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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 1,369 records · Page 76Linked to original sources

Increased biliary cholesterol secretion in alloxan diabetic mice.

Plasma and liver cholesterol levels and biliary cholesterol, phospholipid and bile acid concentrations were examined in normal and alloxan diabetic mice fed ordinary and 0.5 per cent cholesterol diets. The plasma and liver cholesterol levels markedly increased in the diabetic mice, and the cholesterol diet further increased the liver cholesterol level but not that in the plasma. The gallbladder bile weight increased in the diabetic mice, but not after the cholesterol diet. The biliary lipid concentrations markedly increased in the diabetic mice, and the increases of the cholesterol and phospholipids exceeded that of the bile acids, resulting in increases of the cholesterol molar concentration ratio (mole percent) and the lithogenic index. The cholesterol diet increased the biliary cholesterol concentration and slightly the phospholipid, but not the bile acids. Therefore, the cholesterol mole percent and the lithogenic index increased. Among the biliary bile acid composition, cholic and deoxycholic acids increased and beta-muricholic acid decreased in the diabetic mice, whereas the cholesterol diet feeding decreased cholic acid and increased chenodeoxycholic and alpha-muricholic acids. These data suggest that the mechanism of the increase of biliary cholesterol secretion in diabetic mice is different from that after cholesterol diet.

Animals↗

Neurotrophic influences are not affected by miniature end-plate potentials.

We investigated whether or not miniature end-plate potentials (MEPPs) play a part in neurotrophic influences. The sciatic nerve of mice, which supplies the extensor digitorum longus muscles, was cut either close to, or far from, the muscle. Denervation changes were evaluated using the resting membrane potential and dose-response curves obtained by plotting acetylcholine-induced contractures of muscles denervated 3 days earlier. The cessation of MEPPs and the manifestation of denervation changes occurred significantly later in muscles with long nerve stumps than in those with short nerve stumps. A single administration of ethidium bromide, a specific inhibitor of mitochondrial protein synthesis, accelerated the cessation of MEPPs in muscles with long nerve stumps without affecting the manifestation of denervation changes. We therefore conclude that MEPPs do not have neurotrophic effects.

Acetylcholine↗

Inhibition of luteinizing hormone secretion during quiescent interval of testicular androgen production in immature mice.

We reported [1] that the proliferation of seminal vesicle cells in mice takes place largely in the neonatal (days 0-15) and pubertal (days 25-35) periods and that between neonatal and pubertal proliferations, a quiescent interval of cell proliferation due to markedly diminished secretion of androgens occurs. The present study was carried out to investigate the mechanism for this quiescent interval of Leydig cell activity. Serum LH concentrations were moderate (0.29 ng NIH-LH-S1/ml) at 8 days of age, low (0.13 ng/ml) at 18 days, and high (0.78-0.60 ng/ml) at 30, 40 and 60 days. The LH level on day 18 was almost the same as that found in hypophysectomized adult mice (0.12 ng/ml). These changes with age in serum LH concentrations paralleled those for serum total androgen (testosterone plus 5 alpha-androgens) concentrations. The injection of HCG (1 IU/day) or LH releasing hormone (0.1 or 0.4 microgram/6h) for 1 or 2 days resulted in significant and marked increases on day 18 in testicular and serum androgen levels and/or the proliferation of seminal vesicle cells measured with 5-[125I]iodo-2'-deoxyuridine uptake by the whole seminal vesicles. These findings lead to the hypothesis that the quiescent interval of testicular androgen production due to inhibition of pituitary LH secretion occurs around day 20 in mice.

Aging↗

Changes in cardiac ultrastructure and myofibrillar proteins during ischemia in dogs, with special reference to changes in Z lines.

