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Biomedical subjects

D J Smith

Publications and source records attributed to D J Smith.

At least 19 recordsLinked to original sources
PubMed1992

Antinociception from the administration of beta-endorphin into the periaqueductal gray of rat is enhanced while that of morphine is inhibited by barbiturate anesthesia.

Pentobarbital anesthesia causes about a 10-fold increase in the antinociceptive potency of beta-endorphin microinjected into the periaqueductal gray (PAG) region of the rat brain. The antinociceptive response to PAG morphine was markedly attenuated during anesthesia, but returned as the rats regained consciousness. As they recovered from anesthesia, muscular rigidity and body stiffness (catalepsy) also occurred in the pentobarbital treated animals receiving morphine. These results are consistent with the activation of separate and distinct descending pain inhibitory neuronal systems by these two opioid agonists, and the differential modulation of the systems by pentobarbital. They also suggest that the mechanism underlying muscular responses to morphine is sensitive to pentobarbital, and is not shared by beta-endorphin.

Analgesics↗
PubMed1992

The Candida albicans PMM1 gene encoding phosphomannomutase complements a Saccharomyces cerevisiae sec 53-6 mutation.

We have constructed an ordered-array genomic DNA library of the pathogenic dimorphic fungus Candida albicans which facilitates the rapid cloning of C. albicans genes by hybridisation. Using the Saccharomyces cerevisiae SEC53 gene encoding phosphomannomutase as a hybridisation probe we have cloned the C. albicans homologue, PMM1, and determined its sequence. This gene shows high similarity, both at the nucleotide (76.2%) and amino-acid (77.7%) level, to the S. cerevisiae SEC53 gene. We have used the C. albicans PMM1 gene, in single copy, to transform temperature-sensitive S. cerevisiae sec53-6 mutant cells, which are defective in PMM activity at 37 degrees C, to growth at 37 degrees C. The C. albicans PMM1 gene is thus the structural and functional equivalent of the SEC53 gene.

Autoradiography↗
PubMed1992

Opioid receptors mediating antinociception from beta-endorphin and morphine in the periaqueductal gray.

beta-Endorphin and morphine produce an increase in the latency of the tail-flick reflex when administered into the PAG of awake rats. The antinociceptive effect of both opioid agonists was blocked by the sequential local injection of either CTP (D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2), a selective mu opioid receptor antagonist, naltrexone, or beta-endorphin (1-27), a putative epsilon opioid receptor antagonist, with minimal selectivity. When either CTP or naltrexone was used as the antagonist, the dose-inhibition curves generated for beta-endorphin and morphine were not parallel, suggesting the involvement of separate and distinct receptors. Also, synergism occurred when a dose of morphine producing submaximum antinociception was administered simultaneously with either a submaximal or ineffective dose of beta-endorphin. Inhibition of the antinociceptive response to beta-endorphin by mu antagonists and the non-selective antagonism of both beta-endorphin and morphine by beta-endorphin (1-27) suggested that epsilon opioid receptors were not involved. Additionally, a mu/delta opioid receptor complex was not involved, since ICI 174,864 (Allyl2-Tyr-Aib-Aib-Phe-Leu-OH), a selective delta opioid receptor antagonist, did not alter the response to beta-endorphin. Thus, although additional characterization is required, beta-endorphin and morphine appear to act (at least in part) through different opioid receptors, demonstrable using selected mu opioid receptor antagonists.

Amino Acid Sequence↗
PubMed1992

5-HT3 receptors are not involved in the modulation of the K(+)-evoked release of [3H]5-HT from spinal cord synaptosomes of rat.

The ability of 5-HT3 receptor agonists to modulate the resting efflux or K(+)-evoked release of [3H]5-HT from superfused synaptosomes from the spinal cord of the rat was investigated. Phenylbiguanide did not alter the resting efflux of [3H]5-HIAA or [3H]5-HT or modify the K(+)-evoked release of [3H]5-HT. 2-Methyl-5-HT (10 microM) caused an increase in resting efflux of [3H]5-HIAA, an effect that was blocked by the inhibitor of the uptake of 5-HT fluoxetine. No effect on K(+)-evoked release of tritium was observed. Bufotenine (100-1000 nM) increased the resting efflux of [3H]5-HT and [3H]5-HIAA. These effects were not antagonized by the 5-HT3 antagonist ICS 205-930 but were antagonized by fluoxetine. The drug ICS 205-930 (1 microM) did not alter resting efflux or block the ability of serotonin (30 and 100 nM) to decrease K(+)-evoked release of tritium. Quipazine, a potent antagonist of peripheral 5-HT3 receptors (subnanomolar concentrations), was also unable to alter resting or K(+)-evoked release of [3H]5-HT. It did, however, attenuate the inhibitory effect 5-HT on K(+)-evoked release. The concentrations required were in the micromolar range, consistent with the ability of the drug to antagonize the 5-HT1B autoreceptor. These results support the idea that 5-HT3 receptors do not act as nerve terminal autoreceptors in the spinal cord of the rat.

