Biomedical subjects

T Takamura

Publications and source records attributed to T Takamura.

At least 55 records · Page 3Linked to original sources

PubMed1998

Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells.

Bcl-2 and a Bcl-2-binding protein BAG-1 function in protection from apoptosis induced by a variety of stimuli. Deregulated expression of Bcl-2 leads to inhibition of apoptosis and is correlated with development of various cancers. Here, we provide evidence that prolonged cell survival introduced by overproduction of Bcl-2 or BAG-1 strongly enhances peritoneal dissemination of human gastric cancer MKN74 cells. Gene transfer-mediated overexpression of Bcl-2 or BAG-1 led to prolonged cell survival of MKN74 cells against serum-starved apoptosis and anoikis. When the viable transfectants were inoculated into the intraperitoneal cavity of BALB/c nude mice, the Bcl-2-expressing MKN74 cells and the BAG-1-expressing MKN74 cells exhibited strongly enhanced peritoneal dissemination in BALB/c nude mice and whole disseminated tumor weights were increased by 4-fold and 3.3-fold, respectively, compared with the control transfectants. The enhanced peritoneal dissemination of MKN74-Bcl-2 and MKN74-BAG-1 transfectants correlated well with resistance to cell death induced by serum-starvation and anoikis. However, the overexpression of Bcl-2 or BAG-1 caused no significant difference among the transfectants in cell growth rates, either in vitro or in vivo. Taken together, these studies demonstrate that resistance to apoptosis is a crucial factor for development of peritoneal dissemination of human gastric cancer cells.

Adenocarcinoma↗

PubMed1998

Amyloid goiter presented as a subacute thyroiditis-like symptom in a patient with hypersensitivity vasculitis.

We present a 25-year-old woman with amyloid goiter due to hypersensitivity vasculitis, who developed transient thyrotoxicosis resembling subacute thyroiditis. She received prednisolone (20 mg/ day) for three years for hypersensitivity vasculitis, and was diagnosed as having secondary amyloidosis by biopsies of the stomach, rectum and kidneys. She noticed neck swelling with severe right neck tenderness, palpitation, hyperhidrosis and weight loss. An elastic firm diffuse goiter was palpable, and the upper pole of the right lobe was extremely tender. Her serum free T4 and T3 levels were high, and the serum TSH was suppressed to subnormal. She was positive for serum C-reactive protein. Anti-thyroidal autoantibodies were all negative. Her thyrotoxicosis subsided spontaneously within one week. Serum titers of antibodies to various viruses were unchanged during the clinical course for two weeks, but she was positive for HLA B35. Examination of a needle-biopsy specimen of the thyroid gland showed extensive amyloid deposition and no evidence of subacute thyroiditis. We considered her transient thyrotoxicosis to be associated with amyloid goiter. The clinical course of this case was similar to the subacute thyroiditis-like syndrome, first described by Ikenoue et al. When patients with primary or secondary amyloidosis have symptoms and signs of subacute thyroiditis, but develop an unusual course, amyloid goiter should be considered.

Adult↗

PubMed1997

Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing.

We have recently demonstrated that cyclic ADP-ribose (cADPR) serves as a second messenger for glucose-induced insulin secretion [Takasawa et al. (1993a) Science 259, 370-373] and that CD38 has both ADP-ribosyl cyclase (ADRC) and cADPR hydrolase activities [Takasawa et al. (1993b) J. Biol. Chem. 268, 26052-26054]. In this study, we determined the structure of the human CD38 gene, and showed that two mRNA forms originated by alternative splicing from the CD38 gene. The human CD38 gene consists of 8 exons that extend more than 77 kb on the human genome. Exon 1 encoded the 5'-untranslated region of the mRNA, the N-terminal end of CD38 and the putative transmembrane domain, and exon 2-8 encoded the remainder of CD38: the exon-intron organization of the human CD38 gene is similar to that of the Aplysia ADRC gene [Nata et al. (1995) Gene 158, 213-218]. This structural conservation between human and Aplysia genes suggests that both genes may have evolved from a common ancestral gene.

ADP-ribosyl Cyclase↗

PubMed1997

Bupivacaine combined with isoflurane synergistically depressed myocardial contractility in rat working heart preparation.

It is well known that both local and volatile anesthetics depress myocardial functions. This study was performed to evaluate the combined effects of commonly utilized local anesthetics (bupivacaine, mepivacaine, and lidocaine) and a volatile anesthetic (isoflurane) on heart rate and myocardial contractility in an isolated rat working heart preparation using each local anesthetic at 0 to 3 x 10(-4) (mol/L) with or without 1 MAC (minimum alveolar concentration) of isoflurane. The three local anesthetics depressed the heart rate and myocardial contractility dose-dependent. Bupivacaine depressed the heart rate more than the other two local anesthetics. One MAC isoflurane showed significant negative inotropic effects, and accelerated the effects of the local anesthetics. By using isobolographic analysis, we concluded that the combined effect of isoflurane and bupivacaine on myocardial negative inotropism was synergistic, while the effects of isoflurane and mepivacaine or lidocaine were additive.

