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Biomedical subjects

A Tanae

Publications and source records attributed to A Tanae.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Sexual precocity].

Sexual precocity results from both GnRH-dependent and GnRH-independent mechanisms. The GnRH-dependent forms of precocious puberty can be treated effectively with long-acting agonist analogues of GnRH. However, for some children who have a poor growth rate during the analogue therapy, an additional growth hormone therapy should be considered to get them near to their normal final height. The analogue treatment could be continued until a bone age of 13 or more. The GnRH-independent forms of precocious puberty have unique mechanisms and unknown pathophysiology. For instance, even though it is known that testotoxicosis and McCune Albright syndrome are caused by the molecular mechanism disorders, further elucidation of their etiologic basis of sexual precocity is needed. Thus being, in treating the GnRH-independent forms they should be assessed for each particular disorder.

Child↗
PubMed1996

Apparent mineralocorticoid excess due to 11 beta-hydroxysteroid dehydrogenase deficiency: a possible cause of intrauterine growth retardation.

A Japanese boy with apparent mineralocorticoid excess (AME) is described. He was born with intrauterine growth retardation (IUGR) and elevated serum level of creatine phosphokinase (CPK). He was studied at 2 years of age because of polyurea and polydipsia of one year's duration and was found to have hypokalaemic alkalosis and sustained hypertension. His plasma renin activity and aldosterone levels were always low and his ratio of urinary tetrahydrocortisol plus allo-tetrahydrocortisol to that of tetrahydrocortisone was very high. Therefore, AME due to 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was diagnosed. He was successfully treated with a combination of spironolactone and nifedipine for at least 16 months. His blood pressure, plasma pH and serum potassium levels were normalized by this treatment, but serum CPK level remained high. We researched the birth records of previously reported AME cases and found that IUGR is a characteristic feature of AME. The mechanism by which IUGR occurs in AME is discussed and we speculate that 11 beta-HSD might be deficient in the placenta and/or fetal tissues, as well as in the kidney, in AME. An explanation for the elevated CPK could not be found.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.

Adult↗
PubMed1994

Precocious puberty in a girl with an hCG-secreting suprasellar immature teratoma. Case report.

Although precocious puberty is common in boys with human chorionic gonadotropin (hCG)-secreting brain tumors, it is extremely rare in girls. The authors describe a 6-year-old girl with an hCG-secreting suprasellar immature teratoma who presented with diabetes insipidus, increased intracranial pressure, and precocious puberty. On admission, breast budding was observed. The serum hCG level was 1230 mIU/ml. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) remained below detectable levels, even after gonadotropin-releasing hormone stimulation. Serum estrogen and androgen were moderately elevated. After chemotherapy, breast budding disappeared with normalization of serum hCG. It has been believed that hCG does not produce precocious puberty in girls in the absence of FSH, and this has been used as an explanation for the rarity of precocious puberty in girls with hCG-secreting brain tumors. However, it has also been reported that hCG has not only LH activity but also intrinsic, although weak, FSH-like activity. In the present case, this FSH-like activity was considered to have played a role in the development of precocious puberty. It is speculated that a very high level of serum hCG can produce precocious puberty in girls. The rarity of intracranial germ-cell tumors with a high potential of hCG secretion may be one of the reasons why hCG-induced precocious puberty is uncommon in girls.

Brain Neoplasms↗
PubMed1994

Clinical significance of growth hormone-binding protein measurements in children.

To investigate the role of growth hormone (GH) and its downstream axis in normal growth and growth disorders, we measured serum GH-binding protein (GHBP) levels in children by ligand-mediated immunofunctional assay (LIFA). Samples were taken from 512 healthy children of normal stature, 146 healthy neonates, 153 short but otherwise normal children, and 27 patients with GH deficiency. Serum GHBP showed no significant diurnal variation. Serum GHBP levels were low in neonates, acutely rose within 6 months, and gradually increased toward midpuberty in normal children (r = 0.2, P < 0.01, assessed among subjects over 1 year old). Neither significant sexual dimorphism nor rapid pubertal changes were observed. In normal short children and patients with GH deficiency, GHBP was lower than normal, but not significant. These data suggest that one of the etiologies for growth disorder in children could be resistance to, or low efficacy for, utilization of GH.

