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Biomedical subjects

W B Zipf

Publications and source records attributed to W B Zipf.

At least 37 records · Page 2Linked to original sources

Energy expenditure in adolescents during low intensity, leisure activities.

We sought to determine how a stationary activity such as playing a stringed instrument may affect energy expenditure (EE) in adolescents. Using automated indirect calorimetry, we measured EE in eight adolescents (1 male, 7 females, 14.2 +/- 2.1 yr) while they each performed the following activities: watching television (TV) (60 min), playing a stringed instrument (60 min), and walking at 40% of peak oxygen uptake (43 min). Measurements were made during three, 6- to 7-min steady state periods of each activity. EE (mean +/- SD) was lower during TV (1.0 +/- 0.2 kcal.min-1) and instrument playing (1.4 +/- 0.2 kcal.min-1) than during walking (3.4 +/- 0.4 kcal.min-1) (P < 0.05). EE during instrument playing was 41% greater than during television viewing (P < 0.05). We conclude that relatively sedentary activities such as playing a stringed instrument can elevate EE. Conceivably, other stationary, leisure activities performed by adolescents may increase EE and have substantial, cumulative effects on long-term energy balance and fat accretion.

Adolescent↗

Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication.

The correlation of many HLA-associated autoimmune and genetic diseases with the polymorphic complement C4 genes may be attributed to the presence of disease susceptibility genes in the close proximity of C4. We have cloned and characterized a pair of partially duplicated genes, RP1 and RP2, located 611 base pairs upstream of the human C4A and C4B genes, respectively. The putative RP protein, consisting of 364 amino acid residues, is basic and highly hydrophilic. There is a bipartite nuclear localization signal at residues 114-131 and therefore RP may be a nuclear protein. Northern blot analysis suggested that RP is ubiquitously expressed. The 5' region of the RP1 gene is CpG rich, which is a characteristic of housekeeping genes. The RP1 gene contains nine exons. Located in the fourth intron is a cluster of Alu elements, and a newly defined composite retroposon SVA with a SINE, multiple copies of GC-rich VNTRs and an Alu element altogether enclosed by direct terminal repeats. Members of SVA are also present in the complement C2 gene located about 20 kilobases upstream of RP1 in the HLA and in the cytochrome CYP1A1 gene. Determination of the DNA sequences for RP2 from two different HLA haplotypes revealed identical hybrid sequences which resulted from fusion of RP with the tenascin-like Gene X and truncation of the 5' regions of both genes. Cumulative data suggest that the four tandemly arranged genes RP, complement C4, steroid 21-hydroxylase (CYP21), and Gene X altogether form a modular structure, RCCX. The number of RCCX modules varies from one to three or more in the population. Absence of the truncated genes RP2 and Gene XA have been detected in genomes with single RCCX modules. Duplication of the RCCX modules probably occurred before the speciation of great apes and humans as they contain the same breakpoint region of RP and Gene X gene duplication.

Alleles↗

Bone mass in healthy children: measurement with quantitative DXA.

Dual-energy x-ray bone densitometry was used to study the lumbar vertebral bone mass in 218 healthy children (134 girls and 84 boys) aged 1-19 years. Vertebral bone mass increased with weight, age, and pubertal Tanner stage. Results of multiple regression analyses showed that Tanner stage and weight were the best predictive indicators of bone mass and bone mineral density. The influences of age, sex, race, physical activity, and diet were not significant when Tanner stage and weight were controlled. Two tables of predictive intervals for lumbar vertebral bone mineral density in healthy children (one based on Tanner stage and weight; the other, on age and weight) are presented. With normative data now available for use with this precise technique, clinicians can better detect abnormal bone mineral density in children and evaluate changes in mineralization over time.

Absorptiometry, Photon↗

Effects of tolbutamide on growth and body composition of nondiabetic children with cystic fibrosis.

