Biomedical subjects

H Davis

Publications and source records attributed to H Davis.

At least 19 recordsLinked to original sources

PubMed1997

Relationships between children's cardiovascular stress responses and resting cardiovascular functioning 1 year later.

Resting cardiovascular parameters were predicted from anthropometric data, resting baseline cardiovascular data, and cardiovascular responses to three laboratory stressors completed 1 year earlier. Subjects were 106 male and female children (72 Whites, 34 Blacks) aged 6-7 years at the initial evaluation. During initial testing, blood pressure, heart rate, cardiac output, and total peripheral resistance were assessed at rest and also during a forehead cold pressor task, postural change, and treadmill exercise. The same cardiovascular parameters were then assessed at rest 1 year later. After controlling for significant anthropometric measures and the pertinent previous year's resting data, systolic and diastolic responses to the cold pressor were predictive of respective follow-up resting levels. Postural change heart rate responses were predictive of follow-up resting heart rate after controlling for initial resting levels. Exercise cardiac index reactivity predicted follow-up cardiac index after controlling for earlier resting levels and adiposity. Follow-up total peripheral resistance index was predicted by earlier resting levels.

Blood Pressure↗

PubMed1997

Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice.

Obesity occurs whenever energy intake exceeds energy expenditure. The ob gene product leptin is a potent anorectic agent when administered to ob/ob mice, but its effects on energy expenditure have not been investigated in detail. The present study was designed to analyze the acute metabolic effects of leptin in vivo. Analysis of oxygen consumption in ob/ob mice demonstrated a reduction in energy expenditure compared with lean controls; this reduction showed a diurnal fluctuation and was most evident during the light cycle. A single intraperitoneal dose of leptin increased oxygen consumption during the light cycle in ob/ob mice, ablating the circadian fluctuation in this parameter. In addition, leptin had a profound effect on fuel selection: the respiratory quotient was markedly reduced, indicating a reduction in carbohydrate oxidation and an increase in fat oxidation. These acute effects of leptin on metabolic parameters are consistent with the selective loss of body fat observed on chronic leptin treatment and suggest that increased energy utilization plays an important role in the anti-obese actions of leptin.

Analysis of Variance↗

PubMed1997

National trends in the mortality of children with sickle cell disease, 1968 through 1992.

OBJECTIVES: This paper describes national trends in mortality of children with sickle cell disease and the settings in which death occurred. METHODS: United States death certificate data from 1968 through 1992 were used to calculate mortality rates of Black children with sickle cell disease 1 to 14 years old. Deaths from trauma, congenital anomalies, and perinatal conditions were excluded. RESULTS: Between 1968 and 1992, mortality rates of Black children with sickle cell disease decreased 41% for 1- to 4-year-olds, 47% for 5- to 9-year-olds, and 53% for 10- to 14-year-olds. During 1986 through 1992, children who died before hospital admission accounted for 41% of deaths among 1- to 4-year-olds, 27% among 5- to 9-year-olds, and 12% among 10- to 14-year-olds. CONCLUSIONS: Survival of Black children with sickle cell disease has improved markedly since 1968. A substantial proportion of deaths continue to occur prior to hospital admission. Trends in sickle cell mortality can be monitored inexpensively with death-certificate data.

Adolescent↗

PubMed1997

Validation of the MCMI-III PTSD scale among combat veterans.

The new MCMI-III Posttraumatic Stress Disorder (PTSD) scale was validated on 104 combat veterans who were divided into two groups, PTSD Treatment Group and Non-PTSD Treatment Group. PTSD status was carefully determined by clinical interview and therapists' reports. The Combat Exposure Scale, the Mississippi Scale for Combat-related PTSD, and the Impact of Events Scale were also given. Analysis showed that the MCMI-III PTSD scale had a low internal consistency, but that it significantly differentiated the two groups and significantly correlated to those on other PTSD self-report scales. This scale appeared to be influenced by an acquiescent response style. Further validation studies are needed.

Adult↗

PubMed1997

Effects of benzothiophene on male rats following short-term oral exposure.