Adolescent↗
PubMed1992

Analysis of HLA-DQA1 in Japanese patients with type 1 diabetes mellitus, using DNA-PCR-RFLP typing.

DNA-polymerase chain reaction(PCR)-RFLP(restriction fragment length polymorphism) typing of the DQA1 gene was performed on 39 patients with type 1 diabetes and 30 controls. Analysis of the frequency of the subtypes of DQA1 alleles, using the DNA-PCR-RFLP typing technique, showed that the DQA1*0301 subtype was most strongly associated with the disease (97.4% vs 56.7%, R.R. = 19.8, pc less than 0.00005). These results indicated that DQA1*0301 may determine the disease susceptibility in the Japanese. In addition, we analyzed the frequency of the subtypes of DQA1 genes in the ten patients carrying the DRW8-DQW8 haplotype, and found that at least eight of them (80%) were classified as having DQA1*0301. The DRW8-DQW8-DQA1*0301 may be one of the susceptible haplotypes among the Japanese.

Diabetes Mellitus, Type 1↗
PubMed1992

Combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) treatment in gonadotropin-deficient males with pituitary dwarfism.

The effects of hCG-hMG treatment in 13 boys with pituitary dwarfism associated with gonadotropin deficiency, were assessed. No patients except one showed signs of puberty at a bone age of 13 years or above. The one patient with some signs of puberty did not become fully mature. The hCG-hMG was started at a mean age of 20.4 years. The hCG at a dose of 5,000 IU was injected intramuscularly twice a week and the hMG at a dose of 75 IU was given once a week at first. During treatment, the frequency of hMG injections was increased to twice a week in six patients who still had not produced normal sperm counts. After a mean duration of 19.23 months, spermatozoa appeared in eight patients, of whom four showed more than 20 x 10(6) sperm/ml. Among six patients who did not have normal sperm counts and had increased hMG injections, one produced a pregnancy and four achieved sperm counts of more than 35 x 10(6)/ml. One patient had refractory azoospermia. In 13 boys with growth hormone and gonadotropin deficiency, hCG-hMG treatment produced normal spermatogenesis in nine patients, one of whom fathered a girl. Thus, hCG-hMG treatment, especially twice-a-week injections of both hCG and hMG, appears to be effective for gonadotropin deficiency in males.

Adolescent↗
PubMed1991

Deoxyribonucleic acid and cytological detection of Y-containing cells in an XX hypospadiac boy with polyorchidism.

A hypospadiac boy with a hypoplastic penis and an apparent 46,XX karyotype in blood and testis cultures is described. Exploratory laparotomy and bilateral gonadal biopsy revealed the presence of 2 testes in the right and 1 in the left hemiscrotum, each of which only showed hypoplastic testicular tissues histologically. Uncultured testis smears showed Y chromatin in approximately 20% of the cells. Also, the Southern blot and polymerase chain reaction analyses detected a weak but distinct signal of Y chromosome-derived deoxyribonucleic acid sequences in the perineal skin but not in the blood lymphocytes. The results indicated that the boy had a small proportion of Y chromosome-containing cells in the form of mosaicism in limited tissues, such as the testes and perineal skin. This finding may have implications in the genesis of testes in some cases of XX patients, and true hermaphrodites or male pseudohermaphrodites with an apparent 46,XX karyotype. To our knowledge, this appears to be the first case of polyorchidism with an identified chromosome abnormality.

Blotting, Southern↗
PubMed1991

Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21-hydroxylase deficiency.

