Biomedical subjects

T R Smith

Publications and source records attributed to T R Smith.

At least 37 records · Page 2Linked to original sources

PubMed1997

Growth hormone-induced insulin resistance: role of the insulin receptor, IRS-1, GLUT-1, and GLUT-4.

Treatment of rats with growth hormone (GH; 1 mg/kg sc) twice daily over 2.5 days did not alter fasting plasma glucose or glucose tolerance but increased fasting plasma insulin levels 65% and peak insulin response to a glucose load 35% over controls, indicating the development of insulin resistance. Studies on partially purified insulin receptors from soleus muscles showed that GH increased the abundance of insulin receptor beta-subunits by 48% as measured by immunoblotting. Despite this increase, GH abolished the increase in autophosphorylation of the insulin receptor beta-subunit in response to physiological hyperinsulinemia and diminished by 28% the response to supraphysiological hyperinsulinemia. Similarly, insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) was decreased 25% by GH, but the abundance of IRS-1 was not affected. Studies on rats pretreated with streptozotocin suggested that the effects of GH are direct and not secondary to GH-induced hyperinsulinemia. GH decreased basal GLUT-1 abundance in the low-density microsome and plasma membrane fractions of epididymal adipocytes by 50 and 42%, respectively, but decreased basal GLUT-4 abundance only in the low-density microsome fraction by 24%. Despite these alterations, the abundance of both transporters in the plasma membrane fraction of adipocytes incubated with 0.1 U insulin/ml was not diminished by GH.

Adipocytes↗

PubMed1997

Effect of monensin on 2-deoxyglucose uptake, the insulin receptor and phosphatidylinositol 3-kinase activity in rat muscle.

Preincubation of rat soleus muscle with 1 and 10 microM monensin for 2 h increased the subsequent basal 2-deoxyglucose uptake by muscle 76 and 121% respectively. Under the same conditions, monensin decreased the insulin-stimulated (1 mU/ml) 2-deoxyglucose uptake by 29 and 37% respectively. The monensin-induced augmentation of basal 2-deoxyglucose uptake was inhibited 92% by cytochalasin B suggesting that the uptake is mediated by glucose transporters. Monensin did not increase the cellular accumulation of L-glucose in muscle indicating that it does not affect the cell membrane integrity. Neither the stimulatory effect of monensin on basal 2-deoxyglucose uptake nor the opposite, inhibitory action of monensin on the insulin-stimulated 2-deoxyglucose uptake were influenced by the removal of Ca2+ from the medium or by dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, suggesting that the actions of monensin are not mediated by calcium. Monensin had no effect on muscle ATP concentration. The monensin-induced augmentation of basal 2-deoxyglucose uptake was neither associated with stimulation of muscle phosphatidylinositol 3-kinase activity nor inhibited by wortmannin, demonstrating that the increase in basal 2-deoxyglucose uptake is not mediated by activation of phosphatidylinositol 3-kinase. The inhibition of insulin-stimulated 2-deoxyglucose uptake by monensin was associated with a 31% decrease in the abundance of insulin receptors in muscles, a 64% decrease in the insulin-induced autophosphorylation of the insulin receptor beta-subunit, and a 44% reduction of the insulin-stimulated phosphatidylinositol 3-kinase activity. Addition of monensin into the phosphatidylinositol 3-kinase reaction had no effect on the activity of the enzyme, demonstrating that the inhibition in monensin-treated muscles is indirect and occurs upstream of phosphatidylinositol 3-kinase. It is concluded that monensin has a dual effect on 2-deoxyglucose uptake by skeletal muscle: it stimulates basal uptake but inhibits the insulin-stimulated uptake. The primary cause of the latter, inhibitory effect of monensin is at the level of the insulin receptor.

Adenosine Triphosphate↗

PubMed1997

Metabolic characteristics of induced ketosis in normal and obese dairy cows.

