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Biomedical subjects

M Kawaguchi

Publications and source records attributed to M Kawaguchi.

At least 199 records · Page 11Linked to original sources

In vitro and in vivo effects of somatostatin on the growth of A431 cells.

We previously reported that the octapeptide somatostatin (SS) analogue SMS 201-995 (SMS) unexpectedly stimulates the growth of A431 human epidermoid carcinoma cells in vitro. In the present study, we found that both SS-14 and SS-28 also stimulated the growth of A431 cells in vitro. The proliferative effect of SS-28 also stimulated the growth of A431 cells in vitro. The proliferative effect of SS-28 was greater than that of SS-14. In contrast, there was no difference in A431 cell tumor weight or area between the SMS-treated or untreated athymic, tumor-bearing mice. The serum epidermal growth factor (EGF) level of the SMS-treated mice was significantly lower than that of the untreated mice. Decreases in serum EGF may attenuate the proliferative effect of SMS in vivo.

Animals↗

Preoperative evaluation for risk of venous air embolism in the sitting position.

We report a patient with meningioma and radiological findings of erosive bony change, who developed venous air embolism via the diploic vein in the eroded inner table of the skull during craniotomy in the sitting position. The findings in our case suggest that preoperative radiological imaging evaluation can increase an awareness of the possibility of venous air embolism.

Aged↗

Do recently developed techniques for skull base surgery increase the risk of difficult airway management? Assessment of pseudoankylosis of the mandible following surgical manipulation of the temporalis muscle.

We report our experience with anesthetic care for six patients with pseudoankylosis of the mandible following neurosurgical procedures, four of whom required fiberoptically guided intubation for anesthesia. We suggest that the development of operative approaches and reconstruction techniques in skull base surgery may increase the risk of difficult airway due to limitation of mouth opening.

Adult↗

[Receptive systems for drugs in salivary gland cells].

Investigators have demonstrated many types of receptors or acceptors for endogenous substances in salivary glands. These suggest that salivary glands contain receptive systems for many drugs. These receptors can be classified into three types based on the property of saliva secretion: (1) receptors involved in fluid secretion, (2) receptors involved in exocytosis for the protein secretion, (3) receptors involved in both types of secretion. The receptors involved in fluid secretion include the group of alpha 1B, M3, NK-1 receptors coupled with IP3; the group of beta 2 and VIP receptors coupled with cAMP; and the group of P2Z and P2U receptors coupled with the ATP-gated calcium channel. Whereas alpha 1A, beta 1, VIP, M3, insulin and H2 receptors mediate exocytosis via the cAMP-proteinkinase A pathway. Moreover, the another pathway of diacylglycerol-proteinkinase C has also been demonstrated to be involved in the exocytosis occurring via NK-1 and M3 receptors. Thus, salivary gland cells have many kinds of drug-receptor system. These receptors are all positive to fluid and/or protein exocytosis. Recently our study on the inhibitory regulation of saliva secretion have suggested the existence of GABA and the GABA-synthetic/metabolic pathway, GABA(A) receptors and benzodiazepine (BDZ) receptors of both central and peripheral types, and furthermore, the coupling of GABA(A) and the central type of BDZ receptors. These receptors are involved in decreasing fluid secretion and amylase release elicited by secretagogues. In the future, mechanisms of the intracellular transduction elicited by BDZ or GABA must be clarified.

Animals↗

Existence of gamma-aminobutyric acid and its biosynthetic and metabolic enzymes in rat salivary glands.

