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T Suda

Publications and source records attributed to T Suda.

At least 433 records · Page 24Linked to original sources

The mechanisms of regulation of vitamin D metabolism in the kidney.

Recently, the 24-hydroxylase enzyme of 25-hydroxyvitamin D3 was purified from rat and chick kidney, and its complementary DNA was cloned. The length of the rat 24-hydroxylase gene is about 15 kbp with 12 exons. Cloning of the 24-hydroxylase gene made it possible to examine the mechanism of regulation of vitamin D metabolism at the gene level. Expression of renal 24-hydroxylase mRNA is regulated by a balance of plasma parathyroid hormone and 1 alpha,25-dihydroxyvitamin D3 levels, whereas intestinal 24-hydroxylase mRNA is regulated mainly by plasma 1 alpha,25-dihydroxyvitamin D3. This article reviews recent progress in understanding the molecular aspects of vitamin D metabolism.

Animals↗

Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow.

We have found that an estrogen deficiency causes a marked increase in bone marrow cells. To examine the effect of estrogen on hemopoiesis, we characterized the increased population of bone marrow cells after ovariectomy (OVX). In OVX mice, the percentage of myeloid cells and granulocytes was decreased, whereas that of B220-positive B lymphocytes was selectively increased 2-4 wk after surgery. The total number of myeloid cells and granulocytes did not change appreciably, but that of B220-positive cells was greatly increased by OVX. When OVX mice were treated with estrogen, the increased B lymphopoiesis returned to normal. B220-positive cells were classified into two subpopulations, B220low and B220high. The majority of the B220low cells were negative for the IgM mu chain, whereas most of the B220high cells were mu-positive. OVX selectively increased the precursors of B lymphocytes identified by B220low. mu-negative phenotype, suggesting that an estrogen deficiency stimulates accumulation of B lymphocyte precursors. When bone marrow-derived stromal cells (ST2) were pretreated with estrogen then co-cultured with bone marrow cells in the presence of estrogen, the stromal cell-dependent B lymphopoiesis was greatly inhibited. The present study suggests that estrogen plays an important role in the regulation of B lymphocyte development in mouse bone marrow.

Animals↗

Regulation of messenger ribonucleic acid expression of 1 alpha,25-dihydroxyvitamin D3-24-hydroxylase in rat osteoblasts.

We have reported that PTH inhibits 25-hydroxyvitamin D3-24-hydroxylase messenger RNA (mRNA) expression induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] in rat kidney but not intestine. In the present study, we examined whether the suppression of 24-hydroxylase mRNA expression by PTH occurs commonly in tissues and cells which have PTH receptors. Administration of 1 alpha, 25-(OH)2D3 into rats fed a synthetic vitamin D-repleted diet containing adequate calcium greatly increased serum levels of calcium and 1 alpha, 25-(OH)2D3. Also, there was a 4-fold increase in bone 24-hydroxylase activity in response to 1 alpha, 25-(OH)2D3 administration. In rats fed a low calcium diet, renal 24-hydroxylase activity was suppressed probably due to secondary hyperparathyroidism. In contrast, the low calcium feeding did not suppress bone 24-hydroxylase activity. The expression of 24-hydroxylase mRNA in rat osteoblastic C-26 and C-11 cells was similar and attained maximal levels 24 h after cells were incubated with 10(-8) M 1 alpha, 25-(OH)2D3. Induction of 24-hydroxylase mRNA expression by 1 alpha, 25-(OH)2D3 was much greater and earlier in immature C-26 cells than mature C-11 cells. Simultaneous addition of PTH, prostaglandin E2, or cAMP together with 1 alpha, 25-(OH)2D3 did not down-regulate mRNA expression of 24-hydroxylase induced by the vitamin in both C-26 and C-11 cells. Of the three osteoblastic cells (C-26, C-20, and C-11) examined, C-26 cells showed the least mRNA expression of vitamin D receptors, in spite of the highest expression of 24-hydroxylase mRNA. These results suggest that unlike in the kidney, bone 24-hydroxylase mRNA expression is not down-regulated by PTH despite of the presence of PTH receptors. They also suggest that the degree of the induction of 24-hydroxylase mRNA by 1 alpha, 25-(OH)2D3 is not explained simply by the vitamin D receptors content.