Four groups of 6 cows were used to determine the effects of body condition on induction of ketosis. At calving, obese cows were heavier by 108 kg and had a higher body condition score by 0.74 units than did normal cows. Susceptibility to induced ketosis was evaluated by restricting dry matter intake by 20% and feeding 7% 1,3-butanediol from 15 to 49 d in milk (DIM) to one group of obese cows and to one group of normal cows. No normal or obese cows fed the control diet developed ketosis. Two normal and 2 obese cows developed ketonemia because of the induction protocol, and 1 cow in each of the two groups developed clinical ketosis. Obese cows lost 59% more body weight during the first 14 DIM than did normal cows, and cows fed the restricted diet plus 7% 1,3-butanediol lost 15% more body weight than did cows fed the control diet during the induction period. Concentrations of nonesterified fatty acids increased at parturition, peaked at 7 to 14 DIM, and returned to prepartum concentrations by 21 DIM. Plasma beta-hydroxybutyrate concentrations increased after calving and was increased additionally by the induction protocol. At the onset of lactation, plasma insulin decreased, plasma glucagon increased, hepatic triacylglycerols increased, and hepatic glycogen decreased. The incidence of ketonemia and clinical ketosis was the same for obese and normal cows, but, on the basis of changes of blood and liver composition, incidence of ketosis would probably increase if obese cows were overfed throughout the entire dry period.

Animals↗

PubMed1996

Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle.

The effects of sphingomyelinase, phosphorylcholine, N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or 200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and that at 0.1 and 1.0 m-unit of insulin/ml 32-82% and 19-25% respectively compared with control muscles studied at the same insulin concentrations. The sphingomyelinase-induced increase in basal and insulin-stimulated 2-deoxyglucose uptake was inhibited by 91% by 70 microM cytochalasin B, suggesting that it involves glucose transporters. Sphingomyelinase had no effect on the cellular accumulation of L-glucose, which is not transported by glucose transporters. The sphingomyelinase-induced increase in 2-deoxyglucose uptake could not be reproduced by preincubating the muscles with 50 microM phosphorylcholine, 50 microM C2-ceramide or 50 microM C6-ceramide. Preincubation of muscles with 50 microM sphingosine augmented basal 2-deoxyglucose transport by 32%, but reduced the response to 0.1 and 1.0 m-unit of insulin/ml by 17 and 27% respectively. The stimulatory effect of sphingomyelinase on basal and insulin-induced 2-deoxyglucose uptake was not influenced by either removal of Ca2+ from the incubation medium or dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum. This demonstrates that Ca2+ does not mediate the action of sphingomyelinase on 2-deoxyglucose uptake. Sphingomyelinase also had no effect on basal and insulin-stimulated activities of insulin receptor tyrosine kinase and phosphatidylinositol 3-kinase. In addition, 1 and 5 microM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, failed to inhibit the sphingomyelinase-induced increase in 2-deoxyglucose uptake. These results suggest that sphingomyelinase does not increase 2-deoxyglucose uptake by stimulating the insulin receptor or the initial steps of the insulin-transduction pathway. The data suggest the possibility that sphingomyelinase increases basal and insulin-stimulated 2-deoxyglucose uptake in skeletal muscle as the result of an unknown post-receptor effect.

Androstadienes↗

PubMed1996

Metabolic evaluation of the criteria used to fit elbow crutches by measurement of oxygen consumption.

OBJECTIVE: To investigate if elbow crutches fitted using conventional guidelines are the most metabolically efficient. DESIGN: Repeated measure connivance sample using crutch length as the independent variable. SETTING: A university exercise physiology laboratory. OTHER PARTICIPANT: Connivance sample of 10 students free from cardiovascular disease, with previous experience in crutch ambulation, and between heights of 160 and 175 cm. Four potential subjects refused to participate in the study. INTERVENTIONS: Crutch length was adjusted using conventional guidelines, and to lengths 2.5 cm above and below this setting. Oxygen consumption was measured using indirect open-circuit spirometry during the final 3 minutes of ambulation using self-selected walking speeds. MAIN OUTCOME MEASURE: Crutches adjusted to the convention setting are not the most efficient in terms of metabolic energy expenditures. RESULTS: A significant reduction in oxygen rate (p = .012), oxygen cost (p = .010), and respiratory exchange ratio (p = .009) were observed when comparing crutches adjusted to -2.5 cm of the standard height with conventional crutch height. Crutches adjusted 2.5 cm above the standard height also required less energy, but these values failed to reach any statistical significance (p > .05). CONCLUSION: The importance of fitting crutches to the correct length using conventional guidelines has not been substantiated in this study. Clinically, there should be a move away from adherence to crutch-fitting criteria and more incorporation of patient feedback to fit crutches to the optimal height. Future research should evaluate the reliability of practical clinical measures such as heart rate and perceived exertion to fit crutches to the optimal height.