To obtain more insight into the physiological role of gamma-aminobutyric acid (GABA) in rat salivary glands, we measured the concentration of GABA and the activities of its biosynthetic and metabolic enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T). The GABA concentrations in rat parotid and submandibular glands were 10.0 and 14.3 nmol/g weight, respectively, which were 0.6-0.8% of the levels in the brain (cerebellum and medulla oblongata), whereas glutamic acid (Glu) was abundant in the two glands. These GABA levels in the two glands were significantly decreased by administration of semicarbazide (200 mg/kg, i.p.), a GAD inhibitor, and increased by gabaculine (50 mg/kg, i.p.), a GABA-T inhibitor. The activities of both GAD and GABA-T were also detected in homogenates of the two salivary glands, but they were lower than those in the brain. However, kinetic analysis showed that the values of Michaelis constants for Glu and GABA in both enzyme reactions in these two glands were similar to those in the brain. These results indicate that GABA and its biosynthetic and metabolic enzymes are present in rat salivary glands as well as the brain.

4-Aminobutyrate Transaminase↗

Isolation of an antioxidant from Penicillium roquefortii IFO 5956.

In the search for antioxidants from microbial organisms, we found that Penicillium roquefortii IFO 5956 produced an antioxidant. This antioxidant was isolated from a culture broth of the strain, and its structure was identified to be 2,3-dihydroxy benzoic acid (1). The antioxidative activity of 1 was nearly equal to that of tert-butyl-4-hydroxyanisol (BHA).

Antioxidants↗

A study of effect of CS-045, a new antidiabetic drug, on hypertension in spontaneously hypertensive rat.

Several lines of evidence have suggested that insulin resistance may play an important role in the pathogenesis of hypertension. CS-045 is a new hypoglycemic drug by which improves insulin sensitivity in peripheral tissues. We assessed the effect of CS-045 on hypertension in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) as a control. At 20 weeks of age, the treatment with CS-045 was started by being mixed with chow pellets in the proportion of 0.2% (w/w) and continued for 6 weeks. Nonfasting plasma glucose levels were not changed in either strain of rats treated with CS-045, but plasma insulin levels decreased in SHR 4 and 5 weeks after the start of CS-045 therapy. Blood pressure increased with age in SHR without treatment, but CS-045 decreased blood pressure only 4 and 6 weeks after the treatment. These findings suggest that insulin resistance is not strongly associated with the pathogenesis of hypertension in SHR.

Animals↗

[Usefulness of 123I-BMIPP myocardial imaging in patients with stable effort angina and unstable angina].

We evaluated the clinical significance of myocardial imaging using 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy in patients with stable effort angina pectoris (SAP) and unstable angina pectoris (UAP). Thirty-three patients with SAP were studied using rest BMIPP and stress 201TlCl (Tl) myocardial scintigraphy, and 13 patients with worsening effort type of UAP were also examined using both rest BMIPP and Tl scintigraphy. We compared those BMIPP findings with myocardial perfusion images obtained with Tl and the regional wall motion determined by left ventriculography. In 45% of 282 segments of myocardial ischemia of SAP, the degree of myocardial uptake of BMIPP was concordant with that of stress Tl and the defect score of Tl was higher than that of BMIPP. On the other hand, in 32% of 62 segments of ischemia of UAP, the degree of myocardial BMIPP and Tl uptake was concordant and BMIPP defect score was higher than Tl score. In SAP, the decrease in regional wall motion agreed better with the decrease in myocardial uptake of BMIPP than that of Tl. These results suggest that myocardial ischemic regions decreased BMIPP uptake show the disturbance of fatty acid metabolism and lead to abnormal wall motions. Such ischemic regions may be clinically severe state in patients with angina pectoris.

Aged↗

[Identification of viable myocardium using 99mTc-tetrofosmin scintigraphy--comparison with 201Tl redistribution-reinjection images].