Previously, we reported that nondiabetic children with cystic fibrosis show a blunted insulin response to a meal stimulus. In the study presented here, using tolbutamide, we determined the effects of augmented insulin secretion/action on height and lean body mass of children with cystic fibrosis. Twelve subjects (mean +/- SEM age, 11.0 +/- 0.5 y) were studied for three 4-mo periods: 1) pretreatment, 2) treatment, consisting of 750 mg/d of tolbutamide, and 3) posttreatment. Before the pretreatment period, insulin response to a meal stimulus was evaluated in relation to three doses of tolbutamide: 0, 250, and 500 mg. Growth was monitored during each period, and incremental changes in lean body mass were calculated from height data. To validate the change in lean body mass based on height measurements, we determined lean body mass in seven subjects during the treatment period by using a criterion method (H218O). Growth velocity (cm/4 mo) significantly increased (p less than 0.05) during the treatment (2.58 +/- 0.31) compared with the pretreatment period (0.88 +/- 0.20). The increase in lean body mass calculated from height was greater during the treatment (1.61 +/- 0.29 kg/4 mo) than during the pretreatment period (0.44 +/- 0.18 kg/4 mo) (p less than 0.05). There was also a significant increase (p less than 0.05) in lean body mass during the treatment as measured with H218O (1.91 +/- 0.65 kg/4 mo). Acute administration of either 250 or 500 mg of tolbutamide reduced (p less than 0.05) the area under the glucose concentration curve in response to a meal compared with the control condition of no tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Elevated blood pressure in obese children: influence of gender, age, weight and serum insulin levels.

Prepubescent and early pubescent obese children (n = 114, mean percent IBW = 165, mean age 7.3 years) were studied to determine the relationship of weight (WT), percent of ideal body weight (percent IBW), gender, and insulin (I) to systolic (SBP) and diastolic (DBP) blood pressure. Subjects were assessed for weight, height, percent IBW, systolic and diastolic blood pressure, and Tanner stage; subjects with Tanner stage greater than 3 were excluded. Multiple regression revealed that body weight accounted for the greatest variance in SBP (adj. R2 = 0.34, P less than 0.05), followed by the age. For DBP, weight also accounted for the greatest variance (adj. R2 = 0.16, P less than 0.05) followed by gender. A subgroup (n = 50) was evaluated for oral glucose tolerance. Subjects ingested 1.75 g glucose (GLU)/kg weight and had blood samples drawn at 0, 30, 60, 90, 120 and 180 min. Pearson correlations showed SBP correlated significantly to I at 0 (r = 0.44) and the total integrated area for insulin (r = 0.45); however, adjusting SBP for age by using z-score transformations negated all correlations between SBP and insulin. GLU at 0 and the total integrated area were not significantly correlated to SBP or DBP in absolute or age-adjusted terms. These data on prepubescent, nondiabetic, obese children suggest an association between insulin and elevations in SBP, but not DBP, that is largely due to a mutual association between age and weight. Also, insulin resistance as reflected in GLU response was not related to SBP or DBP.

Age Factors↗

Short-term infusion of pancreatic polypeptide: effect on children with Prader-Willi syndrome.

Ten children with Prader-Willi syndrome (PWS) were given two 90-min infusions of pancreatic polypeptide (PP) (100 pmol.kg-1.h-1) counterbalanced with two saline infusions. Thirty minutes into each infusion, a 60-min appetite test was given. Tests were done after an overnight fast and 1 h after a 275-kcal breakfast meal. Serum assays for biochemistry, glucose, insulin, C peptide, glucagon, cortisol, and PP were performed at the beginning and end of the infusion. Although infusion of PP increased PP concentrations 10-fold, it did not cause physical signs or symptoms, changes in vital signs, or changes in serum biochemistry. Although the test design was sufficiently sensitive to reveal an effect of the pretest meal on subsequent food intake, there was no difference in eating behavior with the saline and PP infusions. This suggests that a short-term normalization of blood PP concentrations does not correct the excessive food intake.

Blood Glucose↗

Colic: idiopathic, excessive, infant crying.

Infantile colic is a common and frustrating condition for parents and health care practitioners. A commonly held belief is that the condition is benign and only results in transient loss of parental sleep; however, a detailed study of the recent literature and clinical studies suggests that not all colic abates without residual consequences. In this article, we outline current understanding of the condition and suggest methods of intervention. In addition, we focus on the potential effect of colic on infant attachment; the later growth and development of the once-colicky child; the evidence that supporting and refuting commonly held beliefs, and areas of intervention.

Colic↗

Temporal relationship of the prolactin-dependent LH-induced LH receptor to the LH stimulus.