The systemic toxicity of benzothiophene, a sulfur-containing heterocyclic present in petroleum, coal, and their derived products, was studied in male rats following short-term oral exposure. Male Sprague-Dawley rats (130 +/- 20 g) (n = 5 per dose group) were treated with benzothiophene by gavage at dosages of 0, 2, 20 or 200 mg/kg/d for 21 d. In another study, male rats were treated with 0, 100, or 500 ppm benzothiophene via the diet for 28 d. In the gavage study, the 200 mg/kg/d rats showed depressed weight gain, increased relative liver and kidney weights, decreased relative thymus weights, and elevated levels of serum gamma-glutamyltransferase (gamma-GT), hepatic aniline hydroxylase (AH), aminopyrine N-demethylase (APDM), pentoxyresorufin O-dealkylase (PROD), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities. A 4.5-fold increase in urine volume on d 14-21 and a transient, 4-fold increase in urinary ascorbic acid on d 1 were also detected. No treatment related changes in urinary N-acetylglucosaminidase (NAGA) activity were observed. Benzothiophene residues were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg rats, but a small quantity was detected in the urine. In the diet study, animals fed the 500 ppm diet had increased absolute and relative liver weights, elevated AH, APDM, and GST activities, decreased red blood cell count, and minor increases in serum urea nitrogen and glucose. In summary, benzothiophene produced adverse effects in male rats that included increased relative liver and kidney weights and increased urine output. Benzothiophene also caused increases in hepatic drug metabolizing enzyme activities of a phenobarbital type and a transient elevation in urinary ascorbic acid.

Administration, Oral↗

PubMed1996

Anthropometric, demographic, and cardiovascular predictors of left ventricular mass in young children.

Left ventricular (LV) mass is a strong independent predictor of cardiovascular morbidity and mortality. Few longitudinal studies have examined predictors of LV mass in children. This study assessed the contributions of anthropometric, demographic, and cardiovascular parameters (at rest and after exposure to laboratory stressors) as predictors of LV mass 3.6 years after the initial examination in a sample of 68 Caucasian and African-American children 7.9 +/- 0.7 years old. At the initial examination, all subjects had standard anthropometrics measured and hemodynamics assessed at rest and during 3 stressors: postural change, forehead cold stimulation, and treadmill exercise. On the follow-up examination 3 to 4 years later, echocardiographic evaluations were conducted to estimate LV mass and related LV geometry. LV mass and LV internal diameter in diastole were adjusted for linear growth (LV mass/height2.7 and LV internal dimension during diastole/height0.80, respectively). Hierarchical stepwise multiple regression analyses were conducted using parameters significant in univariate comparisons (p < 0.05). Initial weight (R2 = 0.38), height (R2 = 0.42), and cardiac output reactivity to standing and treadmill exercise (final model R2 = 0.55) were significant predictors of LV mass, whereas LV mass/height2.7 was predicted by initial adiposity (R2 = 0.07) and cardiac output and systolic pressure reactivity to postural change (final model R2 = 0.25). Follow-up relative wall thickness was significantly predicted by ethnicity (African-Americans greater than Caucasians, R2 = 0.15), adiposity (R2 = 0.20), and systolic pressure reactivity to postural change (final model R2 = 0.28). These findings suggest the potential benefit of weight control in childhood as a primary prevention for later onset of cardiovascular disease.

Anthropometry↗

PubMed1996

Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.

We present here the complete primary structure of human gp330, the human variant of the principal kidney autoantigen causing Heymann membranous glomerulonephritis in rats. The deduced 4655 amino acid residues give a calculated molecular mass of 519636 Da for the mature protein and consists of a probable 25-amino-acid N-terminal signal peptide sequence, an extracellular region of 4398 amino acids, a single transmembrane-spanning domain of 23 amino acids, and an intracellular C-terminal region of 209 amino acid residues. Three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) superfamily are present in human gp330. In the extracellular region, there are a total of 36 LDLR ligand-binding repeats, comprising four distinct domains, 16 growth factor repeats separated by eight YWTD spacer regions, and one epidermal growth factor-like repeat. No consensus cleavage sequence for the processing endoprotease furin is detected in human gp330. The intracellular tail contains not only two copies of the F(X)NPXY coated-pit mediated internalization signal characteristic of LDLR superfamily members, but also intriguing and potentially functional motifs including several Src-homology 3 recognition motifs, one Src-homology 2 recognition motif for the p85 regulatory subunit of phosphatidylinositol 3-kinase, and additional sites for protein kinase C, casein kinase II and cAMP-/cGMP-dependent protein kinase. There is approximately 77% amino acid identity between human and rat gp330 with minor differences between the extracellular and intracellular regions. Recently gp330 has been implicated in Ca2+ regulation in the parathyroid, the placenta, and the renal tubule, but its overall physiological and pathological role still remains uncertain.

