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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 847 records · Page 47Linked to original sources

Oral candidosis in HIV-infected patients.

Over 80% of all HIV-infected patients develop oral candidosis at some stage during their disease. This provides a marker for the development of fullblown AIDS--in one study more than 50% proceeded to the full syndrome within three months of the development of buccal lesions, although some of these may have had asymptomatic oesophageal candidosis at the time of initial presentation. Oral candidosis appears to be particularly common in young children and Africans who are HIV-infected. Both pseudomembranous and atrophic forms occur, but the atrophic manifestation, which is often asymptomatic, often occurs earlier and is frequently missed. Median rhomboid glossitis and angular cheilitis are common. Topical treatment appears to be sufficient for atrophic candidosis and many cases of pseudomembranous infections also respond, although many clinicians would prefer to use a systemic antifungal agent in this situation because of the risk of oesophageal infection. Fluconazole, ketoconazole and itraconazole are all effective agents. In a prospective double-blind control study comparing itraconazole and ketoconazole, clinical response, mycological clearing and relapse rate were similar with both drugs. More than 95% of patients were free of symptoms within three weeks.

Candidiasis, Oral↗

Human papillomavirus detection in cervical lesions nondiagnostic for cervical intraepithelial neoplasia: correlation with Papanicolaou smear, colposcopy, and occurrence of cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is associated with cervical intraepithelial neoplasia (CIN) and carcinomas. The present study involved women who had an abnormal Papanicolaou smear and whose cervix contained acetowhite area(s) that lacked the histologic features of CIN. Sequences homologous to HPV DNA, determined by Southern blot hybridization analysis, were detected in 20 of 59 cervical biopsy specimens (34%) that lacked the histologic features of CIN. When compared with the group in which HPV DNA was not detected, the HPV DNA-positive group had a lower chance of having a normal Papanicolaou smear (30 versus 61%) at the time of the biopsy. There was no difference in the colposcopic findings between the HPV DNA-positive and -negative cases for the biopsy specimens that lacked the features of CIN. However, there was a difference in the rate of histologically proved CIN in the two groups. Twelve of 17 women (71%) in the HPV DNA-positive group for whom there was follow-up information had a biopsy-proved CIN lesion noted at another location in the cervix at the time of biopsy (six) or 3-12 months after the biopsy (six). This rate was significantly higher (P less than .05) than the rate (five of 25, 20%) in the HPV DNA-negative cases, most of whom had no colposcopic abnormalities and a normal Papanicolaou smear at the follow-up examination. These findings indicate that HPV DNA detection in women with cervical lesions that lack the histologic features of CIN predicts current or future CIN in such patients.

Biopsy↗

Trauma scoring methods.

Trauma scoring methods are recommended for use in the management of trauma patients. Currently used methods are reviewed for their use in triage, the determination of injury severity and the assessment of prognosis and outcome in comparative evaluation of trauma care within or between institutions.

Critical Care↗

Cerebrospinal fluid changes after 48 hours of effective therapy for Hemophilus influenzae type B meningitis.

Interval cerebrospinal fluid (CSF) analysis is often performed to assess efficacy of treatment for bacterial meningitis. The authors reviewed 101 cases of pediatric bacterial meningitis resulting from Hemophilus influenzae type b in which analysis of CSF occurred on admission and between 48 and 72 hours after initiation of parenteral antibiotic therapy; of these, only one patient had a positive repeat CSF culture. Of the 100 cases with sterile CSF on repeat culture, there was no instance of recrudescence of infection during hospitalization. The following characterized the interval changes in CSF profile of this group: 100 (100%) with persistence of pleocytosis; 14 (14%) with differential cell count conversion from polymorphonuclear neutrophil leukocyte (PMN) predominance to relative lymphocytosis; 96 of 98 (98%) with initial positive Gram-stained smear with negative results for organisms; 53 of 75 (71%) with normalization of initial hypoglycorrhachia; and 10 of 94 (11%) with normalization of initial abnormally elevated protein levels. The differences in mean values of CSF total white blood cell counts, percentage PMNs, and glucose and protein concentrations on presentation and between 48-72 hours of therapy were highly significant (P less than 0.0001). After 48 hours of effective antibiotic therapy for H. influenzae type b meningitis, CSF pleocytosis and abnormally elevated protein concentration are usually preserved, whereas hypoglycorrhachia usually resolves; it is not uncommon for the differential cell count to convert from a PMN predominance to a relative lymphocytosis. Significant alteration in all CSF parameters associated with H. influenzae type b meningitis can occur after 48 hours of effective parenteral antibiotic therapy.