Adenylyl Cyclases↗

Microinjection of norepinephrine into the paraventricular nucleus of the hypothalamus stimulates corticotropin-releasing factor gene expression in conscious rats.

To examine the physiological effects of norepinephrine (NE) in the paraventricular nucleus of the hypothalamus (PVH) on CRF gene expression and CRF release, NE was microinjected bilaterally into the PVH of conscious rats, and kinetic studies were performed on the levels of POMC messenger RNA (mRNA) in the anterior pituitary (AP), CRF mRNA in the PVH-containing hypothalamic fragment, and plasma ACTH. Plasma ACTH levels were increased dose dependently by NE (5-50 nmol/side) injection into the PVH. They reached their peaks after 30 min and returned to the basal values after 90 min. The POMC mRNA level in the AP and hypothalamic CRF mRNA level increased significantly 90 min after NE injection and increased further after 120 min. The POMC mRNA level in the AP and hypothalamic CRF mRNA level were increased dose dependently by NE (5-50 nmol/side) after 120 min. Intracerebroventricular pretreatment with prazosin abolished completely the increase in plasma ACTH levels after intrahypothalamic NE injection, whereas pretreatment with propranolol was without significant effect. These results suggest that NE stimulates CRF gene expression in the PVH and CRF secretion into the portal circulation, thus regulating positively the hypothalamic-pituitary-adrenal axis. alpha 1-Adrenergic receptors may mediate the action of NE on CRF neurons.

Adrenocorticotropic Hormone↗

Studies on thermophile products. X. Further biological properties of isofatty acid-containing phosphatidylglycerol that enhances the induction of suppressor T cells.

Isofatty acid-containing phosphatidylglycerol (Fr. 7-C), isolated from Bacillus stearothermophilus UBT8038, enhances the induction of concanavalin A (Con A)-activated suppressor T (Ts) cells in a dose dependent manner (0.01-1 microgram/ml). Its further biological properties on mouse mixed lymphocyte reaction (MLR) has been demonstrated. Fr. 7-C (0.01-1 microgram/ml) suppressed the MLR at 4 d in a dose-dependent manner when added at the start of splenocyte cultivation. Moreover, Fr. 7-C was effective in preventing the generation of cytotoxic T lymphocytes after the MLR. On the other hand, this fraction significantly enhanced the induction of Ts cells in the MLR carried out in any of the antigen-specific, antigen-nonspecific and major histocompatibility complex antigen-nonrestricted fashions. Fr. 7-C increased prostaglandin E2 (PGE2) release approximately 2-fold in the culture supernatant of Con A-activated splenocytes, and PGE2 release decreased dose-dependently when cultured with indomethacin. The inhibitory effect by Fr. 7-C on the MLR was abrogated by the addition of indomethacin. The enhancement by Fr. 7-C on Ts cell induction was blocked by indomethacin in a dose dependent manner. These results strongly suggest that Fr. 7-C suppresses the MLR via the enhancement of antigen-nonspecific Ts cell induction mediated at least partly by PGE2.

Animals↗

Observation of sleep-related breathing disorders in patients with coronary artery disease by ambulatory electrocardiogram-respiration monitoring system.

Eighty-five coronary artery patients examined using an ambulatory electrocardiogram-respiration monitoring system (AERMS) in which a respiratory sensor was strapped to the right upper abdominal wall. Apnea was defined as a cessation of abdominal wall movement lasting at least 10 sec. Sleep-related breathing disorder (SRBD) was diagnosed if at least 30 apneic episodes were observed during sleep. The cardiac events evaluated during follow-up included occurrence of sudden death, myocardial infarction and ventricular tachycardia. SRBD was detected in 9 of 85 patients (11%). There were more patients with low EF (EF < 50%) in the SRBD group than in the non-SRBD group (p < 0.01). During follow-up for a mean period of 18.4 +/- 7.6 months after ambulatory recording, four of nine (44%) patients in the SRBD group had cardiac events, compared with only four of 79 (6%) patients in the non-SRBD group (p < 0.001). Thus, coronary artery patients who were complicated with SRBD showed poor cardiac function and had a high incidence of cardiac events.

Aged↗

Corticotropin-releasing factor-binding protein concentrations in plasma of patients with hypothalamic-pituitary-adrenal disorders.

