Search PubMed⌕ Search

Biomedical subjects

E Hosoi

Publications and source records attributed to E Hosoi.

At least 37 records · Page 2Linked to original sources

Analysis of the Gs alpha gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues.

We investigated the prevalence of Gs alpha gene mutations in growth hormone (GH) secreting pituitary adenomas from Japanese patients with acromegaly. Forty-five GH-secreting adenomas were examined for the presence of point mutations in codons 201 or 227 of the Gs alpha gene using the polymerase chain reaction-direct sequencing method and deoxyribonucleic acid extracted from paraffin-embedded tumor specimens. Mutation of codon 227 of the Gs alpha gene was not observed in any of the tumors, but a mis-sense mutation of codon 201 was identified in two tumors (4.4%). One lesion was a densely granulated GH cell adenoma in a patient with adenomatous goiter and breast cancer. The other was a mixed GH cell-prolactin cell adenoma in a patient with multiple endocrine neoplasia type 1 associated with parathyroid hyperplasia and a pancreatic islet cell tumor. The Gs alpha gene detected in parathyroid tissue and pancreatic tumor tissue was of the wild type in this second patient, and the mutation was specific to the pituitary tumor. These results suggest that point mutations of codons 201 or 227 of the Gs alpha gene may not be important mediators of oncogenesis for GH-secreting pituitary adenomas in Japan.

Adenoma↗

[Genetic analyses of the genotypes of ABO and cisAB blood groups].

The genotypes of genomic DNAs of 20 normal subjects with ABO blood group and 12 subjects with cisAB blood group were analysed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a combination of PCR-RFLP and direct sequencing method, respectively. To identify the codon 87, 249 bp DNA fragment was amplified by PCR and digested with Bst EII and Kpn I. To identify the codon 176, 506 bp DNA fragment was amplified by PCR and digested with Bss HII and Ban I. To identify the codon 235, 266 and 268, 506 bp DNA fragment was amplified by PCR and determined by direct sequencing. Analyses of the digested DNA fragments of codon 87 and 176 in 20 normal subjects with ABO blood group revealed the ratio of homotype (AA, 20%; BB, 20%) and heterotype (AO, 80%; BO, 80%) in subjects with phenotype A or B. Same results were obtained in subjects with phenotype AB or O. The analyses of nucleotide sequence at codons 87, 176, 235, 266 and 268 in 12 subjects with cisAB blood group (6 cisA2B3, 3 cisA2 B and 3 cisA1B3) revealed chimera structure of A allele and B allele on the same gene. These results indicate the usefulness of PCR-RFLP method for determining the genotype of A and B bloods group, and a combination of PCR-RFLP and direct sequencing for determining the genotype of cisAB blood group.

ABO Blood-Group System↗

[The right chest electrocardiogram in normal subjects].

Right chest electrocardiograms (ECGs) of 75 healthy subjects (19 men and 56 women; age 18 to 25 years) were recorded in order to study characteristic features of right precordial ST-T and QRS waves. The diagnostic criteria for right ventricular infarction (RVI) by ECG were also tested in healthy subjects to reascertain their value for diagnosing RVI. 1) The QRS configuration in right chest leads was usually the rS pattern in normal subjects (95% of V3R and 80% of V4R). 2) The Q wave was found in 5% of V4R, 20% of V5R and 51% of V6R. 3) ST elevation of 0.05-0.1 mV at 40 ms and 80 ms after the end of QRS deflection was found in 16 and 28% of V3R, 3 and 4% of V4R, respectively. 4) The T waves were usually negative in all right chest leads (79-88%). 5) The Q waves in V5R and V6R and ST elevation in V3R were relatively frequent findings in normal subjects. Therefore, the presence of a Q wave or ST elevation in these leads are not necessarily specific indicators of RVI by ECG. Furthermore, our data revealed that ST elevation with a Q wave in right chest leads was not present in any of the healthy subjects. This finding may be a more specific indicator for the diagnosis of RVI by ECG.