Recent observations have suggested that the pathological mutations in human P-450(C21) deficiency are generated through gene conversion-like events between the functional gene [P-450(21)B] and the pseudogene [P-450(C21)A]. To address this point more extensively, we investigated the effects of the base changes in the A pseudogene on the P-450(21) activity by using the COS cell expression system. In addition to the defective mutations found previously in the pseudogene, four single base changes with amino acid substitutions of Pro(30), Ile(172), Val(282), or Arg(356) were further identified as causing complete [Arg(356)] or partial [Pro(30), Ile(172), and Val(282)] inactivation of P-450(C21). Blot hybridization analysis of patient DNAs using oligonucleotide probes specific for these mutations revealed that the splicing mutation in the 2nd intron was distributed most frequently in both simple-virilizing and salt-wasting forms. The mutation Ile(172) seemed to be frequent in patients with the less severe simple-virilizing form, whereas the mutation Arg(356), together with other most serious mutations reported previously, was preferentially associated with salt-wasting, the most severe form of the disease. In combination with the present results of the effects of various mutations on the P-50(C21) activity, a survey of the distribution of the various mutations in the patient genomes so far reported suggests that the heterogeneous clinical symptoms of this genetic disease are somehow related to the degree of attenuation of the activities of the mutated gene products.

Adrenal Hyperplasia, Congenital↗
PubMed1990

HLA class II (DR, DQ) in Japanese patients with type 1 diabetes mellitus.

DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115 controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and decreased frequencies of DR2 and DRW6 among patients compared to controls. In the RFLP typing of BamHI-digested DNA to DQ beta probe (BamHI-DQB1), the incidence of the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly elevated in the patients, whereas the incidence of DQW6 was reduced. The predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8 and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When serological typing of the 13 DRW8 patients was performed, all the 11 DRW8 patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3. These results indicated that the HLA-DQ locus may play an important role in the development of type 1 diabetes in the Japanese as well as other ethnic groups and that the DRW8-DQW8 haplotype may predispose to the disease in Japan.

Alleles↗
PubMed1990

Clinical usefulness of urinary growth hormone measurement in short children.

Growth hormone (GH) levels in nocturnal urine were measured in 96 short children and 73 children of normal height in order to investigate whether urinary GH levels reflect spontaneous GH secretion and whether they might be used to screen short children for GH treatment. GH levels in 24-hour urine samples were significantly correlated with urinary albumin and beta 2-microglobulin levels in normal children, demonstrating an influence of renal function on urinary GH measurements. Nocturnal urinary GH levels showed significant positive correlations with mean serum GH levels during 3 hours of sleep (r = 0.26, p less than 0.05) and plasma insulin-like growth factor I (IGF-I) levels, reflecting physiological GH secretion. Urinary GH levels were significantly lower in the eight children with complete GH deficiency (3.1 +/- 2.3 ng/g creatinine) than in the normal children (13.8 +/- 11.2 ng/g creatinine). Urinary GH levels in three other groups of short children, partial GH deficiency (11.1 +/- 16.9 ng/g creatinine), impaired GH secretion during sleep (10.4 +/- 12.6 ng/g creatinine) and non-endocrine short stature (18.8 +/- 19.5 ng/g creatinine), were not significantly different from those in the normal children. However, when the cut-off point for defining GH insufficiency was set at 5 ng/g creatinine, 87.5% (21 out of 24) of the short children with low urinary GH levels were suitable subjects for GH treatment (i.e. had complete GH deficiency, partial GH deficiency or impaired GH secretion during sleep).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Relationships between puberty and growth at adolescence in growth-hormone-deficient males: effect of growth hormone and of associated gonadal suppression therapy.

125 boys with idiopathic GH deficiency who received GH treatment were followed until they reached their final height. In 85 patients who had spontaneous puberty (group I), the mean final height was 151.5 +/- 6.6 cm. In 23 patients with combined GH and gonadotropin deficiency (group II) whose pubertal development was induced artificially at age 19.4 +/- 2.1 years, the mean final height was 163.7 +/- 3.9 cm (p less than 0.01 vs. group I). Final height was strongly related to height at the onset of pubertal development in combined groups I and II when the time of gonadal replacement treatment was taken as the onset of pubertal development in group II. In 17 patients (group III) who developed spontaneous puberty, gonadal suppression treatment was started at their early stage of puberty and was continued for a mean duration of 4.3 +/- 1.1 years. The mean final height in group III was 157.9 +/- 3.0 cm (p less than 0.01 vs. group I, group II). Longitudinal growth pattern analysis demonstrated that this beneficial effect on final height by gonadal suppression treatment was attributed to the elongation of pubertal growth spurt and pubertal height gain.