Immunoreactive corticotropin-releasing factor-binding protein (CRF-BP) concentrations in human plasma were determined by means of radioimmunoassay for human CRF-BP. CRF-BP antiserum to the C-terminal fragment of human CRF-BP (298-322) was produced, and CRF-BP (298-322) was used as the tracer and the standard. Large amounts of human CRF did not affect measurement of plasma CRF-BP with this radioimmunoassay. The basal plasma CRF-BP concentration in normal subjects was 4.19 +/- 0.57 nmol/L (mean +/- SD). The CRF-BP concentration was low in patients with Cushing's syndrome, except those with preclinical Cushing's syndrome, and high in patients with Addison's disease, hypopituitarism and isolated ACTH deficiency. After surgery, the plasma CRF-BP concentration in patients with Cushing's syndrome rose, peaked, and then decreased to the control level. In patients with Addison's disease, the high plasma CRF-BP concentration decreased to the control level after hydrocortisone replacement, the same as plasma ACTH concentration. These findings suggest that the immunoreactive CRF-BP concentration in human plasma was decreased by glucocorticoids, at least under chronic conditions.

Addison Disease↗

Dyskeratosis congenita showing usual interstitial pneumonia.

A 46-year-old man was admitted to our hospital with cough and dyspnea on exertion. A chest X-ray film showed diffuse interstitial shadows. He had hyperpigmentation forming a network pattern around his neck and dystrophy of the fingernails and toenails, and was diagnosed as having dyskeratosis congenita. Histological examination of the lung specimen obtained from the left S4b by open lung biopsy revealed usual interstitial pneumonia pattern with neither asbestos bodies nor silicotic nodules. Taken together with previously published findings, pulmonary involvement is considered to be an important complication of dyskeratosis congenita.

Age Factors↗

Weekly low-dose methotrexate therapy for sarcoidosis.

Low-dose methotrexate therapy has been used to treat a variety of chronic inflammatory diseases; a few studies have discussed the efficacy of this therapy for sarcoidosis. We present a patient with symptomatic sarcoidosis who was successfully treated with low-dose methotrexate after being refractory to steroids. This patient showed significant clinical improvement without development of any severe side effects. These findings suggest that low-dose methotrexate therapy may be a useful alternative treatment for sarcoidosis.

Adult↗

[A case of thoracic empyema extended into the abdominal cavity].

A case of thoracic empyema after artificial pneumothorax for lung tuberculosis was presented, which extended into the abdominal cavity. 65 years old man, who was operated on for lung tuberculosis about 30 years ago, took the routine physical examination and the abdominal mass was picked up on examination. Echogram and CT showed huge homogeneous mass in the right thorax and the right upper abdominal cavity. The operative finding showed that thoracic empyema extended into the abdominal cavity and formed a huge mass. Decortication and extirpation of thoracic empyema and abdominal mass was performed with a combined partial resection of the lung, diaphragma, and thoracic wall. The histopathology of the abdominal mass showed chronic empyema and hematoma.

Abdomen↗

Characterization of mouse non-receptor tyrosine kinase gene, HYL.

We previously reported a novel human non-receptor tyrosine kinase gene, HYL (hematopoietic consensus tyrosine-lacking kinase) (Sakano et al., 1994), which consists of each of the SH2 (src homology 2), SH3 and tyrosine kinase catalytic domains. HYL has unique structural features shared with CSK (C-terminal Src kinase). Recently it has also been reported that matk (Bennett et al., 1994) and Ctk (Klages et al., 1994) are isolated as novel kinases with structural similarity to CSK. Comparisons of cDNA sequence indicate the HYL, matk and Ctk are the same gene. We further characterized the mouse HYL genomic structure and HYL mRNA expression in mouse brain. The mouse HYL gene is distributed over 5.8 kb and is composed of 12 exons. The exon-intron organization is almost identical with that of human CSK. The mouse HYL gene was assigned to the R-positive C1 band of chromosome 10 by fluorescent in situ hybridization. RNA in situ hybridization demonstrated the broad distribution of HYL mRNA expression in various neuronal cells. Especially, strong signals were detected in Purkinje cells, pyramidal cells in the hippocampus, granule cells in the dentate gyrus, and mitral cells in the olfactory bulb, indicating that mRNA expression of HYL in brain is very similar to that of SRC-family kinases. These findings establish close relationship between the HYL and CSK genes and also suggest that HYL may play an important role in signal transduction through SRC-family kinases in the central nervous system.

