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Biomedical subjects

H Endo

Publications and source records attributed to H Endo.

At least 235 records · Page 13Linked to original sources

Identification of metabolites of KE-298, a new antirheumatic drug, and its physiological properties in rats.

To characterize the pharmacokinetic properties of a new antirheumatic drug, KE-298, the metabolic fate of [14C]labeled KE-298 in rats was investigated, focussing especially on the identification of metabolites and its physiological properties. [14C]KE-298 was rapidly and almost completely absorbed after oral administration, and was well distributed throughout the body. In plasma, only a small amount of unchanged KE-298 was detected and the major component was an active metabolite, deacetyl-KE-298, which accounted for approximately 50% of the radioactivity in the plasma. Further evidence was obtained by 1H-NMR analysis that deacetyl-KE-298 existed as ketone-thiol and thiohemiacetal forms in a tautomeric equilibrium. As the second main metabolite in plasma, S-methyl-KE-298, a methyl conjugate of deacetyl-KE-298, was detected. Neither deacetyl-KE-298-amino acid mixed disulfide nor any disulfide of the drugs was found. Though a thiol-containing drug generally remains in the body due to the formation of mixed disulfide with protein, no evidence of retained radioactivity was found in any tissues after the administration of [14C]KE-298. Further, in the ex vivo studies of plasma protein binding, the formation of drug-protein conjugate was scarcely detected. These results suggest that the metabolic pattern of deacetyl-KE-298 is different from that of common thiol-containing drugs, and that the reactivity of the thiol moiety of deacetyl-KE-298 to protein is extremely low. This property of deacetyl-KE-298 may be principally responsible for the nonaccumulation of radioactivity in the tissues after the administration of [14C]KE-298.

Animals↗

Testicular morphology of a greater Indian rhinoceros (Rhinoceros unicornis).

The testis of a greater Indian rhinoceros (Rhinoceros unicornis) was examined by naked eyes and light microscopy. The animal sampled was estimated to be 42 years old. Testis was ellipse-shaped and weighed 1,300 g. Although a number of elongated spermatids were distinguishable in some seminiferous tubules, the lumen of seminiferous tubules was closed and connective tissues conspicuously increased in amount in the intertubular space. These findings in testicular morphology of the animal may be due to ageing.

Animals↗

Classification of the cycle of the seminiferous epithelium in the common tree shrew (Tupaia glis).

The classification of the cycle of the seminiferous epithelium was carried out in the common tree shrew (Tupaia glis). The tree shrew captured in Thailand were fixed with Bouin's fixative, embedded in paraffin wax, and stained with PAS-hematoxylin. The cycle was classified into twelve stages on the basis of the acrosomal changes of spermatids. Relative frequencies of stages form I to XII were 11.9, 7.2, 8.9, 22.5, 12.9, 9.7, 8.0, 5.9, 4.0, 3.2, 2.9, and 3.6%, respectively. Different stages did no appear in a cross-sectioned tubule as did in primates. The head of matured spermatid was discoidal in shape and different from that of primates and rodents. Spermatogenesis of the common tree shrew is different from that of primates and rodents according to its morphological features.

Animals↗

[An preliminary study on Quality of Life Scale for Elderly: an examination in terms of psychological satisfaction].

The purpose of this study was to construct Quality of Life Scale for Elderly (QOLS-E), which was to evaluate the older person's physical, social, and psychological states synthetically, and to find out which factors most influenced the person's psychological satisfaction. Two groups of people, 42 in total who were between 65 and 90 years old, participated in the study, with 25 living in the nursing home, and 17 in the hospital. Although the factor structure of QOLS-E was reasonable, the reliabilities were not very high, meaning further research was necessary to improve the scale. Multiple regression showed that Satisfaction with Activities of Daily Life was apt to be related to psychological satisfaction. Also, enjoying a hobby and positive relationships with institutional staff members appeared important for other facets of psychological satisfaction. As for subscales of psychological satisfaction, enjoying a hobby was significantly related to Acceptance of Own Life, and number of diseases to Mental Stability. Another subscales of QOLS-E, Satisfaction with Family Relationships, was also related to Acceptance of Own Life.

Activities of Daily Living↗

[Development of scales of relationships between grandchildren in adolescence and grandparents].

