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Biomedical subjects

H Endo

Publications and source records attributed to H Endo.

At least 217 records · Page 12Linked to original sources

Relationship between the metabolic chiral inversion and chemical structure of 4-phenyl-4-oxobutanoic acids, derivatives of anti-rheumatic agent KE-298.

The relationship between metabolic chiral inversion and chemical structure of various 4-phenyl-4-oxobutanoic acids (4-OBA), derivatives of anti-rheumatic agent KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid], was investigated in rats. Chiral inversion occurred with the thio-alkyl group, whereas the thio-acyl group played no role in the inversion of 4-OBA. A 2-methylene moiety was required for the inversion. When the 4-carbonyl moiety was removed, chiral inversion was significantly decreased, which provided an affinity for the intramitochondrial medium chain fatty acid CoA ligase. In addition, the distance between the chiral center and the carbonyl moiety was also an important factor for chiral inversion. While a sulfur atom was not indispensable for the chiral inversion, the existence of the sulfur atom influenced its affinity to the long chain fatty acid CoA ligase.

Animals↗

Osteometrical and CT examination of the Japanese wolf skull.

The skulls of Japanese wolf (Canis hodophilax) were osteometrically examined and compared with those of Akita-Inu. The skull total length was not statistically different between two species. However, significant differences were demonstrated between two species in some ratios concerning the frontal bone. CT examination was carried out in the Japanese wolf skull. The data indicated that the frontal sinus is not be largely developed and compressed in the dorso-ventral direction in parasagittal area. The narrow frontal sinus fitted to external shape of the frontal bone. The cribriform plate had a well-developed complicated structure in a caudal part of the ethmoid bone. These data will be useful to examine the respiratory function and the olfactory sense in the Japanese wolf.

Animals↗

Pancreas morphology of the striped hyena (Hyena hyena).

The pancreas of a striped hyena (Hyena hyena) was examined by the naked eyes and light microscopy. The distribution of A, B, D and PP cells in the islets of Langerhans was investigated immunohistochemically. The pancreas, located in the mesoduodenum, consisted of three lobes. It was about 420 mm in total length, about 10-30 mm in width and about 10 mm in maximum thickness. The smallest lobe was caudally separated from two cranial lobes. This characteristic lobe was named as a caudal lobe. Two pancreatic and one accessory pancreatic ducts opened into the duodenum. The pancreatic acini, secretory ducts and endocrine islets were arranged as shown in other carnivores. A cells were located in the peripheral region of the islets, whereas B cells were equally distributed in the islets. Both D and PP cells were also discerned in the islets.

Animals↗

[Effects of administration of Clostridium butyricum to patients receiving long-term tube feeding].

In patients who require total parenteral or enteral nutrition the intestinal lining may atrophy and the ability to absorb nutrients may be lost. To prevent atrophy of the small intestine, we administered a suspension of Clostridium butyricum to elderly patients receiving tube feeding, and then measured the activation of serum diamine oxidase and the number, form, water content, and bacteria content of stools, indicators of intestinal structure. We found a significant increase in diamine oxidase activity and an improvement in stool condition: the number of stools per day decreased, form improved, and water content and the number of aerobic bacteria decreased significantly. These results indicate that in patients receiving long-term tube feeding, administration of Clostridium butyricum can restore condition to a near-normal state.

Aged↗

Pathological investigation of armadillos infected with Mycobacterium leprae.

An infection experiment with M. leprae was carried out using 20 nine-banded armadillos. As a result, the development of leprous lesions and a marked multiplication of AFB were confirmed in a high rate of 13 out of 15 cases (86.8%) in the inoculated groups. These changes were found to be progressing at post mortem of one case even with the shortest life period for 7.5 months and were very serious in one case with the longest life period for 33 months, suggesting the continuation of symptoms, though it is an expression neglecting the individual difference in susceptibility to leprosy. Among infected viscera with AFB, the most conspicuous lesions were found in the liver and spleen. The developed lesions were found in the lung, stomach and kidney which had been never seen in HD in human cases, and so, which may characterize armadillos' leprosy. The change in the peripheral nerve was not so severe when compared with that in HD in human cases. This difference will remain as a future pathological problem to be solved.

Animals↗

[Application of gene gun for local-regional cancer].

