hydroxytryptophan↗

Triphasic changes in plasma ACTH concentration and brain serotonin synthesis rate following adrenalectomy in rats.

Following bilateral adrenalectomy in adult male rats, there occurs a pattern of triphasic change in basal plasma concentration of radioimmunoassayable ACTH. Plasma ACTH is markedly elevated at 2 h, has returned down almost to normal at 20 h and is again markedly elevated 96 h after adrenalectomy. We have examined serotonin (5HT) synthesis rats in several brain regions, anterior hypothalamus, posterior hypothalamus, and brain stem, at these times after adrenalectomy using the accumulation of 5-hydroxytryptophan (5HTP) after inhibition of aromatic L-amino acid decarboxylase with m-hydroxybenzylhydrazine. In both anterior hypothalamus and brain stem, decrease 5HT synthesis rates were observed at 2 and 96 h after adrenalectomy, but at 20 h 5HT synthesis rates were normal. This pattern was not observed in the posterior hypothalamus. Thus, we demonstrated inverse correlations between 5HT synthesis rates in anterior hypothalamus and brain stem, but not posterior hypothalamus, and basal plasma ACTH concentration throughout the period of triphasic change following adrenalectomy in adult male rats. Both the adrenalectomy-induced increases in plasma ACTH concentration and the adrenalectomy-induced decreases in brain 5HT synthesis rates were inhibited by treatment with dexamethasone, suggesting that the changes resulted from glucocorticoid withdrawal. The data are consistent with a role of brain 5HT neurons with cell bodies in brain stem and nerve endings in anterior hypothalamus in the regulation of the triphasic changes in plasma ACTH concentration following adrenalectomy in rats.

5-Hydroxytryptophan↗

Inhibition of serotonin synthesis within the medulla and posterior hypothalamus by cardiac vagal afferents during acute myocardial ischemia in the rat.

Serotonin synthesis, as estimated by the accumulation of 5-hydroxytryptophan 25 min following aromatic-L-amino acid decarboxylase inhibition, was measured in the medulla, pons-midbrain and posterior and anterior hypothalamus of rats subjected to left coronary artery ligation and their sham-operated controls. Left coronary artery ligation led to reduction in the rate of serotonin synthesis in the medulla and posterior hypothalamus. The topical administration of lidocaine to the left ventricle or vagotomy completely obviated these occlusion-induced changes. We conclude that there is an inhibition of serotonergic activity in the medulla and posterior hypothalamus after left coronary artery occlusion in the rat. The afferent signal arises from receptors in the ischemic left ventricle and is conducted by the vagus.

Afferent Pathways↗

Decreased brain serotonin turnover after short term (two-hour) adrenalectomy in rats: a comparison of four turnover methods.

Within the first 2 h after adrenalectomy in rats there is a marked decrease in hypothalamic, brain stem, and hippocampal serotonin (5HT) turnover. This adrenalectomy-induced decrease in brain 5HT turnover was demonstrated in this study using four different methods. These include 1) accumulation of 5HT after monoamine oxidase inhibition with pargyline, 2) decline of 5-hydroxyindoleacetic acid after pargyline, 3) accumulation of 5-hydroxytryptophan after aromatic L-amino acid decarboxylase inhibition with m-hydroxybenzylhydrazine, and 4) accumulation of 5-hydroxyindoleacetic acid after probenecid. The adrenalectomy-induced decreases in 5HT turnover in these areas were prevented by glucocorticoid treatment with either corticosterone or dexamethasone. The similarity of the results obtained with four different methods of assessment of brain 5HT turnover provides strong evidence to suggest that the activity of 5HT neurons, in at least three brain areas, is decreased within the first 2 h after adrenalectomy. Also, it seems likely that glucocorticoid withdrawal is the important factor in this adrenalectomy-induced decrease in brain 5HT turnover. In addition, an increase in hypothalamic 5HT turnover in response to the surgical stress of sham adrenalectomy could be demonstrated. The adrenalectomy-induced decreases in brain 5HT turnover were also prevented by the administration of the serotonin receptor antagonist, pizotifen. In addition, serotonin receptor blockade with pizotifen inhibited the effect of corticosterone to normalize the adrenalectomy-induced changes in both the plasma ACTH concentration and brain 5HT turnover. These data provide further support for an interaction between glucocorticoids and brain 5HT neurons.

Adrenalectomy↗

Brain serotonin turnover correlates inversely with plasma adrenocorticotropin during the triphasic response to adrenalectomy in rats.

After bilateral adrenalectomy in adult male rats a triphasic change occurs in the plasma concentration of radioimmunoassayable ACTH. Plasma ACTH is markedly elevated at 2 h, returns almost to normal at 20 h, and is again markedly elevated 92 h after adrenalectomy. We have examined brain serotonin (5HT) turnover during this period using two nonsteady state methods: accumulation of 5HT after monoamine oxidase inhibition with pargyline and decline of 5-hydroxyindoleacetic acid (5HIAA) after pargyline. Both endpoints demonstrated decreases in hypothalamic and brain stem 5HT turnover 2 and 92 h after adrenalectomy, but normal 5HT turnover 20 h after adrenalectomy. Thus, we demonstrated inverse relationships between 5HT turnover in both the hypothalamus and brain stem and the plasma ACTH concentration throughout the period of triphasic change after adrenalectomy. The adrenalectomy-induced increases in plasma ACTH and decreases in brain 5HT turnover both 2 and 92 h after adrenalectomy are inhibited by treatment with small doses of corticosterone. The data strongly suggest that the activity of some brain 5HT neurons changes after adrenalectomy in a triphasic pattern and, further, that these changes are related in part to glucocorticoid withdrawal. 5HT receptor antagonists blunted corticosterone inhibition of the adrenalectomy-induced decreases in brain 5HT turnover, providing further evidence for an interaction between glucocorticoids and brain 5HT neurons. The data are consistent with a role of brain 5HT neurons in the adrenalectomy-induced triphasic changes in ACTH secretion.

Adrenalectomy↗

Left ventricular receptors inhibit brain serotonin neurons during coronary artery occlusion.

Acute coronary artery ligation in pargyline-treated rats decreased serotonin and increased 5-hydroxyindoleacetic acid in the medulla and posterior hypothalamus. Lidocaine applied topically to the left ventricle completely prevented these alterations. No changes in serotonin were observed in the other brain regions examined. These data suggest a reflex inhibition of bulbar and hypothalamic serotonergic nerves by left ventricular receptors following acute coronary artery occlusion in the rat.

Animals↗

Alterations in brain serotonin during congestive heart failure in the cardiomyopathic Syrian hamster.

Serotonin and its major metabolite 5-hydroxyindoleacetic acid were measured in the pons-medulla, midbrain, posterior hypothalamus, anterior hypothalamus, thalamus, and cerebellum of cardiomyopathic hamsters and their age-matched controls during the early and terminal stages of the cardiomyopathy. During the stage of cardiac decompensation, significant increases were observed in the concentration of serotonin in pons-medulla (2.30 +/- 0.07 vs 1.74 +/- 0.04; P less than 0.001) and posterior hypothalamus (3.49 +/- 0.04 vs. 3.04 +/- 0.11; P less than 0.005) and in 5-hydroxyindoleacetic acid in pons-medulla (1.42 +/- 0.05 vs 0.97 +/- 0.05; P less than 0.001) and posterior hypothalamus (1.65 +/- 0.02 vs 1.32 +/- 0.07; P less than 0.001). No changes were noted in any of the brain regions of control animals. We conclude that congestive heart failure may be associated with alterations in activity of bulbohypothalamic serotonergic nerves.

Animals↗