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Biomedical subjects

W J Smith

Publications and source records attributed to W J Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of caloric or protein restriction on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in children and adults.

Serum concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1), -2, and -3 are influenced by dietary intake in normal adults. These studies were undertaken to determine the influence of dietary factors on these proteins in children and to compare the responses in children to those in adults. Eight adults and eight pubertal children underwent energy restriction (50% reduction intake) for 6 days and were refed a normal diet for an additional 6 days. Basal energy intakes during the prerestriction periods were 70 Cal/kg in children and 35 Cal/kg in adults. A second group of 8 adults and 6 children underwent protein restriction (decreased from 1.0 to 0.66 g/kg in both groups) for 6 days and were refed a normal diet for 6 days. Calorie restriction resulted in a significant decrease in nitrogen balance in adults and children. Likewise, IGF-I concentrations declined significantly in both adults and children. In contrast, IGFBP-1 concentrations were significantly increased in adults (from 40 +/- 6 to 62 +/- 4 ng/mL; P < 0.05), but not in children. Serum concentrations of IGFBP-2 did not change in either group in response to energy restriction. IGFBP-3 declined significantly in the children (3189 +/- 90 to 2843 +/- 96 ng/mL; P < 0.05), but not in the adults. Protein restriction also caused negative nitrogen balance in both children and adults and a decline in the mean IGF-I concentration in the adults. IGFBP-2 concentrations rose significantly in both adults (131 +/- 15 to 164 +/- 15 ng/mL; P < 0.005) and children (126 +/- 13 to 158 +/- 15 ng/mL; P < 0.05) in response to protein restriction and returned to normal during refeeding. IGFBP-3 was slightly, but significantly, reduced in response to protein restriction in adults (3518 +/- 180 to 3328 +/- 151 ng/mL; P < 0.05), but not children. The findings indicate that protein or energy restriction in children leads to changes in IGF-I or specific IGFBPs. Changes in IGFBP-2 are sensitive to protein restriction, and measurement of IGFBP-2 may be useful in monitoring the response to refeeding in children who have been ingesting suboptimal amounts of protein.

Adult↗
PubMed1994

An analysis of the causes of piglet mortality in a breeding herd kept outdoors.

The 229 piglets which died on an outdoor unit during a period of eight months were examined post mortem to determine the cause of death. The majority of the deaths (72 per cent) had occurred by the time that the litter was first inspected and of these 27 per cent had uninflated lungs and 53 per cent of the piglets born alive had no food in the stomach. Seventeen per cent of the stillborn pigs were of type I and 83 per cent were of type II. It was impossible to identify stillborn piglets reliably from their external appearance alone. At all ages, crushing was the most common cause of death (72 per cent of liveborn piglets). Six per cent of the corpses of the piglets had been damaged by birds, and attacks on live piglets occurred in the later stages of the study.

Animal Husbandry↗
PubMed1994

An estimate of the number of serine protease genes expressed in sheep blowfly larvae (Lucilia cuprina).

A large and diverse family of serine protease genes was identified in first-instar larval cDNA of the sheep blowfly (Lucilia cuprina). This complex repertoire of genes was identified via a PCR approach using highly degenerate primers based on structurally conserved regions which surround the active site His and Ser residues found in all serine proteases. PCR products from entire first-instar larval cDNA, or from third-instar larval salivary glands or cardia, generated using a microscale RT-PCR method, were cloned into a plasmid vector. Comparison of the restriction fragment patterns of PCR products generated from the three different sources suggests a highly diverse tissue-specific pattern of serine protease expression in this organism. Detailed analysis of the restriction fragment patterns of sixty-nine randomly selected clones from entire first-instar larvae revealed forty-nine different classes of PCR product. Maximum likelihood analysis of these data indicate that between 125 and 220 different serine protease genes are expressed in first-instar larvae of L. cuprina. DNA sequence analysis of ten randomly-selected clones, derived from the three tissue sources, indicated that all ten encoded serine protease gene fragments. A frequently occurring PCR product, generated from both first-instar total cDNA and third-instar cardia cDNA, showed 73% amino acid identity to a digestive protease expressed in Drosophila melanogaster larval gut cells.

Amino Acid Sequence↗
PubMed1994

Right latissimus dorsi cardiomyoplasty improves left ventricular function by increasing peak systolic elastance (Emax).

