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Biomedical subjects

Y Takiguchi

Publications and source records attributed to Y Takiguchi.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effects of an aldose reductase inhibitor, ONO-2235, insulin and their combination on the altered responsiveness to the nerve stimulation and agonists of the isolated atria of diabetic rats.

To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac autonomic nerves disturbance, we examined the effects of ONO-2235, an ARI, as well as insulin on the responsiveness to the nerve stimulation and agonists of the isolated atria of the streptozotocin-induced diabetic rats. Insulin, 4 U/animal/day, was administered s.c. for 4 weeks before the experiment and ARI (ONO-2235), 40 mg/kg/day, was administered p.o. 3 weeks before the experiment. The transmural nerve stimulation (TNS) of sympathetic nerves and parasympathetic nerve was performed in the presence of atropine and metoprolol plus prazocin, respectively. The positive chronotropic and the inotropic responses of the atria to sympathetic TNS and to norepinephrine decreased in the rats diabetic for 8 and 12 weeks. In the rats diabetic for 8 weeks, the insulin treatment restored completely both the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment partially improved the positive chronotropic response and did not improve the positive inotropic response. In the rats diabetic for 12 weeks, the insulin treatment partially improved the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment only slightly improved the positive chronotropic response and did not improve the positive inotropic response to TNS. The combination treatment with insulin and ARI restored completely both the positive chronotropic and the inotropic responses in the rats diabetic for 12 weeks. In rats diabetic for both 8 and 12 weeks, the decreased positive chronotropic and the inotropic responses to norepinephrine recovered completely with the insulin treatment, but did not with the ARI treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1990

[A case of Pryce's type I intralobar pulmonary sequestration diagnosed by noninvasive techniques].

The patient was a female who came to our hospital with a chief complaint of hemoptysis. Radiography of the chest demonstrated a funicular shadow, and CT of the chest also revealed a similar shadow in contact with the thoracic aorta enhanced by the contrast material. Pulmonary arteriography and aortography showed that the left S8, S9 and S10 areas were supplied by abnormal blood vessels bifurcating from the thoracic aorta, rather than the pulmonary artery. This finding was supported by scintigraphy of the pulmonary blood flow and pulmonary RI angiography. Since bronchography revealed no obvious abnormality in the bronchial system, the diagnosis of Pryce's type I intralobar pulmonary sequestration was established, and left lower lobectomy was carried out. While the evidence of abnormal blood vessels is important for the definitive diagnosis of pulmonary sequestration, concurrent image processing of the results of scintigraphy of the pulmonary blood flow and pulmonary RI angiography permits noninvasive demonstration of the fact that the sequestral pulmonary tissue is regulated by the systemic circulatory system, rather than the pulmonary circulatory system and thus is a useful technique.

Adult↗
PubMed1990

[Smoldering leukemia with pyoderma gangrenosum].

A 76-year-old male admitted to Surugadai Nihon University hospital complaining of general fatigue, slight fever and anorexia. The laboratory examination revealed anemia and an appearance of a few myeloblasts and 7% of monocytes in the peripheral blood. The nucleated cell count was 2 x 10(4)/microliters with 43% myeloblasts in the bone marrow aspirate. He was diagnosed as acute myelomonocytic leukemia. He did not receive any chemotherapy for leukemia because of his old age and smoldering disease. Pyoderma gangrenosum developed in the left submandibular and axillary regions about 6 months later. Three more month later, significant increase of myeloblast was recognized in the peripheral blood and the bone marrow. It has been reported that pyoderma gangrenosum precedes a remarkable increase of leukemic cells in the patients with acute leukemia in complete remission and with myelodysplastic syndrome. In our case, to, the same process was strongly suggested.

Aged↗
PubMed1989

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration.

The safety, pharmacological action and pharmacokinetics of the thromboxane (TX) synthetase inhibitor Y-20811, a prospective medication for ischemic vascular disorder, were investigated in Phase I clinical trials in which single and repeated doses were administered orally to 32 healthy adult male volunteers. In the single-dose study, subjects were given single doses of 2.5, 5, 10, 25, 50, and 100 mg; in the repeated-dose study, a single dose of 50 mg was administered daily for 5 days. In the repeated-dose study, slight elevation of liver function test parameters in 1 subject was observed, but throughout the trials, no abnormality attributable to the test drug was found in other routine laboratory tests, subjective and objective findings, vital signs (blood pressure, pulse rate, body temperature, respiration rate), ECG, or bleeding time; nor did any finding indicate a problem concerning the safety of Y-20811. In both single- and repeated-dose studies, inhibition of the serum TXB2 production and an increase in the 6-keto-prostaglandin F1 alpha production during whole-blood coagulation, and inhibition of arachidonic acid-induced platelet aggregation were observed from 1 hour after administration of Y-20811. The duration of these actions was long, the former two lasting 168 hours (1 week) and the latter 48-72 hours or more. Slight inhibition of adenosine diphosphate-induced secondary platelet aggregation was also observed. The maximum plasma concentration time (tmax) of Y-20811 was 0.5-1.1 hours. The initial-phase half-life (t1/2 alpha) was 0.8-1.1 hours and the final-phase half-life (t1/2 beta) was 4.7-9.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Involvement of thromboxane and leukotriene in arachidonate induced coronary constriction in diabetic rats.

