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S D Frasier

Publications and source records attributed to S D Frasier.

At least 19 recordsLinked to original sources
PubMed1994

Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads.

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.

Adolescent↗
PubMed1994

Short stature.

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Adolescent↗
PubMed1993

Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads.

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.

Adolescent↗
PubMed1992

Effect of somatotropin of mammalian cell origin in growth hormone deficiency.

Sixty-nine growth hormone-deficient patients were treated for 1 year with somatotropin (recombinant DNA-derived human growth hormone) produced in mouse cells. The growth velocity of the 50 patients (72%) in whom the effectiveness of this growth hormone could be evaluated increased from a mean (+/- SD) of 3.5 +/- 1.1 to 8.7 +/- 1.6. cm/y. An enhanced rate of weight gain was also observed. Bone age was not unduly accelerated. One of 66 patients developed antibodies to recombinant growth hormone, which did not affect the response to therapy. No patient developed antibodies to host cell proteins. An increased insulin response to a standard glucose load, without any change in glucose tolerance, was observed after 1 year of treatment. This authentic sequence human growth hormone preparation produced in mammalian cells is both effective and safe in the treatment of children with growth hormone deficiency.

Adolescent↗
PubMed1992

Growth response to recombinant human growth hormone of mammalian cell origin in prepubertal growth hormone-deficient children during the first two years of treatment.

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 +/- 2.7 cm/year (group 2) versus 8.6 +/- 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 +/- 1.9 cm/year (group 2) versus 7.2 +/- 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (delta H SDS) for chronological age (CA) were +1.3 +/- 0.6 (group 2) versus +0.8 +/- 0.5 (group 1) for naive patients (p < 0.01), and +1.1 +/- 0.3 (group 2) versus +0.6 +/- 0.4 (group 1) for transfer patients (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Excessive growth.

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Adolescent↗
PubMed1986

Antithyroid antibodies in Hispanic patients with type I diabetes mellitus. Prevalence and significance.

Antithyroglobulin antibodies (ATA) and antithyroid microsomal antibodies (AMA) were sought and thyroid function was determined in 90 Hispanic patients with type I diabetes mellitus followed up for up to seven years. We detected ATA in 7.5% of our patients and AMA in 34.8%. All serum samples positive for ATA also contained AMA. There was no sex difference in the prevalence of thyroid autoimmunity. A small, firm goiter was present in eight patients, one of whom developed Graves' disease. Our results suggest that a relatively high prevalence of AMA and no sex difference in thyroid autoimmunity may be unique features of Hispanic children and adolescents with type I diabetes mellitus. Such patients should be clinically evaluated for thyroid dysfunction and should be screened annually for the presence of AMA. When antibodies are present, laboratory evaluation of thyroid function should be performed frequently.

Adolescent↗
PubMed1984

Cord serum thyroid-stimulating hormone and thyroglobulin levels decline with increasing birth weight in newborns.

Cord serum thyroglobulin (Tg) and TSH levels were related to birth weight in 3 groups of newborn infants composed of 101 infants. Serum free T3 index, free T4 index, and/or T4 also were determined. Group I consisted of normal term newborns (20 females and 19 males), whose mean +/- SD gestational ages (40.1 +/- 0.7 vs. 40.1 +/- 0.5 weeks) did not differ, but whose mean birth weights (3299 +/- 282 vs. 3757 +/- 447 g) differed significantly (P less than 0.005). In female infants, serum Tg levels (r = -0.401; P less than 0.05) and the log of TSH levels (r = -0.576; P less than 0.005) correlated negatively with birth weight, while Tg levels correlated positively with the log of TSH levels (r = 0.401; P less than 0.05). In contrast, none of these correlations was significant for male infants. However, T4 levels and birth weight correlated positively (r = 0.499; P less than 0.025) in male infants, but not in female infants. Group II consisted of newborns whose birth weights were less than 2500 g (19 females and 19 males). Mean birth weights of female (2032 +/- 301 g) and male (1850 +/- 413 g) infants did not differ significantly (P greater than 0.05). Both the Tg levels and the log of the TSH levels correlated negatively with birth weight in female (Tg, r = -0.891 and P less than 0.005; log TSH, r = 0.600 and P less than 0.005) and male (Tg, r = -0.849 and P less than 0.005; log TSH, r = -0.660; P less than 0.005) infants. Also, Tg levels correlated positively with the log of the TSH levels in female (r = 0.554; P less than 0.01) and male (r = 0.412; P less than 0.05) infants. Free T4 index levels correlated positively with free T3 index levels in female (r = 0.443; P less than 0.05) and male (r = 0.570; P less than 0.01) infants. Group III consisted of 12 normal female term newborns whose mean birth weight (3685 +/- 623 g) was not significantly (P less than 0.2) different from that of the males of group I, and 12 normal male term newborns whose mean birth weight (4104 +/- 248 g) was significantly (P less than 0.005) greater than that of the males of group I. Unlike in lower weight female or male infants, serum Tg levels did not correlate with birth weight or the log of TSH levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Birth Weight↗
PubMed1983

Ullrich-Turner syndrome associated with interstitial deletion of Xp11.4 leads to p22.31.

