Search PubMed⌕ Search

Biomedical subjects

D E Smith

Publications and source records attributed to D E Smith.

At least 91 records · Page 5Linked to original sources
PubMed1998

Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults.

This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated.

Adolescent↗
PubMed1998

Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging.

Caloric restriction (CR) initiated in young rodents has been thoroughly documented to enhance longevity, but its efficacy when introduced at older ages has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1 hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented with corn oil and sweetened condensed milk (S). The C control rats were fed ad libitum, R rats were restricted to 32% of the caloric intake of the controls, and S rats were allowed to consume not more than 8% more calories than C rats. After 6 weeks, the average weights were significantly different between all diet and age groups. Although calorie manipulation altered body weight, no significant effect of the dietary intervention on longevity was found. The average lesion burden, including tumor burden and prevalence of nearly all commonly occurring lesions, were comparable between the groups. Thus, the manipulation of weight at ages beyond middle age has a much less profound impact than similar interventions during growth and maturation in rats.

Adrenal Gland Neoplasms↗
PubMed1998

Tubular localization and tissue distribution of peptide transporters in rat kidney.

PURPOSE: To define the tubular localization and tissue distribution of PEPT1 (low-affinity, high-capacity transporter) and PEPT2 (high-affinity, low-capacity transporter) in rat kidney. METHODS: mRNA expression of PEPT1 and PEPT2 was assessed with reverse transcription-polymerase chain reaction (RT-PCR) methods using cDNA prepared from microdissected nephron segments in rat. Tissue localization of rat renal PEPT1 and PEPT2 mRNA was further assessed by in situ hybridization with radiolabeled probes. RESULTS: RT-PCR analysis of microdissected segments from rat nephron showed that both PEPT1 and PEPT2 are confined to a proximal tubule. While PEPT1 is specific for early regions of the proximal tubule (pars convoluta), PEPT2 is overwhelmingly but not exclusively expressed in latter regions of the proximal tubule (pars recta). All other segments along the nephron were negative for PEPT1 or PEPT2 mRNA transcripts. These finding were supported by in situ hybridization results in which PEPT1 was selectively expressed in kidney cortex and PEPT2 in the outer stripe of outer medulla. CONCLUSIONS: Contrary to current opinion, the data suggest that peptides are handles in a sequential manner in proximal regions of the nephron, first by the low-affinity, high-capacity transport system and second by the high-affinity, low-capacity transport system.

Animals↗
PubMed1998

Competitive inhibition of p-aminohippurate transport by quinapril in rabbit renal basolateral membrane vesicles.

The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 microM, a value similar to that of probenecid and eight-times lower than the K(m) value of 165 microM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter findings suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug-drug interactions may occur with other organic anions at the basolateral membrane of proximal cells.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Dietary supplementation with mushroom-derived protein-bound glucan does not enhance immune function in young and old mice.

Decline in immune response is a well-documented age-associated biological change. Protein-bound polysaccharides (PSP) are biological response modifiers and have been shown to have immunoenhancing and antitumor effects. This study was conducted to examine the effect of dietary supplementation with PSP-containing extract derived from mycelia of Coriolus versicolor on in vitro and in vivo indices of immune function of young and old mice. Young (5 mo) and old (23 mo) C57BL/6NIA mice were fed purified diets containing 0, 0.1, 0.5 or 1.0% PSP for 1 mo at which time indices of immune function were measured. PSP supplementation had no significant effect on mitogenic response to concanavalin A (Con A), phytohemagglutinin (PHA) or lipopolysaccharide (LPS), or on production of interleukin (IL)-1, IL-2, IL- 4 and prostaglandin E2 (PGE2). Of the in vivo indices of immune function tested, old mice fed 1.0% PSP had significantly higher delayed-type hypersensitivity (DTH) response than those fed 0% PSP. No significant effect of PSP was observed on the DTH response of young mice. The antibody response to sheep red blood cells was not significantly influenced by PSP in young or old mice. These results suggest that PSP-containing extract from mycelia of Coriolus versicolor might have a modest immunoenhancing effect in aged mice, but not in young mice.