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.

Animals↗

[Home care problems of new long-term care insurance in Japan].

The Japanese government will start new long term care insurance for the elderly in the year 2,000, which will completely change care systems for institutionalized and non-institutionalized patients, will need to be established. Frail patients will be assessed through municipal government. Physical or mental disability will be determined by six different grades and patients will get different services for each grade. The key person in handling this new long term care insurance as new assessment tools. The attitude for candidates of care manager were surveyed: 41% think that the quality of care will improve with this new system; 89% think the medical aspect of the care of the elderly will change. A nurse station in each local area will be requested first. In conclusion, the new long term care insurance will change the care of the elderly and the quality of services. The support of Geriatricians will be needed in this new care system.

Health Services for the Aged↗

Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas.

The S100A4 gene (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin /FSP1/CAPL) encoding an S100-related calcium-binding protein is implied to be involved in the invasion and metastasis of murine tumor cells. In the present study, the expression of S100A4 in human colorectal adenocarcinoma cell lines (SW837, LoVo, DLD-1, HT-29, SW480, SW620, WiDr, and Colo201) and surgically resected neoplastic tissues was examined to investigate whether S100A4 plays a role in the invasion and metastasis of human tumor cells. Northern blot analysis using total RNA isolated from the adenocarcinoma cell lines revealed that five of the eight cell lines expressed substantial amounts of S100A4 mRNA. Normal colon fibroblasts (CCD-18Co) expressed little of the RNA. Using surgically resected specimens, it seemed that the amount of S100A4 mRNA in adenomas was nearly equal to that in normal colonic mucosa, whereas adenocarcinomas expressed a significantly higher amount of the RNA than did the adjacent normal colonic mucosa. Immunohistochemical analysis using formalin-fixed paraffin-embedded surgical specimens and monoclonal anti-S100A4 antibody demonstrated that none of 12 adenoma specimens were immunopositive, whereas 8 of 18 (44%) focal carcinomas in carcinoma in adenoma specimens and 50 of 53 (94%) adenocarcinoma specimens were immunopositive. Interestingly, the incidence of immunopositive cells increased according to the depth of invasion, and nearly all of the carcinoma cells in 14 metastases in the liver were positive. These results suggest that S100A4 may be involved in the progression and the metastatic process of human colorectal neoplastic cells.

Adenocarcinoma↗

The primary gustatory area in human cerebral cortex studied by magnetoencephalography.

Magnetic fields (MFs) from gustatory stimulation with 1 M NaCl and 3 mM saccharin were recorded from the human brain by using a whole-cortex SQUID system. The averaged onset latency of MFs was 93 ms for NaCl and 172 ms for saccharin and no response was obtained for water. A high correlation coefficient was noted between the difference of onset MFs latencies in two tastants and that of behavioral reaction times, and responses to saccharin were delayed or abolished after treatment of a subject's tongue with a sweet-suppressing agent. This finding indicates that the MFs obtained were caused by gustatory stimulation. By plotting the estimated current dipole on the magnetic resonance image, we could locate the primary gustatory area at the transition area between the operculum and insula, as reported in macaque monkeys.

Adult↗

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.

Afibrinogenemia↗

Immobilization stress-induced increase of hippocampal acetylcholine and of plasma epinephrine, norepinephrine and glucose in rats.

We investigated the role of the hippocampal cholinergic neurons during immobilization stress in rats using a microdialysis technique. Blood levels of glucose, epinephrine and norepinephrine during immobilization stress were also determined. Acetylcholine release was initially increased by immobilization stress, then gradually decreased. Plasma level of epinephrine increased gradually and reached significance at 30 min after the start of immobilization and remained at the elevated level during immobilization. Plasma level of norepinephrine initially increased and reached significance at 30 min after the start of immobilization and remained at the elevated level during immobilization. Plasma level of glucose increased gradually and reached maximum and significance 45 min after the start of immobilization, then decreased. Fifteen min after immobilization, acetylcholine release increased again, while concentrations of epinephrine and norepinephrine were still elevated. Thus the response of acetylcholine and the other responses to immobilization stress were not parallel.

Acetylcholine↗

Effect of KCA-098 on the function of osteoblast-like cells and the formation of TRAP-positive multinucleated cells in a mouse bone marrow cell population.