Animals↗
PubMed1992

Physical, physiological and performance differences between Canadian national team and universiade volleyball players.

Volleyball has been described as an 'interval' sport with both anaerobic and aerobic components. At the higher skill levels, technical performance may be limited by physical characteristics as well as physical fitness, and performance characteristics such as speed and vertical jump. This investigation compared teams at the two uppermost levels of men's volleyball in Canada for differences in physical, physiological and performance characteristics. The subjects were members of the national (n = 15) and universiade teams (n = 24). The parameters examined included percent body fat, maximal oxygen uptake (VO2 max), anaerobic power, bench press, 20-m sprint time and vertical jumping ability. The only significant difference in physical characteristics between the two teams was in age. Despite similarities in standing and reach height, the national team players had significantly higher block (3.27 vs 3.21 m) and spike (3.43 vs 3.39 m) jumps. An evaluation of anaerobic power measures produced similar power outputs during a modified Wingate test, yet the national team members had higher scores (P less than 0.05) for spike and block jump differences as well as 20-m sprint time. The large aerobic component of elite volleyball play was supported by the high VO2 max value recorded for the national team players (56.7 vs 50.3 ml kg-1 min-1). The results suggest that either years of specific physical conditioning and playing or the selection of individuals for the national team who possess more desirable characteristics as a consequence of genetic endowment, plays a significant role in the preparation of international calibre volleyball players.

Anthropometry↗
PubMed1992

Ethanol-fed Sprague-Dawley rats maintain normal levels of insulin-like growth factor I.

Ethanol-fed rats do not gain weight as fast as their isoenergetically pair-fed controls; the reasons for this slower rate of growth remain uncertain. Insulin-like growth factor I (IGF-I) is a major component of the growth-promoting endocrine system. To determine whether ethanol impairs growth by interfering with this component of the endocrine system, rats were pair-fed ethanol-containing and control liquid diets. When rats were meal-fed on the day before the experiment there were no differences in serum IGF-I concentrations or hepatic IGF-I mRNA levels between ethanol-fed and control animals after 2, 3 or 4 wk. These results indicate that ethanol consumption per se does not interfere with IGF-I production and that energy derived from ethanol sustains this component of the growth-promoting endocrine system as well as carbohydrate energy. The schedule used to administer the diets, however, did have a significant effect on hepatic IGF-I mRNA levels. When after 4 wk of dietary treatment rats were not meal-fed but received their entire dietary ration in a single morning feeding on the day before the experiment, the ethanol-fed animals had significantly higher hepatic IGF-I mRNA levels than their pair-fed controls. This finding indicates that these animals are nutritionally dissimilar despite isoenergetic pair-feeding.

Animals↗
PubMed1992

Longitudinal monitoring of humoral antibody in subjects with destructive periodontal diseases.

Fifty-one subjects (16-61 years old) with evidence of prior destructive periodontal disease were monitored clinically and immunologically at bi-monthly intervals for up to 5 yr. Periodontal disease activity, determined as new attachment loss, was detected in 33 of these subjects. Only 4 of 51 subjects failed to show an elevated serum antibody level to any of the 18 subgingival species tested. The antibody level threshold established for periodontally healthy subjects was exceeded most often in diseased subjects with serum antibody to Actinobacillus sp., P. gingivalis, E. corrodens, C. concisus, F. nucleatum and P. intermedia in that order. In general, most serum antibody levels to subgingival species remained relatively consistent for periods as long as 5 yr. However, major increases and decreases in antibody could be detected to at most one or two species in individual subjects. In addition, prolonged, steady increases and decreases in antibody to specific species could be detected in certain subjects. These findings suggest that major changes occurring in serum antibody may reflect fluctuations in the nature of the infection. Differences were observed in the antibody level to specific species when subjects were divided into subsets on the basis of clinical criteria. These included high levels of antibody to A. actinomycetemcomitans Y4 in LJP and RPP subjects and to A. actinomycetemcomitans 29523 in LJP and GJP subjects.

Adolescent↗
PubMed1992

The osmotic integrity of the yeast cell requires a functional PKC1 gene product.