Aging↗
PubMed1998

Analysis of responses to angiotensin I (3-10) and Leu3 angiotensin (3-8) in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to angiotensin (3-8) (Ang IV), leu3 angiotensin (3-8) (LeuAng IV), an Ang IV analog and angiotensin I (3-10) [Ang I (3-10)], the precursor for Ang IV, were investigated in the intact-chest cat under conditions of controlled blood flow. Intralobar injections of Ang IV, LeuAng IV, and Ang I (3-10) caused dosage-related increases in lobar arterial pressure. When responses were compared, Ang IV, LeuAng IV, and Ang I (3-10) were equipotent and were approximately 100- to 300-fold less potent than Ang II when dosages are expressed on a nanomolar basis. DuP 753, an angiotensin II type 1 (AT1 ) receptor antagonist, attenuated pulmonary vasoconstrictor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10), but did not significantly change pressor responses to serotonin, norepinephrine, or U46619. PD 123319, an angiotensin II type 2 (AT2 ) receptor antagonist, and WSU 3033, a putative angiotensin II type 4 (AT4 ) receptor antagonist, did not significantly change pressor responses to LeuAng IV, Ang IV, and its precursor, Ang I (3-10). Captopril, an angiotensin-converting enzyme (ACE) inhibitor, decreased pulmonary vasoconstrictor responses to Ang I (3-10) but did not significantly change responses to serotonin, norepinephrine, U46619, LeuAng IV, or Ang IV. These data show that LeuAng IV, Ang IV, and its precursor, Ang I (3-10), increase pulmonary vascular resistance by activating AT1 receptors, and that Ang I (3-10) is rapidly and efficiently converted by an ACE-dependent pathway into an active peptide. The present data suggest that Ang IV and LeuAng IV increase pulmonary vascular resistance by activating AT1 receptors and that activation of AT2 or AT4 are not involved in mediating or modulating responses to these peptides. These data provide support for the hypothesis that Ang I (3-10) is converted into an active peptide by ACE at or near the site of action within the pulmonary vascular bed.

Angiotensin I↗
PubMed1998

Noncompetitive inhibition of glycylsarcosine transport by quinapril in rabbit renal brush border membrane vesicles: effect on high-affinity peptide transporter.

Angiotensin converting enzyme (ACE) inhibitors are important therapeutic agents for treating patients with hypertension and cardiovascular diseases. Although most ACE inhibitors are cleared by the kidney via glomerular filtration and tubular secretion, little is known about their reabsorption potential. In particular, it is believed that while certain ACE inhibitors are transported by the intestinal peptide transporter (PepT1), these same compounds do not interact with the renal peptide transporter (PepT2). In the present study, we examined the interaction of quinapril with the high-affinity peptide transporter, PepT2. Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of [14C]glycylsarcosine (GlySar), at low substrate concentrations, was examined in the absence and presence of quinapril (and other ACE inhibitors). We found that quinapril was capable of cis-inhibiting the uptake of GlySar and in a concentration-dependent manner. While the Ki for quinapril ( approximately 1 mM) was several-fold higher than the Km for GlySar ( approximately 160 microM), the interaction was unique in that inhibition of PepT2 was of a noncompetitive type. Overall, the data suggest that quinapril is a low-affinity inhibitor of the renal peptide transporter and that it binds to a site distinct from that of the GlySar binding site.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice.

