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Biomedical subjects

P Fort

Publications and source records attributed to P Fort.

At least 109 records · Page 6Linked to original sources

Polycythemia in hypothyroid infants.

Twenty-three infants with congenital hypothyroidism were evaluated for the presence of anemia. Though no patient was found to be anemic, six (26%) had elevated hemoglobin levels, some with significant elevations. Pathogenesis of this finding is unclear, as none of the effects of thyroxine on erythropoiesis previously described would result in polycythemia. Pediatricians caring for hypothyroid infants should be aware of this association so as to be better prepared for any complication related to the hyperviscosity syndrome.

Humans↗

Pituitary-hypothalamic response in adolescents with growth failure due to fear of obesity.

Nine patients (4F, 5M) aged 12-17 years with "fear of obesity" were studied with a sequential stimulation test utilizing insulin, LRH, TRH, and L-dopa. The comparative groups were nine female with classic anorexia nervosa, five males with undifferentiated nutritional dwarfing, and nine children (1F, 8M) with constitutional growth delay. The serum TSH, glucose, cortisol, somatotropin, prolactin, LH, and FSH were sampled periodically over 2 hours. Basal T3, T4, transferrin, and Somatomedin-C levels were also obtained. The "fear of obesity" patients did not have any pituitary function changes that were unique. These patients, as well as the comparison groups, revealed a delayed TSH response in proportion to the weight deficit which, when expressed as an integrated response, correlated well to the weight deficit for height (P less than 0.001) and to the ability to recover from hypoglycemia (p less than 0.001). The Somatomedin-C level was low and correlated to the T3 level (p less than 0.05) and not correlated to the elevated Somatotropin levels. The pituitary response to combined stimulation in patients with fear of obesity was determined to be a component of the spectrum starting at normal and proceeding to the extreme undernutrition of anorexia nervosa. Pituitary responsiveness, therefore, changes not as a function of the etiology of the malnutrition, but simply as a function of its severity.

Adolescent↗

Glycemic response in children with insulin-dependent diabetes mellitus after high- or low-glycemic-index breakfast.

To examine the effects of various carbohydrate foods on postprandial glycemia in diabetic children, we fed a mixed, isocaloric diet containing either high- or low-glycemic-index (GI) breakfast foods to 22 children with poorly controlled insulin-dependent diabetes mellitus (IDDM) and measured blood sugar response with and without adjustment of insulin doses. We found that IDDM children fed a high-GI meal showed a significantly higher serum glucose level than those fed a low-GI meal. However, such differences were not seen when the preprandial dose of regular insulin was adjusted to the amount of carbohydrate in feedings. Thus, as long as proper adjustment of insulin is made, the type of carbohydrate in a single mixed meal does not appear to have a significant effect on the postprandial glycemic response in children with long-standing poorly controlled IDDM.

Adolescent↗

Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.

To test the hypothesis that the capacity to develop left ventricular (LV) hypertrophy might diminish with advancing age, we examined the hypertrophic response to ascending aortic constriction in 3 groups of adult Fischer 344 rats (9 months, 18 months, and 22 months of age). Aortic constriction was created so that aortic cross-sectional areas would be the same for the 3 groups of rats. Four weeks after imposition of aortic constriction, there was no significant difference in peak LV pressure, peak-to-peak and mean systolic pressure gradients between left ventricle and aorta, cardiac output, LV minute work, or cross-sectional area of the aortic constrictions in the 3 groups. In 9-month-old aortic-constricted rats, LV dry wt (LVDW)/body wt, LVDW/tibial length, and myocyte width increased by 23% (p less than 0.01), 14% (p less than 0.01), and 27% (p less than 0.01), respectively, compared with sham-operated rats. In contrast, in 18-month-old and 22-month-old aortic-constricted rats, LVDW/body wt and LVDW/tibial length were unchanged compared with sham-operated controls, and increases in myocyte width were only modest 4 weeks following constriction. RNA concentration in the myocardium 5 days after constriction increased by 21% (p less than 0.001) in 9-month-old rats but showed no significant rise in 18-month-old rats. These results suggest that advancing age is associated with a diminished capacity to develop myocardial hypertrophy in response to acute pressure overload and that a reduced ability to synthesize protein may be one of the major contributing factors to a diminished capacity for hypertrophy in advanced age.