Seven temperature-sensitive cell lysis (cly) mutant strains of Saccharomyces cerevisiae were isolated which lyse at the restrictive temperature on hypotonic but not on osmotically supported medium. The seven mutants fell into four complementation groups, CLY12 to CLY15. The wild-type CLY15 gene was isolated by complementation of the cly15 temperature-sensitive growth defect. Sequence analysis revealed that the complementing DNA fragment encoded a partial PKC1 gene, which has previously been isolated as an S. cerevisiae homolog of mammalian protein kinase C genes (D. E. Levin, F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner, Cell 62:213-224, 1990). Subsequent genetic analysis showed that CLY15 and PKC1 represent identical loci in the yeast genome. A truncated PKC1 gene encoding only the predicted catalytic domain of Pkc1p was able to complement pkc1 mutant strains. Similar to what has been reported recently (D. E. Levin and E. Bartlett-Heubusch, J. Cell Biol. 116:1221-1229, 1992), we observed that cells deleted for the PKC1 gene are viable when grown on osmotically stabilized medium but are osmotically fragile and lyse rapidly after a shift to hypotonic medium. As shown by light and electron microscopic examinations, the delta pkc1 strain exhibits many cells with a strongly elongated bud or chains of incompletely budded cells when grown on solid medium.

Culture Media↗
PubMed1992

PMI40, an intron-containing gene required for early steps in yeast mannosylation.

We have previously described a temperature-sensitive pmi40-1 mutant of Saccharomyces cerevisiae which is defective in glycosylation and secretion because of a thermolabile phosphomannose isomerase (PMI) activity. Inactivation of PMI at the restrictive temperature of 37 degrees C prevents synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions and results in cell death. Here, we report the isolation of the PMI40 gene by complementation of the corresponding mutation. The PMI40 gene contains an efficiently spliced intron which differs from the majority of those so far identified in S. cerevisiae in that it is short and the branch-forming structure has an AACTAAC motif replacing the highly conserved consensus TACTAAC. The 48.2-kDa protein predicted to be encoded by PMI40 contains amino acid sequences corresponding to those of internal peptides derived from purified S. cerevisiae PMI. Deletion of the PMI40 coding sequence results in a strain requiring D-mannose for growth. The PMI40 gene is located on chromosome V, and its transcription is increased 12-fold when cells are grown on D-mannose as sole carbon source instead of D-glucose. PMI enzyme activity, however, is not increased in D-mannose-grown cells, and PMI protein levels remain constant, suggesting that the PMI40 gene is subject to additional levels of regulation.

Amino Acid Sequence↗
PubMed1992

Glucose and amino acid metabolism in chronic renal failure: effect of insulin and amino acids.

The effects of hyperinsulinemia and hyperaminoacidemia on glucose and amino acid metabolism were examined in 16 control and 13 chronic renal failure (CRF) patients under two conditions: 1) euglycemic hyperinsulinemia and 2) amino acid infusion. All studies were performed with continuous indirect calorimetry and [1-14C]leucine infusion. In CRF patients insulin-mediated whole body glucose metabolism was reduced by 35% (4.41 +/- 0.50 vs. 6.76 +/- 0.73 mg.kg-1.min-1, P less than 0.01), primarily due to a decrease in nonoxidative glucose disposal (1.70 +/- 0.70 vs. 4.32 +/- 0.60 mg.kg-1.min-1, P less than 0.01); glucose oxidation was similar in both groups. In the postabsorptive state total leucine turnover (1.56 +/- 0.06 vs. 1.75 +/- 0.06), leucine oxidation (0.25 +/- 0.01 vs. 0.30 +/- 0.01), and nonoxidative leucine disposal (1.29 +/- 0.06 vs. 1.40 +/- 0.07 mumol.kg-1.min-1) were reduced in CRF vs. control subjects (all P less than 0.05). In response to hyperinsulinemia, endogenous leucine flux (index of proteolysis), leucine oxidation, nonoxidative leucine disposal (NOLD) (index of protein synthesis), and net leucine flux into protein were similar in CRF and control subjects. In contrast, the ability of hyperaminoacidemia to enhance NOLD (1.54 +/- 0.11 vs. 2.10 +/- 0.10 mumol.kg-1.min-1, P less than 0.01) and net leucine balance (0.27 +/- 0.05 vs. 0.41 +/- 0.05, P less than 0.05) was reduced in CRF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Humoral IgG antibodies to oral microbiota in a population at risk for root-surface caries.