Dietary calorie restriction extends both mean and maximum life span and retards age-related diseases, including eye lens cataract in Emory mice. The beneficial effects of calorie restriction have been hypothesized to reflect enhanced tissue antioxidant capacity. As a test of this hypothesis, we reared male and female Emory mice on control (C) or 40% calorie-restricted (R) diets. We then determined activities of total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) in eye lens, liver and kidney of young (4.5 or 6 months), mature (11 or 12 months) and old (22 months) animals. Effects of diet, age and sex were evaluated by multi-factor ANOVA. Only kidney GR activities (mean +/- S.E.M.) were significantly enhanced with the R diet (R, 61 +/- 2 vs. C, 54 +/- 3 U/mg protein; P = 0.03). More frequently, we noted reduced antioxidant enzyme activity in R as compared with C animals, including reduced activities of T-SOD in lens, liver and kidney, Cu/Zn-SOD in liver and kidney, liver Mn-SOD and liver CAT (P < 0.05). Effects of age on antioxidant enzyme activity in C mice included age-dependent decreases in lens and kidney CAT and in liver Mn-SOD. There was also an age-dependent increases in liver and kidney Cu/Zn-SOD and liver GR. None of these age-dependent alterations in antioxidant enzyme function were attenuated in tissues of mice fed the R diet. Values for liver CAT were significantly lower in females than in males (P = 0.05). These results indicate that antioxidant enzyme activities in Emory mouse tissues are influenced by diet, age and sex. However, it is unlikely that increased lifespan and attenuation of cataract (and perhaps other age-dependent debilities), which are associated with the R diet in the Emory mouse, are due to enhanced antioxidant enzyme capabilities.

Age Factors↗
PubMed1997

Single polymer dynamics in an elongational flow.

The stretching of individual polymers in a spatially homogeneous velocity gradient was observed through use of fluorescently labeled DNA molecules. The probability distribution of molecular extension was determined as a function of time and strain rate. Although some molecules reached steady state, the average extension did not, even after a approximately 300-fold distortion of the underlying fluid element. At the highest strain rates, distinct conformational shapes with differing dynamics were observed. There was considerable variation in the onset of stretching, and chains with a dumbbell shape stretched more rapidly than folded ones. As the strain rate was increased, chains did not deform with the fluid element. The steady-state extension can be described by a model consisting of two beads connected by a spring representing the entropic elasticity of a worm-like chain, but the average dynamics cannot.

Bacteriophage lambda↗
PubMed1997

Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal.

PURPOSE: To determine the efficacy and tolerance of a standardized protocol of chemotherapy and low-dose radiotherapy in the treatment of anal cancer in human immunodeficiency virus (HIV)-infected patients. METHODS AND MATERIALS: Between 1987 and 1995, eight HIV-positive patients with squamous cell carcinoma of the anal canal, four of whom had acquired immunodeficiency syndrome (AIDS), received therapy at the Kaiser Permanente Medical Center. All patients were treated using a combined modality approach consisting of low-dose radiotherapy (30 Gy in 15 fractions delivered 5 days/week), and chemotherapy [1000 mg/m2 of 5-fluorouracil (5-FU) delivered on days 1-4 and 29-32 as a continuous infusion over 96 h, and 10 mg/m2 of mitomycin C delivered as a bolus injection on day 1]. Patients have been followed from 4 to 81 months (mean 41, median 38). RESULTS: All eight patients completed the therapy with minor variations to the protocol, and all have attained a clinical complete response. Four patients are alive and free of disease, and four died as a result of complications of AIDS, but remained free of anal carcinoma. There were no mortalities from the protocol and the morbidity was acceptable. Only one patient each was noted to have Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 4 hematologic and gastrointestinal acute toxicity, and no Grade 4 skin toxicity was noted. CONCLUSION: This combined therapy is effective for HIV-infected patients and appears to be tolerable with acceptable toxicities. It is best applied to patients who are HIV positive, or who have AIDS without concurrent major opportunistic infections. This approach is reasonable and affords patients a reasonably good chance at sphincter preservation by avoiding abdominoperineal resection. The optimal therapy for HIV-positive patients with advanced AIDS remains less well defined.

Adult↗
PubMed1997

Adjuvant arthritis as a model of inflammatory cachexia.

