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Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 559 records · Page 31Linked to original sources

Genetic controls of T cell-independent Thy-1 alloantibody responses.

Early and late primary IgM antibody responses of mice to Thy-1.1 antigens showed different antigenic and cellular requirements. We studied genetic controls of the early primary responses, which could be induced by subcellular thymocyte antigens independently of host T-cell activity. All Thy-1.2 mouse strains of Igha (BALB/c and BC8), Igh-VaCb (BAB14), Ighd (AKR/Cum), Ighj (CBA/J, C3H/HeN, C3H.SW, and C3H.JK), and Ighn (NZB) definitely responded early to Thy-1.1 antigens from AKR/J (Ighd), A.Thy-1.1 (Ighe), or B10.Thy-1.1 (Ighb) mice or SD rats, whereas all strains of Ighb (C57BL/6, C57BL/10, B10.D2, B10.BR, B10.A, CB20 and CWB), Ighc (DBA/2), Ighe (A/J), and Igho (C.AL20) responded poorly to the same antigens. This contrasts with the observation that both strains of Ighj (C3H/HeN) and Ighb (B10.BR) responded well at later times. As was the case for late responses, the matching of H-2 between donor and recipient resulted in early responses of exceptional quality in high-responder strains. It was concluded that under the influence of H-2, whose incompatibility between donor and recipient partially interferes with responses, early but not late primary Thy-1.1-specific antibody responses are selectively controlled by Igh-V or closely linked Ir gene(s) as a new VH marker.

Animals↗

The effect of blood pressure on inner ear blood flow.

We investigated the effects of blood pressure on the blood flow in the inner ear as compared with other organs in normotensive rats (NR), spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR). The cardiac output and the regional blood flow were measured by a radioactive microsphere technique in conscious rats. The haemodynamics of the inner ear and other organs and the effects of a converting-enzyme inhibitor (SA-446) on the regional blood flow were compared among NR, SHR, and RHR, the blood pressure being 107, 152, and 185 mm Hg, respectively. With the exception of the heart, the organ blood flow was lower in SHR than in NR in all organs, including the inner ear. It was also lower in RHR than in SHR. The blood pressure dropped after i.v. injection of SA-446, while the regional blood flow increased. The effect was strongest in RHR, followed by SHR and finally NR.

Animals↗

Electrophoretic and ultrastructural analysis of the rabbit's striated external urethral sphincter.

The male rabbit's external urethral sphincter was investigated with O'Farrell's 2-dimensional electrophoretic analysis of myosin light chains and electron microscopy. Its pattern of myosin light chains was different from that of the soleus (predominantly slow twitch muscle) but was very similar to that of the psoas (predominantly fast twitch muscle). Ultrastructurally it was shown to be red muscle resembling the soleus. Therefore the fiber type of the rabbit's external urethral sphincter was determined to be the red (fast) type.

Animals↗

Connectin filaments in stretched skinned fibers of frog skeletal muscle.

Indirect immunofluorescence microscopy of highly stretched skinned frog semi-tendinous muscle fibers revealed that connectin, an elastic protein of muscle, is located in the gap between actin and myosin filaments and also in the region of myosin filaments except in their centers. Electron microscopic observations showed that there were easily recognizable filaments extending from the myosin filaments to the I band region and to Z lines in the myofibrils treated with antiserum against connectin. In thin sections prepared with tannic acid, very thin filaments connected myosin filaments to actin filaments. These filaments were also observed in myofibrils extracted with a modified Hasselbach-Schneider solution (0.6 M KCl, 0.1 M phosphate buffer, pH 6.5, 2 mM ATP, 2 mM MgCl2, and 1 mM EGTA) and with 0.6 M Kl. SDS PAGE revealed that connectin (also called titin) remained in extracted myofibrils. We suggest that connectin filaments play an important role in the generation of tension upon passive stretch. A scheme of the cytoskeletal structure of myofibrils of vertebrate skeletal muscle is presented on the basis of our present information of connectin and intermediate filaments.

Animals↗

Fatty acid composition of cardiolipin from guinea pig Harderian gland.

The fatty acid composition of cardiolipin from the Harderian gland of guinea pig was examined by gas chromatography and gas chromatography-mass spectrometry. At least 33 kinds of fatty acids were detected. Oleic acid was the most prominent component, accounting for 18.2 mol% of the total fatty acids. About 70.2 mol% of fatty acids had methyl branches. Ethyl branches were also detected (1.3 mol%). Straight chain saturated acids comprised only 10.3 mol%. On the other hand, linoleic, linolenic, and arachidonic acids were not found in this lipid. The 2-(2'-) acyl moieties contained larger amounts of oleic acid and smaller amounts of branched chain acids than the 1-(1'-)acyl moieties, but the saturated straight chain acids showed even distribution between the 1-(1'-) and 2-(2'-)positions. The fatty acids of cardiolipin from the liver of the same animal were also examined. Linoleic acid was the most abundant component (66.9 mol%), and saturated straight chain acids occupied 21.9 mol%. Branched chain acids were detected but comprised only 11.2 mol%.