The purposes of this study are (1) to make scales of relationships between grandchildren in adolescence and grandparents, and (2) to clarify functions of grandparents perceived by grandchildren and functions of grandchildren perceived by grandparents. Subjects were 517 students in junior high schools, high schools and universities (mean of age: 17 years old), and 107 elderly persons at home (mean of age: 73 years old). As a result, factorial validity and reliability of the scales were confirmed. We found the functions of "daily emotional support", "acceptance of existence", "time perspectives", and "succession of generations" in both the grandchildren scale and the grandparents scale. Additionally we identified the function of "instrumental informational support" in the grandparents scale. The fact that the functions of "time perspectives", and "succession of generations" were found in two groups suggested the facilitation of mutual development between the generations. In addition, the function of "acceptance of existence" suggested possibilities of genuinely supportive relationships.

Adolescent↗

[Comparative studies on the time course of proliferating cell nuclear antigen and bromodeoxyuridine staining pattern in regenerating rat liver cells].

Immunohistochemical staining pattern of proliferating cell nuclear antigen (PCNA) was examined in regenerating rat liver specimens fixed under the various conditions (10% buffered formalin for 6hr, 1% paraformaldehyde for 6hr, 100% methanol for 4hr, 70% ethanol for 6hr). Time course of PCNA staining pattern after hepatectomy in the specimens fixed with 100% methanol or 70% ethanol coincided closely with that of bromodeoxyuridine (BrdU) staining pattern, which is known to be standard marker of cell proliferation. Similar result was obtained in fixation with 10% buffered formalin (10% BF) or 1% paraformaldehyde (1% PFA) when only granular staining pattern of PCNA was evaluated. These findings suggest that granular immunostaining of PCNA in tissue specimens fixed with 100% methanol, 70% ethanol, 10% BF or 1% PFA is useful for evaluating the extent of cell proliferation.

Animals↗

An ultrastructural and lectin-histochemical study on the seminiferous epithelium of the common tree shrew (Tupaia glis).

The seminiferous epithelium of the common tree shrew (Tupaia glis) was investigated using transmission electron microscopy and lectin-histochemistry. It was compared with that of shrews examined in previous studies. Some peculiar structures were detected in the tree shrew spermatid at the electron microscopic level. The most characteristic feature was the disposition of mitochondria in early spermatids. In cap and early acrosome-phase spermatids, mitochondria accumulated in one area of the spermatid cytoplasm and then dispersed in the late acrosome phase. Subsequently they again clustered to form the middle piece of spermatozoa. While the lamellar structure was clearly seen in the caudal region of the spermatid nucleus, it gradually disappeared during the process of elongation. The dilated area in the postacrosomal space of early round spermatids was also characteristic. The dilation was not detected in elongated spermatids. These structures were not recognised in the seminiferous epithelium of shrews. With respect to lectin histochemistry, the binding patterns in the spermatid acrosome of the tree shrew were similar to those of the musk shrew. However, PNA and BPA, which reacted with the Sertoli cell cytoplasm of the musk shrew, showed no reaction in the tree shrew Sertoli cell. Thus, except for some lectin binding patterns in the spermatid acrosome, no close similarity was recognised in the morphology of the seminiferous epithelium between tree shrews and shrews.

Acrosome↗

Functional anatomy of the radial sesamoid bone in the giant panda (Ailuropoda melanoleuca).

The function of the radial sesamoid bone (RS) in the giant panda (Ailuropoda melanoleuca) was examined by macroscopic study of RS-related bones and muscles. The RS was observed to be connected to the scapholunar and the 1st metacarpal bones. A joint cavity was present between the proximal surface of the RS and the distal area of the scapholunar bone but the RS possessed a fibrous joint connecting it to the proximal radial surface of the 1st metacarpal bone. It is suggested that the RS possesses no substantial abductor-adductor function as the articulation between the RS and the 1st metacarpal bone (FM) seems not to permit flexible movement of the RS. The RS may be a supporting process opposite the digits in the palm when the animal flexes its 5 digits to grip objects, but it is not an active grasping apparatus. In the muscular system, abductor pollicis longus provided strong tendons to the RS as an RS-abductor, whereas the abductor pollicis brevis, opponens pollicis and aponeurosis palmaris were well developed as an RS-adductor muscle group. Observation of RS articulations, however, showed that the muscles do not provide appreciable abduction-adduction actions for the RS.

Animals↗

[Assessment of biological age and indices of aging].

People age at different rates. Accurate assessment of aging is indispensable for research in gerontology and geriatrics. Biological age can be estimated from age-related changes in physiological and physical functions. Disease, physical activity, and life-style have been shown to affect aging. Biological age was estimated by multiple regression. We studied how external appearances, diet, job status, smoking and alcohol consumption were related to aging. The subjects were 2,385 people of both sexes whose ranged from 15 to 87 years. Aging estimated by external appearance strongly correlated with changes in physiological functions and in physical strength. Diet was also found to be significantly related to aging. Biological age was significantly lower than calendar age in subjects with managerial jobs in non-smokers, and in those who drank a moderate amount of alcohol. These results show that biological age can be useful in aging research.