BACKGROUND: Dynamic cardiomyoplasty remains a promising but poorly understood surgical modality for selected patients with dilated cardiomyopathy. Despite encouraging clinical results, objective evidence of enhanced ventricular function using traditional indexes (cardiac output, ejection fraction, and dP/dt) has been difficult to document after cardiomyoplasty. Several investigators have suggested that cardiomyoplasty acts partly by unloading the left ventricle. These indexes all depend somewhat on loading conditions, however, and might not detect such an interaction. The time-varying elastance model provides an index of contractility, Emax, that is relatively insensitive to changes in loading conditions. We applied this model to study the effect of right latissimus dorsi cardiomyoplasty on left ventricular function in an acute canine model. METHODS AND RESULTS: Five dogs underwent acute cardiomyoplasty using untrained right latissimus dorsi muscle. Instrumentation included Millar pressure transducers in the left ventricle and aortic root, an electromagnetic flow probe around the ascending aorta, and a volume conductance catheter in the left ventricle. A cuffed nerve electrode around the thoracodorsal nerve and a right ventricular sensing lead were connected to a Medtronic Cardiomyostimulator (5 V, 30 Hz, 1:1 synchronization). Transient caval occlusions were performed with the stimulator both off and on to calculate Emax and the slope of the end-systolic pressure-volume relationship (Ees). Turning the stimulator on significantly increased peak systolic elastance (Emax) and end-systolic elastance (Ees) in all five dogs by an average of 56% and 78%, respectively (P < .05). End-diastolic volume and end-systolic volume decreased by 18% and 28%, respectively (P < .05). All other measured hemodynamic parameters, including peak left ventricular pressure, mean arterial pressure, cardiac output, stroke volume, stroke work, ejection fraction, preload-recruitable stroke work, and dP/dt, did not change significantly. CONCLUSIONS: These results show that, in this acute canine model, right latissimus dorsi cardiomyoplasty significantly improves left ventricular function while decreasing left ventricular volumes. The results are consistent with the theory that cardiomyoplasty increases contractility while unloading the ventricle by decreasing end-diastolic volume. This increase in Emax despite inconsistent changes in other indexes underlies the importance of using load-insensitive indexes of ventricular function when studying cardiomyoplasty.

Animals↗
PubMed1994

Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism.

The effect of complement activation on the pulmonary vascular system and on right ventricular function was studied in sheep (n = 12) by injection of cobra venom factor. Animals were instrumented for measurement of pulmonary flow, mean pulmonary artery pressure, right ventricular stroke work, arterial blood gases, and systemic vascular resistance. Blood was sampled from the left atrium and pulmonary artery to measure thromboxane B2, the metabolite of thromboxane A2, by radioimmunoassay. After baseline measurements, animals were randomly assigned to receive a selective thromboxane receptor antagonist SQ30741 as a 10 mg/kg bolus with an infusion of 10 mg/kg per hour or else to receive vehicle. Cobra venom factor was then injected (30 U/kg) in all animals, and data were recorded at 15, 30, 60, 90, and 120 minutes. In control animals there was a 2.4-fold increase in mean pulmonary artery pressure and a 76% increase in right ventricular stroke work at 15 minutes from baseline (p < 0.05); these values remained elevated for 30 minutes and returned to baseline by 1 hour with no change in systemic vascular resistance. Arterial oxygenation decreased by 124% at 15 minutes and remained depressed through the experiment, but in treated animals oxygen tension remained unchanged from baseline. Thromboxane B2 increased 95% from baseline in the control group and 1.5 fold in treated animals and followed a similar time course as the functional measurements (p < 0.05). A pulmonary vascular thromboxane B2 gradient of approximately 1000 pg/ml was measured at 15 and 30 minutes in both control and treated groups. (p < 0.05) We conclude that after complement activation in this model pulmonary hypertension and decreased oxygen tension are mediated by thromboxane release from the pulmonary vascular bed. This increased afterload causes a stress on the right ventricle as demonstrated by the increased right ventricular stroke work. Selective thromboxane receptor antagonism may be a beneficial therapy for pulmonary hypertension in patients after cardiopulmonary bypass.

Animals↗
PubMed1993

Prevention of CD18-mediated reperfusion injury enhances the efficacy of UW solution for 15-hr heart preservation.

