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Biomedical subjects

K Ohtsuki

Publications and source records attributed to K Ohtsuki.

161 records · Page 9Linked to original sources
PubMed1978

Electron microscopical and histochemical studies of outer hair cells in normal rabbits.

The outer hair cells of the rabbit were electron microscopically and histochemically investigated. The results clearly showed that the outer hair cells of the rabbit have no agglomeration of mitochondria in its infranuclear region. This anatomical fact means that the functional mechanism in the outer hair cells of the rabbit may be substantially different from that of other animals which have agglomeration of mitochondria. From the results of the histochemical study, it is reasonably supposed that the anaerobic energy metabolism may ordinarily play the leading part in sustaining the cellular functions in the infranuclear region of the outer hair cells of the rabbit.

Anaerobiosis↗
PubMed1978

Potentiation and its mechanism of cochlear damage resulting from furosemide and aminoglycoside antibiotics.

The severe ototoxic interaction of the combined administration of furosemide and aminoglycoside antibiotics (kanamycin, streptomycin and gentamicin) was studied in rabbits, and its mechanism clarified. Severe damage occurred not only in the inner ear but also in the kidney when both furosemide and aminoglycoside antibiotics were administered to rabbits. Kanamycin concentration after a single injection of kanamycin with furosemide was much higher not only in the perilymph but also in the cerebrospinal fluid and serum than that after a single injection of kanamycin alone. The ototoxic interaction following the combined use of furosemide and aminoglycoside antibiotics seems to be caused mainly by the inhibitory effect of furosemide on the excretion of aminoglycoside antibiotics from the kidneys.

Aminoglycosides↗
PubMed1978

A detection method for lactic dehydrogenase activity in the inner ear.

A method for the detection of lactic dehydrogenase enzymatic activity in outer hair cells of the rabbit is described. The membranous labyrinth with temporal bone was prefixed in glutaraldehyde. After being placed into the incubation medium, it was postfixed in osmium tetroxide. Specimens of the organ of Corti were removed. Then the specimens were embedded in water-soluble glycol and cut with a cryostat for light microscopy, and also they were embedded in Epon and cut for light and electron microscopy. Sectioning of the membranous labyrinth was very easily made when the specimens were embedded in both the water-soluble glycol and the Epon. The structures of the frozen sections as well as the Epon-embedded ones were well preserved. In the frozen sections the preservation and localization of reaction products were thoroughly kept, but monoformazan of the Epon-embedded sections was soluble.

Animals↗
PubMed1978

Evaluation of succinyl neocarzinostatin in vivo.

The toxicity of the bis-succinyl derivative of the protein antibiotic, neocarzinostatin, was compared with the parent compound, neocarzinostatin (NCS), in rats. The derivative was found to be about two to five fold more active than NCS in vivo. The antitumor activity in rats bearing eleven distinct Yoshida hepatoma ascitic cell lines was tested under four possible combinations with regard to sites of drug and tumor cell administration. The results indicate that the antitumor spectrum of the derivative had changed slightly. Antitumor activity in mice was also tested with L1210 and P388 lymphatic leukemia, and with B16 melanocarcinoma. When the effect of the derivative was compared with parental NCS at the molecular level with respect to the inhibition of DNA synthesis in vitro, the specific activities of the two were found to be almost identical. These results were interpreted to indicate that the succinyl derivative of NCS was more stable to inactivation and proteolytic break-down in vivo than NCS as observed previously in in vitro studies.

Animals↗
PubMed1977

Isolation and purification of double-stranded ribonuclease from calf thymus.

A RNase from calf thymus, which specifically cleaves native or synthetic double-stranded RNA molecules endonucleolytically, has been isolated and purified from calf thymus. For optimal activity, the enzyme requires a sulfhydryl reagent and divalent cations; over 95 per cent of the activity is inhibited by 0.5 mm ethidium bromide. The degradation of [3H]poly(C)-poly(I) by purified enzyme preparations yields labeled dinucleotides and octanucleotides; the latter oligonucleotide contained 5'-phosphate and 3'-hydroxyl termini. The enzyme cleaves high molecular weight RNAs such as RNA products formed in vitro by T3 phage-induced RNA polymerase from T3 phage DNA, heterogeneous RNA isolated from duck reticulocyte nuclei, and 45 S RNA isolated from rat liver nucleoli. The mode of degradation of RNA in vitro with the double-stranded RNase is similar to that of Escherichia coli RNase III and appears to act endonucleolytically. The degradation of 45 S RNA with the enzyme results in the production of 29 S and 19 S RNA fragments. These findings suggest that the enzyme may be involved in the processing of high molecular weight precursor RNAs to mRNA or rRNAs in a manner analogous to that reported for RNase III of E. coli.

