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Biomedical subjects

M E Hamilton

Publications and source records attributed to M E Hamilton.

At least 19 recordsLinked to original sources

Effects of administration of cholecystokinin into the VTA on DA overflow in nucleus accumbens and amygdala of freely moving rats.

The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present study, in vivo microdialysis in freely moving rats was used to assess the relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala. Consistent with electrophysiological findings, microinjection of CCK-8S, but not CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In the absence of anatomical evidence of CCK-containing fibers in the VTA region, it seems reasonable to conclude that the modulation of terminal DA overflow by CCK-8S through actions at the somatodendritic region represents a form of autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors. Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK-8S on VTA DA neurons.

Amygdala

Striatal extracellular dopamine in conscious vs. anesthetized rats: effects of chloral hydrate anesthetic on responses to drugs of different classes.

Many investigations using the microdialysis technique have been performed in anesthetized animals, both in this laboratory and elsewhere. Concern arises with this preparation that the anesthetic may compromise neuronal function, or that it may interact with test drugs affecting neurotransmitter overflow. In addition, in these studies the microdialysis probe typically is introduced into the brain on the day of testing, and data collection commences within an hour or two following probe insertion. It has been suggested that transmitter recovered in the perfusate probably represents leakage due to tissue damage as well as exocytotic release, and may not accurately reflect neuronal responses to the manipulations of interest. Such potential confounds present important implications for the interpretation of data from these studies. The present investigation examined the effects of chloral hydrate anesthetic on (1) basal dopamine (DA) overflow in the anterior striatum, and (2) DA responses to systemically delivered drugs of two different classes known to influence DA activity. Three putative indices of impulse-dependent release were measured: (a) the time course and stability of basal DA overflow over several hours; (b) sodium channel involvement by adding tetrodotoxin (TTX) to the artificial CSF; and (c) calcium channel involvement using magnesium (Mg) in a calcium-free perfusate. Basal DA levels became stable in both conscious and anesthetized preparations by the second hour after probe insertion. Levels of recovered DA overflow in the anterior striata of conscious rats were approximately double those in chloral hydrate-anesthetized rats. Consistent with other findings, this suggests a general depression of CNS function by chloral hydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Oral health knowledge and habits of senior elementary school students.

Despite improvements in children's dental health, and significant resource allocation to health education programs, few recent studies have investigated the associations of oral health knowledge, behaviors, and status. This study of 11-year-old children (N = 6,329) in northeastern Ontario used a supervised self-complete questionnaire and a clinical examination to gather baseline data on, and test associations of, caries and periodontal knowledge, self-reported oral health behaviors and source of knowledge, and oral health status. Results show the children had poor knowledge of caries preventive measures such as water fluoridation, dental sealants, and choice of snack foods. Periodontal knowledge was better, but children confused plaque and calculus. Respondents claimed good oral health habits, with 73 percent claiming to brush at least twice daily, 88 percent claiming to use toothpaste, 42 percent claim to floss at least twice weekly, and 84 percent claiming an annual dental visit. Children with the best knowledge claimed dentist and school as the sources. High knowledge was associated with good oral health habits (P less than .001) and low DMFT score (P less than .001). Good habits were not related to DMFT score (P = .1095). Logistic regression showed high knowledge was associated with English cultural status, urban school area, good habits, having a dental sealant, and attending a fluoride-rinse school (P less than .05). Findings suggest a need to reinforce caries preventive teaching, to investigate the effect of cultural status, dental experience, and residence status on oral health knowledge, and to further test the efficacy of different oral health education programs delivered by different sources.

Analysis of Variance

Eosinophilic fasciitis associated with L-tryptophan ingestion.

A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in development of the eosinophilia-myalgia syndrome it is suggested that the use of L-tryptophan might have contributed to the development of eosinophilic fasciitis in this patient. Similarities with toxic oil syndrome are noted. Additional studies are warranted to determine the prevalence of L-tryptophan ingestion among patients diagnosed as having eosinophilic fasciitis.

Arm

Feeding elicited by dynorphin (1-13) microinjections into the ventral tegmental area in rats.

Both the endogenous opioid peptide, dynorphin (1-13) (DYN), and morphine elicited dose-dependent feeding when microinjected into the ventral tegmental area of food-satiated rats. DYN was 50,000 times more potent than morphine in producing feeding. Whereas the ED50 for morphine was in the nanomole range, the ED50 for DYN was in the femtomole range. Administration of a narcotic antagonist attenuated DYN-elicited feeding. These data suggest a possible role for DYN in the VTA in opioid modulation of feeding behavior.

Animals

Influence of p-chloroamphetamine and methysergide on the escape deficits provoked by inescapable shock.

