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Biomedical subjects

T Harvey

Publications and source records attributed to T Harvey.

At least 19 recordsLinked to original sources
PubMed2005

Effects of ribose supplementation prior to and during intense exercise on anaerobic capacity and metabolic markers.

This study examined whether ribose supplementation before and during intense anaerobic exercise impacts anaerobic capacity and metabolic markers. Twelve moderately trained male cyclists (22.3 +/- 2.2 y; 181 +/- 6 cm, 74.8 +/- 9 kg) participated in the study. Subjects were familiarized and fasted for 8 h after standardizing nutritional intake. In a double blind and crossover manner subjects ingested either a 150 mL placebo or ribose (3 g ribose + 150 microg folate). Subjects rested for 25 min and completed 5 x 30 s anaerobic capacity tests with 3 min passive rest. Six capillary blood samples were taken prior to and after sprints for adenine nucleotide breakdown determination. The experiment was repeated 1 wk later with alternative drink. Data were analyzed by repeated measures ANOVA. No significant interactions were observed for any performance or blood variables. D-ribose supplementation has no impact on anaerobic exercise capacity and metabolic markers after high-intensity cycling exercise.

Administration, Oral↗
PubMed2004

Anal sphincter injury after forceps delivery: myth or reality? A prospective ultrasound study of 93 females.

PURPOSE: This study was designed to estimate the prevalence of anal sphincter injury after forceps delivery in a large population of females managed by trained obstetricians in a French hospital and to identify factors predictive for anal sphincter injury. METHODS: We performed a prospective study of healthy females older than 18 years with no history of anal incontinence, anorectal abnormalities, or anorectal surgery after their first vaginal delivery. All females were interviewed using a standardized questionnaire concerning intestinal transit and continence status. Physical examination and endoanal ultrasonography were performed after delivery. RESULTS: Between November 1999 and November 2000, 93 females were included in the study after their first forceps delivery. Eleven patients (11.8 percent) had a partial defect involving the external sphincter, visible on ultrasonography. One patient (1.1 percent) had a partial defect of external sphincter with complete defect of internal sphincter (sequelae of primary repair of a third-degree perineal tear). Seventeen patients (18.2 percent) had flatus incontinence, and four patients (4.3 percent) had liquid stool incontinence. A high daily number of stools was significantly associated with sphincter defect visible on ultrasonography (P=0.02). The development of anal incontinence was not related to sphincter defect on ultrasonography. There was a strong association between perineal tear and sphincter defect visible on ultrasonography (odds ratio, 4.5 (range, 1.2-16.7)). CONCLUSIONS: Anal sphincter injury after forceps delivery was identified in <13 percent of our large population of healthy females. Our study does not confirm previous observations that anal sphincter injury is common after forceps delivery; previously published studies may have overestimated the prevalence of this condition. The only factor with significant predictive value for anal sphincter injury was perineal tear. Anal endosonography should be recommended after obstetric perineal tear.

Adult↗
PubMed2001

Urinary cadmium elimination as a biomarker of exposure for evaluating a cadmium dietary exposure--biokinetics model.

The Cadmium Dietary Exposure Model (CDEM) utilizes national survey data on food cadmium concentrations and food consumption patterns to estimate dietary intakes in the U.S. population. The CDEM has been linked to a modification of the cadmium biokinetic model of Kjellström and Nordlberg (KNM) to derive predictions of kidney and urinary cadmium that reflect U.S. dietary cadmium intake and related variability. Variability in dietary cadmium intake was propagated through the KNM using a Monte Carlo approach. The model predicts a mean peak kidney cadmium burden of approximately 3.5 mg and a 5th-95th percentile range of 2.2-5.1 mg in males. The corresponding peak renal cortex cadmium concentration in males is 15 microg/g wet cortex (10-22, 5th-95th percentile). Predicted kidney cadmium levels in females were higher than males: 5.1 (3.3-7.6) mg total kidney, 29 (19-43) microg/g wet cortex. Predicted urinary cadmium in males and females agreed with empirical estimates based on the NHANES III, with females predicted and observed to excrete approximately twice the amount of cadmium in urine than males. An explanation for the higher urinary cadmium excretion in females is proposed that is consistent with the NHANES III data as well as experimental studies in humans and animals. Females may absorb a larger fraction of ingested dietary cadmium than males, and this difference may be the result of lower iron body stores in females compared to males. This would suggest that females may be at greater risk of developing cadmium toxicity than males. The predicted 5th-95th percentile values for peak kidney cadmium burden are approximately 60% of the peak kidney burden (8-11 mg) predicted for a chronic intake at the U.S. Environmental Protection Agency (EPA) chronic reference dose of 1 microg/kg-d.