This study was designed to examine whether or not coronary ligation produces changes in myofibrillar proteins, especially Z line proteins including alpha-actinin and the 55 kDa protein, in the dog. Changes in ultrastructure of the myocardium after coronary ligation were also studied. A branch of the left anterior descending coronary artery was ligated for a period of 3, 6, 24 or 72 h. Coronary ligation produced ultrastructural changes in Z lines (characterized by broader and wavy Z lines) as well as changes in glycogen granules, mitochondria, and nuclei. Myofibrils were isolated from the myocardium that had been made ischemic by coronary ligation. The yield of myofibrils was reduced as the ischemic period was increased. Phase microscopic examination of the isolated myofibrils from the ischemic myocardium revealed that there were spread Z lines with wider I bands, these changes being essentially the same as those observed by the electron microscope in the ischemic myocardium. The effect of coronary ligation on the myofibrillar proteins was studied by means of polyacrylamide gel electrophoresis. In the isolated myofibrils from the myocardium 3 h after coronary ligation, there were decreases in the percentage of actin, alpha-actinin and the 55 kDa protein, and these changes progressively increased with lengthening of the ischemic period. These results suggest that coronary ligation decreases actin, alpha-actinin and the 55 kDa protein, in association with ultrastructural changes of the Z lines.

Actinin↗

Carcinogenic effects of 3-di(hydroxymethyl)-amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine in the small intestine of Ishibashi and Wistar rats.

The carcinogenic effect of an oral administration of 3-di(hydroxymethyl)-amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazin e (DHNT) was studied in two strains of rats. Ishibashi (IS) rats have a perpetual absorption disturbance while Wistar Imamichi (WI) rats have no such disturbance. Small intestinal carcinomas developed in 10 out of 15 (66.7%) IS rats and in all 8 (100%) Wistar rats given 3,500 ppm DHNT for 43 weeks. The total number of lesions in the small intestine was 24 in IS rats and 21 in WI rats. Histologically, the lesions consisted of 7 mucosal dysplasias, 4 adenomas and 12 tubular and 1 papillary adenocarcinoma in IS rats, and 3 mucosal dysplasias, 1 adenomas, and 15 tubular and 2 papillary adenocarcinomas in WI rats. The levels of plasma leucine aminopeptidase, copper and total protein were lower, while blood urea nitrogen was higher in both strains of rats given DHNT than in control rats.

Adenocarcinoma↗

Studies of Angiostrongylus cantonensis in two experimental hosts.

Lung infection with Angiostrongylus cantonensis was established in experimentally infected Indian soft-furred rats (Millardia meltada) and Indian spiny mice (Mus platythrix). Pulmonary arterial migration occurred earlier (at day 20 after infection) in M. meltada than in Wistar rats. M. meltada and M. platythrix could serve as useful animal models for comparative studies of mechanisms determining host specificity of A. cantonensis.

Angiostrongylus↗

Two-dimensional electrophoresis of troponin complex with nonequilibrium pH gradient-sodium dodecyl sulfate polyacrylamide slab gel.

A two-dimensional electrophoresis procedure for the separation and analysis of troponin subunits is described in which the protein solution supplemented with 50 mM each of both glutamic and aspartic acids is subjected to nonequilibrium pH gradient electrophoresis in the first dimension. Complete dissolution and gelation of the sample with agarose are essential for analysis of constituent proteins of cardiac myofibrils. Electrophoresis in the first dimension gel is carried out for a relatively short time, 2-3 h. In combination with sodium dodecyl sulfate slab gel electrophoresis (second dimension), three subunits, troponin T, troponin I, and troponin C, of dog cardiac troponin-tropomyosin complex and myofibrils can be simultaneously analyzed quantitatively on a slab gel. The contents of troponin and tropomyosin of cardiac myofibrils were 275 +/- 34 pmol/mg of myofibrillar protein. The molar ratio of troponin T, troponin I, troponin C, and tropomyosin was close to 1 : 1 : 1 : 1 in troponin-tropomyosin complex and myofibrils.

Animals↗

Subtotal versus total parathyroidectomy with forearm autograft for secondary hyperparathyroidism in chronic renal failure.