Amino Acid Sequence↗

PubMed1996

Systemic toxicity of a bitumen upgrading product in the rat following subchronic dermal exposure.

The subchronic toxicity following dermal exposure to a synthetic fuel, heavy gas oil No. 2 fraction of bitumen upgrading product (B-HGO II) was studied in the rat. B-HGO II was applied on the dorsal skin of rats at doses of 8, 20, 50 and 125 mg/kg bw/day daily for 13 weeks. Control animals received normal saline and positive controls received a medium-boiling coal liquefaction product (CLP) at 125 mg/kg bw/day. Both male and female rats in the treatment groups had reduced body weight gain, and males in the highest dose group were terminated in the 5th week due to overt toxicity. Increased liver weight relative to body weight was observed in males and females starting at 8 mg/kg. Increased relative heart and spleen weights were observed in males and females starting at the two intermediate doses (20, 50 mg/kg). Increased relative kidney weight was detected in males at 50 mg/kg and females at 125 mg/kg. Increased serum cholesterol was observed in both sexes starting at 50 mg/kg while elevated serum glucose was present in females starting at 8 mg/kg. Significant changes in AH, APDM and EROD activities were observed in treated rats of both sexes. Reduced red blood cell counts were detected in males starting at 8 mg/kg and females at 20 mg/kg. Microscopic examination of blood smears, spleen and hemosiderin accumulation patterns, as well as analysis of FEP and serum TIBC levels indicated that the cause of anemia was primarily intravascular hemolysis and secondarily iron deficiency. Marked thymic atrophy and thyroid abnormalities were the most prominent histological changes followed by changes in bone marrow (myelofibrosis) and liver. Both B-HGO II and CLP (positive control) caused kidney changes characterized by cytoplasmic inclusions and lesions in the tubular cells, which were observed in 50 mg/kg males but not in the females. B-HGO II was considered to be toxic at a subchronic dermal exposure level as low as 8 mg/kg/day.

Aminopyrine N-Demethylase↗

PubMed1996

Inhibitors of acyl CoA:cholesterol acyltransferase.

Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in an in vitro rat hepatic microsomal ACAT assay, ED50 = 0.72 mg/kg/day in cholesterol-fed hamster.

Animals↗

PubMed1996

DNA-based immunization against the envelope proteins of the hepatitis B virus.

Intramuscular injection in mice of DNA expression vectors encoding the envelope proteins of the hepatitis B virus induced humoral responses specific to several antigenic determinants of the viral envelope. The use of different promoter elements in the plasmid vectors influenced the kinetics and specificity of antibodies produced to the envelope proteins. The first antibodies appeared within 1-2 weeks after injection of DNA and included antibodies of the IgM isotype. Over the following weeks, an IgM-to-IgG class switch occurred, indicating helper T-lymphocyte activity. Peak IgG titers were reached by 4 weeks after a single DNA injection and were maintained for at least 6 months without further DNA injections. The antibodies to the envelope proteins reacted with both group- and subtype-specific antigenic determinants of the HBV surface antigen (HBsAg). The nature of the immune response to the envelope proteins provides indirect evidence that the proteins have adopted a native conformation and have probably been assembled into particles after intramuscular expression from the plasmid vectors. These results indicate that it may be possible to rationally design DNA expression vectors to induce a particular type of immune response for vaccination against hepatitis B or other pathogens.

Animals↗

PubMed1996

Underestimating the rat's intelligence.

Although rats are a much maligned species, it appears that their intelligence has been underestimated. This paper surveys evidence of cognition in rats from traditional categories (e.g. temporal and numerical competence) as well as from less ordinary test situations (e.g. transitive inference; recognition of individual humans). Although rats may not approach cognitive tasks using strategies observed in human subjects, they are frequently successful on their own terms. Indeed, rats are adept at exploiting procedural loopholes and confounded variables overlooked by human test designers. While not lending itself to the conventional classification of intelligence, this form of 'intellectual optimal foraging' may be an apt general description of the rat's cognitive prowess.