University of Wisconsin solution (UW) has been demonstrated to improve donor heart preservation. During reperfusion, however, myocardial performance may still remain limited by neutrophil (PMN)-mediated injury, manifested by the "low-reflow" phenomenon and myocardial "stunning." Since PMN adhesion is an important mechanism of PMN-mediated injury, we tested whether blocking PMN adhesion molecule CD18 would enhance the efficacy of UW for 15-hr heart preservation. Rabbit hearts (n = 15) were arrested with, and preserved for 15 hr in, 4 degrees C UW. After insertion of an left ventricular (LV) balloon, hearts were heterotopically transplanted into recipients pretreated with either intravenous (i.v.) saline (vehicle, n = 8) or i.v. anti-CD18 monoclonal antibody R15.7 (anti-CD18, n = 7). After 1 hr reperfusion the slope of the peak systolic pressure-volume (P-V) relation (Emax), the exponential coefficient (beta), the volume-axis intercept (Vo) of the end-diastolic P-V relation, and the time constant of the exponential LV pressure decay after dP/dt min (tau) were measured. Blood flow was measured with microspheres from which coronary vascular resistance (CVR) was calculated. Tissue %H2O was also measured. Between groups there were no significant differences in Emax (70.5 +/- 6.1 vs 63.7 +/- 6.0 mm Hg/ml, P > 0.05), beta (3.3 +/- 0.5 vs 4.3 +/- 0.5, P > 0.05), Vo (-0.4 +/- 0.1 vs -0.4 +/- 0.2 ml, P > 0.05) or %H2O (81.3 +/- 1.1 vs 80.0 +/- 0.9, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Use of insulin-like growth factor-binding protein-2 (IGFBP-2), IGFBP-3, and IGF-I for assessing growth hormone status in short children.

Insulin-like growth factor-binding protein-2 and -3 (IGFBP-2 and -3) are members of a family of proteins that are present in extracellular fluids and bind IGF-I and -II. IGFBP-2 is regulated differently from IGF-I and IGFBP-3, because its serum concentrations are elevated in some adults with GH deficiency (GHD), whereas IGF-I and IGFBP-3 concentrations are usually decreased. The purposes of this study were to define the normal range of IGFBP-2 concentrations in children, to determine its efficacy in the diagnosis of GHD, and to compare the diagnostic value of measurements of the serum GH response to provocative testing with results of measurements of IGFBP-2, IGFBP-3, and IGF-I. Mean serum IGFBP-2 concentrations ranged from 263 +/- 101 ng/mL (mean +/- SD) during infancy to 136 +/- 38 ng/mL in normal 15- to 18-yr-olds (P < 0.001), whereas IGFBP-3 increased from 1211 +/- 384 to 2781 +/- 382 ng/mL in the same age groups. Thirty-nine of 49 children with GHD and low IGF-I values (serum GH response, < or = 1 ng/mL after 2 provocative tests) had serum IGFBP-2 concentrations that were greater than 2 SD above their corresponding age-adjusted means. In contrast all 49 of these children had IGFBP-3 values that were below normal for age. Because serum IGFBP-2 concentrations are regulated by GH directly and not through IGF-I, the IGFBP-2 to IGF-I ratio was used to determine whether it improved diagnostic accuracy. Fifty of 57 GH-deficient children had IGFBP-2/IGF-I ratios that were greater than 2 SD above the mean. This included 48 of 49 children with low IGF-I and 2 of 8 children with normal IGF-I. Fifty-three of the 57 children with GHD had decreased IGFBP-3 values. Among 23 children with idiopathic short stature (ISS) who had normal responses to GH stimulation testing (serum GH, > 10 ng/mL), 7 had low IGF-I values. Of the 7, all had an increased IGFBP-2/IGF-I ratio and a low IGFBP-3 level. Of the remaining 16 children with normal IGF-I, 13 had a normal IGFBP-2/IGF-I ratio and normal IGFBP-3 values. Three had low IGFBP-3 and an increased IGFBP-2/IGF-I ratio. In 76% of the 80 short-statured patients studied, there was concordance among serum GH responses to provocative tests, IGF-I, IGFBP-2/IGF-I ratio, and IGFBP-3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

FROGS (Far North Regional Obstetric and Gynaecological Service)--the development of a specialist outreach service.

The Peninsula and Torres Strait Health Region of Far North Queensland is a vast area with a widely scattered population. The Far North Regional Obstetric and Gynaecological Service (FROGS) is a cost-effective outreach service which provides equitable access to specialist care for remote people and aims to address many of the significant problems of women's health care in this region.

Community-Institutional Relations↗
PubMed1993

Salvage of the diabetic foot with exposed os calcis.