Mutans streptococci have been strongly implicated in the initiation of dental caries on coronal surfaces. Their role in development of root-surface caries is less clear. The etiologic agents of both types of dental caries are likely to elicit systemic immune responses. The objective of the present study, therefore, was to study the association of clinical variables of disease with humoral IgG antibodies to nine oral micro-organisms in 314 adult subjects, aged 45-65 years, who were at risk for root-surface caries. Antibody activity to Streptococcus mutans strain Ingbritt, S. mutans/S. sobrinus GTFs, S. faecalis strain 19433, Actinomyces viscosus strain WVU 626, Actinomyces naeslundii strain 12, Lactobacillus casei, Actinobacillus actinomycetemcomitans strain Y4, Porphyromonas gingivalis strain 381, Eikenella corrodens strain 1073, and Wolinella recta strain 371 was measured by ELISA. Pearson correlation coefficients among log10 antibody levels within subjects revealed marked positive correlations among subgingival bacteria, generally weak positive correlations among supragingival micro-organisms, and no correlations between elements of the supragingival battery with the subgingival battery. IgG antibody levels to mutans streptococcal antigens were significantly correlated with subject DMF scores (r = 0.23; p less than 0.0001). No significant correlation was seen between DMF scores and antibody to any other supragingival micro-organism tested. Further relationships between levels of S. mutans antibody and individual clinical variables were analyzed by step-wise multiple linear regression, resulting in a model that was highly significant (p = 0.0001), with an r2 = 0.14. Numbers of missing teeth, coronal caries, root-surface caries, and root-surface restorations were each positively associated with antibody levels to mutans streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effect of age on immunoglobulin content and volume of human labial gland saliva.

Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p < 0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18-20-year-old group (n = 46) secreted at least 10 microL of labial saliva in a 7-10-minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 microL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as microgram/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age.

Adolescent↗
PubMed1992

Ontogeny of immunity to oral microbiota in humans.

This article reviews the ontogeny of immune systems in the human oral cavity that may influence the colonization, accumulation, or pathogenesis of oral microbiota. The prenatal development of cellular components associated with the secretory immune system reveals that the initial organization of tissue into Peyer's patches can first be detected immunohistologically at 11 weeks gestation. Epithelial cells positive for secretory component and immunocytes positive for IgM can be detected in salivary gland tissue by 19 to 20 weeks and continue to predominate during gestation. After birth, immunocytes containing IgA begin to dominate. Essentially, no IgA can be detected in saliva at birth. However, salivary IgA and IgM often appear soon thereafter, presumably in response to environmental antigenic and mitogenic challenges. Salivary IgA in young infants has molecular characteristics of secretory IgA and becomes the quantitatively predominate Ig in saliva. Both IgA subclasses are present in proportions characteristic of adult pure glandular salivas in many 1- to 2-month-old infants, although the appearance of IgA2 is delayed in some subjects. Many innate, antibody, and cellular immune components are found in maternal colostrum and breast milk. The antibacterial properties of these maternal factors are diverse and can exert multifaceted protective effects on the infant's alimentary tract. The infant apparently can mount mucosal immune responses quite early in life. For example, salivary antibody activity to organisms that originally colonize the gut (e.g., E. coli) or the oral cavity (e.g., S. mitis, S. salivarius) can be detected by 1 to 2 months of age. Most of this antibody activity has characteristics of secretory IgA, although some IgM antibody can also be initially detected. Salivary IgA1 and IgA2 antibody specificities to S. mitis and S. salivarius components increase qualitatively and quantitatively during the first few years of life. Salivary IgA antibody to components of streptococci that require hard surfaces for colonization (e.g., S. sanguis and mutans streptococci) generally appear after tooth eruption. The loss of placentally derived maternal IgG antibody specificities to these microbiota in the circulation is replaced by de novo synthesis, presumably as a result of the teething process. These IgG antibodies can enter the oral cavity in the gingival crevicular fluid and by the process of teething.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed1992

Inhibition of human and rabbit liver steroid and xenobiotic UDP-glucuronosyltransferases by tertiary amine drugs--implications for adverse drug reactions.

1. To investigate the hypothesis that disruption of glucuronidation of endogenous compounds by drugs represents a potential mechanism for pathogenesis of adverse drug reactions, the effects of a range of tertiary amine and amide drugs (many with effects on sex hormone function) on steroid hormone and xenobiotic UDP-glucuronosyltransferase activities in human and rabbit liver microsomes were studied in vitro. 2. Chlorpromazine, amitriptyline, imipramine, promethazine and cyproheptadine were consistently the most potent inhibitors of the glucuronidation of testosterone, androsterone, oestriol and 1-naphthol, the steroid activities being more susceptible to inhibition (up to 90%). 3. Carbamazepine, diphenhydramine, sulphadimethoxine, dimenhydrinate and (+/-)-chlorpheniramine had little effect on the UDPGT activities measured. 4. The structural features within this group of compounds required for inhibitory potency were the presence of a rigid tricyclic ring (e.g. phenothiazine) and either a dimethylaminopropyl or a methylpiperidine side-chain. 5. The implications of these data for involvement of disruption of the normal cellular function of glucuronidation in the pathogenesis of frequently observed adverse side-effects associated with these compounds are discussed.

Amines↗