Animals↗

Renal actinomycosis associated with a duodenorenal fistula caused by foreign body.

We are reporting a case of a rare renal actinomycosis in a 12-year-old mentally-retarded girl. Proteinuria and hemopyuria were pointed out one year before the operation by an annual medical check-up and IVP subsequently performed showed foreign bodies at the upper pole of the right kidney. The patient continued to have pyuria and right nephrectomy was performed. There was a fistula between the duodenum and the upper portion of the right kidney. Foreign bodies (two bobby pins) were found in the kidney. Subsequent pathologic examination of the resected kidney revealed an actinomycotic lesion.

Actinomycosis↗

Timing of sexual receptivity and the release of gonadotrophins during puberty in female rats.

In about 60% of rats that were paired with fertile males before vaginal opening, vaginal opening occurred between 15:00 and 21:00 h under controlled lighting conditions (lights on 06:00-18:00 h). No rats mated before 12:00 h or after 03:00 h. Most of the rats (52/82) mated within 3 h after vaginal opening. About 90% of the rats that were paired with fertile males before vaginal opening mated and most conceived. Serum LH and FSH levels rose from 14:00 h to a peak at 18:00 h, whereas hypothalamic LHRH content suddenly decreased by 18:00 h. This study shows that the timing of sexual receptivity, ovulation and the release of gonadotrophins during puberty are similar to those at pro-oestrus in adult rats and suggest that the diurnal rhythm of hormonal changes plays an important role in timing of the first oestrus.

Animals↗

Clinical pharmacokinetics and pharmacological actions of a long-acting formulation of propranolol.

The pharmacokinetics and pharmacodynamics of a long-acting formulation of 60 mg propranolol (Inderal LA; in the following briefly called LA) once a day were compared with those of conventional propranolol (Inderal; in the following called CV) 20 mg three times a day, by a double-blind cross-over method in healthy volunteers. After a single oral dose with LA in 10 subjects, the blood level slowly increased to reach the peak plasma level (Cmax) of 11.56 +/- 2.15 ng/ml (mean +/- SE) at 5 h which was lower than that of CV (42.93 +/- 19.26 ng/ml). However, the peak plasma level was almost constant for another 5 h with LA (11.03 +/- 2.38 ng/ml at 10 h). The elimination half-life with LA was significantly longer than with CV (6.5 +/- 1.0, 3.9 +/- 0.5 h, respectively). The plasma level at 24 h did not differ between LA and CV (3.34 +/- 0.92, 5.47 +/- 1.38 ng/ml, respectively). LA and CV were orally administered for 8 consecutive days in 6 subjects. The plasma level after LA accumulated and Cmax was 1.6 times higher and the area under the time-concentration curve (AUC) 1.7 times higher than on Day 1, but no accumulation of the plasma level was seen after CV. On Day 8 the plasma level after 24 h of LA turned-out to be higher than that of CV (4.4 +/- 2.2, 3.5 +/- 1.5 ng/ml). Although the exercise heart rate was significantly more suppressed by CV than LA on Day 1, the difference disappeared on Day 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endoscopic intramural injection of anti-neoplastic emulsion.

With the aim of establishing a topical chemotherapy against stomach carcinoma, 5-fluorouracil (5-FU) emulsion (oil/water type) for injection has been developed. The drug distribution was analyzed by 5-FU bioassay and radiographic examination of soft parts, for which radiopaque Lipiodol was employed in an oil phase. In order to examine local toxicity, tissue retention, and transfer to lymph nodes of 5-FU emulsion, the drug was administered perorally to rats and injected intramurally through the gastric serosa into laparotomized dogs. Following this series of experiments, which gave satisfactory results, the time courses of drug concentration in the gastric wall and regional lymph nodes were studied as a pre-clinical trial, by applying endoscopic intramural injection of 5-FU emulsion or solution in dogs. The anti-metastatic and anti-neoplastic effects of 5-FU emulsion were investigated in an experimental model of lymph node metastasis in mice. The emulsion was more effective in subduing metastasis and tumor growth than the solution, and the effectiveness of the former was further augmented by the use of repeated injections rather than a single injection. This method of endoscopic injection of 5-FU emulsion should be of great value as a local therapeutic measure against stomach carcinoma itself as well as against metastatic lesions in the lymph nodes.

Administration, Oral↗

Pharmacokinetics and the antiarrhythmic effect of mexiletine in patients with chronic ventricular arrhythmias.

