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Biomedical subjects

H Miyajima

Publications and source records attributed to H Miyajima.

At least 73 records · Page 4Linked to original sources
PubMed1995

Mechanism for species-specific induction of Leydig cell tumors in rats by lansoprazole.

Lansoprazole is a substituted benzimidazole which inhibits gastric acid secretion by inhibiting the hydrogen-potassium ATPase (proton pump) in the parietal cell. The finding of Leydig cell hyperplasia and Leydig cell tumors in 2-year oral studies in Sprague-Dawley rats but not in CD-1 mice prompted investigative studies to determine the mechanism for the Leydig cell changes. hCG challenge studies in Sprague-Dawley rats revealed decreased testosterone responsiveness in rats treated orally for 1 or 2 weeks with lansoprazole. After 4 weeks of daily oral treatment increases in serum LH and decreases in serum testosterone were detected within a few hours after dosing. In a study where 9-month-old male F344 rats were given testosterone supplementation via Silastic implants and then treated with lansoprazole for 6 months, a high incidence of Leydig cell tumors was seen in lansoprazole-treated, unsupplemented rats, whereas no Leydig cell tumors were seen in testosterone supplemented rats. This implied that reduction of the normal feedback inhibition at the level of the hypothalamus and/or pituitary due to reduced testosterone levels, thus giving rise to elevated levels of LH, was involved in the induction of Leydig cell tumors by lansoprazole. In vitro studies with Leydig cells from rats using various stimulators and precursors of testosterone biosynthesis demonstrated that the most sensitive site for inhibition of testosterone synthesis by lansoprazole is the transport of cholesterol to the cholesterol side chain cleavage enzyme. The IC50s for inhibition of LH or hCG-stimulated testosterone synthesis in Leydig cells from rats, mice, and monkeys were 11-12, 8, and 24.7 micrograms/ml, respectively. In vitro studies with metabolites of lansoprazole revealed that three metabolites were more potent inhibitors of testosterone synthesis than the parent drug, two of them being at least 10 times more potent. These metabolites are present in rats at substantial levels but are undetectable in humans. The lack of induction of Leydig cell tumors in mice, lower sensitivity of primate Leydig cells, and the absence of testosterone synthesis-inhibiting metabolites in man suggest that Leydig cell tumors found in rats represent a species-specific sensitivity and does not imply a risk for clinical use in man.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Frequent detection of hepatitis C virus subtype 3a (HCV-3a) isolates in Thailand by PCR using subtype-specific primers.

By means of a polymerase chain reaction (PCR) method using subtype-specific primers for hepatitis C virus (HCV) subtypes 1a, 1b, 2a, 2b and 3a, the prevalence of each subtype among HCV isolates in Chiang Mai, Thailand, was determined. HCV-3a appeared to be the most common subtype in blood donors, and was also frequently found in patients with liver disease. HCV-1b, but not HCV-2a or -2b, was also commonly found in this area, while a considerable percentage of the total HCV isolates still remained unclassifiable by the above methods. Serotype analysis of the HCV isolates using C14-1 and C14-2 recombinant peptides revealed that HCV-3a was likely to carry an antigenic determinant(s) different from those of the major types 1 (HCV-1a and -1b) and 2 (HCV-2a and -2b).

Adult↗
PubMed1995

Genetic analysis of a family of lactate dehydrogenase A subunit deficiency.

Lactate dehydrogenase A subunit (LDH-A) deficiency is an inherited metabolic myopathy of glycolysis. The severity of this disease varies from case to case. We reported non-consanguineous male sibling cases who had severe muscle pain and rhabdomyolysis during anaerobic exercise. Genetic analysis revealed 20 base pair deletion of the sixth exon of the LDH-A gene. There was no difference in the gene abnormality between our patients and previously reported female cases who had history of consanguinity and lower degree of symptoms. The differences in disease severity were not due to genomic abnormality in our two families.

Adult↗
PubMed1995

Characterization of the oxidative metabolism in lactate dehydrogenase A deficiency.

Recurrent rhabdomyolysis due to decreased glycolysis occurred during strenuous exercise in patients with lactate dehydrogenase A subunit (LDH-A) deficiency. We report the features of oxidative metabolism of four patients from two families in whom the severity of the disease differed. Enzyme activities of muscle LDH were decreased to < 5% of control. There was no difference in the gene abnormality. Maximal oxygen uptake in the patients with severe and mild symptoms was approximately 73% and 92% of control. Respiratory exchange ratio was increased to more than 1.0 during maximal exercise. These findings suggest that in these patients, the oxidative functions of glycogenolysis in which pyruvate is required for fuel of maximal oxidative metabolism are preserved, and that disease severity may be related to the degree of muscle oxidative capacity.

