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Biomedical subjects

E Hosoi

Publications and source records attributed to E Hosoi.

At least 19 recordsLinked to original sources

Correlation between permeability-related glycoprotein expression and susceptibilty to oxygen radicals in vincristine-resistant hematologic cell lines.

This study was designed to test the correlation between the expression of permeability-related glycoprotein (P-GP) and susceptibility to oxygen radicals derived from the reaction of hypoxanthine (HX)-xanthine oxidase (XO) in wild type and vincristine (VCR)-resistant hematologic cell lines. A marked correlation between P-GP expression and susceptibility to oxygen radicals was found in VCR-resistant cells, while it was weak in wild cell lines. In contrast, there was neither correlation between sensitivity to VCR and oxygen radicals nor between sensitivity to VCR and P-GP expression in both wild type and VCR-resistant cells. No correlation between sensitivity to adriamycin or oxygen radicals and P-GP expression were observed in both cells tested. These results may suggest a new mechanism of drug resistance in cells expressing P-GP.

ATP Binding Cassette Transporter, Subfamily B, Mem

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Adult

Secretory profile of immunoreactive growth hormone-releasing hormone (IR-GHRH) during sleep in man and its clinical value.

To clarify the role of growth hormone-releasing hormone (GHRH) in the regulation of the episodic growth hormone (GH) secretion which is known to occur constantly in the initial slow wave stage of nocturnal sleep in man, we studied the relation between the secretions of plasma immunoreactive(IR)-GHRH and GH while recording electroencephalograms. In subjects who showed a normal sleep pattern, the plasma IR-GHRH level increased 3- to 4-fold just before the surge of plasma GH, suggesting that GH release in the initial slow wave stage of sleep is mainly mediated by GHRH. However, when there was an apparent GH surge just before the onset of sleep, the magnitude of the GH response associated with the initial slow wave stage tended to be blunted, even when sufficient IR-GHRH was released. We also observed no appreciable fluctuations of plasma IR-GHRH during nocturnal sleep in a patient diagnosed as having GH-deficient dwarfism, suggesting the primary lesion was on the hypothalamus level, not the pituitary, in such a patient. In a case of multiple endocrine neoplasia (MEN) type I with an ectopic (GHRH-producing pancreatic tumor, no remarkable elevation of plasma IR-GHRH was detected in the initial slow wave stage of nocturnal sleep. We conclude that the present study is significant not only in demonstrating the physiology of GHRH release, but also in establishing a safe, reliable and practical test for routine clinical use to investigate intrinsic ability to release GHRH and the primary lesions in patients with disorders of GH secretion.

Acromegaly

[Genetic analyses of the ABO blood groups and application of the clinical laboratories].

Gene technology using polymerase chain reaction (PCR) has markedly advanced in recent year and has been introduced in clinical laboratories. In this paper, the genotypes of genomic DNAs of subjects with cisAB blood group were analysed using three methods, polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and the PCR-direct sequencing method, and directly determined using the polymerase chain reaction (PCR) amplification of specific alleles (PASA)-method. The differences among the methods were as follows, PCR-RFLP and PCR-direct sequencing method require 2-step procedures, and are complicated for clinical laboratories. The PASA method is based on the fact that PCR amplification occurs only when the 3' endbase of the primer is matched to sites of the nucleotide substitution of ABO allelic cDNA. Three of five regions of allelic DNAs were co-amplified in a single PCR (multiplex-PCR) in this study. ABO and cisAB blood group genotypes were directly determined, based on the molecular size of allele-specific amplification products. The PASA method requires only about 4 hours from starting PCR to results, making it rapid, simple and useful for detecting the genotype of ABO and cisAB blood groups in comparison with PCR-RFLP and the direct sequencing methods and will allow this procedure to be very versatile and widely used throughout the research and clinical diagnostic communities. The analyses of the nucleotide sequence at nucleotides No. 261, 526, 703, 796 and 803 in 3 major subjects in the cisAB blood group (cisA2B3, cisA1B3 and cisA2B) revealed chimeric structures of the A allele and B allele on the same gene.

ABO Blood-Group System

Takayasu's arteritis associated with antiphospholipid antibodies. Report of two cases.

The authors describe 2 patients with Takayasu's arteritis in whom lupus anticoagulant was positive and the titer of anticardiolipin antibody was elevated. One patient developed diffusely stenotic and occlusive changes in the multiple larger arteries. Histology of the small-sized arteries in another patient showed occlusive vasculitis without thrombosis, in addition to the findings in large-sized arteries compatible with Takayasu's disease. These findings are uncommon in Takayasu's arteritis. These findings suggest that antiphospholipid antibodies may have contributed to the pathogenesis of the extensive vasculopathy and may have triggered vasculitis in these patients.