Adolescent↗

A pituitary specific point mutation of codon 201 of the Gs alpha gene in a pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1.

The DNA from a pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1 was analyzed to detect a point mutation of the Gs alpha gene (gsp) by the PCR direct-sequencing method. The patient had galactorrhea, amenorrhea and acromegalic features. Hormonal examination revealed high serum levels of PRL and GH. The tumor was histologically diagnosed as a mixed GH cell-PRL cell adenoma in which GH and PRL were produced by different cells. Sequence analysis of the DNAs extracted from paraffin sections of pituitary, parathyroid, and pancreas tumors demonstrated the substitution of thymidine for cytidine in codon 201 of the Gs alpha gene that resulted in replacement of arginine (CGT) with cysteine (TGT) only in the pituitary adenoma, but not in the parathyroid and pancreas tumors. These results suggest that a pituitary specific point mutational activation of the Gs alpha gene may be involved in the development of the pituitary adenoma in this patient.

Adenoma↗

Extension of the jaw opening reflex and effects of a central muscle relaxant (afloqualone) in the rat.

How widely the jaw opening reflex (JOR) extends was examined in the rat. Recording was done in the anterior (AD) and posterior (PD) digastric, sternohyoid (SH) and sternomastoid (SCM) muscles. Electric stimulation was given to the mandibular incisor pulp. Evoked electromyogram (EMG) activities could be recorded in each muscle. The thresholds for JOR increased from AD to SCM. Intravenously administered afloqualone, a centrally acting muscle relaxant, inhibited both JOR and its parallels promptly and dose-dependently. The possible clinical significance in temporomandibular joint dysfunction will be discussed.

Animals↗

[The effects of PGE2, 2-DG and L-arginine on hypothalamic GHRH and SRIF releases in conscious rats, with respect to GH secretion].

The effects of prostaglandin E2 (PGE2), 2-deoxy-D-glucose (2-DG) and L-arginine on hypothalamic GHRH and SRIF release with respect to GH secretion were studied in conscious male rats. Intracerebroventricular (icv) injection of 5 micrograms PGE2 and intravenous (iv) infusion of 1 g/kgBW L-arginine caused an increase in plasma GH levels, but icv (36 micrograms) or iv (400 mg/kgBW) injection of 2-DG suppressed spontaneous GH surge in conscious rats. The concentration of hypothalamic GHRH was decreased in all three groups of the animals, but the concentration of hypothalamic SRIF was decreased only in 2-DG-treated animals. In the perifusion system using rat hypothalamus, PGE2 (0.28 microM, 2.8 microM), 2-DG (22 mM) and L-arginine (3 mM) stimulated GHRH release from rat hypothalamus. 2-DG also stimulated SRIF release more predominantly than GHRH release. Passive immunization with anti-GHRH serum inhibited the GH secretion induced by icv injection of 5 micrograms PGE2 and by iv infusion of 1 g/kgBW L-arginine in conscious rats. In contrast, GH secretion induced by iv injection of 50 micrograms/kgBW PGE2 was not affected by the pretreatment with the antiserum. These results suggest that the central effect of PGE2 and peripheral effect of L-arginine to stimulate GH secretion are mediated by hypothalamic GHRH release, and that the inhibitory effect of 2-DG on GH secretion is predominantly mediated by hypothalamic SRIF release rather than GHRH release in rats.

Animals↗

Subclinical pseudohypoparathyroidism type II: evidence for failure of physiologic adjustment in calcium metabolism during pregnancy.

