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Biomedical subjects

Y Ogata

Publications and source records attributed to Y Ogata.

At least 181 records · Page 10Linked to original sources

Bilateral vestibular neuronitis.

Bilateral vestibular neuronitis with a different onset time for each affected side was reported in two cases among 74 cases observed. The first case appeared 3 weeks and the other 5 years before involvement of the second ear. In the case with a short period before the second attack, the direction of nystagmus was unchanged throughout the clinical course. It is suggested that the direction of nystagmus depends upon the severity of each vestibular dysfunction. In the case with a long period when the vestibular compensation has been completed, paralytic nystagmus was observed and its direction corresponded with the side affected by canal.

Adolescent↗

Development of the chick vestibular ganglion and its nerve terminating in the endorgan.

We investigated the morphological maturation of the vestibular ganglion and its dendrites terminating in the sacculus of the chick embryo. The cytoplasm of the ganglion cells had acquired a granular feature due to the abundance of ribosomal clusters and rER by the 13th day of incubation. The myelination of the dendrites occurred before that of the perikarya. Compact myelin of the dendrites was observed on the 13th day of incubation, while that of the perikarya was observed in the 20th day of incubation. Nerve endings of afferent and efferent character were observed first in the sacculus on the 13th day of incubation. Positive immunoreactvity of substance P was observed on the 13th day of incubation. It is suggested that the morphological basis of functional activity is present on or around the 13th day of incubation.

Age Factors↗

The otolithic organ in the developing chick embryo. Scanning electron microscopic study on the utricular macula.

The long and short axes of utricular maculae were measured to calculate growth curves using an ocular micrometer under stereomicroscope. The mean lengths of the long and short axes on the 6th incubation day were 0.06 mm and 0.05 mm, respectively. Thereafter: 1.00 mm and 0.74 mm on the 11th incubation day; 1.34 mm and 1.03 mm on the 15th incubation day; and on hatching 1.51 mm and 1.07 mm, respectively. The surface structure, particularly the otoconia and the sensory hairs of the utricular maculae, on the 4.5th incubation day to the 7th post-hatching day of White Leghorn chicks were observed with a scanning electron microscope (SEM). A number of microvilli and primary cilium on the inner surface of the otocyst were found between the 4.5th and the 5th incubation day. Immature sensory hairs appeared on the 5th incubation day. The polarity of the sensory hairs became evident on and after the 9th incubation day. Mature sensory hairs were seen all over the utricular maculae between the 1st and the 3rd post-hatching day. Mature sensory hairs were mainly seen near the striola, and immature ones peripherally. Then, the various forms in the maturation phase of sensory hairs were seen between the striola and the periphery. These arrangements suggest some process of maturity from the peripheral region to the central striola region. Immature otoconia were first seen on the 6th incubation day. Mature otoconia were recognized on and after the 11th incubation day, and they were observed on the whole surface of the utricular maculae. Global substances on the macula with a rough surface and spongy structure were observed suggesting otoconial precursors transforming themselves into otoconial crystals.

Animals↗

[Motility of isolated vestibular hair cells induced by potassium].

Many studies of the outer hair cells in cochlea have demonstrated active motility. However, very few studies have been done on vestibular hair cells. This study was designed to demonstrate the motile responses of isolated vestibular hair cells of the chick, induced by potassium promoting contraction. Reversible cell shape changes were observed in 4 of 6 type I hair cells and 3 of 5 type II hair cells by applying the contraction solution. The cell shape changes were revealed mainly in the cuticular plate and infracuticular region. It was suggested that contraction in the cuticular plate of the isolated hair cells might be converted into tension which increases the stiffness of the sensory hairs and restricts their motions, based on the results of the present study, and the structure of contractile proteins and hair behaviors reported by previous investigators.

Animals↗

[Paranasal sinusitis due to Pasteurella multocida].

A case of paranasal sinusitis due to Pasteurella multocida (P. multocida) is reported. A 39-year-old woman presented with chief complaints of rhinorrhea and headache. The patient kept a cat in her house and kept such close contact with it as to wake up by being licked every morning. Bacteriological examination revealed P. multocida isolated from her nasal discharge and also from the saliva of the cat kept by the patient. The two isolates were compatible with respect to biochemical properties, serotype and drug susceptibility. Therefore, P. multocida infection in this case was considered to have originated from the pet cat. P. multocida infection has been increasing recently. One of the reasons is a pet boom. In order to prevent acquiring the infection from a pet animal, we should have knowledge about this infection, advise the patient to avoid close contact with pets, and provide valuable information concerning these problems to society from the viewpoint of zoonosis.

Adult↗

Survival ability of clinical isolates of methicillin-resistant Staphylococcus aureus.

The survival abilities of methicillin-resistant strains of Staphylococcus aureus were compared with those of sensitive strains. Absorbent cotton was inoculated with 10(8) cells of each strain tested and stored at 30% humidity at 25 degrees C. The numbers of cells of sensitive strains decreased significantly to well below those of resistant strains after 4 weeks, while cells of resistant strains remained above 10(3) after 14 weeks.