The time course for LH induction of luteinizing hormone (LH) receptors as reflected in binding of 125I-labeled hCG was investigated in hypophysectomized adult male rats. A low dose of oLH (10 micrograms) was administered to hypophysectomized adult male rats following pretreatments with prolactin, follicle-stimulating hormone (FSH), growth hormone (GH), or saline. Testicular binding of hCG was determined at different times following the LH injection using Leydig cell membrane preparations from a testicular homogenate. Seven days after hypophysectomy, hCG binding was at a nadir of 19 +/- 7% (mean +/- SD) of control values. Pretreatment with prolactin (100 micrograms/day) for 7 days was associated with a nonsignificantly different hCG binding that was 30 +/- 5% of control values. Prolactin pretreatment plus a single 10 micrograms LH i.p. injection increased 125I hCG binding up to 56 +/- 10% of control values within 30 minutes of the LH injection. Luteinizing hormone-induced hCG binding persisted at a high level (51 +/- 4% of control values) for 2 hours but returned to hypophysectomized control levels 6 hours after the i.p. LH injection. Seven days pretreatment with FSH or GH at 100 micrograms/day plus 10-micrograms LH injections was also tested. Neither FSH nor GH had a statistically significant effect on hCG binding nor could they mimic the ability of prolactin to allow for LH induction of hCG binding in the hypophysectomized adult male rats. These studies suggest that the induction or "up-regulation" of Leydig cell hCG binding by ovine LH is rapid and specifically dependent upon pre-exposure to prolactin.

Animals↗

Short stature and thyroxine-binding globulin excess: improvement with triiodothyronine treatment.

Thyroxine-binding globulin (TBG) excess with increased total thyroxine (T4) and triiodothyronine (T3) levels has not been thought to produce symptoms. We report on a white boy, initially seen at 4.3 years of age and observed for 4 years, who has short stature caused by the excess thyroxine binding. At his initial examination his thyroxine-binding globulin (TBG) levels were elevated (17 mg/dL), and he had a T4 level of 25.8 micrograms/dL, short stature, a bone age of 19 months, normal vital signs, and hyperthyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) testing (maximal value 58 microIU/mL). Results of tests obtained during the next 6 months showed other abnormalities related to thyroid function. Tests showed the following values: T3 412 ng/dL, thyroid uptake 24%, and low T3 resin uptake. They also showed these values: an elevated basal TSH of 8.7 microIU/mL, a slightly low preejection period to left ventricular ejection time ratio of 0.29 (normal 0.35 +/- 0.04), and WISC-R IQ within normal limits. Because of the persistent short stature, T3 supplementation was started at age 7 years and gradually increased to 35 micrograms/d. The patient showed no thyrotoxic symptoms. Serum T4 level decreased from 25.8 to 4.2 micrograms/dL, T3 increased to 1,240 ng/dL, the TRH/TSH test result was suppressed (maximal level 1.8), and the preejection period to left ventricular ejection time ratio decreased to 0.24. Growth velocity increased by 65%. Both of the child's parents had normal thyroid test results. A younger brother also showed similar elevations of TBG level and even greater T4 values (36 micrograms/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Characteristics of abnormal food-intake patterns in children with Prader-Willi syndrome and study of effects of naloxone.

Prader-Willi syndrome (PWS) is characterized by morbid obesity and abnormal appetite. It has been suggested that appetite is reduced by the administration of the opioid antagonist, naloxone. This has led to the hypothesis that appetite disturbance is a consequence of an abnormal hypothalamic response to appetite effects of endogenous opiates and opiate antagonist may be a useful treatment. To characterize the feeding patterns of PWS children and test this hypothesis, we administered an appetite test to 10 PWS children and 9 obese control children. We also examined the effects of naloxone on eating behavior of the children with PWS. While initial rate of eating did not differ, the PWS group showed a much delayed satiety resulting in a longer period of food intake. No difference in food intake was observed with naloxone (1.6 mg im, 30 min before the feeding test) treatment as compared with saline treatment.

Adolescent↗

Exercise adaptation responses for gastric inhibitory polypeptide (GIP) and insulin in obese children. Possible extra-pancreatic effects.

Thirteen obese children and matched controls were fed a mixed meal, and responses were evaluated at fixed intervals for glucose, insulin, and gastric inhibitory polypeptide (GIP). The obese children were evaluated before and within 48 h after completion of a 5-mo exercise training program (ETP). The ETP included three aerobic exercise sessions per week and modest diet restrictions. Caloric expenditure was increased by approximately 300 kcal/exercise session. Weight gain was minimal over the 5 mo. An unexpected increase in GIP response and improved insulin tolerance were recorded for the obese children post-ETP. GIP values were higher (P less than 0.05) at 30 and 60 min and led to a highly significant elevation (P less than 0.01) of the integrated GIP response for post-ETP obese versus both pre-ETP and normal-weight controls. Insulin values were lower (P less than 0.05) at 30 and 60 min and led to a lower integrated insulin response (P less than 0.0585) for post-ETP obese children. However, the obese children continued to secrete more insulin (P less than 0.05) than normal-weight controls. Glucose tolerance, similar for pre-ETP obese subjects and controls, did not change in post-ETP children. Exercise-induced improvement in glucose utilization in these obese children was associated with an increase in GIP secretion. This contrasts with reports that calorie restriction will improve glucose utilization with decreased insulin and GIP secretion. The study demonstrates a previously unreported uncoupling of GIP and insulin secretion and suggests shifts in peripheral tissue sensitivity to insulin-induced glucose uptake. These shifts may, in part, be influenced by GIP.