Adolescent↗
PubMed2001

The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions.

The tissue kallikreins are serine proteases encoded by highly conserved multi-gene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13-26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5' or 3' untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25-44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.

Amino Acid Sequence↗
PubMed1998

Impaired activation of phosphoinositide 3-kinase by insulin in fibroblasts from patients with severe insulin resistance and pseudoacromegaly. A disorder characterized by selective postreceptor insulin resistance.

Some patients with severe insulin resistance develop pathological tissue growth reminiscent of acromegaly. Previous studies of such patients have suggested the presence of a selective postreceptor defect of insulin signaling, resulting in the impairment of metabolic but preservation of mitogenic signaling. As the activation of phosphoinositide 3-kinase (PI 3-kinase) is considered essential for insulin's metabolic signaling, we have examined insulin-stimulated PI 3-kinase activity in anti-insulin receptor substrate (IRS)-1 immunoprecipitates from cultured dermal fibroblasts obtained from pseudoacromegalic (PA) patients and controls. At a concentration of insulin (1 nM) similar to that seen in vivo in PA patients, the activation of IRS-1-associated PI 3-kinase was reduced markedly in fibroblasts from the PA patients (32+/-7% of the activity of normal controls, P < 0.01). Genetic and biochemical studies indicated that this impairment was not secondary to a defect in the structure, expression, or activation of the insulin receptor, IRS-1, or p85alpha. Insulin stimulation of mitogenesis in PA fibroblasts, as determined by thymidine incorporation, was indistinguishable from controls, as was mitogen-activated protein kinase phosphorylation, confirming the integrity of insulin's mitogenic signaling pathways in this condition. These findings support the existence of an intrinsic defect of postreceptor insulin signaling in the PA subtype of insulin resistance, which involves impairment of the activation of PI 3-kinase. The PA tissue growth seen in such patients is likely to result from severe in vivo hyperinsulinemia activating intact mitogenic signaling pathways emanating from the insulin receptor.

Acromegaly↗
PubMed1998

Correlation between the 1.6 A crystal structure and mutational analysis of keratinocyte growth factor.

A comprehensive deletion, mutational, and structural analysis of the native recombinant keratinocyte growth factor (KGF) polypeptide has resulted in the identification of the amino acids responsible for its biological activity. One of these KGF mutants (delta23KGF-R144Q) has biological activity comparable to the native protein, and its crystal structure was determined by the multiple isomorphous replacement plus anomalous scattering method (MIRAS). The structure of KGF reveals that it folds into a beta-trefoil motif similar to other members of fibroblast growth factor (FGF) family whose structures have been resolved. This fold consists of 12 anti-parallel beta-strands in which three pairs of the strands form a six-stranded beta-barrel structure and the other three pairs of beta-strands cap the barrel with hairpin triplets forming a triangular array. KGF has 10 well-defined beta strands, which form five double-stranded anti-parallel beta-sheets. A sixth poorly defined beta-strand pair is in the loop between residues 133 and 144, and is defined by only a single hydrogen bond between the two strands. The KGF mutant has 10 additional ordered amino terminus residues (24-33) compared to the other FGF structures, which are important for biological activity. Based on mutagenesis, thermal stability, and structural data we postulate that residues TRP125, THR126, and His127 predominantly confer receptor binding specificity to KGF. Additionally, residues GLN152, GLN138, and THR42 are implicated in heparin binding. The increased thermal stability of delta23KGF-R144Q can structurally be explained by the additional formation of hydrogen bonds between the GLN side chain and a main-chain carbonyl on an adjoining loop. The correlation of the structure and biochemistry of KGF provides a framework for a rational design of this potentially important human therapeutic.

Amino Acid Sequence↗
PubMed1997

Integrating communicative goals for real-time clinical decision support.

A critiquing system evaluating a physician's management plan may produce a set of individual comments that, taken together, appear repetitious or incoherent. This paper presents TraumaGEN, a system for integrating sets of possibly inter-related communicative goals into one or more coherent messages. TraumaGEN takes account of the purpose of the messages, the situation in which the messages will be received, and the social role of the system. Preliminary evaluation of TraumaGEN indicates that it produce coherent integrated messages.

Communication↗
PubMed1996

Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

Aged↗
PubMed1995

Holistic risk assessment: an emerging process for environmental decisions.

