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Biomedical subjects

K Tsuda

Publications and source records attributed to K Tsuda.

At least 361 records · Page 20Linked to original sources
PubMed1984

Neurotransmitter release, vascular responsiveness and their calcium-mediated regulation in perfused mesenteric preparation of spontaneously hypertensive rats and DOCA-salt hypertension.

To investigate the role of norepinephrine release from the sympathetic nerve endings and vascular responsiveness to endogenous and exogenous norepinephrine in the pathogenesis of hypertension, the perfused mesenteric preparations from spontaneously hypertensive rats (SHR) and DOCA-salt hypertension were used. In addition, the effects of two calcium antagonists on norepinephrine release by electrical stimulation and the vasoconstrictor responses to norepinephrine were examined to evaluate the calcium dependency of norepinephrine release and the vascular responsiveness in hypertension. The vascular responsiveness was increased in SHR and DOCA-salt hypertension in both early and later phases. Norepinephrine overflow from the sympathetic nerve terminals was enhanced only in young SHR and the chronic phase of DOCA-salt hypertension. After infusion of verapamil, a calcium antagonist, into the perfusate, the pressor responses and norepinephrine overflow by electrical stimulation were more inhibited in SHR, especially in young SHR, and the chronic phase of DOCA-salt hypertension than in controls. These results suggest that calcium dependency in both pre- and postsynaptic sites of neurotransmission may contribute to the pathogenesis of hypertension.

Animals↗
PubMed1983

Effect of 1,25-dihydroxyvitamin D3 on pancreatic B and D cell function.

To investigate the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on pancreatic B and D cell function in normal rats, 1 microgram of 1,25(OH)2D3 was administered intravenously 20 hours before the experiment. The plasma 1,25(OH)2D3 and calcium concentrations were significantly elevated, and plasma insulin levels also increased in 1,25(OH)2D3-administered rats compared with controls. Glucose-induced insulin and somatostatin release from the isolated pancreas perfused with lower calcium, however, was the same between the 1,25(OH)2D3-administered group and the controls. On the other hand, when the isolated pancreas was perfused with higher calcium, the glucose-induced insulin release was significantly increased in the 1,25(OH)2D3-administered group, while no significant difference in somatostatin release was observed in any group. These results suggest that the sensitivity of pancreatic B cells to glucose perfused with more calcium may increase when 1,25(OH)2D3 has been previously administered. In addition, 1,25(OH)2D3 does not seem to affect the somatostatin release from the pancreatic D cells.

Animals↗
PubMed1983

A Japanese family with high density lipoprotein deficiency.

Two siblings with marked reduction of plasma high density lipoprotein (HDL) were found in a Japanese family. Their plasma cholesterol levels were very low (30-60 mg/dl), especially in the HDL fraction (0-1 mg/dl). The concentration of apolipoprotein (Apo) A-I in their plasma was 2-3 mg/dl and that of Apo A-II was 1.5-2.0 mg/dl, determined by means of a single radial immunodiffusion technique. An ultracentrifugally separated HDL fraction contained two different populations of lipoprotein particles, as shown by electron microscopy; a small particle with a diameter of 50-70 A and a relatively large particle at 200 A. Plasma lecithin: cholesterol acyltransferase activity was substantially retained in both cases. Hepatosplenomegaly was present and liver biopsy revealed lipid deposition in reticuloendothelial cells, although the tonsils were apparently normal. No severe atherosclerotic lesions were noticed. The results from these two cases were consistent with the characteristic features of homozygotes of familial HDL deficiency (Tangier disease). HDL cholesterol levels were relatively low in the parents and two children from one patient, which is consistent with the heterozygote state. Two other cases in the kindred were also found to have relatively low HDL cholesterol levels, besides these 4 cases of obligate heterozygotes. Apo A-I and Apo A-II levels in the plasma of the obligate heterozygotes, however, were within the normal range. Plasma low density lipoprotein in the patients moved faster in polyacrylamide gel electrophoresis than those of normal subjects, as did those in the heterozygotes.

Adult↗
PubMed1983

Hyperfunction of the entero-PP axis in non-insulin dependent diabetes mellitus.

