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Biomedical subjects

I Morimoto

Publications and source records attributed to I Morimoto.

At least 55 records · Page 3Linked to original sources
PubMed1995

Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1.

The two major processes of bone metabolism--bone formation and resorption--are regulated by cellular interactions. Osteoblasts and osteoclasts play a significant role in bone metabolism, which is known to be regulated by local soluble factors and systemic hormones. Although bone is a heterogeneous tissue comprised of osteogenic and hematopoietic cells, cellular adhesion of osteoblasts and its regulation remains to be understood. We first demonstrate that cellular adhesion by which osteoblasts communicate with opposing cells in bone milieu is involved in the osteoblast activation: (a) purified human osteoblasts obtained from osteoarthritis patients expressed particular adhesion molecules, ICAM-1, VCAM-1, and LFA-3; (b) toe osteoblasts adhered to T cells which were used as representative adhesive partners, since T cells possess all the receptors to these adhesion molecules; (c) mRNA transcription and secretion of IL-1beta and IL-6 were induced in the osteoblasts by the cellular adhesion to T cells and they were reduced by interrupting the adhesion; (d) cross-linking of ICAM-1 and VCAM-1 on the osteoblasts induced IL-6 secretion from the osteoblasts. These results indicate that osteoblasts adhere to opposing cells through particular adhesion molecules on their surface and that the adhesion molecules on the osteoblasts not only function as glue with opposing partners but transduce activation signals that facilitate the production of bone-resorbing cytokines. We propose that cellular adhesion of osteoblasts as well as soluble factors is significant for the regulation of bone metabolism.

Base Sequence↗
PubMed1995

Stimulatory effect of interleukin-1 alpha on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM 1.

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1 alpha (IL-1 alpha) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of 3H-thymidine (3H-TdR). The stimulatory effect of IL-1 alpha was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1 alpha on both 3H-TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1 alpha on 3H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca2+, inhibition of 3H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1 alpha stimulates cell proliferation through a Ca2+/calmodulin-dependent pathway in NIM 1 cells.

Biological Transport↗
PubMed1995

Siblings with ACTH insensitivity due to lack of ACTH binding to the receptor.

We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH insensitivity. They were referred to our hospital because of pigmentation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z administration, but plasma aldosterone responded normally to increased plasma renin activity after a low sodium diet. We examined the characteristics of ACTH receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the patients and their family. Adenylate cyclase generation caused by an addition of ACTH did not occur in MNLs from the patients. In studies on ACTH binding to MNLs, a lack of high-affinity ACTH binding was observed in the patients. These results suggest that the patients have a defect in ACTH binding to the receptors, resulting in ACTH insensitivity. The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients.

17-Hydroxycorticosteroids↗
PubMed1995

Endemic goiter in the Jos Plateau region of northern Nigeria.

This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 1.3 microgram/dl (32-154 microgram/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5 mg/dl, suggesting that the role of the thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.

Adolescent↗
PubMed1995

Autopsy findings of Addison's disease caused by systemic cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.

We previously reported a case of Addison's disease associated with acquired immunodeficiency syndrome (AIDS) (Endocr J, 41:13, 1994). A 46-year-old man with hemophilia B and AIDS was diagnosed as Addison's disease. The positive cytomegalovirus (CMV) antigen in urine suggested that CMV adrenalitis may have caused the adrenal insufficiency. Despite treatment with ganciclovir, the patient died one year later. Autopsy findings revealed that the typical inclusions of CMV were seen in the lung, adrenal glands (both cortex and medulla) and small intestine. Here, we describe the subsequent clinical course and postmortem findings of this case.

AIDS-Related Opportunistic Infections↗
PubMed1995

Germ line mutation in the RET proto-oncogene associated with familial multiple endocrine neoplasia type 2B: a case report.

Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome. MEN 2B is characterized by the combined occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and Marfanoid habitus. Recently, a missense mutation in codon 918 of the proto-RET has been reported in the germ line of apparently distinct families with MEN 2B. In the present paper we first show a familial case of MEN 2B in Japan also to be associated with a germ line mutation in codon 918 of the proto-RET. The mutation was the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein. The germ-like mutations of the proto-RET in MEN 2A and MEN 2B are the first examples of a dominantly acting oncogenic point mutation initiating human hereditary neoplasia.