A holistic risk assessment (HRA) strategy is proposed as an alternative, inclusive paradigm which builds upon the traditional risk assessment process described by the National Academy of Sciences. This proposed process expands beyond the traditional process in that it: (i) includes parallel and integrated assessments for ecological risk and human health risks; (ii) recognizes the presence of competing risks that may arise from implementation of risk management decisions; (iii) is an iterative and nonsequential process that highlights the importance of risk characterization and the need for comparisons; (iv) has focus on presenting a series of risk choices that take into consideration parameters specific to exposed populations and ecosystems; and (v) involves communication as the first step between risk assessors and risk managers, with subsequent communication of the results of the assessment to clients and the public. This HRA strategy is illustrated by a case study on methyl mercury. Specific research is proposed for future improvements in this area.

Animals↗
PubMed1993

In vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis.

We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This result correlated with the observed therapeutic efficacies of the quinolones.

Animals↗
PubMed1992

A new approach to the management of Broviac catheter infection.

Infection continues to be a major complication of the use of indwelling venous catheters. In an attempt to avoid removal of the catheter and to minimize the systemic side-effects of antibiotics, the potential value of in-situ treatment of confirmed Broviac catheter infection was assessed in carefully selected patients attending an oncology unit. Fourteen episodes from 11 children were included in the study. A variety of organisms were encountered. Infective episodes were divided into two categories: (a) those occurring in patients with negative peripheral blood cultures and neutrophil count greater than 1.5 x 10(9) l-1 which were treated only by local instillation of heparinized antibiotic 8-hourly for 7-14 days (N = 8); (b) those occurring simultaneously with positive peripheral blood culture (or peripheral blood culture not performed) regardless of neutrophil count, or infection restricted to Broviac catheter but with a neutrophil count of less than 1.5 x 10(9) l-1; these were treated, with one exception, as above with the addition of systemic antibiotics (N = 6). Treatment was successful in 100% of infective episodes with negative cultures achieved between 5 and 12 days. Catheters remained in use a mean of 118 days following treatment of infection. This approach has obvious advantages but requires careful patient selection and monitoring. It prolongs the catheter life, obviates the need for systemic antibiotics for a local infection, and with appropriate instruction to parents and family practitioner, treatment may be administered on an outpatient basis.

Adolescent↗
PubMed1991

Conformation of sarafotoxin-6b in aqueous solution determined by NMR spectroscopy and distance geometry.

The solution structure of sarafotoxin-6b in water has been determined using high-resolution NMR spectroscopy. 127 proton-proton distance measurements and three phi dihedral angle constraints derived from NMR spectra were used to calculate the solution structure using a combination of distance geometry and restrained molecular dynamics. The major structural feature of the resulting family of five structures was a right-handed alpha-helix extending from K9 to Q17. In contrast, the C-terminal region of the peptide appears not to adopt a preferred conformation in aqueous solution. The present structure is compared with those previously determined for endothelin peptides in non-aqueous solvents.

Amino Acid Sequence↗
PubMed1985

Relation of gene expression (allotypes) of the fourth component of complement to insulin dependent diabetes and its microangiopathic complications.

About a quarter of insulin dependent diabetics have low concentrations of the fourth component of complement (C4), and a low concentration of C4 is associated with diabetic microangiopathy. The variability of the expression of the C4 gene was compared in insulin dependent diabetics with and without microangiopathy and controls. Of the two genes coding for C4, the A gene (C4A) was not expressed--that is, C4A null--in 16 (13%) of the 126 insulin dependent diabetics compared with none of the 93 controls (p less than 0.001), and all these 16 subjects had low concentrations of C4. Lack of expression of the other C4 gene (C4B) was not associated with insulin dependent diabetes, but a rare variant, C4B3, was significantly increased in the diabetics (21/126; 17%) compared with the controls (none) (p less than 0.001). The prevalence of C4B3 was also increased in the diabetics with complications when compared with those without (14/50 (28%) v 7/76 (9%), p less than 0.01). Low plasma C4 concentrations in insulin dependent diabetics are at least partly due to variation in the expression of the C4 gene. The association of the rare C4B3 variant with microangiopathy suggests a genetic component of its aetiology.

Adolescent↗
PubMed1985

On the brain of a scientist: Albert Einstein.

Neuron:glial ratios were determined in specific regions of Albert Einstein's cerebral cortex to compare with samples from 11 human male cortices. Cell counts were made on either 6- or 20-micron sections from areas 9 and 39 from each hemisphere. All sections were stained with the Klüver-Barrera stain to differentiate neurons from glia, both astrocytes and oligodendrocytes. Cell counts were made under oil immersion from the crown of the gyrus to the white matter by following a red line drawn on the coverslip. The average number of neurons and glial cells was determined per microscopic field. The results of the analysis suggest that in left area 39, the neuronal: glial ratio for the Einstein brain is significantly smaller than the mean for the control population (t = 2.62, df 9, p less than 0.05, two-tailed). Einstein's brain did not differ significantly in the neuronal:glial ratio from the controls in any of the other three areas studied.

Aged↗