Anti-Bacterial Agents↗

Serum ferritin values in elite speed and synchronized swimmers and speed skaters.

Reports of subnormal serum ferritin values for elite athletes are widespread. Human studies evaluating performance in the ferritin-depleted state have led to a questioning of the significance of low ferritin levels for athletic performance. However, the accelerated iron metabolism and subnormal iron intake-uptake demonstrated by some athletes suggests that a point occurs in training at which the body must draw on its reserves. In consideration of this problem, serum ferritin, hemoglobin, hematocrit, serum Fe, and total iron-binding capacity levels were measured in elite Canadian female synchronized swimmers (n = 9), male speed swimmers (n = 7), and male and female speed skaters (n = 6, n = 6) over the course of two seasons of training and competition. Training sessions were monitored to document the workload carried out by each athlete. The midseason serum ferritin team values for the first and second years (mean +/- SEM) were as follows: synchro 48 +/- 10 micrograms.1 L, 24 +/- 6 micrograms.1 L; female speed skaters 57 +/- 14 micrograms.1 L, 51 +/- 7 micrograms.1 L; male speed skaters 94 +/- 27 micrograms.1 L, 72 +/- 19 micrograms.1 L; and male swimmers 66 +/- 13 micrograms.1 L, 56 +/- 7 micrograms.1 L. A significant decrease was seen in both serum ferritin and hemoglobin for the synchronized swimmers and in serum ferritin for the male speed skaters (p less than 0.05). These results suggest that a tendency exists for a decrease in serum ferritin levels from season to season.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Humoral factors and nonspecific immune suppression in Syrian hamsters infected with Leishmania donovani.

Leishmania donovani produces progressive wasting and ultimately fatal visceral leishmaniasis in Syrian hamsters and provides an excellent model of progressive disease in humans. Experimentally infected hamsters were used to investigate the development of nonspecific immune suppression during visceral leishmaniasis and its association with humoral factors and wasting. At 2 wk all infected hamsters had developed antibody against a 59-kDa parasite antigen not recognized by sera of control hamsters. By 4 wk, strong antibody responses were noted against antigens of 26, 35, 46, 69, 107, and 120 kDa. No additional antigen was recognized at 6 or 8 wk or in hamsters treated with high doses of a pentavalent antimonial (stibogluconate sodium, 100 mg/kg/day for 5 days). Weight loss was first noted in infected hamsters at 8 wk. No difference in splenic lymphocyte proliferation in response to concanavalin A (Con A) was noted at 2 wk, but by 6 wk infected animals had only 20% of the Con A response of controls, and by 8 wk only 13%. Furthermore, incubation of splenic lymphocytes from uninfected control animals with 5% fetal calf serum and 5% serum from infected hamsters obtained at 4, 6, or 8 wk suppressed Con A responses by 50%, 99%, and 100%, respectively. Spleen cells from drug-treated animals exhibited no suppression of Con A responses when incubated with 5% autologous serum, but there was profound suppression when they were incubated with 5% autologous serum obtained during the acute phase of infection. Humoral factors, but not wasting, contributed to the suppression of lymphocyte responses.

Animals↗

The relationship between beliefs about nutrition and dietary practices of the elderly.