Anesthetics, Inhalation↗

PubMed1997

[A case report: surgical treatment of hypertrophic obstructive cardiomyopathy with acute hemodynamic deterioration due to chordae rupture of the mitral valve].

A 70-year-old woman was found to have new heart systolic murmur and was transferred to our hospital for the treatment of high fever and dyspnea. The chest X ray showed cardiomegaly (CTR 63%) and marked pulmonary congestion. The UCG revealed that there was no evidence of infective endocarditis, but there was hypertrophic obstructive cardiomyopathy with the left ventricular pressure gradient of 90 mmHg accompanied by mitral regurgitation (grade 3/4). Two weeks after the admission, mitral regurgitation progressed due to chordae rupture confirmed by UCG. Transaortic subvalvular myectomy and mitral valve replacement were underwent. Post-operative electrocardiogram demonstrated right and left anterior bandle branch block. Eleven months after the operation left ventricular outflow pressure gradient was not detected by echocardiogram and she has been in I/IV NYHA functional class.

Aged↗

PubMed1997

Follow-up study of neonatal hypoglycemia.

A follow-up study was done on the neurological handicap and intellectual development of high-risk infants with neonatal hypoglycemia. The frequency of neonatal hypoglycemia in high-risk infants is 8.6%, and the incidence of a major neurological handicap in high-risk infants with neonatal hypoglycemia is 11%. Risk factors for the handicap group are very low birthweight, intrauterine growth retardation, perinatal asphyxia and mothers with pregnancy-induced hypertension. Average DQ at 1.5 and 2.5 years and IQ at 4 and 6 years of very low birthweight infants with neonatal hypoglycemia showed no significant difference, in contrast to the control group.

Central Nervous System Diseases↗

PubMed1996

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Animals↗

PubMed1996

Inhibitory effect of cyclosporin A on prolactin synthesis in GH3 cells.

Cyclosporin A (CsA), a potent immunosuppressant, is known to have various effects on the endocrine system, including the pituitary gland, the adrenal cortex, the testes, and the pancreatic islets. In this study, the effects of CsA on prolactin (PRL) synthesis and release were investigated in GH3 cells, a clonal strain of rat pituitary tumor. After incubation of confluent GH3 cells with various concentrations of CsA for 24 hr, the PRL content of the media decreased in a dose-dependent manner: by 28.5% with 100 ng/ml CsA (p < 0.01); and 45.8% with 2,000 ng/ml CsA (p < 0.001), compared with control. However, no significant change was observed in the intracellular PRL content. After removal of CsA from the medium, GH3 cells fully recovered normal secretory activity within 24-48 hr, thus indicating that the inhibitory effect of CsA on PRL secretion was reversible. Northern blot analysis revealed a decrease in the PRL mRNA level in cells treated with CsA. In conclusion, these data suggest that CsA inhibits PRL secretion by reducing the rate of biosynthesis. A possible site of action is on PRL gene expression at the level of mRNA transcription.

Animals↗

PubMed1996

[Studies of allergen specific IgE antibodies with atopic dermatitis--evaluation of house dust 6 (house dust Japan) specific IgE antibody].

We examined the usefulness of allergen housedust-6 measurement in 44 patients (22 males and 22 females) with atopic dermatitis. The positivity for each of housedust HD-2 and HD-6 and that for each of D-1 and D-2 was well correlated in more than 90% of the patients (correlation coefficient > 0.85). The positivity for HD-2 and for HD-6 was also correlated in 93.2% of the patients. However, there was a discrepancy between D-1 or D-2 and HD-2 or HD-6 in only a few patients. The positivity for antibody against specific IgE was higher in atopic dermatitis-patients with allergic rhinitis, allergic conjunctivitis or bronchial asthma as compared with patients with only atopic dermatitis. Only one patient with severe atopic dermatitis had a negative result for specific IgE, suggesting the contribution of other circumferencial factors in the development of the disease. In conclusion, our study suggested that housedust-6 is useful in clinical evaluation of patients with atopic dermatitis.

Adolescent↗

PubMed1996

[Effect of intra-operative fluid on renal function during hypotensive anesthesia with trimethaphan].

