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Biomedical subjects

H Endo

Publications and source records attributed to H Endo.

At least 289 records · Page 16Linked to original sources

Cardiac musculature of the cranial vena cava in the rat.

The distribution and morphological features of cardiac musculature in rat cranial venae cavae were examined by light and transmission electron microscopy. Cardiac myocytes are encountered from the right atrium to the root of the subclavian vein. The musculature consists of several well-developed circular or spiral myocyte layers. The ultrastructure of myocytes in the cranial venae cavae exhibits a similar structure to that of atrial myocytes. Abundant myofibrils and mitochondria are detected within the cytoplasm of these myocytes, suggesting an active contraction of the musculature. Characteristic caveolae are accumulated near the sarcolemma of cardiac myocytes in the cranial venae cavae showing their high pinocytotic activity. Immunohistochemical analysis reveals the presence of an atrial natriuretic polypeptide-like substance in the cranial vena cava and the proximal portion of the subclavian vein. Ultrastructural studies also demonstrate the distribution of atrial granules within the musculature. This musculature in the vena cava may be considered part of the endocrine atrium.

Animals↗

Effect of KCA-098, a new benzofuroquinoline derivative, on bone mineral metabolism.

The effect of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one designated as KCA-098) on the bone mineral metabolism of chick embryonic bone was examined. KCA-098 dose-dependently inhibited bone resorption of cultured chick embryonic femora and calvariae. It increased the length, dry weight, and calcium and phosphorus contents of 9-d-old chick embryonic femurs cultivated for 6 d, indicating that it stimulated bone formation. These results show that KCA-098 has the unique effects of inhibiting bone resorption and stimulating bone formation of chick embryo. In addition, in an in vivo experiment, oral administration of KCA-098 (3.0 mg/kg/d) for 16 weeks led to an increase in calcium and phosphorus content as well as an increase in the amount of force required to break the femur from ovariectomized rats, suggesting that it may be useful for the treatment of bone diseases.

Animals↗

Induction of osteopenia in confined rats.

We have developed a simple model of osteopenia in rats which is induced by confinement without requiring surgical operation. Each rat was maintained for 8 weeks in a compartment of a commercially-available wire netting cage subdivided into 10 areas (compartment size, 9 x 16 x 14 cm) to restrict exercise. The femora isolated from the confined rats showed significant decreases in mineral (calcium and phosphorus) content, compared with the level in normal rats, 2 weeks after the start of their confinement. Confined rats showed significantly lower values for the physical properties of bones such as breaking energy and breaking force and also density composed with normal rats 4 weeks after the start of confinement. KCA-098 (1 mg/kg), a new benzofuroquinoline derivative that inhibits bone resorption and at the same time stimulates bone mineralization in organ culture, protected against these decreases when given orally for 8 weeks. All these results show that confinement of rats offers a simple and useful animal model of osteopenia.

Animals↗

Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone.

We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.

24,25-Dihydroxyvitamin D 3↗

An osteometrical study of the cranium and mandible of Ryukyu wild pig in Iriomote island.

We measured crania and mandibles of Ryuku wild pigs from Iriomote Island. Sex and age were determined by observation of lower teeth. From the present data, the growth pattern was established for some items. For several parts of the cranium and mandible, the relative growth coefficient was compared. The results obtained here are summarized as follows: (1) Although sexual dimorphism was already shown in the younger group, a significant difference in profile length and length from the angle was not seen in the adult group. (2) As the animal grew, the proportion of length to width became larger in the skull. (3) The visceral cranium grew more rapidly in length than the cerebral cranium. On the other hand, growth of the cerebral cranium contributed to width in cranial development. (4) The body of the mandible was shown to grow more rapidly in length than the ramus of the mandible. (5) The growth pattern of some items was related to that of their associated muscles. These basic data are expected to be compared with data from other population of the same subspecies and Japanese wild pig. The comparisons will contribute to the establishment of origin and phylogeny of this animal.

Age Factors↗

[A survey on elderly patients' knowledge of management of health care].

We conducted a questionnaire survey on the awareness of elderly patients in our hospital concerning medical management. As to the recognition of their own diseases, patients aged 80 or older, showed a lower degree of understanding than those under age 80. The proportion of patients who wished to known about their diagnosis decreased with age, although no statistical significance was recognized. Those who wished to known about their diagnosis, even if it were malignant, reduced significantly depending on the increase in age. In addition, the proportion of patients who would not like to know their diagnosis, if it were malignant, increased significantly as age increased. Proportions of patients who wanted to know other information, such as prognosis, the aims, methods and results of medical examination, the methods and adverse effects of treatment, and the names, effects and side effects of drugs, also decreased significantly as age increased. However, there were no statistical significant differences in the proportion of answers between cases of malignant and non-malignant disease. These data show that elderly patients had more anxiety or fear about malignancy, and wished to know less about medical management than non-elderly patients.