Data were collected from home interviews of 424 noninstitutionalized individuals, 58 to 100 years old, in the Houston metropolitan area, to assess the relationships between dietary intake, socioeconomic variables, beliefs about nutrition, and use of nutritional supplements. Two-thirds of the subjects took nutritional supplements. The most common forms were vitamin C, calcium, and multivitamins. With the exception of vitamin B-6, magnesium, and dietary fiber, which were higher in diets of users of nutritional supplements than in diets of nonusers, nutrient density (amount of nutrient per 1,000 kcal) did not differ between the two groups. Attitudes toward the use of nutritional supplements, health foods, and/or nutritional quality of conventional foods differed with sex, age, income, and educational level. Nutrient intake of those with more positive feelings about nutritional supplements was higher, perhaps as a result of increased awareness of diet and health. Nutrition education that is targeted to issues of interest to people in this age group is needed; topics such as the role of nutrients in disease prevention and appropriate nutritional supplementation might be explored. This survey indicates that, although the practice of supplementation may be beneficial to augment nutritional quality of the diet for elderly people, use of nutritional supplements is not restricted to those whose dietary intake is of lower nutrient density than that of nonusers.

Age Factors↗

Measurement and characterization of postischemic free radical generation in the isolated perfused heart.

Electron paramagnetic resonance spectroscopy has been applied to measure radical generation in the postischemic heart; however, there is controversy regarding the methods used and the conclusion as to whether radicals are generated. In order to resolve this controversy, direct and spin trapping measurements of the time course and mechanisms of radical generation were performed in isolated perfused rabbit hearts. In reperfused tissue, 3 prominent radical signals are observed: A, isotropic g = 2.004 suggestive of a semiquinone; B, anisotropic g parallel = 2.033 and g perpendicular = 2.005 suggestive of ROO.; and C, a triplet g = 2.000 and aN = 24 G suggestive of a nitrogen centered radical. B and C, however, are highly labile and disappear at temperatures probably encountered in some previous studies. In normally perfused hearts, A is observed with only small amounts of B and C. During ischemia, B and C increase reaching a maximum after 45 min while A decreases. On reflow with oxygenated perfusate all 3 signals increase. With varying duration of ischemia and reflow, peak signal intensities occurred after 15 s of reflow following 30 min of ischemia. Reperfusion with superoxide dismutase, deferoxamine, or mannitol abolished the reperfusion increase of B. Measurements performed with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrated a similar time course of radical generation with prominent DMPO-OH and DMPO-R signals peaking between 10 and 20 s of reflow. Superoxide dismutase and deferoxamine also quenched these signals. Thus, .O2- derived .OH, R., and ROO. radicals are generated in postischemic myocardium. While the experimental techniques used can result in loss of intrinsic radicals and generation of extraneous radicals, with proper care and controls valid measurements of free radicals in biological tissues can be performed.

Animals↗

Isolation and characterization of two new drosophila protein kinase C genes, including one specifically expressed in photoreceptor cells.

We have isolated and characterized two new protein kinase C (PKC) genes from D. melanogaster. One, dPKC98F, maps to chromosome region 98F and displays over 60% amino acid sequence identity with members of a recently described "PKC-related" subfamily in mammals. The other, dPKC53E(ey), maps to region 53E4-7 on the second chromosome and lies within 50 kb of PKC gene previously characterized (dPKC). While dPKC98F transcripts are expressed throughout development, expression of the two genes mapping at cytogenetic location 53E is primarily in adults. dPKC98F and the previously reported 53E gene are transcribed predominantly in brain tissue. In contrast, dPKC53E(ey) is transcribed only in photoreceptor cells. We will discuss the significance of this tissue-specific localization with regard to phototransduction.

Amino Acid Sequence↗

Transfer RNA structure and coding specificity. I. Evidence that a D-arm mutation reduces tRNA dissociation from the ribosome.

The mutation G to A24 in the D-arm of Escherichia coli tRNA(Trp) or its UAG suppressor derivative Su7 has two known phenotypes: (1) an altered or relaxed coding specificity at the codon third position; and (2) partial rescue of an anticodon loop mutation. In order to study the mechanism responsible for these effects we constructed, by in vitro mutagenesis, a series of tRNAs with alterations in the anticodon loop or at the third position of the anticodon. Evaluation of the effects of the A24 mutation on the in vivo ribosomal activity of these tRNAs leads us to conclude that the mutation reduces the rate at which the ribosome is able to reject tRNAs that are structurally defective or non-cognate. The apparent interaction of the D-arm mutation with the anticodon and anticodon loop is thus primarily kinetic, rather than through the structure of the tRNA. The Appendix describes the calculation of tRNA ribosomal activity from in vivo measurement of suppression efficiency.