OBJECTIVE: To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis. METHODS: AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) was measured by bioassay. Weight and food intake were also measured. RESULTS: Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 +/- 8.6% (mean +/- SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 +/- 7.9%) (P < 0.03). Pair-fed animals lost one-fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNF alpha production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 production (r = 0.45, P < 0.04). CONCLUSION: AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis.

Animals↗
PubMed1997

Pharmacokinetics of pirmenol enantiomers and pharmacodynamics of pirmenol racemate in patients with premature ventricular contractions.

The pharmacokinetics and pharmacodynamics of pirmenol were investigated in 12 patients with premature ventricular contractions (PVCs) after oral administration of racemic pirmenol, 100 mg and 200 mg every 12 hours. Holter monitoring was performed and serial blood samples were collected after the seventh doses. Plasma concentrations of pirmenol enantiomer were determined using a stereospecific liquid chromatographic assay. Clearance of total (-)-pirmenol was 20% higher than that of total (+)-pirmenol, and the difference in unbound clearance was 45% between enantiomers. Total pirmenol showed a smaller difference because of stereoselective protein binding, with 25% (100-mg dose) or 27% (200-mg dose) higher fraction unbound for (+)-pirmenol than for (-)-pirmenol. Distribution volume was similar for both enantiomers. Dose-dependent clearance was observed for unbound pirmenol enantiomers, as both enantiomers showed 20% lower unbound clearance at the higher dose. Antiarrhythmic effect (% reduction in PVCs from baseline) was correlated with plasma concentrations of pirmenol using a sigmoid maximum drug effect model, and patients showed a large variability in their antiarrhythmic response to plasma concentrations of pirmenol. The median value for minimum effective plasma concentration of racemic pirmenol was 1.5 micrograms/mL.

Adult↗
PubMed1997

Laryngeal mask airway facilitated fibreoptic bronchoscopy in infants.

PURPOSE: To assess the efficacy of the laryngeal mask airway (LMA) for fibreoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in infants. METHODS: Observations were made in 19 consecutive infants undergoing FOB under general anaesthesia (GA) plus topical local anaesthesia. Anaesthesia was induced with N2O, O2, and halothane or sevoflurane except in two patients who received propofol and one who received thiopentone. Anaesthesia was maintained with oxygen and either sevoflurane, halothane, desflurane, or propofol infusion. No neuromuscular blockers were used. Size #1 or #2 LMAs were used through which a 3.5 mm fibreoptic bronchoscope was introduced. ECG, noninvasive blood pressure, pulse oximetry and, PETCO2 were measured. Intra- and post-procedural complications were recorded. RESULTS: Mean age was 6 months; mean weight was 6.6 kg. Chronic wheezing was the indication for FOB in eight patients. Minor complications occurred in five patients: difficult LMA placement in one patient required changing size from #2 to #1; two patients had laryngospasm and bronchospasm that resolved with deepened anaesthesia and nebulised bronchodilator; one patient had transient arterial O2 desaturation, responding to increased FIO2, and one patient required tracheal intubation because ventilation via LMA became inadequate. CONCLUSION: The minor complications observed were similar to other series and did not result in morbidity or mortality. We feel that GA via LMA facilitates safe FOB in infants. It affords excellent airway management, a quiet patient, and passage of a large fibreoptic bronchoscope for better imaging and suction channel required for BAL.

Anesthesia↗
PubMed1997

Steady-state pharmacokinetics of delavirdine in HIV-positive patients: effect on erythromycin breath test.