Adult↗

PubMed1996

Effects of nicotinamide on milk composition and production in dairy cows fed supplemental fat.

Thirty-two cows, averaging 112 DIM, were assigned to four dietary treatments: 1) control, 2) Ca salts of fatty acids, 3) nicotinamide, and 4) Ca salts of fatty acids blended with nicotinamide during manufacture. Preliminary studies showed that nicotinamide survives blending with Ca salts of fatty acids during manufacture and that a blended mixture of nicotinamide and Ca salts of fatty acids gave results similar to those from nicotinamide plus Ca salts of fatty acids supplemented separately. Calcium salts of fatty acids increased milk fat percentage, decreased milk protein percentage, but had no effect on production of milk, FCM, fat, or protein. Nicotinamide increased production of milk and protein, decreased fat percentage, but had no effect on either production of FCM and protein or percentage of protein. Calcium salts of fatty acids increased NEFA in blood, and dietary nicotinamide increased concentrations of nicotinamide in blood, but glucose and BHBA in blood were unaffected by either dietary ingredient. Therefore, in these midlactation cows, the decreased milk protein percentage caused by supplemental dietary fat was prevented by nicotinamide. Supplementation with only nicotinamide increased total production of milk protein.

3-Hydroxybutyric Acid↗

PubMed1996

Use of lactation curves for analysis of milk production data.

Nonlinear equations were compared with categorical analysis to account for DIM effects on milk production. Five different models for lactation curves were evaluated. Derived from a multiphasic lactation curve, the selected lactation curve appeared to result in random residuals and performed more consistently than the multiphasic curve. Residuals from the fitting of lactation curves were then used for split-plot analysis (continuous model) to estimate treatment effects. Statistical performance of this model was compared with split-plot analysis based on a discrete model with regularly spaced intervals to account for DIM effects (discrete model). The fitting of lactation curves accounted for herd, lactation number, and interaction effects of herd and lactation number and accounted for 34.1 and 44.3% of variance among cows for primiparous and multiparous cows, respectively. The continuous model detected interactions of genetic and management factors with treatment of multiparous cows that were not detected by the discrete model. No statistically significant differences were detected between the two modeling approaches. The continuous model appeared to violate fewer assumptions regarding data distribution than did the discrete model, which reduced the risk of introducing bias during the estimation of treatment effects. The continuous model seemed to be more sensitive to subtle interactions of treatment and other factors.

Animals↗

PubMed1995

Insulin-stimulated phosphatidylinositol 3-kinase activity and 2-deoxy-D-glucose uptake in rat skeletal muscles.

To date there is suggestive evidence that phosphatidylinositol 3-kinase participates in insulin-stimulated glucose transport. However, its involvement in skeletal muscle, a major site of insulin-stimulated glucose disposal, has not been addressed. Therefore, we tested the effects of wortmannin, a known inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated 2-deoxyglucose uptake by rat soleus muscle in vitro: Wortmannin (1 microM) reversibly inhibited insulin-induced 2-deoxyglucose uptake in soleus muscle by 44%. Inclusion of 5 microM wortmannin in the incubation medium completely abolished the insulin-induced increment in 2-deoxyglucose uptake. In conclusion, the insulin-signaling cascade linking insulin-receptor tyrosine kinase activation to glucose uptake in skeletal muscle.

Androstadienes↗

PubMed1995

Mortality, growth, swimming activity and gill morphology of brook trout (Salvelinus fontinalis) and Atlantic salmon (Salmo salar) exposed to low pH with and without aluminum.