Adult

[Direct determination of ABO and cisAB blood group genotypes using polymerase chain reaction amplification of specific alleles (PASA)--method].

The genotypes of genomic DNAs of 20 normal subjects with ABO blood group and 12 subjects with cisAB blood group were directly determined using polymerase chain reaction (PCR) amplification of specific alleles (PASA)-method. This method is based on the fact that PCR amplification occurs only when the 3' endbase of the primer is matched to the nucleotide of No. 261, 526, 796 or 803 of ABO allelic cDNA. And three of five regions of allelic DNAs are co-amplified in a single PCR (multiplex-PCR) in this study. ABO and cisAB blood group genotypes are directly determined, based on the molecular size of allele specific amplification products that contain 261, 526, 796 and 803 nucleotide (the sites of amino acid substitutions). The method requires only about 4 hours from starting up of PCR to the results, so it is rapid, simple and useful for detecting the genotype of ABO and cisAB blood groups.

ABO Blood-Group System

Increased serum IgE level and interleukin-4 release from cultured lymphocytes from a patient with adult onset Still's disease.

OBJECTIVE: To evaluate the relationship between high serum levels of IgE and the release of interleukin-4 (IL-4) from cultured lymphocytes of a patient with adult onset Still's disease. METHODS: IL-4 concentrations in plasma and culture from inactivated peripheral blood mononuclear cells were assessed by enzyme immunoassay during febrile episodes and remission. RESULTS: A high level of IL-4 was detected by enzyme immunoassay in the peripheral blood mononuclear cells cultured from the patient. These seemed to correspond with a febrile episode and a high serum IgE concentration. CONCLUSION: Increased serum IgE concentrations during a febrile episode are rare in patients with adult onset Still's disease, but the relationship between the high levels of serum IgE and IL-4 in cultured lymphocytes may provide clues to pathogenesis of the condition.

Adult

Two different pituitary adenomas in a patient with multiple endocrine neoplasia type 1 associated with growth hormone-releasing hormone-producing pancreatic tumor: clinical and genetic features.

The clinical and genetic features of a 43-year-old male patient with multiple endocrine neoplasia type 1 were reported. He developed hyperparathyroidism, a GHRH-producing pancreatic tumor, and acromegaly between 1980 and 1983. Because his pituitary gland increased in size even after resecting the GHRH-producing pancreatic tumor, transsphenoidal hypophysectomy was performed six years later. The pituitary contained two histologically-different adenomas composed of somatotroph cells and null cells. Genetic analyses revealed loss of heterozygosity on chromosome 11 in common in the pituitary adenomas, the pancreatic endocrine tumors, and a parathyroid hyperplasia. On the other hand, mutations of ras, p53, Gs alpha, and Gi2 alpha genes were not found in these tumors. The loss of the tumor suppressor gene on chromosome 11q12-13 was involved in the formation of two pituitary adenomas, two pancreatic endocrine functioning tumors, and a parathyroid hyperplasia in this patient, but the tumorigenic factors in the specific endocrine organs remain to be studied.

Acromegaly

[Genetic analysis of the genotype of ABO blood group with the DNA from a hair].

The genotype of the hair genomic DNA from 14 subjects with the ABO blood group was determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. The amino acid substitutions of codon 87 and 176 of ABO allelic cDNAs were analyzed to distinguish A, B, and O alleles by restriction enzyme digestion. To identify codon 87, the 249bp DNA fragment was amplified by PCR and digested with Kpn I. To identify codon 176, the 285bp DNA fragment was amplified by PCR and digested with Ban I. The genotype of the 14 ABO type-known subjects could be identified by the analysis of the digested DNA fragments. These findings indicate the usefulness of the PCR-RFLP method for determining the ABO genotype with the DNA from only one hair.

ABO Blood-Group System

Familial occurrence of two patients with malignant rheumatoid arthritis.

In Japan, patients with rheumatoid arthritis associated with severe extra-articular manifestations due to vasculitis are diagnosed as having malignant rheumatoid arthritis. We report the occurrence of two cases of malignant rheumatoid arthritis in a Japanese family. Both patients, a father and son, expressed HLA-DR4 (Dw15), and were infected with Epstein-Barr virus. Moreover, the father developed malignant rheumatoid arthritis during reactivation of the Epstein-Barr virus. An unaffected male family member with the same HLA haplotypes was not infected by the virus. The possible role of the virus infection in the pathogenesis of malignant rheumatoid arthritis in a genetically susceptible family is discussed.

Adult

Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma.

The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1-44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1-44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125-2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992 +/- 68-1872 +/- 32 ng.1.7 x 10(5) cells-1 x 3 h-1), similar to that observed with synthetic GHRH(1-44)NH2. (control value 640 +/- 30 ng.1.7 x 10(5) cells-1 x 3 h-1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.

Adrenal Gland Neoplasms

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