KCA-098 (3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinol ine-6-one), an analogue of coumestrol (a naturally occurring weak phytoestrogen), dose-dependently increased alkaline phosphatase activity of osteoblastic ROS 17/2.8 cells and freshly-isolated osteoblasts from neonatal mouse calvaria, and reduced cell proliferation. In addition, KCA-098 increased the synthesis of collagenese-digestible protein (CDP) of ROS 17/2.8 cells. On the other hand, KCA-098 had no effect on the basal synthesis of osteocalcin but reduced the 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)(2)D3)-induced increase in osteocalcin synthesized by ROS 17/2.8 cells. Therefore, KCA-098 had a bidirectional effect on the differentiation of osteoblasts (i.e., stimulating both alkaline phosphatase activity and synthesis of CDP and inhibiting osteocalcin synthesis). However, as KCA-098 stimulated the mineralization of chick embryonic bone in organ culture and recovered the bone density reduced by ovariectomy of rats, it would serve overall to stimulate the differentiation of osteoblasts. On the other hand, KCA-098 inhibited the formation of tartrate-resistant, acid phosphate-positive multinucleated cells (TRAP(+)MNC) induced by 1 alpha,25(OH)(2)D(3), parathyroid hormone (PTH), and prostaglandin E2 (PGE2) in cultures of mouse bone marrow cells, showing that it inhibits the formation of osteoclast-like cells. Coumestrol and 17beta-estradiol had no effect on the proliferation and alkaline phosphatase activity of ROS 17/2.8 cells. They did, however, dose-dependently inhibit osteoclast-like cell formation as well as KCA-098 did, indicating that the main action of coumestrol and 17beta-estradiol on bone tissue is the inhibition of bone resorption.

Acid Phosphatase↗

Stereoselective pharmacokinetics of [14C]-labeled KE-298, a new anti-rheumatic drug, in rats.

The stereoselective pharmacokinetics of two enantiomers of [14C]-labeled KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid] were investigated in rats. The blood levels of radioactivity after the oral administration of (+)-(S)-[14C]KE-298 were higher than that for (-)-(R)-[14C]KE-298; the AUC of the former was approximately twice that of the latter. No significant stereoselectivity was observed in absorption rate. The tissue/ plasma level ratios at 30 min after oral administration of (-)-(R)-[14C]KE-298 in the liver and kidney, the major metabolic and/or excretory organs, were 2 to 3 times higher than those for (+)-(S)-[14C]KE-298. Neither was evidence of stereoselectivity found in the excretion of radioactivity. During incubation with isolated rat hepatocytes in vitro, the metabolic rates of KE-298 enantiomers were not significantly different. Plasma protein binding 20 min after the oral administration of (+)-(S)-[14C]KE-298 and (-)-(R)-[14C]KE-298 was 99.3% and 97.0% respectively. Comparing the unbound fraction, (-)-(R)-[14C]KE-298 was approximately 4 times higher than (+)-(S)-[14C]KE-298. In order to make clear the relationship between stereoselective pharmacokinetics and protein binding for [14C]KE-298, the comparative pharmacokinetics of (+)-(S)-[14C]KE-298 and (-)-(R)-[14C]KE-298 were investigated in analbuminemic rats. In these animals, no evidence of stereoselectivity was found for either blood level-time profiles or plasma protein binding. These results revealed that the stereoselective pharmacokinetics of KE-298 in rats might be due to enantiomeric differences in binding to plasma albumin.

Animals↗

Signal transduction in Th clones: target of differential modulation by PGE2 may reside downstream of the PKC-dependent pathway.