The effects of serotonergic manipulations on the escape interference engendered by exposure to inescapable shock were assessed. Consistent with the view that the behavioral interference was related to reductions of serotonin (5-HT), treatment with the 5-HT receptor blocker methysergide mimicked the effects of inescapable shock in that it increased escape latencies. Conversely, acute treatment with a moderate dose of the 5-HT releasing agent p-chloroamphetamine (PCA) effectively antagonized the escape interference ordinarily provoked by inescapable shock. The effects of PCA were behaviorally distinguishable from the previously observed effects of catecholamine stimulants. Whereas catecholamine stimulants applied prior to either inescapable shock or escape testing eliminated the interference, PCA antagonized the behavioral disruption only if it was administered before testing. It is suggested that catecholamine alterations may be fundamental in the provocation of the interference, whereas 5-HT variations may contribute to the expression of the behavioral disturbance.

Amphetamines

Age influences the clinical and serologic expression of systemic lupus erythematosus.

The clinical and serologic characteristics of 17 patients with onset of systemic lupus erythematosus (SLE) after age 50 were compared with those of 49 younger patients. All patients were followed prospectively for a mean duration of 47 months. A clinical and serological data base was established for each patient, and information collected at each visit to a lupus clinic was analyzed by computer. The clinical featured distinguishing old-age SLE were a low incidence of significant renal disease and prominent pleuropericarditis and arthritis throughout the period of followup. Serologic abnormalities were milder in older patients. Thus, hypocomplementemia, anti-DNA antibodies, and C1q precipitins occurred less frequently, and rheumatoid factor was more often present than in younger patients with SLE. Regression analysis suggested linear change in disease expression with age rather than distinct age-related subgroups.

Adult

Simultaneous gout and pyarthrosis.

Although infrequently reported, the simultaneous occurrence of gout and infection in the same joint has been noted recently in three patients at the University of Virginia Hospital. Our report suggests that gout and pyarthrosis may coexist more often than is generally recognized and emphasizes the necessity of carefully searching for both conditions in an inflamed joint. The importance of adequately treating gout occurring with infection is also illustrated. Although speculative, factors such as synovial fluid pH, endotoxin, and enzymatic digestion of articular cartilage may predispose an infected joint to acute gout.

Aged

Tgamma cells in systemic lupus erythematosus. Variation with disease activity.

Circulating T cells bearing receptors for the Fc portion of IgG (T gamma) were identified by sensitive immunofluorescent techniques with rabbit IgG b4 allotype/anti-b4 complexes. A twofold decrease in both proportion and absolute number of T gamma cells was found in patients with active systemic lupus erythematosus (SLE) relative to values obtained during disease remission. The reduction in T gamma cells was most evident in patients with severe hypocomplementemia. A deficit of T gamma cells in active patients was not demonstrated. The percentage of total T cells rosetting with sheep erythrocytes was reduced in peripheral blood of most patients regardless of disease activity status, but particularly during SLE exacerbation. Cells lacking intrinsic surface immunoglobulin, IgG Fc receptors, and receptors for sheep erythrocytes were increased. These cells, operationally termed null, exhibited an inverse linear relationship with T cells that was not apparent in regression analyses performed against other lymphocyte subpopulations. Such differences were not found for B cells and IgG receptor-bearing non-B/non-T cells which were present in normal proportions in virtually all patients. The origin and functional significance of these unusual lymphocyte subpopulation abnormalities are discussed.

B-Lymphocytes

Fc receptor heterogeneity: immunofluorescent studies of B, T, and "third population" lymphocytes in human blood with rabbit IgG b4/anti-b4 complexes.

IgG Fc receptors on human peripheral blood lymphocytes (PBL) were characterized by immunofluorescence studies with defined rabbit IgG b4 allotype/anti-allotype complexes. Three discrete types of Fc receptor-bearing cells, totaling approximately 33% of PBL, were identified. Fc receptors of the three types differed in their sensitivity to trypsin and in either absolute or localized density (topography) as determined by variable requirements for anti-IgC cross-linking in order to visualize bound complexes microscopically. The question of additional heterogeneity related to differences in individual Fc receptor affinity for complexed IgG was not approached in this study. Ten to 15% of PBL had pronase-sensitive, trypsin-resistant Fc receptors readily detected by direct immunofluorescence by using large fluorescein-conjugated complexes prepared near equivalence. Double label and lymphocyte fractionation experiments established this population to be largely distinct from suface IgM+ B cells and T cells, and identical to EA Ripley rosette-forming cells. Approximately 50% of surface IgM+ B cells and approximately 10% of T cells had lower density Fc receptors identified by indirect immunofluorescence with small complexes prepared in antigen excess or by cross-linking fluorescein-conjugated complexes with anti-rabbit IgG anti-serum. An additional approximately 15% peripheral T and B cells had very low density Fc receptors detectable by complexing the IgG on the cell surface by sequential incubations of cells with b4 IgG and anti-b4. Fc receptors on B and T cells were sensitive to both pronase and trypsin digestion. The heterogeneity of IgG Fc receptors on different lymphocyte subpopulations as defined by these these experiments may be of relevance for further analysis of normal and abnormal immune function.

Animals