During induced hypotensive anesthesia in 26 cases with trimethaphan, either Ringer's lactate solution (LR group) or 2/3 lactate-saline solution (2/3 LS group) was infused at the same rate. Urine volume, creatinine clearance (Ccr), FENa, urinary gamma-GTP index and urinary Na/K ratio were determined before hypotension, during hypotension and after the operation. During hypotension, FENa and urine Na/K ratio decreased in both groups. In 2/3 LS group, these remained low after the operation compared with the values before hypotension and in LR group. These results suggest that LR solution might depress an endocrine response which is induced by hypotensive anesthesia. As urine volume and Ccr were unchanged by hypotension, and infusion of colloid solution (Hespander) could not increase these figures, circulating blood volume might not be decreased during hypotensive anesthesia. Since urinary gamma-GTP index increased slightly during hypotension or after the operation, there might have been a slight epithelial cell damage of tubules with hypotensive anesthesia.

Adult↗

PubMed1996

[Non-specific elevation of anti-dsDNA antibody measured by Farr method found in a patient with liver cirrhosis].

In a patient with liver cirrhosis, an elevation of serum anti-dsDNA antibody titer (100-193.3 IU/ml) measured by Farr method was found. This anti-dsDNA antibody was not identified by Crithidia Luciliae method, and the analysis using ELISA method showed that the DNA-antibody is an anti-ssDNA antibody (IgG) and that it is reactive only with ssDNA by the suppression test using purified DNA with lambda phage. Based on this finding, the high titer of anti-dsDNA antibody found in this patient using Farr method was considered to be non-specific cross-reaction with ssDNA.

Antibodies, Antinuclear↗

PubMed1995

Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion in CD38-expressing transgenic mice.

Cyclic ADP-ribose (cADPR) serves as a second messenger for Ca2+ mobilization in insulin secretion, and CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here, we produced transgenic mice overexpressing human CD38 in pancreatic beta cells. The enzymatic activity of CD38 in transgenic islets was greatly increased, and ATP efficiently inhibited the cADPR hydrolase activity. The Ca2+ mobilizing activity of cell extracts from transgenic islets incubated in high glucose was 3-fold higher than that of the control, suggesting that ATP produced by glucose metabolism increased cADPR accumulation in transgenic islets. Glucose- and ketoisocaproate-induced but not tolbutamide- nor KCl-induced insulin secretions from transgenic islets were 1.7-2.3-fold higher than that of control. In glucose-tolerance tests, the transgenic serum insulin level was higher than that of control. The present study provides the first evidence that CD38 has a regulatory role in insulin secretion by glucose in beta cells, suggesting that the Ca2+ release from intracellular cADPR-sensitive Ca2+ stores as well as the Ca2+ influx from extracellular sources play important roles in insulin secretion.

ADP-ribosyl Cyclase↗

PubMed1995

The structure of the Aplysia kurodai gene encoding ADP-ribosyl cyclase, a second-messenger enzyme.

The complete nucleotide (nt) sequences of the cDNA and gene encoding the marine mollusk Aplysia kurodai (Ak) ADP-ribosyl cyclase (ADRC) which synthesizes cyclic ADP-ribose (cADP-ribose), a second messenger for Ca2+ mobilization from endoplasmic reticulum, were determined. Ak ADRC consists of 258 amino acids (aa) (29 kDa). It shares 86% aa sequence homology with that from A. californica, and 31-32% homology with the human, rat and mouse cluster of differentiation 38 (CD38) that has both ADRC and cADP-ribose hydrolase activities. The Ak ADRC-encoding gene (ADRC) spans approx. 7 kb and contains eight exons and seven introns. The transcription start point (tsp) determined by primer extension analysis and S1 mapping is 28 bp downstream from the TATA box. This gene is expressed specifically in the ovotestis, although the mammalian CD38-encoding gene is expressed in many kinds of tissues and cells. The 5'-flanking region contains several consensus sequences responsible for the germ-cell-specific expression of the mouse zona pellucida 3 (ZP3) and Drosophila melanogaster chorion genes. The existence of the consensus sequences located at nt -1649, -1161, -234 and -90 may account for the ovotestis-specific expression of the Ak ADRC gene.

ADP-ribosyl Cyclase↗

PubMed1995

Elongation of the side chain of analogs of 1 alpha,25-dihydroxyvitamin D3 prevents osteopenia in a rat model.