Anti-Bacterial Agents↗

[Etoposide, doxorubicin, cisplatin and 5-FU (EAP-F) therapy of advanced gastric cancer--its antitumor effect and evaluation of quality of life].

Fourteen patients with advanced gastric cancer were treated with EAP-F therapy. The regimen was CD DP 40 mg/m2 day 1 and 6, 5-FU 600 mg/m2 day 2 and 4, leucovorin 20 mg/m2 day 2 and 4, etoposide 60 mg/m2 day 3 and 5, and doxorubicin 20 mg/m2 day 7, with repetition every 28 days. Thirteen patients were evaluable; one patient was CR, four were PR, five were NC and three were PD. The response rate was 38.5% and median survival was 7 months. Hematologic toxicities were moderate to severe but tolerable, gastrointestinal toxicities were mild and renal toxicity was absent. Quality of life (QOL) of the patients was evaluated by means of symptom-free ratio (duration of symptom-free to survival time) and outpatient ratio (duration at home in relation to survival time). Patients with lymph node metastasis showed a higher symptom-free ratio and outpatient ratio than those with liver metastasis or peritoneal dissemination. All high-QOL patients were chemotherapy responders. In conclusion, EAP-F therapy is effective for advanced gastric cancer and its side effects are tolerable. CR or PR is necessary to achieve a high QOL.

Antineoplastic Combined Chemotherapy Protocols↗

Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells.

The precursor of matrix metalloproteinase 9 (proMMP-9), also known as '92 kDa progelatinase/type IV procollagenase', was purified from the conditioned medium of U937 monocytic leukaemia and HT1080 fibrosarcoma cell lines stimulated with phorbol 12-myristate 13-acetate. ProMMP-9 in these culture media is non-covalently complexed with the 29 kDa tissue inhibitor of metalloproteinases (TIMP), but free proMMP-9 was separated from the TIMP-proMMP-9 complex by chromatography on Green A Dyematrex gel. The final product was homogeneous on SDS/PAGE, with a molecular mass of 88 kDa without reduction and 92 kDa with reduction. Treatment of proMMP-9 with 4-aminophenylmercuric acetate converted the 88 kDa precursor into 80 kDa and 68 kDa forms. Gelatin-containing zymographic analysis showed zones of lysis associated with all three species. However, only the 68 kDa species was shown to be catalytically active by its ability to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, only the 80 kDa species was generated by treatment with 4-aminophenylmercuric acetate, but no enzyme activity was detected. This indicates that TIMP binds to the 80 kDa intermediate and inhibits the generation of the active 68 kDa species. Eight endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, cathepsin G, neutrophil elastase and thermolysin) were tested for their ability to activate proMMP-9. Of them, trypsin was the most effective activator of proMMP-9. Only partial activation (10-30%) was observed with plasmin, cathepsin G and chymotrypsin. The active forms generated by trypsin were identified as 80 kDa, 74 kDa and 66 kDa by their abilities to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, proMMP-9 was also converted into the same molecular-mass species by trypsin, but they were not proteolytically active. This suggests activated MMP-9 is inhibited by TIMP. Activated MMP-9 digested gelatin, type-V collagen, reduced carboxymethylated transferrin and, to a lesser extent, type-IV collagen and laminin A chain. The specific activity against gelatin was estimated to be 15,000 units/mg (1 unit = 1 microgram of gelatin degraded/min at 37 degrees C) by titration with alpha 2-macroglobulin. Comparative studies on digestion of gelatin and collagen types IV and V by MMP-9 and MMP-2 indicated that both enzymes degrade these substrates into similar fragments. However, the susceptibilities of laminin, fibronectin and reduced carboxymethylated transferrin to these two MMPs were sufficiently different to indicate differences in substrate specificities between these two closely related proteinases.

Electrophoresis, Polyacrylamide Gel↗

Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9.

Matrix metalloproteinase 9 (MMP-9), also known as 92-kDa gelatinase/type IV collagenase, is secreted from neutrophils, macrophages, and a number of transformed cells in zymogen form. Here we report that matrix metalloproteinase 3 (MMP-3/stromelysin) is an activator of the precursor of matrix metalloproteinase 9 (proMMP-9). MMP-3 initially cleaves proMMP-9 at the Glu40-Met41 bond located in the middle of the propeptide to generate an 86-kDa intermediate. Cleavage of this bond triggers a change in proMMP-9 that renders the Arg87-Phe88 bond susceptible to the second cleavage by MMP-3, resulting in conversion to an 82-kDa form. alpha 2-Macroglobulin binding studies of partially activated MMP-9 demonstrate that the 82-kDa species is proteolytically active, but not the initial intermediate of 86 kDa. This stepwise activation mechanism of proMMP-9 is analogous to those of other members of the MMP family, but the action of MMP-3 on proMMP-9 is the first example of zymogen activation that can be triggered by another member of the MMP family. The results imply that MMP-3 may be an effective activator of proMMP-9 in vivo.

Amino Acid Sequence↗

Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition.

To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5-FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.

Adenocarcinoma↗

Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) is induced in rabbit articular chondrocytes by cotreatment with interleukin 1 beta and a protein kinase C activator.