Aged↗

Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1.

Rheumatoid arthritis and related inflammatory joint diseases are characterized by massive infiltration of polymorphonuclear cells (PMN) into inflamed joints. Interleukin-8 (IL-8) has recently been identified as a leukocyte chemotactic and activating factor produced by activated tissue cells as well as monocytes/macrophages. Examination was made of the involvement of IL-8 in acute arthritis induced by injecting lipopolysaccharide (LPS) or interleukin-1 alpha (IL-1 alpha) into the joints of rabbits. The neutralizing antibody to rabbit IL-8 blocked almost completely the infiltration of PMN into the joints and provided protection from damage to tissue in the early phase of inflammation induced by LPS or IL-1 alpha. Mononuclear cell infiltration observed later was not inhibited by this antibody. This is the first paper to clearly demonstrate that IL-8 is an essential and major mediator determining whether PMN infiltration will occur in the early phase of experimental acute arthritis.

Animals↗

Antineutrophil cytoplasmic autoantibodies in 6 patients with renal failure and systemic sclerosis.

OBJECTIVE: To elucidate the distribution and frequency of antineutrophil cytoplasmic autoantibodies (ANCA) in systemic sclerosis. METHODS: Patient sera were analyzed by indirect immunofluorescence and by enzyme linked immunosorbent assay. RESULTS: High titers for perinuclear ANCA correlated with rapid deterioration of renal function. Patients were normotensive with normal plasma renin levels, but anemia, pulmonary hemorrhage and thrombocytopenia were problematic. All patients had anti-myeloperoxidase antibodies and some had anti-nRNP, anti-DNA, anti-Sm and LE cell antibodies. Outcome was poor except for one patient treated by plasmapheresis and cyclophosphamide. CONCLUSION: A renal specific subset of systemic sclerosis is suggested.

Acute Kidney Injury↗

Cloning and sequence analysis of the gene encoding a thermostable chitinase from Streptomyces thermoviolaceus OPC-520.

The gene (chi40) encoding a thermostable chitinase from Streptomyces thermoviolaceus OPC-520 was cloned in Escherichia coli JM109 using pUC18. The nucleotide (nt) sequence of chi40 has been determined. A single open reading frame (ORF) encoded a protein consisting of 414 amino acids (aa) with a M(r) of 43,838. The deduced aa sequence of the cloned chitinase (Chi40) showed striking homology (74%) with Chi63 from Streptomyces plicatus. Comparison with other chitinases revealed that Chi40 contained the two conserved regions common to microbial and plant chitinases. Furthermore, the putative promoter region of chi40, which might be involved in the repression and induction of such catabolite-controlled genes, was detected by the DNA sequence alignments.

Amino Acid Sequence↗

Gene structure of human mitochondrial ATP synthase gamma-subunit. Tissue specificity produced by alternative RNA splicing.

We completely sequenced the human gene for ATP synthase gamma-subunit, which was approximately 23 kilobases long and was composed of 10 exons. Exons 1 and 2 encoded the N-terminal presequence required for mitochondrial import, while exons 9 and 10 encoded the C-terminal portions of mature protein. Enzymatic amplification of human heart and liver cDNAs using the polymerase chain reaction revealed two mRNA transcripts that were predicted to encode two 30-kDa isoforms of the gamma-subunit, which differed by the addition of a single amino acid (Asp273) at the C terminus of the liver type isoform. These two mRNA transcripts of the heart (H) type and liver (L) type were generated by alternative splicing of an exon. The same alternative splicing event was observed in bovine tissue. In human tissues, the H type mRNA devoid of exon 9 was expressed specifically in the heart and skeletal muscle, which require rapid energy supply. The L type mRNA was expressed in the brain, liver, kidney etc. Both transcripts were expressed in the skin, intestine, stomach, and aorta. This tissue specificity of transcript heterogeneity suggests the distinct functional or regulatory roles of the gamma-subunit isoforms in the catalysis of ATP synthase. This is the first report on tissue-specific isoforms generated by alternative splicing in an energy transducing mitochondrial protein.

Alternative Splicing↗

Tissue-specific isoforms of the bovine mitochondrial ATP synthase gamma-subunit.