Lymphokines produced by non-transformed Th clones, Th1 and Th2, were classified into three groups based on their patterns of expression by different stimuli: Group I, GM-CSF and IL-2, characterized by a strict requirement of activation of both the PKC- and calcium-dependent pathways; Group II, IFN-gamma, IL-3, and IL-4, partially induced by calcium ionophore alone; and Group III, IL-5, IL-6, and IL-10, partially induced by either PMA or calcium ionophore alone. Transfection of constitutively active PKC or p21ras replaced the requirement for PMA in expression of these lymphokines, with the exception of GM-CSF. Production of Group II lymphokines was partially induced by constitutively active calcineurin. Production of Group I and II lymphokines was highly sensitive to cyclosporin A, while Group III lymphokines were relatively resistant. Addition of prostaglandin E2 (PGE2) and overexpression of catalytic subunit of protein kinase A inhibited lymphokine production in Th1 cells, but not in Th2 cells, with the exception of GM-CSF. Production of Group III lymphokines induced by PMA alone was upregulated by PGE2, but that of Group II and III lymphokines induced by calcium ionophore alone was not affected. These results suggest that one of the targets of PGE2 is downstream of the PKC-dependent pathway.

Animals↗

Development of cardiac musculature in the cranial vena cava of rat embryos.

Development of cardiac musculature in the rat cranial vena cava (common cardinal vein or duct of Cuvier) was examined by immunohistochemistry and transmission electron microscopy. Undifferentiated cardiac myocytes were detected in the cranial vena cava wall of rat embryos after 12.5 days post-coitum (dpc). The tunica media of the cranial vena cava was composed of cardiac myocytes after formation of the endothelium. Therefore, the cranial vena cava may be not only a part of the venous system but also of the heart. Myocytes in the cranial vena cava contained developing myofibrils, mitochondria and intercalated discs similar to those found in the myocytes in heart. Striated myofibrils began to differentiate as soon as myocytes appeared in the vena cava wall, and myocytes with differentiating myofibrils occur in the wall as the first component of the tunica media at 12.5 dpc. We concluded that the cardiac musculature in the vena cava is not a secondary extension into the tunica media after birth only in the rat, but a basic structure formed in all mammals during early embryonic development.

Animals↗

Development of an ultra high sensitive tissue biosensor for determination of swellfish poisoning, tetrodotoxin.

A simple tissue biosensor for measuring Na+ channel blockers such as tetrodotoxin (TTX) and saxitoxin (STX) has been developed. The membrane of frog bladder has Na+ channels which control the passage of Na+. It is well known that TTX blocks Na+ channels. The tissue biosensor consists of a Na+ electrode integrated within a flow cell. The tip of the electrode was covered with frog bladder membrane sandwiched between two sheets of cellulose acetate membrane, and the electrode was set in a flow cell. A solution of 8% NaCl was carried in the cell and the output of the electrode allowed to stabilize. TTX was injected into the sensor system and measured from the inhibition ratio of the sensor peak output. One assay took approximately 5 min. The lower limit of detection was 86 fg. The continuous determination of TTX was feasible for 250 h in the presence of 0.003% NaN3. A Linear correlation was obtained between TTX activities of F-niphobles and F-parudale determined by the methods of TTX sensor and mouse assay.

Animals↗

Distribution of beta1 integrin during development of chick tarsometatarsal skin in vivo and in vitro.

To determine the role of beta1 integrin in chick tarsometatarsal skin development, we examined the localization of the beta1 integrin immunohistochemically in vivo and in vitro by light and electron microscopy. Beta1 integrin was present over the entire cell surface of undifferentiated epidermis at early stages (Days 5, 9, 13). Marked changes in the localization of beta1 integrin occurred during epidermal keratinization and stratification, i.e., expression of beta1 integrin decreased in the superficial and intermediate cell layers from Day 13 to Day 17. After 17 days in vivo, when keratinization of the epidermis was completed, the distribution of beta1 integrin was confined to the basal layer of the epidermis in a pericellular distribution. During all stages examined, fibroblasts in the dermis were also stained. Immunoelectron microscopic study revealed that beta1 integrin was located on the plasma membrane of keratinocytes and dermal fibroblasts. The change in beta1 integrin localization that occurred in vivo could be reproduced in cultures of developing skin in which keratinization (differentiation) or mucous metaplasia (transdifferentiation) had been induced in vitro by hydrocortisone or retinol treatment, respectively. A monoclonal antibody against beta1 integrin caused striking changes in the epidermal keratinization process and in the basement membrane structure in vitro, i.e., inhibition of keratinization and detachment of the basement membrane from the basal surface of the epidermis. These results indicate that beta1 integrin plays an important role in cell-cell and cell-extracellular matrix interactions, which are important for epidermal development of the tarsometatarsal skin.

Animals↗