The full phenotype of the Ullrich-Turner syndrome (UTS) is thought to be due to loss of the short arm of X. We report a 16-year-old girl with lack of secondary sexual development, amenorrhea, and short stature. She had thyroiditis and numerous other UTS manifestations and was found to have a non-mosaic 46,X,del(Xp) chromosome abnormality. Breakpoints occurred at p11.4 and p22.31, with a loss of the intervening segment.

Adolescent↗
PubMed1983

Importance and accuracy of bone age ratings in a computerized growth evaluation system.

Bone age ratings according to Greulich and Pyle and to Tanner and co-workers (RUS) of 88 children from two pediatric endocrine centers were compared with ratings from 2 trained technicians and independent ratings from a consulting pediatric endocrinologist. Considering the mean of all ratings as 'true bone age', the mean errors of the individual estimations were small (0.15-0.38 years for the Greulich and Pyle method, 0.12-0.27 years for the method according to Tanner and co-workers). Only in 2 of 338 ratings were differences larger than 1 year observed. In these 2 cases, there was marked dissociation between the maturation of carpal and phalangeal bones. It is concluded that estimations of bone maturation can be carried out reliably by properly trained technicians.

Age Determination by Skeleton↗
PubMed1983

Human pituitary growth hormone (hGH) therapy in growth hormone deficiency.

This review has attempted to answer a number of questions regarding human growth hormone therapy in growth hormone deficiency. I believe that the available data support several conclusions which form a suggested current approach to the clinical use of hGH. While these conclusions are derived from data obtained using pituitary growth hormone, it is likely that they are applicable to growth hormone manufactured by recombinant DNA technology, as well. Treatment should be begun as early as the diagnosis can be made in anticipation of a better initial and long-term response in younger patients. Growth hormone should be administered on the basis of body weight in an initial dose of 0.06-0.10 unit/kg 3 times a week. Growth hormone may be administered either intramuscularly or subcutaneously. Therapy should be continuous whenever possible. Treatment should be given until there is no further response which generally will reflect closure of the epiphyses. Associated hormone deficiencies should be adequately treated, and patients should be periodically evaluated for the development of additional deficiencies. Concomitant therapy is not indicated unless deficiencies are clearly demonstrated. Thyroid replacement should be at full dosage, while glucocorticoid replacement should probably not exceed 10-15 mg/m2 x day. Gonadal steroids should be used at the bone age when puberty is expected, and hGH should be continued during pubertal development. There is no general indication for giving anabolic/androgenic steroid in combination with hGH in prepubertal patients. If a waning effect of therapy is observed, the dose of hGH should be incrementally increased, and/or the addition of anabolic/androgenic steroid therapy should be considered. While most reports have focused on the effect of hGH on linear growth, changes in weight, bone age, body proportions, and body composition have also been observed. The effect on bone age is variable, but there is greater enhancement of linear growth than of epiphyseal development in the majority of treated patients. Bone age must be monitored during hGH administration whether or not anabolic/androgenic steroids are used concurrently. Growth hormone administration is remarkably free of side effects. However, neutralizing antibodies to hGH may develop and they should be sought in patients in whom an unexplained decrease in response is observed. Certainly the available incomplete data allow for different conclusions. The expanding supply of hGH should lead to a more systematic evaluation and provide more definite answers to the questions which this review has considered.

Body Composition↗
PubMed1983

Thyroid-stimulating hormone and thyroglobulin levels decrease with chronological age in children and adolescents.

TSH, thyroglobulin (Tg), and the free T4 index were determined and related to chronological age in 24 normal boys (aged 7.6-17.6 yr; mean, 12.6 +/- 1.5 yr) and 20 normal girls (aged 7.8-17.0 yr; mean, 12.2 +/- 1.4 yr). There was no significant (P greater than 0.1) difference in mean serum TSH (3.06 +/- 2.07 vs. 2.97 +/- 2.07 microunits/ml) and Tg levels (25.3 +/- 10.0 vs. 28.0 +/- 14.8 ng/ml) or free T4 index (9.6 +/- 1.6 vs. 9.4 +/- 1.3 micrograms/dl) between boys and girls. Serum TSH levels correlated negatively with chronological age (rs = -0.518; r = -0.562; P less than 0.01), as did serum Tg levels (rs = -0.618; r -0.545; P less than 0.01). On the other hand, a positive correlation was found between serum TSH and Tg levels (rs = 0.455; r = 0.421; P less than 0.01). Free T4 index levels did not correlate with chronological age, TSH levels, or Tg levels. We conclude that both serum TSH and Tg levels vary inversely with chronological age in children and adolescents. Also, a direct correlation was noted between serum TSH and Tg levels. These data as well as those from earlier studies may indicate that pituitary secretion of TSH contributes to serum levels of Tg. The decline in TSH with age may be the result of an increased response of the thyroid gland to TSH or a decline in the MCR of T4 with age.

Adolescent↗