OBJECTIVE: The steady-state kinetics of delavirdine and desisopropyldelavirdine were evaluated in human immunodeficiency virus-positive patients after escalating oral doses and after repeated oral administrations at the same dose level. STUDY DESIGN: Patients (n = 8 males) were given escalating oral doses of delavirdine mesylate, in a sequential fashion, over 14 days for phases 1 (200 mg every 8 hours), 2 (300 mg every 8 hours), and 3 (400 mg every 8 hours). Control patients (n = 4 males) were given 300 mg oral doses of drug every 8 hours for all three phases. Hepatic CYP3A activity was evaluated with the erythromycin breath test (ERMBT). RESULTS: In the escalating-dose group, delavirdine displayed nonlinear kinetics as indicated by the decreasing oral clearance, maximum steady-state plasma concentration/minimum steady-state plasma concentration ratio, and log-linear terminal rate constant, as well as by increasing half-life at higher doses; the ratio of desisopropyl-delavirdine formation clearance to elimination clearance was also reduced. In the control group, the kinetics of delavirdine and desisopropyl-delavirdine were unchanged. Plasma protein binding was linear for delavirdine in the escalating-dose and control groups; on average, the fraction unbound was about 2.3% and 2.0%, respectively. Hepatic CYP3A activity was markedly reduced after short- and long-term exposure to all doses of delavirdine mesylate. Delavirdine could maximally inhibit 70% to 75% of predose ERMBT values, with an IC50 of about 0.9 mumol/L. CONCLUSION: Delavirdine is a potent and reversible inhibitor of hepatic CYP3A; it is also a substrate for this CYP450 isoform. It is likely that delavirdine will exhibit drug-drug interactions when coadministered with other CYP3A substrates.

Administration, Oral↗
PubMed1997

Pharmacokinetics and pharmacodynamics of pirmenol enantiomers in coronary artery ligated dogs.

The pharmacokinetics and pharmacodynamics of pirmenol enantiomers were investigated in coronary artery ligated mongrel dogs. Reduction in frequency of premature ventricular complexes (PVCs) was determined following intravenous administration of 5-mg/kg doses of racemic pirmenol (n = 5), (+)-pirmenol (n = 4), and (-)-pirmenol (n = 4), each given as a 5-min infusion. Electrocardiographic signals and blood samples were obtained serially over a 4-h period. Pirmenol enantiomer concentrations in plasma were determined by a stereospecific assay. Following the racemate dose, (-)-pirmenol had 47% lower clearance and 33% lower steady-state distribution volume than (+)-pirmenol. These differences could be mostly explained by stereoselective plasma protein binding, reflected in a 58% higher unbound fraction for (+)-pirmenol compared with (-)-pirmenol following racemate administration. Unbound pirmenol distribution volumes were nearly identical for both enantiomers, and unbound clearance was only 16% lower for (-)-pirmenol than (+)-pirmenol following administration of the racemate. Similar trends were observed for pirmenol enantiomers administered individually. Both pirmenol enantiomers were equally effective in arrhythmia suppression. The antiarrhythmic response of coronary artery ligated dogs to pirmenol was described by a sigmoid Emax model, and no statistically significant differences were observed in the pharmacodynamic parameters [i.e., EC50 (plasma concentration at 50% of maximum drug effect), S (constant that reflects the sigmoidal shape of the effect-concentration curve), and EC90 (plasma concentration at 90% of maximum drug effect)] for (+)-pirmenol, (-)-pirmenol, or pirmenol racemate.

Animals↗
PubMed1997

Efficient enzymatic synthesis of 13C,15N-labeled DNA for NMR studies.

The power of heteronuclear NMR spectroscopy to study macromolecules and their complexes has been amply demonstrated over the last decade. The obstacle to routinely applying these techniques to the study of DNA has been the synthesis of 13C,15N-labeled DNA. Here we present a simple and efficient method to generate isotope-labeled DNA for NMR studies that is as easy as that for isotope labeling of RNA. The method was used to synthesize a uniformly 13C,15N-labeled 32-nucleotide DNA that binds to human basic fibroblast growth factor with high affinity and specificity. Isotope-edited experiments were applied to the 13C,15N-labeled DNA bound to unlabeled protein, and the 13C,15N-labeled DNA was also examined in complex with 15N-labeled protein. The NMR experiments show that the DNA adopts a well-defined stable structure when bound to the protein, and illustrate the potential of 13C,15N-labeled DNA for structural studies of DNA-protein complexes.

Carbon Isotopes↗