Adolescent↗

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature.

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

Adolescent↗

Pancreatic polypeptide responses to protein meal challenges in obese but otherwise normal children and obese children with Prader-Willi syndrome.

Children with hyperphagia and obesity of Prader-Willi syndrome (PWS) have previously been shown to have blunted pancreatic polypeptide (PP) response to low protein meal stimulation. To evaluate the effects of various protein challenges on PP release in children with PWS, we administered both a low protein (0.2 g/kg) and a high protein (2.0 g/kg) meal stimulation test to 12 children previously diagnosed as having PWS and to an age- and weight-matched group of 19 obese but otherwise normal children. Serum samples were collected just before and for 3 h after meal ingestion. The mean (+/- SD) age was 11.7 +/- 4.2 yr for the PWS group and 10.3 +/- 3.8 yr for the obese group (P = 0.323). The percent ideal body weight for height for the PWS group (mean +/- SD 186 +/- 48%) was not significantly different from the percent ideal body weight for height for the obese group (174 +/- 35%; P = 0.421). Peak PP responses were significantly less for the PWS group than for the obese group for both the low and high protein meal stimulations. The mean (+/- SE) peak PP response with the low protein meal was 76.1 +/- 13 pg/ml for the PWS group and 302 +/- 93 pg/ml for the obese group (P less than 0.05). The mean peak response with the high protein meal was 181 +/- 51 pg/ml for the PWS group and 581 +/- 127 pg/ml for the obese group (P less than 0.01). Glucose rises were similar for both tests, although the PWS group did have a slightly smaller rise in glucose after the low protein stimulation than was observed in the obese group. The insulin response was also significantly less for the low protein meal in the PWS group compared to the low protein insulin response of the obese group. There were no significant differences in the insulin responses observed in both groups with the high protein meal test. This study confirms our previous observation and suggests that many children with PWS have a functional deficiency of PP. Our current study demonstrates that this condition is not a result of their obese condition or an alteration in their response threshold to protein.

Adolescent↗

Direct measurement of testosterone in a pediatric center, with use of a radioimmunoassay kit and unextracted serum.

We evaluated a commercial (Radioassay Systems) radioimmunoassay kit for testosterone in which a double-antibody method and an 125I tracer are used. The 50-microL serum sample is assayed directly with no pre-extraction step. The assay system has good sensitivity (0.01 microgram/L), good precision (CV 5.2%), and little cross reactivity between testosterone and other androgens. Results compared well with those by a tritiated radioimmunoassay involving extraction (r = 0.98). Values obtained for 97 children compared well with published pediatric normal values. Evidently, this kit provides a rapid and reliable measurement of testosterone in serum specimens and is acceptable for use with pediatric patients.

Adolescent↗

Testicular responsiveness to human chorionic gonadotrophin in growth hormone deficient pre-pubertal boys: lack of effect of replacement therapy.

The effect of hGH therapy on testicular response to hCG was studied in 7 pre-pubertal boys with known growth hormone deficiency. Each boy received 2000 IU hCG intramuscularly for 3 consecutive days either before starting hGH therapy or 4 months after temporarily discontinuing hGH therapy. A second 3 day series of hCG injections was administered after each boy had received 4 months of hGH treatment. Before each hCG challenge, serum concentrations of testosterone, LH and FSH were obtained and an iv GnRH test was performed. Growth hormone treatment either maintained or established linear growth velocities equal to or greater than expected for the patient's skeletal age. Testicular response off hGH therapy, either maximum serum concentration of testosterone or maximum rise above baseline, was not significantly different than testicular response while on hGH therapy. Testicular responses did not correlate significantly with either basal concentration of gonadotrophins or gonadotrophin responses to GnRH. Despite its effectiveness in stimulating growth, hGH did not effect testicular responsiveness to hCG in pre-pubertal boys with hGH deficiency.

Adolescent↗