Adolescent↗

Effects of imidazoline antagonists of alpha 2-adrenoceptors on endogenous adrenaline-induced inhibition of insulin release.

We studied the effects of adrenoceptor antagonists and imidazoline derivatives on endogenous adrenaline-induced inhibition of insulin release in anesthetized rats. The intracerebroventricular injection of neostigmine increased plasma levels of catecholamines and glucose but not insulin. Pretreatment with an i.p. injection with phentolamine caused a dose-dependent increase in insulin secretion. When atropine was coadministered with phentolamine, the phentolamine-induced increase in insulin secretion was inhibited. Neither phentolamine nor atropine affected plasma levels of catecholamine. Yohimbine and idazoxan, which are alpha 2-adrenoceptor antagonists, and tolazoline, a non-selective alpha-adrenoceptor antagonist, also reversed adrenaline-induced inhibition of insulin secretion. Phenoxybenzamine, prazosin, propranolol, and antazoline, an imidazoline without alpha 2-adrenoceptor activity, did not affect insulin levels. When agents were preinjected i.p. in rats that were given saline into the third cerebral ventricle, phentolamine and antazoline, but not yohimbine and idazoxan, increased plasma levels of insulin. The results suggest that the inhibition of insulin release induced by adrenaline was reversed by antagonism of alpha 2-adrenoceptors. Phentolamine and antazoline, both of which are imidazoline derivatives, induced insulin secretion independently of the adrenoceptors only under the resting conditions.

Adrenergic alpha-2 Receptor Agonists↗

Histological and immunohistochemical analysis of lung development, with particular reference to lung hypoplasia.

Using immunohistochemical (IH) staining for epithelial membrane antigen (EMA), keratin, Leu-7, Ca 19-9, secretory component (SC) and surfactant protein A (SPA) on formalin-fixed, paraffin-embedded autopsy cases of stillbirth and early neonatal death, the normal profile of IH-positive cells in the airway of the developing fetal lung was clarified. IH-positive cells first appeared in the proximal region of the lung, and then in the distal region. Keratin-positive cells and EMA-positive cells were abundant at the 10th gestational week (10 GW), the earliest stage observed in this study. Cells positive for Leu-7 and Ca 19-9 appeared during the time when bronchial branches developed, and were abundant at around 16 GW, the time of completion of bronchial branching. On the other hand, SPA- and SC-positive cells appeared after the completion of bronchial branching, and were abundant around 29 GW and 34 GW, respectively. Acinous structural development was observed in terms of radial alveolar count (RAC). Cases of lung hypoplasia defined as a lung weight to body weight ratio of under 0.012 at > or = 28 GW or under 0.015 at < 28 GW showed a rather high tendency of abnormalities of cellular differentiation revealed by IH staining.

Bronchi↗

Spermidine-preferential uptake system in Escherichia coli. ATP hydrolysis by PotA protein and its association with membrane.

PotA protein, one of the components of the spermidine-preferential uptake system in Escherichia coli, was purified to homogeneity, and some of its properties were examined. PotA protein showed Mg(2+)-and SH-dependent ATPase activity. The specific activity was approximately 400 nmol/min/mg of protein and the Km value for ATP was 385 microM. The nature of the ATP binding site was explored by identification of the amino acid residue photoaffinity-labeled with 8-azido-ATP. It was found that 8-azido-ATP was attached to cysteine 26. In the spermidine transport-deficient mutant E. coli NH1596, valine 135 of PotA protein, which is located between two consensus amino acid sequences for nucleotide binding (50-57 and 168-173), was replaced by methionine (Kashiwagi, K., Miyamoto, S., Nukui, E., Kobayashi, H., and Igarashi, K. (1993) J. Biol. Chem. 268, 19358-19363). This mutated PotA protein could be labeled with 8-azido-ATP, but showed very low ATPase activity. To identify which cysteine is involved in the function of potA protein, cysteines 26, 54, and 276 were replaced by alanine, threonine, and alanine, respectively. Among the three mutated PotA proteins, the mutated PotA protein C54T only lost both ATPase and spermidine uptake activities. The results taken together indicate that the adenine portion of ATP interacts with a domain close to the NH2-terminal end of PotA protein, and active centers of ATP hydrolysis are located both within and between the two consensus amino acid sequences for nucleotide binding. Association of PotA protein with membranes was strengthened by the existence of channel forming PotB and PotC proteins. ATPase of PotA protein was inhibited by spermidine, suggesting that uptake inhibition by spermidine may function during this process.

ATP-Binding Cassette Transporters↗