Adrenal Gland Neoplasms↗
PubMed1995

[Multiple endocrine neoplasia].

Multiple endocrine neoplasia (MEN) is dominantly inherited tumor syndromes characterized by multiple endocrine hyperfunctions due to hyperplastic or adenomatous as well as carcinomatous abnormalities. The syndromes are classified into MEN 1, 2A and 2B according with the complex of abnormalities. Hyperparathyroidism is the most common manifestation of MEN 1 and is also associated with MEN 2A. Recent genetic studies revealed that alleleic deletions on chromosome 11q13 are involved in the monoclonal development of endocrine cell in MEN 1 and germ-line mutations of RET proto-oncogene are associated with MEN 2A and 2B. This paper reviews clinical characteristics of MEN 1, 2A and 2B in Japan and presents the respective case reports including the gene analysis.

Adult↗
PubMed1994

Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein-stimulated osteoclast formation in mice.

We examined the in vivo effects of recombinant murine IL-4 (rmIL-4) on spontaneous and stimulated mouse osteoclast formation. EC-GI cells, which produce PThrP and IL-1 alpha, were explanted in nude mice. These EC-GI cell-bearing nude mice developed hypercalcemia (4.90 +/- 0.68 mM), and the calcium levels were decreased to near normal (3.48 +/- 0.73 mM, p < 0.05) at day 3 by continuous infusion of rmIL-4 at a dose of 7 micrograms/day. When infused with 0.6 nmol/day of PTHrP(1-34) in ICR mice, rmIL-4 at a dose of 1 or 5 micrograms/day for 3 days caused a marked inhibitory effect on hypercalcemia induced by PTHrP(1-34) (3.73 +/- 0.56-2.54 +/- 0.14 mM, p < 0.01). However, rmIL-4 alone did not change the serum calcium in mice. Histomorphometric analysis revealed that rmIL-4 inhibits both spontaneous and PTHrP(1-34)-stimulated osteoclast formation in mice, with a decrease in osteoclastic surface and in the number of osteoclasts per mm bone surface, respectively. We conclude that IL-4 inhibits spontaneous and stimulated bone resorption resulting from inhibition of osteoclast formation and modulates the development of humoral hypercalcemia of malignancy.

Animals↗
PubMed1994

Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells.

To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (Kd 7.37 nM, Bmax 10.59 fmol/mg protein) and dihydrotestosterone (DHT; Kd 4.89 nM, Bmax 11.37 fmol/mg protein) in VSMC. Measurement of 5 alpha-reductase activity suggested that testosterone is converted to DHT in VSMC (Km 0.36 microM, Vmax 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

The receptor, metabolism and effects of androgen in osteoblastic MC3T3-E1 cells.

We investigated the androgen receptor (AR), metabolism and effects of androgens in osteoblastic MC3T3-E1 cells. AR was proved as a transcript of a 10-kb mRNA and as a 110-kDa protein. An immunocytochemical study showed that AR was located mainly in the nuclei. Specific binding of [3H]DHT was observed in both the nuclear and cytosol fractions. MC3T3-E1 cells possessed approximately 1190 binding sites per cell and most of the sites (1150 sites) situated in the nucleus. The apparent Kd value in the nuclear fraction was 1.35 nM for [3H]DHT binding, and it was similar to that for [3H]testosterone. In the competition analysis, there was not much difference in the displacement of the [3H]DHT binding from AR between the addition of radioinert DHT and testosterone. In studies of 5 alpha-reductase activity and aromatase activity of the cells, both activities were lower than the respective values in classical androgen target tissues. Androgens stimulated the incorporation of [3H]thymidine into the cell, and DHT and testosterone had a similar potency on the cell proliferation. Thus, these results suggest testosterone itself acts mainly on the osteoblasts without conversion to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Adrenal insufficiency in a patient with acquired immunodeficiency syndrome.

A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insufficiency due to a CMV infection in patients with AIDS.

AIDS-Related Complex↗
PubMed1994

Familial primary hyperparathyroidism complicated with Wilms' tumor.

