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Biomedical subjects

L Huston

Publications and source records attributed to L Huston.

10 recordsLinked to original sources

Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus.

OBJECTIVE: This study prospectively evaluated the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom gestational diabetes mellitus developed were evaluated with an oral glucose tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area under the curve during the intravenous glucose tolerance test. Basal endogenous glucose production was estimated from isotope tracer dilution during steady state with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin sensitivity to glucose was defined as the glucose infusion rate required to maintain euglycemia during steady-state insulin infusion. Body composition was estimated with hydrodensitometry. Data were analyzed with 2-way analysis of variance with repeated measures for 2 groups. RESULTS: There were increases in first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both groups with advancing gestation, but the increase in second-phase response was significantly greater (P =. 02) in the gestational diabetes mellitus group than in the control group. Basal glucose production increased significantly (P =.0001) with advancing gestation, and there was resistance to suppression during insulin infusion in both groups (P =.0001). There was less suppression of endogenous glucose production however, in the gestational diabetes mellitus group than in the control group (P =. 01). Insulin sensitivity decreased with advancing gestation in both groups (P =.0001), and there was lower insulin sensitivity in the gestational diabetes mellitus group than in the control group (P =. 04). Significant decreases in insulin sensitivity with time (P =. 0001) and between groups (P =.03) remained when the data were adjusted for differences in insulin concentration or residual hepatic glucose production. CONCLUSION: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensitivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These metabolic abnormalities in glucose metabolism are the hallmarks of type 2 diabetes, for which these women are at increased risk in later life.

Adult↗

Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes.

Women who develop gestational diabetes mellitus (GDM) have severe insulin resistance and markedly increased risk to develop subsequent type 2 diabetes. We investigated the effects of pregnancy and GDM on glucose transport activity and the expression and phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1 in human skeletal muscle fiber strips in vitro. Rectus abdominis muscle biopsies were obtained at the time of cesarean section from 11 pregnant women with normal glucose tolerance (pregnant control), 7 pregnant women with GDM, and 11 nonpregnant women undergoing elective surgery (nonpregnant control). Subjects were matched for age and similar degree of obesity. The rate of maximal insulin (10(-7) mol/l)-stimulated 2-deoxyglucose transport was reduced by 32% (P < 0.05) in muscle strips from the pregnant control group and even further in GDM subjects by 54% (P < 0.05 vs. pregnant control). The maximal effect of insulin on tyrosine phosphorylation of the insulin receptor was 37% lower (P < 0.05) in GDM subjects than in pregnant control subjects and was not related to changes in the abundance of the insulin receptor. Compared with nonpregnant control subjects, maximal insulin-stimulated IRS-1 tyrosine phosphorylation was significantly lower by 59 +/- 24% (mean +/- SD) (P < 0.05) and 62 +/- 28% (P < 0.05) in pregnant control and GDM subjects, respectively. This was reflected by a 23% (P < 0.05) and 44% (P < 0.002) reduction in IRS-1 protein levels in muscle from pregnant control and GDM subjects. Both pregnant control and GDM subjects exhibited a 1.5- to 2-fold increase in the levels of IRS-2 (P < 0.01) and p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase (P < 0.05), despite reduced glucose transport activity. These data indicate that insulin resistance to glucose transport during pregnancy is uniquely associated with a decrease in IRS-1 tyrosine phosphorylation, primarily due to decreased expression of IRS-1 protein. However, in GDM subjects, a decrease in tyrosine phosphorylation of the insulin receptor beta-subunit is associated with further decreases in glucose transport activity. Thus, impaired insulin receptor autophosphorylation is an important early distinction underlying muscle insulin resistance in young women with GDM, and it may underlie future risk for the development of type 2 diabetes.

Adult↗

Longitudinal changes in the relationship between body mass index and percent body fat in pregnancy.

OBJECTIVE: To determine the longitudinal relationship between body mass index (BMI) and percent body fat in women before and during pregnancy. METHODS: Twenty-seven healthy, nonobese women were evaluated before conception, in early gestation (12-17 weeks), and in late gestation (33-36 weeks). Height and weight were measured and BMI was calculated. Percent body fat was estimated using hydrodensitometry with correction for residual lung volume. RESULTS: The correlation between BMI and percent body fat before conception was r = 0.693 (P < .005); in early gestation it was r = 0.723 (P < .005) and in late gestation r = 0.633 (P < .005). The mean pregravid BMI was 21.54 and the 95% predictive confidence interval (CI) for percent body fat was 18.2, 26.5%. For the mean BMI of 22.26 in early gestation, the predictive 95% CI for percent body fat was 20.0, 29.0%. In late gestation, the mean BMI was 26.04 with a predictive 95% CI for percent body fat 22.5, 30.8%. CONCLUSION: In nonobese women the correlation between BMI and percent body fat remains significant during pregnancy, although the 95% CI for predicting percent body fat from the mean BMI ranges widely.

Adipose Tissue↗

Child and adolescent anxiety disorders and early attachment.

OBJECTIVE: The major aim of this research is to determine whether infants who were anxiously/resistantly attached in infancy develop more anxiety disorders during childhood and adolescence than infants who were securely attached. To test different theories of anxiety disorders, newborn temperament and maternal anxiety were included in multiple regression analyses. METHOD: Infants participated in Ainsworth's Strange Situation Procedure at 12 months of age. The Schedule for Affective Disorders and Schizophrenia for School-Age Children was administered to the 172 children when they reached 17.5 years of age. Maternal anxiety and infant temperament were assessed near the time of birth. RESULTS: The hypothesized relation between anxious/resistant attachment and later anxiety disorders was confirmed. No relations with maternal anxiety and the variables indexing temperament were discovered, except for a composite score of nurses' ratings designed to access "high reactivity," and the Neonatal Behavioral Assessment Scale clusters of newborn range of state and inability to habituate to stimuli. Anxious/resistant attachment continued to significantly predict child/adolescent anxiety disorders, even when entered last, after maternal anxiety and temperament, in multiple regression analyses. CONCLUSION: The attachment relationship appears to play an important role in the development of anxiety disorders. Newborn temperament may also contribute.