In a previous study we have found that the plasma pancreatic polypeptide (PP) response to oral glucose loading is exaggerated in diabetic patients compared with normal subjects. We have investigated, therefore, the effects of a protein-rich meal or meat extract ingestion on plasma PP secretion and examined also the effects of intravenous arginine administration on PP levels in normal subjects and in patients with noninsulin-dependent diabetes mellitus (NIDDM). Following a 600 Kcal meal ingestion, plasma PP levels increased immediately and showed biphasic secretion in normal subjects and in NIDDM, but the response was exaggerated in NIDDM. A 50 g meat extract administration also produced an exaggerated PP response in NIDDM compared with normal subjects. In NIDDM and normal subjects, plasma PP levels did not change significantly during an arginine infusion (30 g for 45 min) but after the end of the infusion PP levels increased significantly compared with basal levels. In normal subjects, plasma PP rose abruptly after a bolus arginine injection (4 g for 2 min) and then remained at significantly high levels even 30 min after the injection. In NIDDM, however, plasma PP levels tended to increase, but not significantly, after the bolus arginine injection. Since in NIDDM the protein-rich meal and meat extract ingestion produced an exaggerated rise in plasma PP while the PP responses to the intravenous arginine administration were rather impaired compared with normal subjects, we suggest that the entero-PP axis is overactive in NIDDM.

Adult↗
PubMed1983

Construction of plasmid vectors for cloning of promoters using the dihydrofolate reductase gene of Escherichia coli K-12.

Vectors for cloning promoter-DNA fragments were derived from pTP 30-5 which was constructed in our previous work (M. Iwakura et al. (1982) J. Biochem. 91, 1205). The selection was based on the expression of trimethoprim resistance of transformed bacteria in which the enhancement of dihydrofolate reductase production was directed by the cloned promoter. A linear relationship between the content of dihydrofolate reductase and the strength of trimethoprim resistance was observed. It is suggested that the promoter activities can be estimated by trimethoprim resistance without measuring the enzyme activities.

Cloning, Molecular↗
PubMed1983

Purification of dihydrofolate reductase amplified in Escherichia coli K-12.

The Escherichia coli strain carrying pTP 6-10 which was constructed in our previous work (Iwakura, M., et al. (1983) J. Biochem. 93, 927-930) produces more than 400-fold dihydrofolate reductase as compared with the strain without the plasmid. Dihydrofolate reductase was highly purified from the cell-free extract of the plasmid strain simply by two steps; ammonium sulfate fractionation and ion-exchange chromatography. By 10-fold purification, the enzyme was essentially homogeneous as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The restriction map of pTP 6-10 was also determined and the plasmid was shown to have an Ava I, an EcoR I, a Pst I, a Pvu I, and a Pvu II site. Our results indicate that the plasmid strain is suitable as a source of the enzyme and that plasmid pTP 6-10 is promising as a versatile plasmid vector for efficiently yielding the product of the cloned gene.

Base Composition↗
PubMed1983

Multiple conformational equilibria of cyclic octapeptide, cyclo (L-Pro-Sar)4 in solution.

Cyclo (L-Pro-Sar)4 is a synthetic cyclic octapeptide composed of only N-substituted amino acids. The conformation of this peptide in different solvents was examined by 1H- and 13C-n.m.r. spectroscopy. 1H-n.m.r. data of this cyclic peptide demonstrated that multiple conformational equilibria take place in solution and they vary with solvent polarity. Three conformers are interconverting with each other in the nonpolar chloroform (CDCl3); one C4-symmetric conformer (49%) and two C2-symmetric conformers (37% and 14%). While three C2-symmetric (59%, 19%, and 18%) and one asymmetric conformer (4%) are detected to coexist in acetonitrile (CD3CN), one largely populated C2-symmetric one (97%) is favored in the polar dimethyl sulfoxide (Me2SO-d6). N.m.r. measurement employing various strategy predicted the occurrence of trans-cis-cis-cis-trans-cis-cis-cis (two Sar-Pro bonds: trans) (tccctccc) peptide bond sequence in a predominant C2-symmetric conformer of Me2SO-d6 solution. In the same way, tccctccc and ctttcttt (two Sar-Pro bonds: cis) peptide unit arrangement was proposed for the first and the secondly populated conformer in CD3CN, respectively. In CDCl3 a conformer having tctctctc (four Sar-Pro bonds: trans) C4-symmetric peptide bond sequence was deduced.

Magnetic Resonance Spectroscopy↗
PubMed1983

Ring conformation of cyclic octapeptide cyclo (L-Pro-Sar)4 in the crystalline state.

A single-crystal X-ray diffraction analysis has been made of the structure of the cyclic octapeptide cyclo(L-Pro-Sar)4. The material [C32H48O8N8 X (21/4) H2O X (1/2) CH3OH, Mr = 799.43] crystallizes in the monoclinic space group C2 with cell dimensions a = 14.544 (3), b = 11.902 (2), c = 14.064 (3), and beta = 122.26 (2) degrees (lambda = 1.54178 A, T = 293 K). The final R value for the 1980 observed reflections is 0.079. The ring conformation has the peptide bond sequences of cis-cis-trans-trans-cis-cis-trans-trans (Pro-Sar-Pro peptide bond linkages are cis-cis- or trans-trans). The pyrrolidine rings in the four proline residues take an envelope form in which the gamma-carbon atom deviates from the plane of the remaining four atoms in the ring.