Tissue-specific isoforms of the gamma-subunit of the bovine FoF1-ATP synthase were identified for the first time. The two isoforms, heart and liver type, were generated by alternative splicing, the liver-type RNA transcript containing a 37-nucleotide sequence as a cassette exon. Protein sequencing of the C-terminal fragments of the two isoforms of the F1 gamma-subunit indicated that the liver-type isoform had an additional aspartate residue at the C terminus, not present in the heart type one.

Alternative Splicing↗

Acrylamide induces immediate-early gene expression in rat brain.

Northern blot analysis was used to study the effects of acrylamide, a potent neurotoxin, on the induction of c-fos and c-jun mRNA in rat brain. Male Sprague-Dawley rats (10-12 weeks old) treated with acrylamide as a single dose (100 mg/kg, i.p.) or via drinking water (0.03% w/v) for 4 weeks, were used to study acute and chronic effects on immediate-early gene expression, respectively. Acute administration of acrylamide caused a statistically significant increase in the expression of c-fos (approx. 37%) and c-jun (approx. 17%) mRNA in rat brain. By contrast, the level of c-fos mRNA in chronic acrylamide treatment was not altered significantly, but the expression of c-jun mRNA was increased almost 100% as compared to control. These data show that the neurotoxin acrylamide induces immediate-early gene expression in the brain. The effects appear to be related to the route of administration, dose and duration of acrylamide treatment.

Acrylamide↗

Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells.

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and interleukin 5. To determine whether interferon gamma (IFN-gamma) regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-gamma and of anti-IFN-gamma monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rIFN-gamma prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-gamma also decreased antigen-induced CD4+ T cell but not CD8+ T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-gamma mAb enhanced antigen-induced eosinophil and CD4+ T cell infiltration in the trachea. These results indicate that IFN-gamma regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4+ T cell infiltration.

Animals↗

Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. Regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor.

OBJECTIVE: To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). METHODS: MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse-transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. RESULTS: High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast-like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin-1 (IL-1) and tumor necrosis factor in vitro. IL-1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. CONCLUSION: Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.

Arthritis, Rheumatoid↗

Secretion of endogenous 16-kDa beta-galactoside-binding lectin from vitamin A-pretreated chick embryonic cultured skin.

Localization of endogenous beta-galactoside-binding 16-kDa lectin and its gene expression pattern were investigated during differentiation of chick embryonic skin in vivo and in vitro and were compared with those of a 14-kDa lectin. By light microscopy, immunostaining of the 16-kDa lectin was weak in the undifferentiated epidermis, while it became intense in the keratinized epidermis, particularly in the intermediate cells. Essentially the same staining pattern was observed both in vivo and in vitro. The gene expression pattern was consistent with these immunohistochemical observations. These results were similar to those of the 14-kDa lectin [1]. On the other hand, in the vitamin A-pretreated cultured skin, mucous metaplasia of the epidermis was induced and marked changes in localization of these two isolectins were observed. The 16-kDa lectin expression was increased in the epidermis, especially in the superficial cells, and the gene expression was detected in all layers of the epidermis. However, 14-kDa lectin expression was markedly reduced in the metaplastic epidermis. In the keratinized epidermis, detailed localization of these lectins under the electron microscope was almost the same. Both of them were located primarily along the plasma membrane, in the intercellular space, and in the desmosomes. In the mucous metaplastic epidermis, however, the localization of the 16-kDa lectin was completely different from that of the 14-kDa lectin; e.g., the former was detected in the mucous granules and on the microvilli of the superficial cells, while the latter was scarcely observed in the epidermis. The present results revealed that (1) the 16-kDa lectin as well as 14-kDa lectin were expressed during the epidermal differentiation and (2) much of the 16-kDa lectin was produced and secreted from the vitamin A-pretreated cultured epidermis, while 14-kDa lectin disappeared. In the view of these facts, it is suggested that (1) both 14- and 16-kDa lectins may play an important role in differentiation of the skin and (2) the gene expression of 14- and 16-kDa lectins is regulated independently.

Animals↗

Inhibitory effect of C-reactive protein on phospholipase D activity.

C-reactive protein (CRP) was found to inhibit the phospholipase D activity significantly with dose dependency. Addition of 15 micrograms/ml CRP resulted in about 60% decrease in phospholipase D activity using phosphatidylcholine dispersed with Triton X-100 as substrate, and more using lipid suspension consisting of only phosphatidylcholine. In Lineweaver- Burk analysis with phosphatidylcholine dispersed with Triton X-100, the apparent Km value of phospholipase D for phosphatidylcholine increased from 2.27 mg/ml to 3.72 mg/ml by addition of 7.5 micrograms/ml CRP whereas the Vmax value was not altered. The possible usefulness of CRP as phospholipase D inhibitor was discussed.

Animals↗