The purpose of this study was to clarify the diagnostic value of identifying viable myocardium using 99mTc-Tetrofosmin scintigraphy. Twenty-one patients with chronic coronary artery disease were studied using 201Tl exercise myocardial scintigraphy with reinjection and 99mTc-Tetrofosmin exercise myocardial scintigraphy. All patients had a history of old myocardial infarction. For 99mTc-Tetrofosmin scintigraphy, 222 MBq of 99mTc-Tetrofosmin was injected during exercise, and exercise images were obtained 20 min thereafter. There hours later, 666 MBq of 99mTc-Tetrofosmin was injected at rest, and images were obtained 40 min and 220 min later. Myocardial viability in the 99mTc-Tetrofosmin scintigraphy was estimated as fill-in findings (FF) or over 50% of %RI uptake (%TF) in the rest image. Myocardial viability in the 201Tl scintigraphy was estimated as redistribution (RD), fill-in findings in the reinjection image (FR) or over 50% of %RI uptake in the reinjection image (% TL). Sixteen of the 21 patients (76%) who underwent 201Tl scintigraphy (RD 10, FR 3, %TL 3 cases) and 15 of the 21 patients (71%) who underwent 99mTc-Tetrofosmin scintigraphy (FF 11, %TF 4 cases) had viable myocardium in the infarcted area. A comparison between the 99mTc-Tetrofosmin rest images obtained 40 min after the injection and that of 220 min revealed no redistribution findings. The %RI uptake of the infarcted area in the resting 99mTc-Tetrofosmin image (47 +/- 16%) was slightly lower than that in the 201Tl reinjection image (52 +/- 16%). In conclusion, viable myocardium was as clearly identified by 99mTc-Tetrofosmin, as by 201Tl scintigraphy.

Aged↗

Synthesis and NMR applications of isotopically labeled 2'-deoxynucleosides. Stereospecific deuteration of the C2' methylene in [ul-11 C/15N]deoxyadenosine.

Stereospecific deuteration of the C2' methylenes of 2'-deoxynucleosides together with 13C label has been found to open up various applications for structural studies of DNA oligomers in solution. Major problems in analyzing the structure and dynamics of larger DNA oligomers by NMR are associated with geminal proton pairs attached to the C2' and C5' of sugar moieties. We have employed, with a minor modification, existing synthetic routes to prepare stereospecific deuteration of the C2' methylene to prepare 13C/2H-doubly labeled nucleosides. For example, [ul-13C/15N] adenosine, which was prepared by microbial fermentation using [13C6]-glucose and [15N]-ammonium salt as precursors, was derived into (2'R)- and (2'S)-[ul-13C/15N;2'-2H1]-2'-deoxy-adenosines. Each of these multiply labeled nucleosides was then incorporated into a DNA dodecamer, 5'-d(CGCG AATTCGCG)-3', which was examined by various NMR techniques in order to evaluate the precision and accuracy of the NMR parameters obtained for the labeled moieties.

Base Sequence↗

Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice.

We have previously reported a new spontaneous recessive mutation that induces a generalized lack of lymph nodes (LNs) and Peyer's patches (PPs) accompanied by immunodeficiency in mice (gene symbol, aly). In this study, we have analyzed gut-associated lymphatic tissues of the mutant aly/aly mice and have compared the intestinal intraepithelial T lymphocytes (IEL) in aly/aly and normal aly/+ littermate mice. Immunohistochemical studies revealed that colonization of IEL and lamina propria T cells takes place in the absence of PPs and IgA-producing B cells in the lamina propria. Absolute numbers of Thy-1- IEL-alpha beta and -gamma delta are not altered in aly/aly mutant mice, whereas absolute numbers of Thy-1+ IEL-alpha beta and -gamma delta in aly/aly mice are about half of those in aly/+ mice. In IEL-alpha beta from aly/aly mice, the major CD8 alpha alpha+ and CD8 alpha beta+ subsets are maintained, whereas CD4+ and CD4+, CD8+ subsets are reduced. Although the population size of major CD8 alpha alpha+ and CD4-, CD8- IEL-gamma delta subsets is slightly reduced, the use of TCR-gamma- and -delta-chain variable gene segments by IEL-gamma delta remains almost the same in aly/aly mice. The constitutive cytolytic activity of IEL-alpha beta and -gamma delta is attenuated sharply in the aly/aly condition. This activity is, however, augmented significantly after in vitro stimulation with anti-CD3 mAb. These results indicate that most of the IEL subpopulations develop independently of passage through PPs and mesenteric LNs and that the aly mutation interrupts cytotoxic IEL development during relatively late differentiation steps that convert cytotoxic precursors to the constitutively cytolytic state.