Crystallization↗
PubMed1983

A case of hypophosphataemic vitamin D-resistant rickets treated with initial massive doses of 1 alpha-hydroxy-vitamin D3 alone.

A 1 5/12-year-old girl with hypophosphataemic vitamin D-resistant rickets was treated with initial massive doses of 1 alpha-hydroxy-vitamin D3 (1 alpha-OH-D3) alone. A dramatic improvement of bone lesions and growth rate and normalization of the characteristic biochemical defects were noted within four months after the start of massive 1 alpha-OH-D3 therapy. The results of this study suggest that early therapy with massive doses of 1 alpha-OH-D3 alone improves the radiological findings and restores to normal the biochemical defects and the growth rate as early as possible. This regimen may improve motor strength and endurance and obviate the need for corrective orthopaedic procedures.

Bone and Bones↗
PubMed1983

Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites.

In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-dihydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Total body irradiation as a primary treatment for adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an extremely difficult disease to treat. The median survival of patients with this disease has been reported to be only about 3 mo even with intensive treatment. We have treated five ATL patients (four males and one female, 42 to 72 yr of age) with total body irradiation (TBI). One patient who received 150 rad of TBI achieved complete remission and has been well without treatment for over a year. One hundred and thirty rad of TBI was administered to another patient, resulting in control of the leukocyte count at around 10,000/microliter and survival for 6 mo. Three patients received 100 rad of TBI. Only one of these patients has lived with leukemic cells for over a year without treatment. The other two patients relapsed rapidly and despite various kinds of treatment, such as a second course of TBI, extracorporeal irradiation of the blood, cytapheresis and combination chemotherapy consisting of pepleomycin, vincristine and a high dose of prednisolone, expired from pneumonia in 3 and 4 mo respectively. In all except the last two patients, thrombocytopenia and anemia developed and lasted for 2.5 wk to 3 mo and granulocytopenia occurred only in the patient who received 150 rad of TBI. Slight nausea and loss of appetite were noticed in one patient. It seems that 100 to 150 rad of TBI is effective against ATL, with acceptable side effects.

Adult↗
PubMed1983

Synthesis of N-protected deoxynucleosides via 3',5'-cyclic silyl derivatives.

Treatment of deoxynucleosides with dichlorosilanes in pyridine gives 3',5'-cyclic silyl derivatives. Dimethylsilanediyl derivatives and tetramethyldisiloxanediyl derivatives are not stable solvolytically and cleavage of these silyl ethers to the parent deoxynucleosides occurs readily on addition of water. These solvolytically labile bifunctional silyl groups serve as simultaneous transient protecting 3'- and 5'-hydroxyl functions. Acylation and successive hydrolysis of 3',5'-cyclic silyl derivatives gives the corresponding N-protected deoxynucleosides. Some N-acylated deoxy-adenosines and N-anisoyldeoxycytidine were synthesized easily by this N-protection method.

Chemical Phenomena↗
PubMed1982

Glucose regulation of arginine-induced pancreatic somatostatin release from the isolated perfused rat pancreas.

The effects of glucose alone, combinations of glucose with arginine or tolbutamide and either arginine or tolbutamide alone, on somatostatin, insulin, and glucagon secretion were investigated using the isolated perfused rat pancreas. When glucose alone was raised in graded increments at 15-min intervals from an initial concentration of 0 mM to a maximum of 16.7 mM, somatostatin as well as insulin in the perfusate increased with the glucose, while glucagon decreased. The similarity of the glucose stimulated somatostatin and insulin release was especially evident when the perfusate glucose was increased from an initial dose of 4.4 mM rather than 0 mM to 8.8 mM or 16.7 mM. In addition, glucose at concentrations varying from 4.4 mM to 11 mM dose-dependently enhanced arginine-induced somatostatin and insulin release and suppressed glucagon release dose-dependently as before. Arginine in the absence of glucose was not capable of stimulating somatostatin secretion whereas tolbutamide, in contrast, was capable of stimulating somatostatin secretion even in the absence of glucose.

Animals↗
PubMed1982

Effect of starvation on somatostatin content of pancreas and gastrointestinal tract of the guinea pig.

The effect of 48-hour starvation on the somatostatin contents of the pancreas and gastrointestinal tract was studied in the guinea pig. Somatostatin contents were higher in various portions of the stomach and pancreas of fed guinea pigs than in fed rats and unchanged after 48-hour starvation, in spite of the decreased blood glucose level. These results suggest that somatostatin may not play the same physiological role in nutrient homeostasis of guinea pigs as it does in other species.

Animals↗