Adult↗
PubMed1995

[A case report of variegate porphyria].

We reported a 30-year-old woman with variegate porphyria. Family history disclosed that her mother had the same skin lesions as the present case. She has had repeated vesicles and brownish pigmentation on her upper extremities since eighteen years of age. Recently she was suffering from common cold, and was treated with drugs. One week later, she started to develop weakness and dysesthesia in all limbs, hallucination, and urinary disturbance. Three weeks later, she was admitted to our hospital because she could not stand any more. On general examination, she had brownish pigmentations and crusts in hands and forearms. Neurologically she had moderate weakness, dysesthesia and hyperreflexia in all limbs. Urine was dark-red. Head and cervical MRI was normal. Nerve conduction studies and somatosensory evoked potentials were within normal limits. Excretion of porphyrins, especially protoporphyrin and X-porphyrin in the feces were markedly increased, and the diagnosis of variegate porphyria was made. Intravenous administration of glucose was effective and her symptoms began to improve in two weeks after her admission. However, recovery of weakness took two months and dysesthesia did not disappear in three months. We considered that her clinical manifestations were caused by involvement of the central and peripheral nervous systems.

Adult↗
PubMed1994

Suppression of IgE production in unseparated spleen cell cultures.

When B cells from BALB/c mice were cultured with lipopolysaccharide (LPS) and interleukin-4 (IL-4), a large amount of IgE was detected in the culture supernatants. The IgE production from unseparated spleen cells cultured with LPS and IL-4 was less than the amount of IgE obtained from separated B cells. When syngeneic T cells were added to separated B cells cultures, which were subsequently stimulated with LPS and IL-4, less IgE was produced, as compared to cultures without T cells. The hypothesis that T cells, or factors secreted by these cells, inhibit IgE production is supported by the fact that the degree of suppression of IgE production paralleled the number of T cells added. CD8(+)-enriched T cells were slightly more suppressive than CD4(+)-enriched T cells. Addition of exogenous IL-3 was only partially suppressive. These observations suggest that IL-4 added to unseparated spleen cells in vitro stimulates B cells for IgE production and also stimulates T cells. Lymphokines secreted by these stimulated T cells may in turn act on B cells. Some of these lymphokines, such as interferon-gamma and IL-2, may have a suppressive action on IgE production.

Animals↗
PubMed1994

Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice.

Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea (ETU) and sodium nitrite (NaNO2) was investigated in ICR (Crj:CD-1) female mice. A mixed solution of ETU (100 mg/kg) and NaNO2 (70 mg/kg) was given to animals orally once a week for up to 6 months and all surviving animals were killed at 12 months of study. During the study, estrous cycle was monitored by vaginal smear and five or 10 selected animals were subjected to interim killing at 3 month interval to observe time-related carcinogenic responses of the uterus. Treatment with ETU and NaNO2 resulted in development of endometrial adenocarcinomas in the uterine horn and the incidence reached 42% in the surviving animals at 12 months. Prior to the development of the tumor, atypical hyperplasia of endometrial glands was frequently observed and regarded as the precancerous lesion. Immunohistochemistry for bromodeoxyuridine (BrdU) incorporation revealed higher labeling indices in both hyperplastic and neoplastic endometrial glandular cells, and the index in the adenocarcinoma was more than 20% on average at any stage of the estrous cycle. Overexpression of p53 protein, which is frequently demonstrated in virulent phenotypes of human corpus cancers, was seen in three out of eight (38%) adenocarcinomas, but not in the atypical hyperplasia or normal endometrial glands. There were no treatment-related changes in the estrous cycle on vaginal smears at any interval of the study. The analyses for plasma ovarian hormones at 12 months disclosed a marked depression of progesterone in the treated animals, while the 17 beta-estradiol (E2) level was comparable to the controls. These results suggest that endometrial carcinogenesis by ETU and NaNO2 could be initiated with atypical hyperplasia of the endometrial gland and a decrease in plasma progesterone level may play an important role in the development of endometrial carcinogenesis. In addition, inactivation of the p53 gene may play a significant role in the malignant transformation of endometrial epithelial cells in mice.

Adenocarcinoma↗
PubMed1994

Analysis of hepatitis C virus isolates among healthy blood donors and drug addicts in Chiang Mai, Thailand.