Measurements were made of mortality, growth, swimming activity, and gill morphology of young-of-the-year brook trout (Salvelinus fontinalis) and Atlantic salmon (Salmo salar), exposed for 30 days to pH 5.6 +/- 0.5 (mean +/- 1 standard deviation) with and without addition of 107 +/- 57 microg liter(-1) exchangeable (labile monomeric) aluminum. The experiment was conducted in artificial stream channels adjacent to a natural stream and subject to daily and seasonal changes in temperature, light, and chemical conditions. There were no differences in survival or growth for brook trout in any treatment; Atlantic salmon survival and growth were significantly decreased in the acid + Al treatment. Scanning electron microscopy showed no damage to gills of either species in the acid treatments, but the acid + Al treatment caused slight swelling of brook trout gills near the filament tips and significant swelling and fusion of secondary lamellae of Atlantic salmon gills. The acid treatment increased swimming activity in brook trout, but both the acid and acid + Al treatments reduced activity in Atlantic salmon.

Journal Article↗

PubMed1995

Effects of rumen-inert fat on lactation, reproduction, and health of high producing Holstein herds.

Two hundred twenty of 443 cows freshening between June 1989 and March 1990 in five commercial Holstein herds were fed .45 kg/d of rumen-inert fat from calving until 200 DIM. Control diets were fed as TMR and contained, on average, 3.7 to 4.8% supplemental fat (DM basis). Test herds had rolling herd averages of 9300 to 13,250 kg of milk. Production of 4% FCM and milk increased 1.01 (3.3%) and 1.50 kg/d (4.6%), respectively, for primiparous cows fed additional fat. Multiparous cows from four herds demonstrated no response; multiparous cows in one herd increased production of 4% FCM by 2.88 kg/d (8.2%), milk by 2.45 kg/d (6.4%), and milk fat by .14kg/d (10.6%) in response to additional fat. An explanation of response differences among herd for multiparous cows was not possible. For primiparous and multiparous cows, increased genetic potential increased treatment response. Increased body condition score at calving influenced treatment response of multiparous cows. Thinner cows produced more milk and less milk fat in response to additional dietary fat than did fatter cows. Most reproductive indices were unaffected by treatment. Cows receiving additional fat had lower, but nonsignificantly lower, incidences of most health disorders. Responses to rumen-inert fat by cows receiving high concentrations of dietary fat were marginal and were affected by body condition score at calving and by genetic potential.

Animal Nutritional Physiological Phenomena↗

PubMed1993

Management of blunt vascular trauma to the extremities.

During a seven and one-half year period from 1984 to 1991, 106 patients admitted to a Level I trauma center had blunt vascular injury to the extremities. This subset of patients was analyzed with respect to mechanism of injury, associated injuries, method of repair, morbidity and mortality. Twenty patients sustained vascular injuries of the upper limb. Eighty percent of the patients (16 patients) underwent primary vascular repairs, 15 percent had primary amputations and 5 percent (one patient) were observed. Eighty-eight percent (14 of 16 repairs) of the vascular repairs demonstrated excellent neurologic function postoperatively. Eighty-six patients had arterial injuries of the lower extremity. Forty-eight percent (41 patients) of the injured legs were amputated, 41 percent (35 patients) underwent vascular repairs, 6 percent (five patients) underwent ligation of the primary vessel with no amputation and 24 percent (21 patients) underwent no surgical procedure. Sixty-two percent of the 37 patients (23 patients) with popliteal injuries required amputation and 57 percent (21 patients) underwent vascular repair. The overall mortality rate was 11 percent--zero percent for injuries to the upper limb and 14 percent for injuries to the lower limb.

Amputation, Surgical↗

PubMed1992

Actinomycosis of the distal colon and rectum.

Actinomycosis of the colon has rarely been reported; two such cases are presented. A predisposing factor appears to be the presence of a pre-existing intrauterine device (IUD). This history was present in one case in which there was perisigmoid abscess, local extension, and fistulous tract or the anterior abdominal wall. A second patient had anorectal involvement which resembled Crohn's disease, and was found to be HIV positive. There was mucosal irregularity, wall thickening, reactive adenopathy, perirectal fascial thickening, and a sinus tract, which responded well to penicillin. It is unclear if there is an increased incidence of clinical actinomycosis in the HIV positive population, as it has not to our knowledge been previously reported.