Animals↗

PubMed1996

An improved training procedure as a precursor to testing young children with the Frisby Stereotest.

We describe a modified version of the Frisby Stereopsis Screening Test which enables a light to be flashed behind the stereo target when the child being tested makes an appropriate pointing or reaching response. The light can be flashed to gain the interest of the child during a training phase in which they are familiarised with the test and its requirements. This phase is then followed by a test phase in which the child is encouraged to demonstrate unaided clear pointing responses to the target to gain a light flash while the plate is held in two or three different positions. This device has proved effective in increasing the chances of administering the test successfully to a sample of 30 very young children (age range 7-23 months).

Depth Perception↗

PubMed1996

Data-gathering tools for "real world" clinical settings: a multisite feasibility study.

OBJECTIVE: To determine the mental health needs and optimal treatments for children and families in "real world" settings, data-gathering strategies are needed that can be easily implemented across a variety of clinical settings. To address this need, the authors developed and piloted a "clinician-friendly" questionnaire that includes demographic, psychosocial, medical, and family history variables, such as those routinely gathered in standard clinical evaluations. METHOD: Optical scanning technology was used to encode data from more than 1,900 children, including 1,458 consecutive referrals in four military child psychiatry clinics, 285 consecutive admissions to a civilian psychiatric state hospital, 71 pediatric patients, and a community sample of 113 children. RESULTS: Despite geographic and logistic obstacles, clinical data were reliably obtained across multiple settings. Data analyses revealed meaningful differences across samples in subjects' presenting complaints, and a range of psychosocial, demographic, and background variables. Data were characterized by an apparently high degree of accuracy and completeness. CONCLUSIONS: Findings illustrate the importance and feasibility of standardized data-gathering approaches in routine clinical settings and clarify the hazards as well as the opportunities afforded by these research approaches. Such data-gathering tools appear to have significant merit and deserve further implementation and testing across a range of clinical and research settings.

Adolescent↗

PubMed1996

Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor.

SCH 51866 is a potent and selective PDE1 and PDE5 inhibitor. The antiplatelet, antiproliferative, and hemodynamic effects of SCH 51866 were compared with those of E4021, a highly selective PDE5 inhibitor. SCH 51866 inhibited PDE1 and PDE5 isozymes with a 50% inhibitory concentration (IC50) of 70 and 60 nM, respectively. SCH 51866 and E4021 inhibited washed human platelet aggregation induced by collagen with an IC50 of 10 and 4 microM, respectively, and attenuated (p < 0.05) the adhesion of 111indium-labeled platelets to the nylon filament-injured rat aorta. The doses of SCH 51866 and E4021 that inhibited platelet adhesion caused significant increases in platelet cyclic guanosine monophosphate (cGMP; p < 0.05). SCH 51866 (1-10 mg/kg, p.o. twice daily) but not E4021 (3-30 mg/kg, p.o twice daily) inhibited neointima formation in the carotid arteries of spontaneously hypertensive rats (SHRs) subjected to balloon angioplasty. Moreover, SCH 51866 (0.3-10 mg/kg, p.o.) elicited dose-dependent reduction in blood pressure in SHRs, whereas E4021 (3-30 mg/kg, p.o.) did not affect blood pressure in SHRs. In conclusion, the data suggest that inhibition of PDE1 and PDE5 isozymes by SCH 51866 exerts antiplatelet and vascular protective effects. In comparison, inhibition of PDE5 alone by E4021 exhibited antiplatelet effects without affecting neointima formation.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1996

Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.

AIDS-Related Opportunistic Infections↗

PubMed1996

Effects of wortmannin analogs on bone in vitro and in vivo.