Codon↗

Transfer RNA structure and coding specificity. II. A D-arm tertiary interaction that restricts coding range.

We investigated the structural basis of the kinetic effect on coding specificity by the D-arm mutant (G24 to A) of Escherichia coli tRNATrp. A set of tRNA genes with structural alterations in the D-arm was constructed by site-directed mutagenesis in vitro, and we determined the in vivo translational activities of these tRNAs. Our results suggest that a hydrogen-bond donor in the major groove of the D-helix at position 24 is required for the expansion of tRNA wobble coding specificity. From inspection of tRNA crystal structure, we identified a potential new tertiary pairing of base 24 with the base at position 9 (this base links the acceptor and D-stems). We constructed tRNAs with mutations at position 9 and showed that the phenotypes of position 11-24 D-arm mutants are indeed dependent on the identity of base 9. Our analysis of the effects of these mutations on the interactions of tRNA with the ribosome and with aminoacyl-tRNA synthetase suggests that the conformation or conformational dynamics of the middle of the tRNA molecule alters the kinetics of the interaction with the ribosomal coding site. The 9-23 and putative 9-24 tertiaries, and perhaps other normal tertiary interactions in this region, modulate these kinetics to increase or decrease coding specificity.

Amino Acyl-tRNA Synthetases↗

Reaction of bovine-liver copper-zinc superoxide dismutase with hydrogen peroxide. Evidence for reaction with H2O2 and HO2- leading to loss of copper.

The reaction of hydrogen peroxide with the copper-zinc bovine-liver superoxide dismutase at low molar ratios (0.2-20.0) of H2O2/active site between pH 7.3-10.0 leads to the loss of native enzyme as a distinct form monitored by electrophoresis. The pH dependence of the loss of native enzyme between 7.3 and 9.0 indicates the involvement of a conjugate base on the enzyme of pKa of 8.7 +/- 0.1. The rate of loss of the native enzyme is first order with respect to the concentration of both enzyme and hydrogen peroxide between pH 7.3 and 9.0 with no evidence for binding of peroxide. A second-order rate constant of 3.0 +/- 1.0 M-1 s-1 is obtained from these data. At pH 10.0 the reaction is first order with respect to enzyme concentration but saturable in H2O2. All data are consistent with the interpretation that H2O2 reacts with the enzyme at the lower pH where the reaction is dependent upon the conjugate base of a functional group on the enzyme. At the higher pH, the data are consistent with the reaction of HO2- and H2O2 with the dismutase. The dissociation constant for HO2- calculated from the kinetic data at pH 10.0 is between 25-50 microM and the rate constant for the breakdown of the HO2- dismutase complex is 1.10 + 0.05 x 10(-2) s-1. The change in the electrophoretic pattern at all pH values is accompanied by the loss of the ability of the enzyme to bind copper. Weakly bound or free copper can be detected using bathocuproine disulfonate. Furthermore copper-defficient forms of the enzyme can be detected by staining gels of the peroxide-treated dismutase with diethyldithiocarbamate.

Animals↗

Congenital cystic hygroma of the neck diagnosed prenatally: outcome with normal and abnormal karyotype.

Twenty-two cases of cystic hygromas were diagnosed prenatally at Eastern Virginia Medical School and followed through the neonatal period. Our series was combined with 131 cases which have been described in the literature. Karyotypes were obtained in 110 fetuses and 80 (72.7 per cent) were abnormal. Fifty-one were not terminated: 30 with abnormal and 21 with normal karyotypes. There were no neonatal survivors in the group with abnormal karyotypes. There were five survivors in the 21 with normal karyotypes but only 2/21 without severe medical complications. Combining our series with those previously reported in the literature would suggest only a 2-3 per cent rate of intact survivors when fetal cystic hygromas are diagnosed in utero. This information should be helpful when counselling patients whose pregnancies carry this diagnosis.

Amniotic Fluid↗