Actinomycosis↗

PubMed1992

Guaiac testing in the diagnosis of rectal trauma: what is its value?

Rectal examination with guaiac testing is a standard part of the emergency department evaluation of acutely traumatized patients. Its major role is in the recognition of occult bowel injury. We questioned its efficacy in detecting occult rectal injury in patients with penetrating trauma. We reviewed the charts of 19 patients with suspected rectal injury. Ten injuries were to the abdomen, nine to the buttock, and three to the thigh. Guaiac testing was 69% (11/16) sensitive and 33% (1/3) specific. Rigid sigmoidoscopy was 100% (12/12) sensitive and 67% (2/3) specific. Sensitivity was 100% (8/8) when the two were combined. Our findings suggest that guaiac testing is not accurate enough to rule out the presence of occult rectal injury. The result of guaiac testing must not influence the decision to further evaluate patients with high-risk injuries.

Adult↗

PubMed1992

Plasticity of the human otolith-ocular reflex.

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

Adaptation, Physiological↗

PubMed1991

Evidence for genetic mediation of alcoholism in women.

This review focuses on the etiology of alcoholism in women, examining the role of genetic vulnerability. The review is organized with respect to (1) the genetic epidemiology of alcoholism in women; (2) genetic models that take gender into account; (3) further discussion of the genetic heterogeneity of alcoholism as it relates to gender; and (4) presentation of data obtained from the Pittsburgh family study. This review concludes that, although much evidence remains to be gathered concerning the question of whether or not alcoholism is genetically mediated to the same degree in women as it is in men, there is no reason to rule out this possibility at the present time.

Alcohol Drinking↗

PubMed1991

Risk markers for alcoholism in high-density families.

This review summarizes the efforts of our research program to identify markers for alcoholism risk, which broadly fall within the domain of temperament and those which may be described as attentional or information-processing capacities. Analyses of three-generation pedigrees that include minor children at higher risk of becoming alcoholic indicate that event-related potential characteristics differ between high- and low-risk children. Newer results concerning cardiac responsivity both in minor children and adult high-risk individuals are presented. These results suggest a relationship between personality or temperament on the one hand, and cardiac responsivity on the other. Additional neurobehavioral markers are addressed including static ataxia. Recent segregation analyses and linkage to particular DNA segments are also included.

Adolescent↗

PubMed1991

Multivariate analysis of family risk factors in predicting appointment attendance in a pediatric otology and communication clinic.

Parents of pediatric patients attending regional otologic medical clinics were given a questionnaire to document family risk factors predictive of poor appointment attendance, and to determine barriers which caused non-attendance of medical appointments. Family risk factors which affected clinic attendance were studied using univariate and multivariate analyses. Univariate analyses revealed all factors except patients' sex and family size to be correlated with attendance. However, multivariate analysis revealed that parental age (p less than 0.0153), ownership of car (p less than 0.0012), parental education (p less than 0.0048), and age of patient (p less than 0.0023) were major predictors of clinic attendance. Although ownership of a car was a major independent factor, it was highly correlated with parental age and parental education and only shown to be significant in the subset of patients not having access to public transportation. The identified parental factors which affect pediatric health care delivery underscores the importance of family centered case management in promoting the health care of children and casts doubt on the effectiveness of interventions which are solely centered on the patient or are designed to mitigate only one of these factors.

Adult↗

PubMed1990

Comparison of computed tomography and contrast enema evaluation of diverticulitis.

A total of 31 patients with diverticulitis were analyzed who had both computed tomography and contrast enema. There was almost equal sensitivity to abnormality of approximately 90 percent. Contrast enema produced a specific diagnosis of diverticulitis in 61 percent, using stringent positive criteria, and an additional 29 percent with suggestive findings. Comparative computed tomography specific diagnoses in those 31 cases was made in 65 percent, and suggestive in 23 percent. Computed tomography was particularly useful diagnostically in cases of retrograde obstruction on contrast enema. The authors conclude that contrast enema should be the primary mode of approach, while computed tomography can be a valuable follow-up when the diagnosis is still in doubt, or if it is possible that patient management might be altered by additional information.

Barium Sulfate↗