Animals↗
PubMed1977

Possible role of initiation factor activity in the action of interferon.

Treatment of mouse L cells with homologous interferon results in the production of a protein which inhibits initiation factor activity. Characterization experiments indicate that the interferon in the preparation is responsible for the induction of an inhibitor protein. The impairment of initiation factor activity induced by interferon is specifically reversed by cAMP. An inhibitor protein may be separated from the initiation factor activity by glycerol density gradient sedimentation. The molecular weight of the inhibitor is about 50,000 dalton and sediments with protein kinase activity.

Cyclic AMP↗
PubMed1975

Neocarzinostatin-induced breakdown of deoxyribonucleic acid in HeLa-S3 cells.

Degradation of DNA in HeLa-S3 cells mediated by an acidic antitumor protein, neocarzinostatin (NCS), was examined. The concentration of NCS required for induction of DNA degradation was considerably higher than that which caused inhibition of DNA synthesis. Sedimentation analysis of DNA revealed that HeLa-S3 cell DNA first received single-strand nicks within 60 minutes after exposure to the antibiotic, whereas detectable double-strand scissions eventually gave rise to the accumulation of double-stranded DNA fragments of heterogeneous size. When the cells exposed to NCS were transferred to NCS-free medium at early stages of the degradation, the single-strand nicks caused in DNA were repaired by a process which was sensititive to puromycin.

Antibiotics, Antineoplastic↗
PubMed1975

Mechanism of DNA degradation induced by neocarzinostatin in Bacillus subtilis.

When logarithmically growing Bacillus subtilis cells were exposed to the antitumor protein, neocarzinostatin (NCS), at a concentration of 50 mug/ml, cellular DNA was gradually degraded into an acid-soluble form (up to 60 percent of total DNA). The degradation appeared to initiate at the growing regions of DNA and to proceed sequentially from the nascent regions to preexistent DNA. Concomitantly with, or perhaps as a consequence of, the degradation of growing regions, DNA detached from the cell membrane and started to show single-strand nicks within 30 minutes after exposure of the cells to NCS, whereas double strand scission in the DNA became detectable in about 90 minutes. Such endonucleolytic breaks in DNA eventually gave rise to the formation of double-stranded DNA fragments of a single-size class (30-S) as determined by sedimentation in either neutral or alkaline sucrose gradients. In contrast to previous results with Sarcina lutea, the NCS-induced DNA degradation was stimulated by chloramphenicol in B. subtilis and the DNA fragment were not the final breakdown products, but were further degraded into acid-soluble materials.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Effects of aging on fluorescein leakage in the iris and angle in normal subjects.

PURPOSE: To determine the presence of fluorescein leakage from the iris and angle in normal subjects, and how it is affected by aging. METHODS: The subjects were 92 normal volunteers and patients with senile cataract who ranged in age from 20 to 93 years and were free from any systemic or ocular diseases. Fluorescein iris and angle photography and color iris and angle photography were performed using a goniolens and a photo slit lamp. RESULTS: Radial ciliary body vessels were found in 22 eyes (24%), radial iris vessels or trabecular vessels in 7 eyes (8%), and circular ciliary band vessels were seen in 4 eyes (4%). Goniovessels were found in 8 of 30 eyes (27%) of those under 50 years of age. No significant difference in the incidence of goniovessels was found between those over and under age 50 (P < .01). In the pupillary margin, fluorescein leakage was seen in 1 of 30 eyes (3%) in the age group under 50 years, whereas leakage was found in 30 of 62 eyes (48%) in the age group over 50 years. In the anterior chamber angle, leakage was seen in 4 of 30 eyes (13%) under age 50 years, and in 38 of 62 eyes (61%) over age 50 years (P < .05). CONCLUSIONS: These findings suggested that the incidence of leakage of fluorescein from the pupillary margin and anterior chamber angle tends to increase with age. Thus, when leakage of fluorescein in angle and iris is observed, it is important to consider the physiological changes resulting from aging.

Adult↗
PubMedDate not supplied

Individual variation and mechanism of kanamycin ototoxicity in rabbits.