Aging↗

Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.

We report the first and complete nucleotide sequence of a human gamma 3 heavy chain constant region gene (C gamma 3). This gene displays the same organization than the others C gamma genes and exhibits normal RNA splice and polyadenylation sites. A comparison of its primary sequence with those of C gamma 1, C gamma 2 and C gamma 4 genes confirms the high degree of homology (95%) of the human family in both coding and non-coding regions, and the divergence of the hinge region. The C gamma 3 gene we sequenced codes for a Gm(b) gamma 3 chain (EZZ). Comparison with other known protein sequences reveals that only two specific aminoacids are involved in the Gm(b) and Gm(g) allotypes, which suggests an important part of the spatial configuration in the allotypic specificities.

Amino Acid Sequence↗

Premarin priming does not alter growth hormone release following exercise.

We evaluated the usefulness of premarin priming on exercise induced growth hormone release and the value of combining several growth hormone screening agents in a large population of prepubertal children. Two hundred five short healthy prepubertal children growing below the 5th percentile in height were studied. One hundred forty-four were screened with exercise following glucose ingestion, while 61 were primed with estrogen prior to glucose and exercise testing. Premarin priming did not significantly increase the number of our patients who responded to exercise nor to glucose; 86% and 88.5% of non-primed and primed patients, respectively, responded with a growth hormone increase greater than or equal to 8 ng/ml following exercise and glucose. Glucose loading alone was not associated with a high enough growth hormone rise to rule out growth hormone deficiency in most of our children. Age (less than or equal to 5 yr) was associated with lower post-exercise growth hormone levels and a higher failure rate to testing in both primed and non primed children. Premarin priming does not seem to alter the growth hormone releasing capacity to exercise of prepubertal children. The combined use of exercise, glucose loading and premarin priming in a single screening test does not improve on the results obtained by growth hormone exercise screening alone.

Adolescent↗

Magnesium status in children with insulin-dependent diabetes mellitus.

We assessed the magnesium status in 67 children with insulin-dependent diabetes mellitus (IDDM) in various degrees of diabetic control and its changes during the evolution of the disease. This was done by measuring fasting serum magnesium and 24-hr urinary magnesium clearances when patients were first studied, as well as subsequently on follow-up. In 23 of these patients the retention of intramuscular magnesium was also assessed in relation to the degree of diabetic control and the duration of the illness. The mean +/- SD serum magnesium levels were significantly lower in diabetic children as compared to nondiabetic controls (1.91 +/- 0.22 vs 2.12 +/- 0.26 mg/dl, p less than 0.001). Serum magnesium in diabetic children correlated with glycosylated hemoglobins (r = -0.358, p less than 0.001), but not with 24-hr glycosuria (r = -0.296). On follow-up of patients, serum magnesium significantly increased when IDDM control improved and decreased when the control worsened. Diabetic patients had increased urinary magnesium clearances compared to nondiabetic subjects (5.26 +/- 3.58 vs 3.60 +/- 1.36 cc/min, p less than 0.05). All but five of the 23 patients given the magnesium load retained more than 40% of the dose, with a mean +/- SD retention of 58.7 +/- 5.1%. There was no correlation between the amount of retained magnesium and the duration of the illness, degree of diabetic control, amount of glycosuria, magnesuria, magnesemia, glycosylated hemoglobins, or serum lipids. The data confirm that lower than control serum magnesium levels occur frequently among children with poorly controlled IDDM. Moreover, there might be magnesium deficiency in IDDM, as indicated by the high retention of magnesium when given intramuscularly. The deficiency of this ion may or may not be accompanied by decreased serum magnesium levels and may result from increased urinary magnesium losses in children with IDDM.

Adolescent↗

Breast feeding and insulin-dependent diabetes mellitus in children.