Animals↗

Distribution of WGA-binding sites on the surface of clinical isolates of Staphylococcus aureus.

Distribution of wheat germ agglutinin (WGA)-binding sites on the surface of clinical isolates of Staphylococcus aureus was examined by WGA-gold. Labelings on three methicillin-sensitive S. aureus (MSSA) isolates were heavier than those on three methicillin-resistant (MRSA) isolates and the 209P (MSSA) strain. These results were confirmed by an alkaline phosphatase-WGA assay. The WGA-binding on the MRSA was consistently poor, whereas wide ranging diversity was observed in WGA-binding among the MSSA. These results strongly suggest diversities in not only distribution, but also the quantity of WGA-binding carbohydrates exposed on the surface of the organisms.

Methicillin Resistance↗

[A case of so-called benign metastasizing leiomyoma].

A 44-year-old female was admitted to our hospital for the purpose of undergoing hysterectomy for removal of multiple uterine tumors. A chest X-ray film obtained on admission revealed a solitary nodule in the right lung field. The resected specimen containing the uterine tumors revealed well differentiated leiomyoma with no nuclear atypia or mitotic figures. The resected specimen from the pulmonary tumor revealed histologic findings similar to those of the uterine myomas, being devoid of any signs of mitosis. Similar cases have been reported as so-called benign metastasizing leiomyoma, and are generally regarded as low grade malignancy or leiomyomatosis. However, we consider this case to have had a primary pulmonary leiomyoma associated with uterine myoma since the pulmonary lesion was solitary and no mitotic figures were detectable. As the concept of metastasizing leiomyoma is confusing, the accumulation of additional case reports is necessary.

Adult↗

[A case of acute promyelocytic leukemia (APL) with myeloblastoma in the oral cavity developing after receiving all-trans retinoic acid (ATRA)].

A 44-year-old woman was diagnosed as having acute promyelocytic leukemia (APL) in April 1988. On her first admission, chromosomal translocation (15; 17), +8, and +12 was detected. When she was readmitted to our hospital with the second relapse in May 1990, t(3; 13) and +8 was detected, instead of t(15;17). Complete remission was re-achieved with VP-16, MIT, and BHAC, but the third relapse occurred in September 1990. After obtaining informed consent, she was given etretinate 40 mg per day orally for 17 days, without any effect on leukemia. She was then given all-trans retinoic acid (ATRA) 60 mg per day orally for 29 days. Although a mild granulocytic recovery was observed, no sufficient hematological recovery was obtained (minor response). Besides common side effects of ATRA, such as dry skin and hypertriglycedemia, she had a myeloblastoma in the oral cavity, but it is unknown whether the symptom was a complication of ATRA therapy or not.

Administration, Oral↗

Molecular cloning of a novel non-receptor tyrosine kinase, HYL (hematopoietic consensus tyrosine-lacking kinase).

We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid sequence of the protein encoded by this gene was most homologous to CSK (c-src kinase). This gene and CSK shared some unique structural properties such as the absence of a myristylation signal and phosphorylation sites of tyrosine residues corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed. The expression of HYL was upregulated when these myeloid cells were differentiated by induction with phorbol myristate acetate. We named this gene, hematopoietic consensus tyrosine-lacking kinase, HYL. The HYL gene was assigned to chromosome 19 at band p13. It is suggested that HYL plays a significant role in the signal transduction of hematopoietic cells.

Amino Acid Sequence↗

Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.

The Fas antigen (Fas) belongs to the tumor necrosis factor (TNF)/nerve growth factor receptor family, and it mediates apoptosis. Using a soluble form of mouse Fas, prepared by fusion with human immunoglobulin Fc, Fas ligand was detected on the cell surface of a cytotoxic T cell hybridoma, PC60-d10S. A cell population that highly expresses Fas ligand was sorted using a fluorescence-activated cell sorter, and its cDNA was isolated from the sorted cells by expression cloning. The amino acid sequence indicated that Fas ligand is a type II transmembrane protein that belongs to the TNF family. The recombinant Fas ligand expressed in COS cells induced apoptosis in Fas-expressing target cells. Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.

Amino Acid Sequence↗