Forty-three patients with chronic renal failure and secondary hyperparathyroidism underwent parathyroidectomy; 20 of the 43 underwent subtotal parathyroidectomy (Group A) and 23 patients underwent total parathyroidectomy and parathyroid autotransplant in the forearm (Group B). Postoperative clinical improvement was similar in both groups. In the immediate postoperative period eight patients in Group A who had severe bone changes and 21 patients in Group B needed supplemental calcium administration. The grafted tissues in all cases functioned well; reimplantation of the cryopreserved parathyroid tissues was unnecessary. One case in each group showed a recurrence. One patient in Group A was submitted to reexploration of the neck with a lateral approach. The other patient in Group B underwent excisions of the transplanted parathyroid tissues on three separate occasions under local anesthesia. The second operation was definitely easier and safer to manage after a total parathyroidectomy with autotransplantation to the forearm.

Adult↗

Ultrastructural evidence for eosinophil-mediated destruction of Angiostrongylus cantonensis transferred into the pulmonary artery of non-permissive hosts.

Ultrastructural and cytochemical analyses were carried out on cellular reactions to the young adult worms of Angiostrongylus cantonensis surgically transferred into the pulmonary arteries of permissive (rat) and non-permissive (rabbit and guinea-pig) hosts. In permissive hosts, no appreciable cellular reactions could be found around worms throughout the course of the observations. By contrast, the infiltration of neutrophils along with eosinophils was observed around worms in non-permissive hosts even at early stages (days 2 to 4). At day 7 and later, the prominent degranulation (solubilization of the whole granule or the matrix alone with preserved crystalloid, tubulovesicular structure formation, and vacuole formation containing lysosomal contents, etc.) of eosinophils, and subsequent release of the lysosomal contents on to the worm surface were noted. Discharge of large amounts of peroxidase on to the worm surface was also demonstrated. The worms were thus damaged and their cuticular fragments were frequently found removed. In addition to this, degenerative changes, such as lipid-droplet and vacuole formations, were detectable in the hypodermis, somatic musculature and intestine of the parasites transferred into the non-permissive hosts, as early as day 4 after transfer. These data suggest that eosinophils would serve as a potential effector cell for killing of pulmonary arterial A. cantonensis in non-permissive hosts.

Angiostrongylus↗

Histamine responses mediated via H1- and H2-receptors in the isolated portal vein of the dog.

The effects of histamine were studied on the isolated circular muscle strip and longitudinal muscle strip of the dog portal vein. Histamine-induced contractions of the circular muscle were inhibited by H1-receptor antagonist pyrilamine but increased by H2-receptor antagonist ranitidine. When the tissues were contracted with PGF2 alpha in the presence of pyrilamine, histamine produced the relaxation of the circular muscle but not longitudinal muscle. The relaxation of the circular muscle was inhibited by ranitidine in a concentration dependent manner, the pA2 value for ranitidine being 6.97 (6.55-7.39). It is concluded that the response of the circular muscle to histamine is the sum of two components, H1-receptor mediated contraction and H2-receptor mediated relaxation.

Animals↗

Adrenal adenoma with 18-hydroxycorticosterone excess and hypertension: a variant of aldosteronomas.

A 46-year-old woman with hypertension, normokalemia, suppressed renin, normal catecholamines, and a left adrenal mass on the CT scan was found to have excessive 18-hydroxycorticosterone (18-OHB) and normal aldosterone levels in plasma, both of which responded poorly to sodium restriction and angiotension II, and supranormally to ACTH. Plasma 18-hydroxydeoxycorticosterone (18-OHDOC) was normal. After adrenalectomy, amelioration from hypertension occurred with a reduction in plasma 18-OHB and aldosterone. The plasma 18-OHDOC remained normal. The adrenal tumor was histologically an adenoma, containing a large amount of 18-OHB and a small amount of aldosterone. Thus, the present adenoma seems to be a variant of aldosteronomas.

18-Hydroxycorticosterone↗

In vivo activity of bifonazole in guinea pigs: its characteristic features and comparison with clotrimazole.