We have evaluated the hypothesis of a protective effect of human milk on the development of insulin dependent diabetes mellitus (IDDM). We studied the feeding histories of 95 diabetic children and compared them with controls consisting of their non-diabetic siblings and a pair matched group of nondiabetic peers of the same age, sex, geographical location, and social background. The incidence of breast feeding in diabetic children was 18%. This was similar to the control group. The duration of breast feedings was also similar among all three groups. There was no difference in the age of introduction of solid food between diabetic and nondiabetic children. Twice as many diabetic children, however, received soy containing formula in infancy as compared to control children. The mean age of onset of IDDM was not related to the type of feeding during infancy. The incidence of positive thyroid antibodies was two and one half times higher in formula-fed diabetic children than in breast-fed ones. In our studies we were unable to document any relationship between the history of breast feeding and subsequent development of IDDM in children.

Adolescent↗

Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family.

We have isolated and sequenced a full-length cDNA clone encoding rat glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, E.C.1.2.1.12). The entire mRNA is 1269 nucleotides long exclusive of poly(A) and contains respectively 71 and 196 bases of 5' and 3' non-coding regions. Primer extension as well as S1 nuclease protection experiments clearly established that a single (or at least a highly prominent) GAPDH mRNA species is expressed in all rat tissues examined. This sequence allowed the determination of the hitherto unknown primary structure of rat GAPDH which is 333 aminoacids long. Comparison between GAPDH sequences from rat, man and chicken revealed a high degree of sequence conservation at both nucleotide and protein levels.

Amino Acid Sequence↗

Low-dose oral clonidine. A simple and reliable growth hormone screening test for children.

We evaluated the efficacy and side effects of a low dose of oral clonidine hydrochloride on growth hormone release in 24 healthy short children; ten received 100 micrograms (group A) and 14 received 50 micrograms (group B). The mean +/- SD growth hormone peak at 60 minutes was 14.5 +/- 6.3 mg/mL in group A v 11.6 +/- 6.1 mg/mL in group B. Failure rate (growth hormone less than 10 mg/mL) was 10% in group A and 36% in group B. The drop in cortisol levels was similar in both groups. Blood pressure did not change significantly, and only mild somnolence was noted in all. A single dose of oral clonidine hydrochloride approximating 100 micrograms/sq m, followed by one blood sample after 60 minutes seems to be an effective and safe screening test for growth hormone deficiency in short children.

Adolescent↗

Effects of transition mutations in the regulatory locus spoIIA on the incidence of sporulation in Bacillus subtilis.

We have determined the changes in DNA sequence corresponding to three mutations in the promoter-proximal open reading frame of spoIIA, a locus that regulates sporulation in Bacillus subtilis. All three mutations prevent the synthesis of two sporulation-associated enzymes, but they differ in their effects on spore incidence. We now find that mutation spo-42, which allows spores to be produced at a low incidence, is a transition that changes Gly95 to Asp in the protein encoded by the open reading frame. Mutation spo-69, which blocks sporulation entirely, consists of two transitions: these change Gly62 to Asp and Ala1 16 to Thr. Mutation sas-1, which partially suppresses spo-69, is also a transition: this changes residue 62 (which had become Asp as a result of the spo-69 mutation) to Asn.

Bacillus subtilis↗

Nucleotide sequence and complementation analysis of a polycistronic sporulation operon, spoVA, in Bacillus subtilis.

We have determined the nucleotide sequence of a 3706 bp stretch of Bacillus subtilis chromosomal DNA that complements all known spoVA mutations. The sequence contains five consecutive large open reading frames capable of encoding proteins of molecular weights ranging from approximately 15000 to 36000. Analysis using integrational plasmids suggests that the region is likely to be transcribed as a single mRNA. A novel form of complementation analysis, based on derivatives of bacteriophage phi 105 carrying the cloned spoVA locus, has been used to define four distinct complementation groups among the eight previously characterized spoVA mutations. The spoVA locus is the largest polycistronic sporulation operon yet characterized.

Bacillus subtilis↗

Impaired somatomedin generation test in children with insulin-dependent diabetes mellitus.