A new antiarrhythmic agent, 1-(2,6- dimethylphenoxy )-2-aminopropane (mexiletine), was investigated in 10 patients with chronic premature ventricular contractions (PVCs) to evaluate the antiarrhythmic efficacy and the pharmacokinetics after single intravenous, single oral and repeated oral dosings of mexiletine 150 mg. Mexiletine was well absorbed from the intestinal tract. The relative bioavailability was 83.2 +/- 8.9% (mean +/- S.E.). The time-concentration curve of mexiletine fitted in well with two-compartment open model. Elimination half-life, volume of distribution and plasma clearance were 10.54 +/- 0.26 h, 2.10 +/- 0.49 l/kg, 6.01 +/- 0.63 ml/min/kg, respectively. The computer-simulated time-concentration curves of multiple oral dosings , which were based on the kinetic parameters from single oral dosing, conformed well with measured concentrations. This might be applied to predict the plasma level of mexiletine. The steady state of plasma mexiletine level was reached 4-5 days after 450 mg/day dosings and ranged 0.75-2.18 micrograms/ml. In 6 of 10 patients, the frequency of PVCs was suppressed more than 75% as compared with the pre-medication value. Mexiletine was well tolerated at a dose of 450 mg/day. However, of 4 patients with the dose increased to 600 mg/day, the administration was ceased in three patients due to gastrointestinal symptoms and tremor. All of these adverse reactions disappeared when the administration was stopped. These results suggest that mexiletine is effective against ventricular arrhythmias and the dosage should be carefully adjusted. The prediction of plasma level would be applied to the dosage regimen of mexiletine.

Adult↗

T cell subsets in the tonsil in relation to age analyzed with monoclonal antibodies (anti-leu antibodies) and fluorescence activated cell sorter (FACS).

The ratio of the cells reacting to anti-leu 1, 3a and 4 antibodies is as low as that of T cells in the tonsil to those in the peripheral blood. The number of the tonsillar cells reacting to anti-leu 2a and 7 antibodies is still smaller. Fluorescence intensity of tonsillar lymphocytes reacting to leu (1, 2a, 3a, and 4) antibodies is lower than that of peripheral blood lymphocytes. Adult tonsillar lymphocytes have higher ratios of the cells reacting to anti-leu 1, 2a, 3a, 4 and 7 antibodies than child tonsillar lymphocytes and fluorescence intensity of the cells reacting to these anti-leu antibodies tended to be higher in adult tonsillar lymphocytes. These findings suggest less cytotoxic/suppressor T and NK/K function cells in the tonsil than in the peripheral blood. From these, it is conceivable that the tonsillar lymphocyte constitution becomes closer to that of peripheral blood as the child grows up. Further, immature T cells are present in the tonsil, though in a small number. This tendency is stronger in children than in adults.

Adult↗

Branched chain fatty acids in phospholipids of guinea pig Harderian gland.

Fatty acid compositions of phosphatidyl ethanolamine and phosphatidyl choline extracted from the guinea pig Harderian gland were examined by gas chromatography and gas chromatography-mass spectrometry. Oleic acid was the major component of both phospholipids, but a large amount of saturated branched chain fatty acids was found: 34.5% in phosphatidyl ethanolamine, and 42.9% in phosphatidyl choline. On the other hand, linolenic and arachidonic acids were not found in these phospholipids. At the 1-position of phosphatidyl choline and phosphatidyl ethanolamine, 54.3% and 40.9% of fatty acids, respectively, had methyl branches. These methyl branches were located at the even-numbered carbon atoms. Branched chain fatty acids were also found at the 2-position of both lipids: 36.2% in phosphatidyl choline and 31.2% in phosphatidyl ethanolamine. The fatty acids of phosphatidyl ethanolamine and phosphatidyl choline from liver, cerebrum, cerebellum, erythrocytes, and plasma of the same animal were also analyzed. Saturated and unsaturated fatty acids, including arachidonic acid, were the major components. Branched chain fatty acids were also found in these lipids, but in very small amounts.

Animals↗

Macrophage migration inhibition factor against cell-surface antigens coded by the major histocompatibility complex and other genes in mice.

We developed an indirect capillary tube method to improve reproducibility of macrophage migration inhibition (MI) tests using a one-way mixed lymphocyte culture. MI response could be induced to cell-surface antigens coded by either H-2 or non-H-2 (background) genes. The sensitivity was more readily induced across H-2 + background differences. The presence of only background difference did not induce the MI response to much extent. High MI activities were obtained to antigens coded by either K end or D end of the H-2 complex + background difference. Moderate activities were induced across the H-2D difference + background. These results suggest that the D region of the H-2 complex may direct a MI response when an H-2I difference is present during sensitization.

Animals↗

Ototoxic effect of an aminoglycoside drug on an immature inner ear.

In order to investigate to what extent an immature inner ear is injured by external causes, the effect of Kanamycin on an immature cochlea was studied in mice by using scanning and transmission electron microscopes. Our results showed that immature cochleae are more highly susceptible to injury than mature cochleae, especially when the Nuel's space and the Corti tunnel open. It is suggested that in humans, during the stage corresponding to the above period, that is, in about the third gestational month, the inner ear is highly susceptible to injury by external causes.

Animals↗