Patients with latent disorders of hormone response mechanism are rarely found. This paper reports a case of subclinical pseudohypoparathyroidism type II in which physiological adjustment of calcium (Ca) metabolism became insufficient only in the second half of pregnancy. A 34-year-old woman examined for a slight bruise on the head was incidentally found to have marked intracranial calcification and a full set of false teeth. From her history of past pregnancy, it was revealed that she suffered from symptoms of hypocalcemia during late gestation (serum total Ca level, 4.8-6.4 mg/dl), which disappeared spontaneously after delivery. When the woman was not pregnant, although only the total Ca level was slightly below the normal range (7.7-8.4 mg/dl), the serum ionized Ca, phosphorus (P), magnesium, 1,25-dihydroxycholecalciferol and 24,25-hydroxycholecalciferol levels, plasma parathyroid hormone (PTH) level and urinary excretion of Ca were all normal without treatment. Intravenous infusion of 30 mg/kg EDTA-2Na resulted in marked elevation of plasma PTH associated with significant reduction of serum ionized Ca. In contrast, although her urinary excretion of phosphorous per hour was within the normal range in the basal state, she showed no proportional change in urinary phosphorous excretion with increase in urine cyclic AMP induced by administration of PTH(1-34). From these findings, she was diagnosed as having an incomplete form of pseudohypoparathyroidism Type II. This abnormality seems to be rare, but we consider that the present observations provide important information for preventive care of pregnant women and fetuses during gestation.

Adaptation, Physiological↗

Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I.

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.

Acromegaly↗

Secretion of growth hormone-releasing hormone in patients with idiopathic pituitary dwarfism and acromegaly.

The plasma levels of immunoreactive-GHRH in patients with idiopathic pituitary dwarfism and acromegaly were studied in the basal state and during various tests by a sensitive and specific RIA. The fasting plasma GHRH level in 22 patients with idiopathic pituitary dwarfism was 6.3 +/- 2.3 ng/l (mean +/- SD), which was significantly lower than that in normal children (9.8 +/- 2.8 ng/l, N = 21), and eight of them had undetectable concentrations (less than 4.0 ng/l). Little or no response of plasma GHRH to oral administration of L-dopa was observed in 7 of 10 pituitary dwarfs, and 3 of the 7 patients showed a response of plasma GH to iv administration of GHRH (1 microgram/kg). These findings suggest that one of the causes of idiopathic pituitary dwarfism is insufficient GHRH release from the hypothalamus. The fasting plasma GHRH level in 14 patients with acromegaly and one patient with gigantism was 8.0 +/- 3.9 ng/l, which was slightly lower than that in normal adults (10.4 +/- 4.1 ng/l, N = 72). One acromegalic patient with multiple endocrine neoplasia type I had a high level of plasma GHRH (270 ng/l) with no change in response to L-dopa and TRH test. In 3 untreated patients with acromegaly L-dopa did not induce any response of plasma GHRH in spite of inconsistent GH release, and in 4 patients with acromegaly, TRH evoked no response of plasma GHRH in spite of a marked GH release, suggesting that the GH responses are not mediated by hypothalamic GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Effect of electric stimulation of the celiac vagus on gastric acid secretion and plasma concentrations of somatostatin and gastrin in the portal and gastroepiploic veins of dogs.

Electric stimulation (ES) of the celiac vagus during tetragastrin infusion reduced significantly the portal plasma concentration of somatostatin (SS) from 113 +/- 11.3 pg/ml to 87.8 +/- 5.8 pg/ml (P less than 0.05) in anesthetized dogs, in parallel with marked decrease of gastric acid secretion (59.9 +/- 7.1% of the prestimulatory value; P less than 0.01). A similar change in the portal plasma SS concentration was observed by ES of the celiac vagus on infusion of saline, with a concomitant significant increase in the portal plasma level of gastrin from a basal value of 65.9 +/- 7.0 pg/ml to a peak value of 129 +/- 29.9 pg/ml (P less than 0.05). However, no fluctuation of the plasma SS or gastrin level in the gastroepiploic vein was detected during or after ES of the celiac vagus. These findings indicate that gastric SS and gastrin are not of primary importance in the mechanism of inhibition of gastric acid secretion induced by ES of the celiac vagus in the dog.

Animals↗

Production and secretion of immunoreactive growth hormone-releasing factor by pheochromocytomas.