Vascular responsiveness to sodium arachidonate was examined in isolated perfused hearts from rats with streptozotocin-induced diabetes. In diabetic rats arachidonate induced a biphasic coronary vascular response characterized by initial vasoconstriction followed by prolonged vasodilation. Non-diabetic rats showed only a vasodilator response. The vasoconstrictor phase found in diabetic rats was abolished by ONO-3708, a selective thromboxane A2 antagonist. Indomethacin partly inhibited the vasoconstrictor response, the residual response being abolished by a leukotriene antagonist, ONO-1078. The vasodilator response, however, was completely abolished by indomethacin in both diabetic and nondiabetic rats. Furthermore, the coronary constrictor response to leukotriene D4 was enhanced in diabetic compared to nondiabetic rats. These results suggest an involvement of leukotriene in the vasoconstrictor response to arachidonate in diabetic rats, especially when cyclooxygenase is inhibited.

Animals↗
PubMed1989

Massive regional differences in the vascular effects of endothelin.

Endothelin was infused into seven anaesthetized open-chest rabbits during three 10-min periods, so that cumulative doses of 0.01, 0.1 and 1 nmol/kg were achieved. Endothelin increased blood pressure and caused systemic vasoconstriction only at the highest dose, but decreased the myocardial contractile force (measured with a strain-gauge) at all doses. In contrast to the modest systemic haemodynamic changes, vascular effects (measured with tracer microspheres) were found at each dose level and varied greatly from vasodilator (hepatic artery), through biphasic (spleen) to pure vasoconstrictor (adrenals, pancreas, stomach, colon) effects. Systemic circulatory parameters poorly reflect the regional vascular activity of endothelin.

Angiotensin II↗
PubMed1989

Reversal effect of thyroxine on altered vascular reactivity in diabetic rats.

The influence of thyroxine treatment on the altered reactivity of the isolated perfused mesenteric vasculature from streptozocin-induced diabetic rats was examined and compared with that of insulin. After 8 weeks of diabetes, the time when the decreased response to isoproterenol appeared, treatment with thyroxine reversed this decreased response to control levels. However, thyroxine replacement did not reverse the decreased responsiveness to norepinephrine, 5-hydroxytryptamine, acetylcholine, and isoproterenol after 12 weeks of diabetes. On the other hand, insulin replacement improved the vascular responsiveness to these agonists at 8 and 12 weeks. Insulin treatment also reversed the attenuated response to nerve stimulation found in diabetic rats, whereas thyroxine treatment did not improve it. Insulin treatment reversed the decreased plasma thyroid hormone levels similarly as thyroxine treatment. These results suggest that thyroid hormone deficiency is likely to be involved partly in the altered reactivity of the rat mesenteric vasculature at the early period of diabetes. On the other hand, adrenergic neuropathy is not induced by hypothyroidism.

Animals↗
PubMed1989

Altered responsiveness to sympathetic nerve stimulation and agonists of isolated left atria of diabetic rats: no evidence for involvement of hypothyroidism.

To clarify the role of hypothyroidism in diabetes-induced sympathetic neuropathy, we examined the responsiveness to sympathetic nerve stimulation and to agonists of the left atria of streptozotocin-induced diabetic rats, and compared it with those in hypothyroid, thyroxine(T4)-treated diabetic or T4-treated hypothyroid rats. Positive inotropic response of isolated left atria to transmural nerve stimulation (TNS) was examined in the presence of atropine. In diabetic rats, plasma triiodothyronine and T4 levels decreased markedly. The responses to TNS and norepinephrine (NE) also decreased. The decrease was greater in response to TNS, which may be due to the reduction of presynaptic NE release. As to the postsynaptic response, the maximal response to NE decreased without any significant change in ED50 value, and a similar decrease in the maximal response to Ca++ was also observed in spite of a slight decrease in the beta receptor density. Therefore, in diabetic rats the decreased response to TNS may result mainly from a decreased NE release from nerve endings and a decreased contractility beyond the adrenoceptor level. In hypothyroid rats, the response to TNS and NE decreased, and the decrease was again greater in response to TNS. The decrease in the NE response was due to the increased ED50 value without any change in the maximal response. Similarly, the maximal response to Ca++ did not change. Thus in the hypothyroid rats, the decreased response to TNS probably results from a decreased NE release from nerve endings as well as a decreased sensitivity to NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Identification of a novel class of elastase isozyme, human pancreatic elastase III, by cDNA and genomic gene cloning.