The synthesis of an 88-kDa gelatinolytic enzyme, identified as a zymogen of matrix metalloproteinase (proMMP)-9, was induced in the primary culture of rabbit articular chondrocytes by cotreatment with recombinant interleukin 1 beta (rIL-1 beta) and the protein kinase C (PKC) agonists, phorbol 12,13-dibutyrate (PDBu) or mezerein. Negligible 88-kDa gelatinolytic activity was produced by unstimulated cells or cells treated with a PKC activator alone at concentrations up to 100 ng/ml, and only a modest induction occurred with rIL-1 beta alone at concentrations of 1-100 ng/ml. However, when these cells were treated with a PKC activator in the presence of IL-1 beta (1 ng/ml), induction was striking, with enzymic activity detectable at a concentration as low as 1 ng/ml of mezerein or 10 ng/ml of PDBu. Rabbit chondrocytes in culture constitutively produced the zymogen of MMP-2 (proMMP-2) and its production was not altered by treatment with IL-1 beta or PKC agonists alone or in combination. Recombinant tumor necrosis factor alpha (rTNF alpha) did not substitute for IL-1 beta in inducing proMMP-9 in the presence of PKC activators, nor was the combination of IL-1 beta or TNF alpha alone effective. These data indicate that rabbit articular chondrocytes have a potential to synthesize and secrete proMMP-9 under certain biological and pathological conditions but that the expression of proMMP-9 is differently regulated from that of other MMPs.

Animals↗

Nephritogenicity of the lprcg gene on the MRL background.

The novel lymphoproliferative and autoimmune lprcg gene, originally discovered in the CBA/K1Jms (CBA) strain of mice, was transferred onto the MRL/MpJ (MRL) strain background, and the resultant partially congenic MRL-lprcg/lprcg carrying 93% or more MRL genomes on average were examined for immune-complex glomerulonephritis and serological aberrations. Ordinary histological studies revealed that MRL-lprcg/lprcg mice developed glomerulonephritis histologically indistinguishable from that in MRL-lpr/lpr but at a lower frequency than in MRL-lpr/lpr mice. Glomerular immune complex deposition was almost the same in MRL-lprcg/lprcg and MRL-lpr/lpr mice. The levels of serum Ig, circulating immune complexes and autoantibodies in MRL-lprcg/lprcg were comparable to or even higher than those in MRL-lpr/lpr mice. Comparison of the serological abnormalities between MRL-lprcg/lprcg with glomerulonephritis and CBA-lprcg/lprcg without it evidenced the enhanced class switch from IgM to IgG responses in both class-specific autoantibody responses and serum Ig levels in MRL-lprcg/lprcg as in MRL-lpr/lpr mice. These results taken together indicate that the lprcg gene functions in much the same manner as lpr in induction of glomerulonephritis and serological abnormalities on the MRL background as expected from the allelism between the two mutant genes.

Animals↗

A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse.

The new mutation at the lpr locus, lprcg, induces massive lymphoproliferation characterized by the selective expansion of CD4-, CD8-, B220+, Thy-1+ cells or double-negative T lymphocytes and production of autoantibodies as does lpr. The thymus is necessary for the induction of anomalous double-negative T lymphocytes and autoimmune symptoms by lpr. To determine whether or not the thymus is also indispensable to expression of the function of lrpcg, lprcg homozygous athymic nude mice (lprcg/lprcg nu/nu; lprcg nudes) were constructed by crossing CBA/KlJms-lprcg/lprcg (CBA-lprcg) and DDD/l-nu/nu mice and observed for lymphoid organ hyperplasia and autoantibody production with or without thymus grafts from various strains of mice including CBA-lprcg. Neither lymphoproliferation nor significantly increased production of autoantibodies was observed in unmanipulated lprcg nudes. In contrast, thymus grafts of both +/+ and lprcg/lprcg genotypes caused lymphoid organ hyperplasia composed of anomalous double-negative T lymphocytes and significantly augmented the production of antibodies against single-stranded DNA (ssDNA). Interestingly, serum Ig and anti-ssDNA antibody levels rose in response to thymus grafts only in IgG but not in IgM classes. These results indicate that the thymus plays a crucial role in the induction of abnormal T-cell differentiation by lprcg and that thymic genotype is irrelevant.

Animals↗

Expression of dipeptidyl aminopeptidase IV activity in thyroid carcinoma.

Dipeptidyl aminopeptidase IV activity staining was performed in various thyroid tissues to evaluate this enzyme activity as a thyroid tumor marker. A total of 195 thyroid tissues were tested for their enzyme activity expression. All papillary and follicular carcinomas, 40 cases and 3 cases, respectively, showed enzyme activity, although two other carcinomas, one medullary and one anaplastic, were not stained. Follicular adenoma expressed enzyme activity in 4 of 26 cases. Fifty-two cases with adenomatous goiter, 54 with Graves' disease and 13 with chronic thyroiditis were judged to be negative. Five normal thyroids expressed no activity except for occasional positive staining of capillary endothelia. These data suggest that dipeptidyl aminopeptidase IV activity staining is very useful for pathological diagnosis of thyroid tumors.

Dipeptidyl Peptidase 4↗