The possible importance of phosphatidylinositol (PI) 3-kinase activity in bone resorption activity in vitro and in vivo were evaluated with synthetic wortmannin analogs in two in vitro bone resorption assays, two in vitro assays for PI 3-kinase activity and for the first time, in two in vivo rat models. Wortmannin and LY301497 were shown to be potent, dose-dependent inhibitors of the bone resorption activity of differentiating chicken osteoclast-like cells and isolated rat osteoclasts. A similar structure/activity profile and potency relationship was observed for the inhibition of osteoclastic activity and of bovine PI 3-kinase activity with purified enzyme, as well as direct inhibition of the PI 3-kinase activity of chicken osteoclast lysates. These in vitro data identified LY301497 as an inhibitor of bone resorption that is 10-fold more potent than wortmannin itself, and the most potent inhibitor of PI 3-kinase activity identified thus far. Wortmannin and analogs also lowered the osteoclast-dependent serum calcium levels like salmon calcitonin in a rat model of secondary hyperparathyroidism. More directly, oral administration of wortmannin analogs prevented the estrogen deficiency-induced loss of trabecular bone in the metaphysis of proximal tibiae from ovariectomized rats. Wortmannin, and especially LY301497, compared favorably in potency in vivo to orally administered estrogen. Taken together, these data are strong evidence to show that wortmannin analogs directly block osteoclastic activity in vitro and in vivo, and confirm that PI 3-kinase activity is a necessary step in the regulation of bone resorption. PI 3-kinase activity appears to be an important component of ovariectomy-stimulated bone loss in rats. This mechanism is supported by the finding that wortmannin had little effect on the activity of myosin light chain kinase in intact osteoclasts. The use of LY301497 should prove useful in elucidating specific molecular interactions important in bone resorption and other PI 3-kinase-mediated cell processes. These data also suggest the possible therapeutic utility of wortmannin analogs to treat conditions characterized by excessive bone loss, such as hyperparathyroidism or hypercalcemia of malignency.

Androstadienes↗

PubMed1996

Young children's cardiovascular stress responses predict resting cardiovascular functioning 2 1/2 years later.

BACKGROUND: Since the pathogenesis of coronary heart disease (CHD) has its origins in childhood, researchers have increasingly evaluated CHD risk factors in youth. In this study we examined the hypothesized behavioral risk factor of cardiovascular responsivity as a predictor of very young children's resting cardiovascular functioning 2 1/2 years later. SUBJECTS AND METHODS: During an initial visit to the laboratory, 97 children (30 blacks and 67 whites, 45 boys and 52 girls) aged 6-7 years completed three laboratory stressor tests (forehead cold pressor, postural change, and treadmill exercise). A comprehensive cardiovascular assessment was conducted during the tests. Resting cardiovascular activity (baseline values) was also assessed. Follow-up resting cardiovascular parameters were measured in the laboratory 2 1/2 years later. RESULTS: Cardiovascular stress responses were predictive of cardiovascular follow-up resting levels 2 1/2 years later. Multiple regression was used to evaluate the independent predictive power of stress responses after controlling for traditional risk factors. Follow-up resting systolic blood pressure (SBP) was predicted by the SBP response to postural change and treadmill exercise. Follow-up resting diastolic blood pressure (DBP) was predicted by the DBP response during treadmill exercise, particularly for blacks. The follow-up resting heart rate was predicted by the heart rate response to the forehead cold pressor and treadmill exercise. CONCLUSION: These results show that in very young children, stress responses are predictive of resting cardiovascular functioning 2 1/2 years later. Further developmental and longitudinal investigations will determine whether such responses are predictive of later preclinical manifestations of cardiovascular disease. If so, incorporation of stress testing in a standardized risk identification protocol might aid the design and practice of cardiovascular preventive medicine.

Analysis of Variance↗

PubMed1996

Widespread HIV counseling and testing linked to a community-based tuberculosis control program in a high-risk population.

The aim of the work reported here was to evaluate community-wide screening for HIV infection that was linked to a tuberculosis control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cité Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and tuberculosis. All of the screened subjects were offered post-test HIV counseling. Those with active tuberculosis received treatment, while those with latent tuberculosis and HIV infection were offered an opportunity to participate in a trial of antituberculosis chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cité Soleil. HIV infection was detected in 1,629 (15.4%) and active tuberculosis in 242 (2.3%). Latent M. tuberculosis infection was found in 4,800 (67.5%) of 7,309 community residents who completed tuberculosis screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection found in this screened population, as compared to other groups undergoing HIV screening in the same community, suggests that people at high risk for HIV infection selectively sought or accepted tuberculosis clinic screening. Also, many people with active tuberculosis were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, the results indicate that community-based screening for HIV infection within a tuberculosis control program can result in effective targeting of screening for both infections.

Adolescent↗