Fifty consecutive heel ulcers were managed in three groups by debridement, split-thickness skin graft (STSG), bypass procedures, and orthotics. Group I consisted of 24 ulcers in patients with diabetes (DM) and peripheral vascular disease (PVD), 14 patients in Group II with DM only, and 12 patients with PVD only (Group III). Healing occurred in 56.5%, 64.3%, and 83.3%, respectively. An average of 2.2 procedures were performed per patient. Follow-up periods were for a minimum of two years or until amputation. Time for complete healing and the number of amputations performed were similar in all groups. Of the diabetics (combined from Groups I and II), a subgroup of 27% required partial excision of the os calcis to facilitate closure. After saline dressing changes, STSG was accomplished over thin granulation tissue. Forty percent of this subgroup healed, 30% remained open, and 30% were amputated. Aggressive management, soft-tissue coverage, and orthotic use can lead to a functional weight-bearing extremity.

Aged↗
PubMed1992

Effects of morphine on the phenotypic expression of cell surface markers on murine lymphocytes.

There is a growing literature indicating that opioid abuse by human addicts and opioid administration to animals have profound effects on the immune system. In the present study, implantation of morphine pellets in mice was associated with reduced phenotypic expression of the cell surface antigens specific to T-lymphocytes and to helper and cytotoxic/suppressor T-lymphocyte subtypes. The effect of morphine, as measured by flow cytometry using monoclonal antibodies specific for antigens expressed by these cells, was dose-dependent. The decrease in expression of antigens was apparent as early as 24 h after morphine pellet implantation and continued for 3 days. In addition, a time-dependent increase in the expression of these antigens was observed in placebo- and morphine-treated mice, suggesting that the pellets had a small antigenic effect. However, at all times studied, morphine-treated mice had fewer cells expressing the antigens than placebo-treated mice. Our results provide additional evidence that the use of opioids by IV drug abusers compromises their immune function.

Animals↗
PubMed1992

Arteriosclerosis obliterans in a rabbit model.

RATIONALE AND OBJECTIVES: The authors induced atherosclerotic occlusions in a rabbit model, using and comparing different experimental methods. METHODS: Lesions were induced in 40 femoral arteries in 20 rabbits. Four combinations of lesion induction methods were used: 1) drying of the endothelium with carbon dioxide gas; 2) gas-drying of the artery plus mechanical injury; 3) gas-drying plus induced thrombosis of the treated segment using thrombin; and 4) gas-drying, mechanical injury, and induced thrombosis. All rabbits were fed a high-fat, high-cholesterol diet for 1 to 2 months after lesion induction. RESULTS: Seventeen rabbits were available for follow-up. Sixty-eight percent (13 of 19) of femoral arteries treated with thrombin-induced thrombosis demonstrated atherosclerotic occlusions, compared with 27% of those that did not receive this treatment (4 of 15; P < .01). CONCLUSIONS: Thrombin-induced thrombotic occlusion of a segment of artery which has been de-endothelialized, followed by a high-fat, high cholesterol diet, results in a higher yield of experimental occlusive atherosclerosis in rabbits than is achievable by other methods.

Animals↗
PubMed1992

Complete prevention of myocardial stunning, contracture, low-reflow, and edema after heart transplantation by blocking neutrophil adhesion molecules during reperfusion.

This study tested the hypothesis that preventing neutrophil adhesion during reperfusion, by blocking either the neutrophil membrane CD18 integrin complex or its endothelial and myocyte ligand, intercellular adhesion molecule-1 (ICAM-1), would reduce myocardial inflammation and edema and improve reflow and ventricular function after heart preservation and transplantation. After cardioplegia and insertion of a left ventricular balloon, rabbit hearts were heterotopically transplanted into recipient rabbits either immediately (immediate, n = 12) or after preservation in 4 degrees C saline (3 hours of ischemia, n = 33). Forty-five minutes before reperfusion, recipients of preserved hearts received intravenous infusions of either saline (vehicle, n = 13), anti-CD18 monoclonal antibody (Mab) R15.7 (2 mg/kg) (anti-CD18, n = 10), or anti-ICAM-1 Mab R1.1 (2 mg/kg) (anti-ICAM, n = 10). During 3 hours of reperfusion the slope of the peak-systolic pressure-volume relation and its volume-axis intercept, the exponential elastic coefficient of the end-diastolic pressure-volume relation, the unstressed ventricular volume, and the time constant of the exponential left ventricular pressure decay after dP/dtmin were serially measured. Myocardial blood flow was measured with microspheres from which coronary vascular resistance was calculated. After explanation, the degree of myocardial inflammation, estimated by tissue neutrophil sequestration (myeloperoxidase assay) and myocardial water content were determined. Within each group no significant differences in measurements made at 1, 2, and 3 hours of reperfusion were noted. Compared with the immediate transplantation group, the vehicle group demonstrated a significant increase in myeloperoxidase activity (3380 +/- 456 versus 1712 +/- 552 microU/gm, p < 0.05), coronary vascular resistance (115.5 +/- 13.4 versus 70.5 +/- 10.6 U/gm, p < 0.05), and myocardial water content (79.8% +/- 0.4% versus 75.6% +/- 1.3%, p < 0.05), a significant decrease in unstressed ventricular volume (a leftward shift in the end-diastolic pressure-volume relation) (-0.49 +/- 0.24 versus 0.28 +/- 0.21 ml, p < 0.05), and a marked prolongation in exponential left ventricular pressure delay after dP/dtmin (156.64 +/- 3.81 versus 37.25 +/- 3.34 msec, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1991