In order to elucidate the mechanism of individual variation of kanamycin ototoxicity, the possible relationship between the outer hair cell damage induced by kanamycin and the levels of kanamycin in serum or perilymph and of renal damage was investigated in rabbits. No relationship was found between the extent of the outer hair cell damage and the level of kanamycin in the serum or the renal damage. The extent of the outer hair cell damage was closely correlated to the levels of kanamycin in the perilymph. These findings suggest that the individual variations in the outer hair cell damage induced by kanamycin are more closely correlated to the individual differences in the transferability of kanamycin into inner ear than to those in the vulnerability of the outer hair cells or kidneys.

Animals↗
PubMedDate not supplied

A biological role of interferon-induced protein kinases.

The experimental data reviewed in this paper suggest that the inhibition of viral polypeptide chain initiation in IFN-treated cells involves the phosphorylation of eIF-2 alpha and intermediate factors (65K and 67K ribosomal proteins) by an IFN-induced dsRNA-dependent ribosomal kinase. However, the discrimination mechanism between viral and host cell mRNAs at the translational level remain to be elucidated, because the mechanism is very complex. IFN will induce, for example, preferential digestion of viral mRNAs by 2',5'-oligo A activated endoribonuclease, will impair tRNAs and elongation factors for the protein synthesis, and will decrease methylation of viral mRNAs, and they are involved in the discrimination mechanism at translational level. The activation of membrane-associated kinase activity by IFNs is very interesting because its among the earliest recognized biochemical events induced in cells and may play an important role in IFN-induced host or cell defense. Further studies focusing on the biochemical roles of the membrane-associated kinase in IFN-treated cells may provide evidence for understanding the biochemical mechanism of cell activation by IFNs.

Animals↗
PubMedDate not supplied

[Myocardial ischemia and abnormality of cardiac sympathetic nervous function in apical hypertrophic cardiomyopathy].

Exercise 201Tl myocardial scintigraphy of patients with apical hypertrophic cardiomyopathy (AH) often shows transient perfusion defect in the apex. Catecholamine may be related to the pathogenesis of AH, but this is not certain. The relationship between hypertrophy, myocardial ischemia, and cardiac sympathetic nervous function were investigated by comparing 123I-MIBG myocardial SPECT with exercise 201Tl myocardial SPECT especially at the apex which is the hypertrophic region. Seventeen patients with AH, mean age of 53 +/- 11 years old, underwent 123I-MIBG myocardial SPECT and exercise 201Tl myocardial SPECT on separate days. Decreased tracer uptake regions and the severity and extent of the defect were evaluated visually and compared. Myocardial clearance of 123I-MIBG in apical, midventricular, and basal regions was calculated from the bull's eye display. 123I-MIBG SPECT showed a decreased uptake or defect in the apex of all patients. 201Tl SPECT showed a reversible perfusion defect in the apex of 10 patients, an irreversible perfusion defect in the apex in 3, and normal perfusion in 4. Comparing decreased uptake on the exercise 201Tl myocardial image and 123I-MIBG 4-hour delayed image, the severity of the defect was: MIBG > Tl in 12 patients (71%), MIBG = Tl in 5 (29%), and the extent of the defect was: MIBG > Tl in 11 (65%), MIBG = Tl in 6 (35%). Mean clearance of 123I-MIBG in the apical and midventricular regions was significantly higher than that in the basal region (apical 46.2 +/- 7.1%, midventricular 44.4 +/- 7.8%, basal 38.7 +/- 7.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMedDate not supplied

[Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy: evaluation by exercise thallium-201 SPECT].

The effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise myocardial 201Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.1 +/- 6.1 weeks of oral administration of verapamil (240 mg/day) on 20 patients with HCM who showed transient 201Tl perfusion defects under control conditions. SPECT images were divided into nine segments. The 201Tl perfusion defect was visually scored and evaluated for four grades in each segment and the sum total grade was calculated as the defect score. Transient dilation index was calculated as a reflection of subendocardial ischemia. Improvements in defect score were demonstrated in 18 of 20 patients after administration of verapamil. The mean defect score decreased significantly from 5.1 +/- 2.3 to 2.5 +/- 2.4 (p < 0.001). Although 18 of 20 patients showed abnormal transient dilation index under control conditions, 16 showed improvement and 12 were normalized after verapamil therapy. Mean transient dilation index decreased from 1.24 +/- 0.19 to 1.08 +/- 0.10 (p < 0.01). Verapamil improves myocardial ischemia in patients with HCM.

Cardiomyopathy, Hypertrophic↗