Five analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] [1], 26,27-dimethyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Me)2D3] [2], 26,27-dimethyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Et)2D3] [3], 26,27-dipropyl-1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2(Pr)2D3] [4], 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3], and [5] 24a-homo-24,24-difluoro-1 alpha,25- dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3] were investigated to clarify the possibility that prevents osteopenia induced in rats by ovariectomy and sciatic neurotomy. The objective of our studies was to determine whether these analogs may be effective for treatment of subjects with osteoporosis. 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3 prevented decreases in bone mineral density (BMD) of the femur, as measured by dual energy X-ray absorptiometry (DXA). The potency of 1,25(OH)2(Me)2D3 in this test was higher than that of 1,25(OH)2D3. The potencies of 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3 were similar to that of 1,25(OH)2D3. On the other hand, though 1,25(OH)2(Et)2D3 and 1,25(OH)2(Pr)2D3 had a preventive effect on the decrease in BMD, the potency of two analogs was lower than that of 1,25(OH)2D3. Decreases in cortical and trabecular bone areas of the femur were prevented by three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2D3. Serum calcium (Ca) concentration was elevated at the last administration of three analogs of 1,25(OH)2D3, 1,25(OH)2(Me)2D3, 24F2-1,25(OH)2-(Me)2D3 and 24aF2-homo-1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed1995

Assignment of CD38, the gene encoding human leukocyte antigen CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase), to chromosome 4p15.

CD38 has been used as a phenotype marker of lymphocyte differentiation. Recently, we have demonstrated that cyclic ADP-ribose can be synthesized and hydrolyzed by CD38 and acts as a second messenger in insulin secretion from pancreatic beta-cells. We have mapped the CD38 gene to human chromosome 4p15 by fluorescence in situ hybridization.

ADP-ribosyl Cyclase↗

PubMed1995

An adult case of neurohypophyseal ectopy presenting ACTH deficiency and partial GH deficiency.

A case of ACTH deficiency and partial GH deficiency associated with neurohypophyseal ectopy is described. A 42-year-old woman of short stature was admitted for hypoglycemic coma. The patient had hypocortisolemia, an increase in urinary 17-OHCS after consecutive injections of ACTH-Z, and a low plasma ACTH level which showed no response to corticotropin-releasing factor. This indicated the presence of ACTH deficiency. The plasma GH level showed a blunted response to insulin-induced hypoglycemia, but its response to GRF was preserved. Other hypothalamo-pituitary axes were intact. T1-weighted magnetic resonance imaging demonstrated ectopic neurohypophyseal tissue and a tiny anterior pituitary remnant. ACTH deficiency and partial GH deficiency might have developed as a consequence of pituitary stalk injury and inadequate regeneration of the anterior lobe.

Adrenocorticotropic Hormone↗

PubMed1995

[Subdural abscess following chronic subdural hematoma].

This is a report of subdural abscess following chronic subdural hematoma. An 86-year-old male was admitted to our hospital due to drowsiness and left hemiparesis. He had been suffering from a spike fever which originated during chronic cholecystitis and cholelithiasis and which had continued since 2 years prior to admission. On admission, CT scans revealed right chronic subdural hematoma, and the collection of a few old hematomas was suspected in the left subdural space. An emergency removal of the right hematoma was carried out by using right single burr hole. It was found that the old hematoma accompanied a yellow-white abscess in the subdural space. Escherichia coli were detected from a bacterial culture of the abscess. Postoperative enhanced MRI clearly showed the capsule of the right subdural abscess, and the left chronic subdural hematoma. Removal of the left hematoma was performed by using a left single burr hole. But the abscess did not exist in the left subdural space, and only old hematomas had collected there. The bacterial culture of the left old hematoma was negative. Escherichia coli might be implanted on the capsule of the right chronic subdural hematoma by bacteremia derived from chronic cholecystitis. It was considered that the formation of the subdural abscess might have developed through the deterioration of the immunological function under the influence of senility.

Aged↗

PubMed1993

Calcium regulating activity of 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3.

Two fluoro analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3], and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3] were examined for calcium (Ca)-regulating activity. The objective of the present study was to determine whether or not fluoro substitution at 24-position would alter activities of the original compounds, that is, 26,27-dimethyl 1 alpha,25-dihydroxyvitamin. D3[1,25(OH)2(Me)2D3] and 24-homo-1 alpha,25-dihydroxyvitamin D3 [24homo-1,25(OH)2D3], respectively. The relative activities of 24aF2-homo-1,25(OH)2D3, 24F2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The relative potencies of the same series of compounds in competition for the vitamin D-deficient rat serum binding sites were 0.04:0.15:1. Bone-resorbing activities of two fluoro analogs in cultures of neonatal mouse parietal bones were more potent than that of 1,25(OH)2D3. Similar results were recognized in stimulating activities of osteoclast-like cell formation. Responses of two fluoro analogs to intestinal Ca absorption were similar to that of 1,25(OH)2D3. The potencies of 1,25(OH)2D3 and its fluoro analogs in bone Ca mobilization were the highest with 1,25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3, in that order. From these results and the data of Paulson et al., fluoro substitution in 24-position of 1,25(OH)2D3 apparently does not alter their activities,hence, the fluoro substitution at 24-position of 1,25(OH)2D3 and the elongation of side chain of 1,25(OH)2D3 may not intensify Ca-regulating activity.

Animals↗