The production and secretion of immunoreactive growth hormone-releasing factor (IR-GRF) by pheochromocytomas were examined immunohistochemically and immunochemically. GRF-immunoreactive (GRF-IR) cells were found, although sparsely, in 2 of 13 tumors (Cases 1 and 2), while somatostatin (SRIF)-IR cells and vasoactive intestinal peptide (VIP)-IR cells were found in nine and five tumors, respectively. Concentrations of tissue IR-GRF of 29.8 and 17.2 ng/g wet weight tissue, respectively, were found in two (Cases 1 and 2) of three tumors examined. These three tumors also contained IR-SRIF at 19.5-105.5 ng/g wet weight tissue and IR-VIP at 13.6-24.8 ng/g wet weight tissue. An increased plasma IR-GRF concentration (30.0 pg/ml) was found in a blood sample taken from the inferior vena cava near the adrenal tumor in Case 1. This is the first report that some pheochromocytomas produce GRF and secrete it into the blood circulation.

Adolescent↗

Immunoreactive somatostatin and calcitonin in pulmonary neuroendocrine tumor.

A well-differentiated neuroendocrine carcinoma of the lung that secreted immunoreactive somatostatin (IR-SRIF) and IR-calcitonin (CT) in a 72-year-old women is described. The plasma concentrations of IR-SRIF (57.5 pg/ml) and IR-CT (340 pg/ml) before operation were significantly higher than the respective normal ranges. After resection of the tumor, the plasma CT level (105 pg/ml) decreased to within the normal range, and the SRIF level (32.7 pg/ml) also decreased, but was still abnormally higher, which suggested the presence of an unidentified remnant of the tumor. Abnormal accumulation of technetium 99m (99mTc) in the lumbar vertebrae was found 6 months after the operation, which indicated a metastatic tumor. The tissue concentrations of IR-SRIF and IR-CT were 103 and 94 ng/g wet weight, respectively, and SRIF-IR tumor cells and CT-IR tumor cells were demonstrated immunohistochemically. On gel-filtration chromatography of the tumor tissue, two peaks of SRIF immunoreactivity were eluted in the positions of synthetic SRIF-28 and SRIF-14, respectively. Conversion of SRIF-28 to SRIF-14 was suggested from results on changes in the two IR-SRIF components during incubation with a crude enzyme preparation extracted from the tumor tissue.

Aged↗

Radioimmunoassay of an analog of luteinizing hormone-releasing hormone, [D-Ser(tBu)]6des-Gly-NH2(10) ethylamide (Buserelin).

A sensitive and specific radioimmunoassay is described for plasma and urinary levels of [D-Ser(tBu)]6des-Gly-NH2(10) ethylamide (buserelin). No appreciable cross-reaction (less than 0.05%) was observed with LH-RH and its analogs other than buserelin fragments (1.6-45%). The sensitivity was 3 pg per tube. At buserelin concentrations of 125, 250 and 500 pg/ml, the intra- and inter-assay coefficients of variation were 7.9, 10.0 and 10.0%, and 19.0, 7.8 and 6.8% respectively. Recovery of buserelin added to plasma was quantitative (62.5 pg/ml, 101.6%; 125 pg/ml, 76.8% and 250 pg/ml, 63.4%). A dose of 5 micrograms buserelin injected subcutaneously into 5 normal male adults, reached a peak plasma level in 45 min (mean value 119.3 +/- 47.3 pg/ml) and remained detectable for at least 4 h. The half disappearance time was 118.8 +/- 26.0 min. Between 9 and 16% of the administered dose was excreted in the urine within 24 h. Buserelin could also be detected in the plasma after intranasal administration of doses of 150, 300 and 450 micrograms. There was a significant difference in the area under the curve (AUC) for plasma levels after subcutaneous injection of 5 micrograms and intranasal administration of 150 micrograms, but not between the AUC values after the three intranasal doses. These results indicate that this method for radioimmunoassay of buserelin is suitable for analyzing the pharmacokinetics and bioavailability of buserelin in man.

Administration, Intranasal↗