Effect of sulfur exposure on protease activity in human peripheral blood lymphocytes.

Sulfur mustard is a chemical warfare blistering agent for which neither the mechanism of action nor an antidote is known. Papirmeister et al. (1985) have postulated a biochemical hypothesis for mustard-induced cutaneous injury involving a sequelae of DNA alkylation, metabolic disruption and activation of protease. Human peripheral blood lymphocytes in cell cultures were employed as an in vitro model for alkylating agent toxicity. A chromogenic peptide substrate assay was used for detection of protease in lymphocytes treated with sulfur mustard or chloroethyl ethyl sulfide. Exposure of human peripheral blood lymphocytes from normal donors to these alkylating agents resulted in an increase in cell associated protease activity. This increase in protease activity may contribute to the pathology or act as an indicator to predict methods of therapeutic intervention for sulfur mustard toxicity.

Alkylating Agents↗
PubMed1991

Central hypoxaemia in rats provokes neurological defects similar to those seen in experimental diabetes mellitus: evidence for a partial role of endoneurial hypoxia in diabetic neuropathy.

Endoneurial hypoxia has been put forward as a factor contributing to diabetic neuropathy. The aim of this study was to determine whether alterations in motor nerve conduction velocity, Na+/K(+)-ATPase activity and substance P content of nerve and skin tissue, characteristic of the diabetic rat, could develop in non-diabetic animals subjected to a central hypoxaemia for five weeks. Compared to normoxic controls, five weeks of central hypoxaemia caused a fall in motor nerve conduction velocity of 30% (P less than 0.01), a decrease in sciatic nerve substance P content (68%; P less than 0.001) combined with elevated substance P content per unit area foot skin (44%; P less than 0.01). This pattern of change is qualitatively similar to that seen in diabetic rats. The Na+/K(+)-ATPase activity, however, was unaltered by the hypoxic environment. These findings support strongly a partial role for hypoxia in the pathogenesis of diabetic neuropathy.

Animals↗
PubMed1991

Medical defense against blistering chemical warfare agents.

First used in World War I, chemical blistering agents present a serious medical threat that has stimulated renewed interest in the light of extensive use in recent conflicts. Current medical management cannot yet prevent or minimize injury from the principal agent of concern--sulfur mustard. Research directed at this goal depends on defining effective intervention in the metabolic alterations induced by exposure to sulfur mustard.

Arsenic Poisoning↗
PubMed1990

The use of human epidermal keratinocytes in culture as a model for studying the biochemical mechanisms of sulfur mustard toxicity.

Human epidermal keratinocytes in culture were studied to evaluate their usefulness in demonstrating toxic events following exposure to sulfur mustard. Exposure of keratinocytes to sulfur mustard over a concentration range of 1-1000 microM HD, reduced NAD + levels from 96% to 32% of control levels. When keratinocytes were exposed to a concentration of 300 microM HD, NAD + levels began to fall at 1 hour and reached a plateau of 47% of control levels at 4 hours. Niacinamide, an inhibitor of the enzyme poly(ADP-ribose) polymerase, partially protected mustard-exposed cells against NAD + depletion. It also protected cellular viability as assessed by vital staining 24 hours after exposure. This protection was not seen in long-term (72 hr) cultures. These studies suggest that human epidermal keratinocytes in culture can serve as a useful in vitro model for research into the biochemical mechanisms of sulfur mustard-induced cutaneous injury.

Cell Survival↗