Recent studies have suggested a partial block in somatomedin (SM) production or growth hormone (GH) action in IDDM. Twelve well-nourished diabetic children (9 males and 3 females with a mean age of 11.2 +/- 3.3 yr), six with an HbA1c of 7.9-11.2% (group A) and six with an HbA1c of 12.5-15.6% (group B), were studied as follows: the GH response after 100 micrograms of oral clonidine and the SM generation capacity after i.m. administration of 0.2 U/kg/dose of human growth hormone (hGH) for 4 days. Group B diabetic subjects had a significantly higher mean +/- SD GH increase after clonidine than did group A patients (delta of 17.4 +/- 4.9 versus 5.7 +/- 6.0 ng/ml, P less than 0.01); the basal GH of both groups were similar (1.6 +/- 0.7 versus 2.3 +/- 1.4 ng/ml). In contrast, the SM response to hGH was significantly decreased in group B children as compared with those in group A (delta of 0.3 +/- 0.3 versus 1.2 +/- 0.4 U/ml, P less than 0.01). The basal SM levels of both groups were normal for age. GH and SM correlated with HbA1c levels (r = +0.80, P less than 0.01; r = -0.79, P less than 0.01, respectively); there was no correlation with plasma and urine glucose or serum cholesterol, cortisol, and transferrin. Our data indicate a blunted SM response to hGH in group B diabetic subjects; this defect in SM generation is apparently not present in group A subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Characterization of the transcription products of glyceraldehyde 3-phosphate-dehydrogenase gene in HeLa cells.

We have partially purified the messenger RNA coding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) from HeLa cells and obtained a cDNA clone containing part of its sequence. Using this clone to probe electrophoregrams of RNA transferred to nitrocellulose, we have investigated the characteristics of nuclear and cytoplasmic transcripts in these cells. In the cytoplasm, nature GAPDH mRNA was detected in Northern blots as an intense band, apparently unique, of approximately 1400 nucleotides. The half-life of this mRNA was determined both from the decay kinetics, after a chase with actinomycin D, and from the labeling kinetics during an accumulation experiment. Both kinds of experiments yielded a half-life value of about 8 h, while the accumulation experiment indicated that steady-state GAPDH mRNA amounted to about 1.6% of cytoplasmic poly(A)-rich RNA. Much longer species, likely to be restricted to the nucleus, were also detected in RNA extracted from total cells. At least three discrete species of 1600, 4000, 5800 and 6800 bases were observed above a trailing background extending up to about 8000 bases. This value is commensurate with a functional size of the GAPDH transcription unit in the order of 13000 bases, which we determined by measuring the size of the ultraviolet inactivation target. Until direct evidence can be obtained at the genomic level, the present results provide the first clue to the existence of introns, presumably at least four, in a GAPDH gene from a higher eucaryote.

Amino Acid Sequence↗

Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues.

We have isolated and identified cDNA clones containing part of the coding sequence for rat glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, E.C. 1.2.1.12). By using one of these clones as a probe, we have shown that: i) the abundance of GAPDH mRNA is different in various tissues of the adult rat and in good correlation with the abundance of the enzyme; ii) the transcription rates are quite similar in all tissues tested. We therefore conclude that the tissue-specific differential GAPDH gene expression is regulated by adjusting the abundance of its mRNA at the post-transcriptional level.

Animals↗

Complete nucleotide sequence of the messenger RNA coding for chicken muscle glyceraldehyde-3-phosphate dehydrogenase.

The complete nucleotide sequence for chicken glyceraldehyde-3-phosphate dehydrogenase mRNA has been determined, thereby extending the longest such sequence previously reported (Dugaiczyk et al. Biochemistry, 1983, 22, 1605-1613) by 27 nucleotides. The complete mRNA with the exclusion of poly(A) is 1284 nucleotides long and contains 56 nucleotides of 5' non coding sequence and 229 nucleotides of 3' non coding region. Knowledge of the complete sequence allows us to propose secondary structures models which may be of biological significance.

Animals↗

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Child, Preschool↗