We describe a familial occurrence of primary hyperparathyroidism. The proband is a 60-year-old woman who had a parathyroid adenoma. Her older sister had a parathyroid adenoma with cementifying jaw fibroma and her younger sister died of parathyroid adenocarcinoma with pulmonary metastasis at the age of 38. We have not yet obtained evidence for other endocrine disorders suggesting multiple endocrine neoplasia (MEN) in this pedigree. The proband is complicated with Wilms' tumor. It is now widely accepted that respective predisposed genes of MEN type 1 and Wilms' tumor, and PTH gene are located on chromosome 11. The manifestation observed in this case may be related to mutational abnormalities on chromosome 11.

Adenocarcinoma↗
PubMed1994

[A study of the relationship between diabetic neuropathy and diabetic retinopathy].

To evaluate the relationship between diabetic neuropathy and retinopathy, we examined autonomic nervous function, postural hypotension, nerve conduction velocity and coefficient of variation of R-R intervals. Forty-five non-insulin dependent diabetic cases were classified as no diabetic retinopathy (group A), simple diabetic retinopathy (group B) and proliferative diabetic retinopathy (group C). These groups did not differ in age or gender. The rate of postural hypotension (depression of systolic blood pressure over 30 mmHg) was 0% in group A, 7% in group Bs and 53% in group C. Nerve conduction velocity in both motor and sensory nerve was delayed over 20% in 0% of group A, 8% of group B, and 33% of group C. In CVR-R, 11% of group A and 7% of group B were decreased, and 44% (during rest) and 33% (during deep breathing) of group C was decreased. Between groups A and B there was no statistical difference. But group C had statistically significant difference from other groups, particularly in postural hypotension. Peripheral neuropathy might be closely related to diabetic retinopathy.

Adult↗
PubMed1994

[Gonadal dysfunctions in liver cirrhosis].

Testicular atrophy, loss of libido and feminization are observed in patients with nonalcoholic liver cirrhosis, Serum total and free testosterone levels are decreased in patients with advanced liver cirrhosis and is normal in compensated cirrhotic patients. In compensated liver cirrhosis, sex hormone binding globulin is increased, and is related with increasing serum total testosterone. Serum total and free estradiol levels and ratio of estradiol to testosterone are increased in cirrhotic patients. Hyperestrogenization is related with female physical characteristics. Gonadal dysfunctions observed in cirrhotic patients are primary in the gonadal failure, then a concomitant with pituitary defect occurs. These abnormalities in liver cirrhosis are reversible.

Adult↗
PubMed1993

Skeletal muscle glucose transporter gene expression is not affected by injecting growth-hormone-secreting cells in young rats.

To elucidate the diabetogenic effect of growth hormone on glucose metabolism the regulation of glucose transporter (GLUT) gene expression was examined in rat skeletal muscles. Female Wistar-Furth rats were implanted subcutaneously with growth-hormone-producing pituitary tumour (GH3) cells. Animals were killed 4 or 9 weeks after GH3 cell injection. Although body weight, serum growth hormone and insulin-like growth factor I levels were remarkably elevated during the 4-9 week period, serum blood glucose levels were within normal range. Muscles were obtained from the quadriceps muscle, diaphragm and heart, respectively. Northern blot analysis and Western blot analysis were performed using specific cDNA probes and antibodies. During the 4-9 week period, the levels of muscle GLUT1 and 4 mRNA (corrected by beta-actin mRNA level) in each muscle from the rats injected with tumour cells were not significantly different from those of control rats. Chronic elevation of growth hormone in these rats did not cause any change in GLUT 1 and 4 expression compared to the controls during the euglycaemic period. These results provide the first evidence that chronic growth hormone elevation itself does not affect a key gene of in vivo glucose metabolism.

Animals↗
PubMed1993

A preliminary study on the interferon-alpha treatment for xerostomia of Sjögren's syndrome.

We studied the therapeutic effect of interferon-alpha on the xerostomia of Sjögren's syndrome by injecting 1 x 10(6) units of interferon-alpha intramuscularly once weekly. Saliva production was quantitated by the Saxon test. Variation of saliva production measured at monthly intervals during the 3-month period prior to administration of interferon-alpha was within +/- 0.30 g/2 min. After administration of interferon-alpha, saliva production increased to greater than 0.30 g/2 min in six patients, and the increase was statistically significant by the paired t-test (P = 0.002). The result suggests a beneficial effect of this agent in increasing the saliva production of patients with primary Sjögren's syndrome.

Adult↗