By using porcine elastase I cDNA as a probe, we have isolated two different but closely related cDNAs encoding elastase-like proteases from a human pancreatic cDNA library. The amino acid sequences deduced from the cloned cDNA sequences showed 56-61% identity with those of both pancreatic elastases I and II, similar to the homology between elastases I and II. The active form of the elastase-like proteases appeared to be composed of 242 amino acids and preceded by a signal peptide and propeptide of 28 amino acids. Dot blot analysis of various tissue mRNAs demonstrated that the genes for the cloned cDNAs are expressed at a high level only in the pancreas. In addition, sequence analysis of the cloned genomic genes corresponding to one of the cDNAs showed that they are members of the elastase gene family. These results indicate that the two enzymes encoded by the cDNAs should be classified into a third class of elastase isozyme. Therefore, we designated them as human pancreatic elastases IIIA and IIIB. They strongly resembled cholesterol-binding pancreatic protease, suggesting that they may possess not only a digestive function but also function(s) related to cholesterol metabolism or transport in the intestine.

Amino Acid Sequence↗
PubMed1988

Phase I clinical studies of 7432-S, a new oral cephalosporin: safety and pharmacokinetics.

Phase I clinical studies of 7432-S, a new oral cephalosporin, including a randomized placebo-controlled trial were conducted with 40 healthy volunteers. In single-dose studies, 7432-S was orally administered at doses of 25, 50, 100, and 200 mg. The mean plasma levels peaked at 2.1 to 3.0 hours and reached 1.9, 3.6, 5.6, and 11.6 micrograms/ml, respectively. Linear correlation was observed between plasma AUC values and doses given. The half-lives of the plasma levels were 0.88 to 2.26 hours with a mean of 1.53 +/- 0.33 hours. The mean urinary recoveries were 67.5 to 75.2% of the dose within 24 hours. 7432-S was partially metabolized to 7432-S-trans which was excreted in urine at 7.2 to 9.2% of the doses. Study of the meal effect showed that AUC values and peak levels were not altered although the time to the peak levels was slightly prolonged. In multiple-dose studies, 100 mg of 7432-S twice daily for 2 weeks and 200 mg twice daily for 1 week were administered and there was no abnormal accumulation of 7432-S in plasma throughout the study. No significant differences were observed in plasma levels and urinary recoveries between single- and multiple-dose regimens. Clinical symptoms, physical tests, laboratory parameters, and fecal levels of vitamins K1 and K2 were in normal ranges. 7432-S was concluded to be safe and well tolerated.

Administration, Oral↗
PubMed1988

Phase I clinical studies of 7432-S: effect of 7432-S on platelet aggregation and blood coagulation.

The effects of 7432-S, a new oral cephalosporin antibiotic, on platelet functions and vitamin K-dependent blood coagulation parameters were studied in human volunteers and animals. Although the ADP- and collagen-induced aggregations of human and animal platelets were inhibited in vitro by extremely high concentrations of 7432-S, the inhibitory effect of 7432-S was weaker than that of latamoxef or cefotaxime. When administered orally to human volunteers or animals, 7432-S caused no inhibition of platelet aggregation. Its administration also caused no change in prothrombin time and activated partial thromboplastin time both in human volunteers and in rats. The conclusion reached was that the new oral antibiotic 7432-S does not affect platelet functions and blood coagulation.

Adenosine Diphosphate↗
PubMed1988

Pharmacokinetics and safety of l-carnitine infused i.v. in healthy subjects.

The pharmacokinetics and safety of a brief i.v. infusion of l-carnitine 0, 20, 40 and 60 mg/kg have been investigated in 10 healthy subjects. The diurnal intraindividual variability of plasma carnitine was small (C. V. = 3.0, 3.9 and 3.9%, respectively), and the total 24 h excretion in urine was also small and relatively constant: 4.6, 21.5 and 13.0 mg/day in the controls vs 4.6, 20.2 and 6.0 mg/day during treatment in the three subjects to whom saline alone was administered according to a single-blind design. Therefore, the pre-dose level of carnitine was subtracted from the level after dosing for the pharmacokinetic analysis. Plasma carnitine fitted well to a three-compartment open model, with Vc of 0.11-0.20 l/kg and a t1/2 gamma of 10-23 h. The urine recovery in 24 h was 77.2-95.4%. There were no objective or subjective side-effects attributable to carnitine, so its i.v. infusion is considered to be safe.