Adolescent↗
PubMed1990

Change in the growth hormone (GH) response to GH-releasing factor (GRF) caused by exogenous GH in short children.

To determine whether exogenous GH induces feedback of GH release in children, growth hormone-releasing factor (GRP) tests were performed before and after 10-day GH administration. Sixteen non-obese short boys, aged 5-14 yr, with normal GH response to pharmacological tests were studied. Mean basal and peak serum GH levels in GRF tests before and after exogenous GH were not significantly different. The subjects were divided into two groups, A and B, according to the percent change in integrated areas under the GH curves in GRF tests (GH AUC) before and after 10-day GH administration. Group A consisted of 6 boys with decreased GH AUC and group B consisted of 10 boys with increased GH AUC. Mean peak GH in GRF tests and mean GH AUC were significantly higher before exogenous GH in group A than in group B. The boys in group A were all prepubertal, while 4 boys in group B had begun their early pubertal change. The mean age in group A (7.8 +/- 1.8 yr) was significantly lower than that of group B (11.9 +/- 2.4 yr). GH AUC before exogenous GH showed a significant correlation with the percent change in AUC (= -0.742, p less than 0.01). These data demonstrated that the exogenous GH suppressed the GH response to GRF in prepubertal children with good response to GRF before exogenous GH, while it exaggerated the GH response to GRF in older children with relatively poor response before GH.

Adolescent↗
PubMed1989

The influence of gonadal function and the effect of gonadal suppression treatment on final height in growth hormone (GH)-treated GH-deficient children.

One hundred and sixty-one children with idiopathic GH deficiency who received GH treatment were followed until they reached their final height. Final height was found to be influenced by gonadal function. In 108 patients who had spontaneous puberty (91 boys and 17 girls; group A), the mean final height was 151.8 +/- 6.6 (+/- SD) cm in boys and 141.7 +/- 7.4 cm in girls. In 29 patients with combined GH and gonadotropin deficiency (23 boys and 6 girls; group C), whose pubertal development was induced artificially at age 19.5 +/- 2.1 yr in the boys and 18.6 +/- 1.8 yr in the girls, the mean final height was 163.7 +/- 3.9 cm in boys and 151.0 +/- 5.1 cm in girls. The differences in final height between groups A and C were significant in both boys and girls. The shorter final height in group A was caused by the shorter pubertal duration and smaller pubertal height gain than those in normal children. In 24 patients (17 boys and 7 girls; group B) who developed early signs of puberty, gonadal suppression therapy with cyproterone acetate and/or medroxyprogesterone acetate was given. The mean SD score of the final height in these 24 patients was -2.1 +/- 0.6, significantly higher than that in group A. This beneficial effect of gonadal suppression treatment on final height was caused by increases in the duration of puberty and the pubertal height gain.

Adolescent↗
PubMed1988

Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products.

Four steroid 21-hydroxylase B [P-450(C21)B] genes (designated P.7, P.10-1, P.10-2, and P.3) from three P-450(C21)-deficient patients were isolated to analyze their structures and functions. Several base changes were observed in the sequences of the four P-450(C21)B genes as compared to that of the functional B gene. Many of these base changes were identical to those of the P-450(C21)A pseudogene. The three DNAs (P.10-1, P.10-2, and P.3) produced no P-450(C21) activity in a functional assay for P-450(C21) by the COS cell expression system, while the P.7 DNA expressed the activity. The P.10-1 and P.10-2 DNAs were shown to have a point mutation in the second intron, causing aberrant splicing. The P.3 DNA carried three clustered missense mutations in the sixth exon, which impaired P-450(C21) activity. All these critical mutations could be seen in the corresponding site of the P-450(C21)A pseudogene. These data strongly suggest the involvement of gene conversion in this genetic disease.

Adrenal Hyperplasia, Congenital↗