To investigate the in vivo antimycotic activity of bifonazole, a new imidazole antifungal agent, the therapeutic effectiveness of several bifonazole preparations in the topical treatment of experimental Trichophyton mentagrophytes infection in guinea-pigs was tested. 1% cream, 1% solution or 1% polyethylene glycol solution of bifonazole was applied to infected sites on the skin at a dose of 0.3 g/day for 14 or 21 consecutive days, starting on the 3rd or 5th day after the infection. In all experiments, clotrimazole was employed as a reference drug in comparable formulations. The estimation of efficacy of treatment with active formulations was made on the basis of the score of skin lesion and the rate of positive skin cultures in comparison with those for infected, untreated or placebo-treated controls. The results are summarized as follows: (1) The treatment with each bifonazole preparation resulted in a significant improvement in local symptoms and complete heal as 6-10 days after initiation of application. After completion of the 14-day or 21-day treatment course, local skin cultures revealed either an elimination of or a significant decrease in the viable fungus count. (2) The therapeutic effectiveness of bifonazole appeared to be dependent on the duration of treatment; treatment in the 21-day course was more effective than that in the 14-day course, irrespective of the type of drug preparation. All these results clearly demonstrate a favorable topical efficacy of each bifonazole preparation in the guinea pig dermatophytosis model.

Administration, Topical↗

Assessment of in vivo activity of bifonazole against dermatophytic infection in guinea pigs on the basis of the amount of a specific fungal cell wall component chitin in the infected skin.

The severity of experimental dermal infection with Trichophyton mentagrophytes in guinea pigs with or without receiving topical treatment with 1% creams of bifonazole or clotrimazole were estimated on the basis of fungal chitin content in the infected tissue. This criterion was favorably comparable with that based on local symptoms and, therefore, proved to be useful as a more objective and quantitative measure for assessment of therapeutic efficacy of such antifungal agents in the animal model of dermatophytosis.

Administration, Topical↗

Pseudohypoparathyroidism (PHP) type II and selective hypoaldosteronism in a patient with retinitis pigmentosa.

A 53-year-old man with retinitis pigmentosa, who had two years' complaints of general malaise and muscle weakness, noticed occasional attacks of the cramps of the lower legs about three months prior to admission. At that time, hypocalcemia (7.6 mg/dl) and hyperphosphatemia (5.2 mg/dl) were pointed out. On admission, serum potassium was high-normal or high (4.4 - 4.9 mEq/l). Endocrinological studies revealed the findings of pseudohypoparathyroidism (PHP) type II, including a normal urinary cyclic AMP but blunted phosphaturic response to synthetic human parathyroid hormone (PTH), a high level of serum amino-terminal fragment of PTH with a low level of serum calcium and its ionized form, and a high-normal level of nephrogenous cyclic AMP. This patient also had selective hypoaldosteronism, as shown by intermittent hyperkalemia, low plasma and urinary levels of aldosterone and normal glucocorticoid levels. Plasma renin activity was normal but responded to a greater extent to furosemide plus upright posture. Plasma aldosterone was low and responded poorly to furosemide plus upright posture and graded angiotensin II infusions. The possible explanations for the association of PHP type II and selective hypoaldosteronism in this patient with retinitis pigmentosa are discussed.

Aldosterone↗

The characteristics of renal mineralocorticoid receptors in glycyrrhizinic acid or deoxycorticosterone-induced hypertensive rats.

The relationship between blood pressure and the characteristics of renal mineralocorticoid receptors was studied in glycyrrhizinic acid (GR) or deoxycorticosterone (DOC) induced hypertensive rats. The apparent maximum binding (Bmax) of aldosterone to renal mineralocorticoid receptors was 3.1 +/- 0.2 X 10(-13) mol/mg cytosol protein and the dissociation constant (Kd) was 1.6 +/- 0.5 nM. GR treatment reduced the concentration of cytosol mineralocorticoid receptors (Bmax) but did not affect the Kd. In unilaterally adreno-nephrectomized rats, GR induced hypertension and hypokalemia as seen in DOC treated rats. After the discontinuation of GR, blood pressure was normalized with concomitant recovery of free cytosol mineralocorticoid receptors in 14 weeks. On the contrary, in DOC treated rats, the characteristics of mineralocorticoid receptors in kidney were already normal one week after the cessation of DOC treatment. However, blood pressure remained high up to 15 weeks. These findings suggest that the persistence of hypertension after GR discontinuation might be caused by a long-standing effect of GR on renal mineralocorticoid receptor mechanisms.

Aldosterone↗