Hepatitis C virus (HCV) isolates obtained from 25 anti-HCV antibody-positive healthy blood donors and 29 drug addicts in Chiang Mai, Thailand, were analyzed. HCV RNA was detected in 23 blood donor samples (92%) and 24 drug addict blood samples (83%) by PCR for a portion of the NS5 region. Subtype analysis revealed that HCV type 3a (HCV-3a) was the prevailing subtype (30%), which was followed in prevalence by HCV-1a (21%), -1b (13%), -3b (13%), and -6a (2%). Six (13%) of the 47 isolates showed low sequence similarities with known types and subtypes. The sequence variants could be grouped into four branches in a molecular evolutionary phylogenetic tree.

Amino Acid Sequence↗
PubMed1993

Molecular characterization of gene expression in human lactate dehydrogenase-A deficiency.

Recurrent rhabdomyolysis due to decreased glycolysis occurred during strenuous exercise in patients with lactate dehydrogenase-A-subunit (LDH-A; muscle) deficiency. Enzyme activities of LDH in the muscle were decreased less than 8% of the control value. The isozyme pattern revealed only one band of B4. The level of LDH-A mRNA was not decreased. The direct sequencing of the reverse transcription-polymerase chain reaction product that corresponds to exon 6 revealed a deletion of 20 nucleotides. Immunofluorescence staining showed the presence of LDH-A protein within the cytoplasm. These findings suggest that an incomplete LDH-A protein lacking the subunit contact subdomain could not assemble into a tetrameric structure that has an enzymatic activity.

Adult↗
PubMed1993

Facioscapulohumeral syndrome with sensorineural hearing loss and abnormality of retinal vessels.

A 23-year-old man was recognized as a sporadic case of facioscapulohumeral syndrome (FSH syndrome). He was a case of early onset, and there was severe atrophy of skeletal muscles, although muscle biopsy was normal. Electromyogram revealed neurogenic changes. This patient also had severe sensorineural hearing loss and a mild abnormality of retinal vessels. It is known that some FSH dystrophy or FSH spinal muscular atrophy patients have such coincidental complications. The cause of these coincidences is still unclear, but their occurrence suggests the pleiotropy of the FSH syndrome.

Adult↗
PubMed1993

The family structure in contemporary Japan.

The applicability of models of the family developed in the disciplines of sociology and cultural anthropology to the modern Japanese family is considered. "Our aim is to understand the contemporary Japanese family from two perspectives: the family as an economic unit and the family as a social security provider based on the arrangement and analysis of materials and statistics concerning current structure, form, type, and size of the contemporary Japanese family." Data are primarily from the annual survey undertaken by the Ministry of Health and Welfare on living conditions.

Asia↗
PubMed1993

In vivo stimulation of endosteal bone formation by basic fibroblast growth factor in rats.

Intravenous administration of human basic fibroblast growth factor (bFGF) for 2 weeks stimulated osteoblast proliferation and new bone formation in various skeletal bones in young and aged rats at dosage levels of 0.1 mg/kg/day and greater. Morphometry of the soft X-ray radiograms of cross sections of the tibia indicated about a 20% increase in the calcified bone area of the diaphysis at 0.1 mg/kg/day. The Ca and hydroxyproline contents showed statistically significant increases at this dosage. The new bone formation was found only on the endosteal side, and no periosteal bone formation was found. Similar systemic osteogenic potential was seen after intravenous administration of other growth factors of the FGF family, human acidic FGF and human heparin-binding secretory transforming protein-1. The above results suggest a potential therapeutic role for these growth factors in bone-loss diseases such as osteoporosis.

Aging↗
PubMed1993

[Clinical features and prognosis of Churg-Strauss syndrome].

We studied the clinical features and prognosis of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 1 man and 10 women with a mean age of 56.3 years. All subjects had a history of bronchial asthma prior to the onset of CSS. It was noted that the age of onset of bronchial asthma was high, and most of the patients had suffered from frequent and severe asthmatic attacks during the periods preceding the vasculitis. Skin tests and IgE RAST revealed that less than half of the subjects were atopic. Therefore it is considered that asthmatics with late onset and severe symptoms have a high risk for CSS, and poor control of asthmatic symptoms may contribute to the onset of the vasculitis. Eleven of 12 cases including 1 patient with a relapse were treated with PSL alone (9 cases) or PSL plus cyclophosphamide (2 cases). Three patients died of heart failure or central nerve involvement. Vasculitis was ameliorated in the other cases (75%). Seven patients received maintenance therapy with low-dose of PSL (5 cases) or cyclophosphamide (2 case). None suffered from relapse of vasculitis during maintenance therapy. Discontinuation of therapy in five cases resulted in a relapse in only one case 62 months after the cessation of low-dose PSL. Although maintenance therapy appears to be useful in some CSS patients, the significance and indications for maintenance therapy should be further clarified.

Adult↗