Animals↗

Superovulation in the cow with a single intramuscular injection of FSH dissolved in polyvinylpyrrolidone.

It is desirable to reduce the number of treatments required to induce superovulation in cows. In this study we examined whether dissolving FSH in polyvinylpyrrolidone(PVP) would reduce the rate of absorption of FSH and allow it to be administered in a single dose for superovulation. In Experiment 1, 10 cows each received a single dose of FSH which contains 0.6% luteinizing hormone (FSH-R; 30 mg i.m.) dissolved in 30% PVP (10 ml) or in saline. In Experiment 2, a single injection of 30 mg FSH-R dissolved in 30% PVP was given to 25 cows, and 32 cows were injected twice daily in declining doses to receive a total of 28 mg FSH-R dissolved in saline. Prostaglandin F2alpha was given to all the cows 48 h after the first FSH treatment. Embryos were collected on Day 7 or 8 post insemination. In Experiment 1, the effect of FSH dissolved in PVP was compared with that dissolved in saline (number of recovered ova and embryos; 9.4+/-4.1 vs. 0). In Experiment 2, the rate of transferable embryos by single injection of FSH-R in PVP were significantly higher (P<0.05) than that of treatment of multiple injection groups. Progesterone concentration measured in serum collected 4 times from estrus (Day-0) to the day of embryo collection, indicated similar patterns in the 2 treatment groups. These findings suggest that PVP is a suitable solvent for prolonging the absorption of FSH given in a single injection thus providing a more practical approach of FSH administration.

Journal Article↗

Embryonic growth impaired by maternal hypoglycemia during early organogenesis in normal and diabetic rats.

The effect of maternal hypoglycemia on early organogenesis was studied in normal and diabetic rats. Female Wistar rats were made diabetic by an intravenous injection of streptozotocin (45 mg/kg) 2-3 weeks before conception. On day 9.5 or 10.5 of embryo development, both control and diabetic dams received saline or Actrapid human insulin (400 mU/rat) intraperitoneally after 19-h starvation. The fasting plasma glucose levels in diabetic dams decreased from approximately 23 to 8 mM. Hypoglycemia as low as 3.5 mM was maintained for 60 min in insulin-treated mother rats. Pregnancy was terminated on day 11.6 of embryo development. A significant growth retardation was found in diabetic embryos as compared with normal embryos. Maternal hypoglycemia lowered the DNA content in normal but not diabetic embryos, while the teratogenic effect of maternal hypoglycemia was not pronounced in either normal or diabetic embryos. These data may suggest that maternal hypoglycemia in vivo in early pregnancy influences the embryogenesis but not teratogenesis of rat embryos.

Animals↗

Three-month oral repeated administration toxicity study of seed saponins of Thea sinensis L. (Ryokucha saponin) in rats.

Ryokucha saponin (RSP), which is one of the ingredients of green tea, was administered orally to rats for 3 months at dose levels of 50, 150 and 500 mg/kg/day to assess any toxic effects. As positive control, 1200 mg/kg/day of quillaia saponin (QSP), which contains saponins equivalent in amount to those in 500 mg RSP/kg/day, was administered. The no-effect level of RSP was 50 mg/kg/day and the lowest-observed-effect level of RSP was 150 mg/kg/day for both sexes, so that the true no-effect level of RSP was estimated to be between these dose levels. In addition, it was confirmed that the toxicity of RSP at 500 mg/kg/day was less than that of QSP at 1200 mg/kg/day and RSP was demonstrated to be safer than QSP, which is a permitted food additive.

Administration, Oral↗