Adult↗
PubMed1988

Changes in vascular reactivity in experimental diabetic rats: comparison with hypothyroid rats.

The responsiveness to vasoactive agents in the perfused mesenteric vascular bed of streptozocin-induced diabetic rats was examined and compared with that of propylthiouracil-induced hypothyroid rats. Diabetic rats at 4 and 8 weeks after the induction of diabetes showed a significant decrease in isoproterenol-induced vasodilatation. In addition, the contractile responses to norepinephrine and 5-hydroxytryptamine and the vasodilative response to acetylcholine were significantly decreased in 12-week-diabetic rats. The contractile response to nerve stimulation was markedly decreased at 8 and 12 weeks. On the other hand, hypothyroid rats showed a decreased response to isoproterenol, but they did not show any change in the response to nerve stimulation. A decrease in plasma thyroid hormone levels in diabetic rats at any time period was similar in extent to that in hypothyroid rats. The data indicate that the progressive changes in vascular reactivity in diabetic rats may be divided into two stages. In the early stage, the altered reactivity of vasculature is likely to be mediated by hypothyroidism, whereas in the later stage, it is induced by other factors, e.g. hyperglycemia and hypoinsulinemia. Adrenergic neuropathy is not caused by hypothyroidism.

Animals↗
PubMed1987

Application of thermography to the evaluation of the histamine skin test in man.

The degree of skin flare 10 min after intradermal injection of histamine (0.06-2 micrograms in 0.1 ml saline) was evaluated both visually and by thermography in 6 healthy male volunteers. Intradermally injected histamine increased the skin flare area in a dose-dependent manner. There was a good exponential correlation (r = 0.963) between the flare area evaluated visually and that evaluated by thermography, indicating that the degree of underestimation of the flare area by visual inspection increased with increasing flare size. This could be due to the fact that the rather irregular shape of a flare was rounded by the eyes. Suppressive effects of an antihistamine, terfenadine (20, 40, 60, and 120 mg, p.o.), on the flare caused by histamine (2 micrograms/0.1 ml saline) were evaluated in a similar way in a single-blind, crossover controlled trial using 15 healthy male volunteers. The histamine skin test was evaluated both visually and by thermography before and 4 hr after administration of placebo or each of 4 doses of terfenadine. Terfenadine (20, 40, and 60 mg) suppressed the skin flare in a dose-dependent manner, but 60 and 120 mg had almost the same effect. In all cases the flare area evaluated visually was smaller than that obtained by the thermography, although the degrees of reduction of flare area by the drug were similar by both methods when expressed as a percentage of placebo. In conclusion, thermography could serve as a tool for the objective evaluation of the histamine skin test.

Adult↗
PubMed1987

Characterization of pancreatic elastase II cDNAs: two elastase II mRNAs are expressed in human pancreas.

The primary structures of porcine and human pancreatic elastase II precursors were elucidated by molecular cloning and cDNA sequence analysis. The sequences of the cDNAs cloned from a human pancreatic cDNA library indicate that at least two elastases II are expressed in this tissue. These two human elastases II have been designated elastases IIA and IIB. All the cDNA sequences obtained, including porcine elastase II cDNA, reveal that elastase II is synthesized as a preproenzyme of 269 amino acids, including a predicted signal peptide of 16 amino acids and a predicted activation peptide of 12 amino acids. Human elastase IIA contains the published amino-terminal sequence (16 residues) for human pancreatic proelastase II, whereas elastase IIB shares 50% homology with the published 16-residue sequence. However, there is 90% homology between the overall amino acid sequences of elastases IIA and IIB. Blot hybridization analysis of the poly-adenylated RNAs isolated from various human tissues demonstrates that the human elastase II mRNAs are specifically detected in the pancreas.

Amino Acid Sequence↗
PubMed1987

Characterization of a silent gene for human pancreatic elastase I: structure of the 5'-flanking region.

A cDNA for porcine pancreatic elastase I has been cloned and used as a probe for blot hybridization analysis. Southern blot analysis of total DNA demonstrated that the elastase I gene is conserved among the porcine, rat, calf, and human genomes. Northern blot analysis, however, indicated that the elastase I gene is not expressed in the human adult pancreas, even though abundant expression is observed in the rat and porcine pancreas. Sequence analysis of the cloned human elastase I gene revealed that the proximal 5'-flanking region from -1 to -200 shows 78% identity with that of the actively transcribed rat elastase I gene, and contains a consensus TATA box and a putative tissue specific enhancer sequence. The transcriptional activity of the human elastase I gene appears to be suppressed in the human adult pancreas.

Amino Acid Sequence↗