Anxiety Disorders↗

Identification of proteins binding to interferon-inducible transcriptional enhancers in hematopoietic cells.

The binding of nuclear proteins of hematopoietic cells to transcriptional enhancers of interferon-inducible genes has been studied before and after exposure to alpha-interferon. Mobility shift assays show that a complex formed with interferon-inducible transcriptional enhancers before interferon induction contains a 73- and 84-kDa protein. Amino acid sequencing of the oligoaffinity column purified 73- and 84-kDa proteins showed that they belonged to a family of DNA-binding proteins which have been previously identified to exhibit binding in a sequence nonspecific manner to the ends of fragmented DNA or the origin of replication of adenovirus Type 2 DNA and sequence-specific binding to the distal regions of the U1 small nuclear RNA promoter, the promoter of the transferrin receptor gene, and the transcriptional regulatory regions of HLA genes. Following exposure to alpha-interferon, more slowly migrating complexes appeared which contained a 48-kDa protein, a 95-kDa protein, and a 105-kDa protein which bound to the 9-27 transcriptional enhancer in a sequence-specific manner.

Affinity Labels↗

Early bone changes in experimental osteoarthritis using microscopic computed tomography.

Alterations in trabecular subchondral bone have been measured using a microscopic computed tomography scanner in the guinea pig hind-limb myectomy model of osteoarthritis. These bone changes can be found as early as histologic changes in cartilage. To evaluate the influence of the myectomy on the animals, a gait study was performed. This data reveals an alteration in acceleration at the foot-flat phase of gait in the operated limb only, providing early quantification of the interaction between mechanics and biology.

Animals↗

Impaired function of bovine alveolar macrophages infected with parainfluenza-3 virus.

Bovine alveolar macrophages (BAM) were harvested from nonsedated cattle, adhered to glass or plastic surfaces, and infected with parainfluenza-3 (PI-3) virus at a multiplicity of infection of 10. Control and PI-3 virus-infected BAM were compared at 24-hour intervals up to 168 hours for their ability to phagocytize antibody-coated sheep erythrocytes (EAC) and latex particles, to kill Staphylococcus epidermidis, and to alter intracellular acid phosphatase concentrations. The effect of antiviral serum on phagocytic functions of virus-infected cells was also evaluated. Compared with noninfected controls, alveolar macrophages infected with PI-3 virus were 15.3% less adherent to the glass or plastic surfaces at postinoculation hour (PIH) 72 and were 64.0% less adherent at PIH 168. Significant differences (P less than 0.05) between the numbers of control and infected BAM phagocytizing EAC were observed at PIH 24 through 72, with final values differing by approximately 50%. Similar changes were observed in the phagocytic efficiencies of individual cells. The PI-3 virus-infected BAM that were exposed to antiserum or to immunoglobulins against PI-3 virus had approximately a 2-fold greater inhibition in EAC phagocytosis than did infected BAM exposed to serum without PI-3 activity. Significant differences in latex particle phagocytosis were not observed between infected and control BAM. Compared with control BAM, the PI-3 virus-infected BAM contained significantly lower concentrations of acid phosphatase from PIH 48 through 96; at PIH 96, acid phosphatase concentrations were 4-fold less in infected than in control BAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Aggregation of bovine platelets by acetyl glyceryl ether phosphorylcholine (platelet activating factor).

Platelet activating factor is a multifaceted mediator of inflammation capable of stimulating platelet aggregation as well as anaphylaxis, neutropenia and numerous other in vitro and in vivo cellular changes. This lipid mediator, or autocoid, is released by a wide variety of inflammatory cells following an equally diverse group of cellular stimuli including phagocytosis or antigenic stimulation. The synthesized form of PAF is acetyl glyceryl ether phosphorylcholine (AGEPC). In this study AGEPC aggregated bovine platelets in a dose dependent manner. Maximal, irreversible aggregation occurred at 3.6 X 10(-11) M AGEPC with unwashed platelets and at 8.8 X 10(-12) M AGEPC with washed platelets. Aggregation failed to occur when platelets were tested with the biologically inactive structural analog of AGEPC. The possible contribution by platelet cyclooxygenase products was eliminated by showing lack of platelet aggregation to arachidonic acid and also by pretreating platelets with aspirin.

Animals↗

Noncontact anterior cruciate ligament injuries: risk factors and prevention strategies.

An estimated 80,000 anterior cruciate ligament (ACL) tears occur annually in the United States. The highest incidence is in individuals 15 to 25 years old who participate in pivoting sports. With an estimated cost for these injuries of almost a billion dollars per year, the ability to identify risk factors and develop prevention strategies has widespread health and fiscal importance. Seventy percent of ACL injuries occur in noncontact situations. The risk factors for non-contact ACL injuries fall into four distinct categories: environmental, anatomic, hormonal, and biomechanical. Early data on existing neuromuscular training programs suggest that enhancing body control may decrease ACL injuries in women. Further investigation is needed prior to instituting prevention programs related to the other risk factors.

Adult↗