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Biomedical subjects

H Mishima

Publications and source records attributed to H Mishima.

At least 163 records · Page 9Linked to original sources
PubMed1983

Milbemycins, a new family of macrolide antibiotics. Fermentation, isolation, physico-chemical properties and bioconversion of milbemycins J and K.

Strain Rf-107, a mutant of Streptomyces hygroscopicus subsp. aureolacrimosus, obtained with ultraviolet irradiation, produced two new macrolide antibiotics, milbemycins J and K without production of any of the other milbemycins described in the previous paper. Fermentation studies on the strain were conducted in shake flasks and 30-liter jar fermentors. Isolation of the antibiotics was performed by adsorption on resinous adsorbent followed by elution with aqueous MeOH. Purification of milbemycins J and K was completed with Lobar Si 60 column chromatography to give colorless crystals. Physico-chemical data, such as UV, IR and NMR spectra are described. Milbemycins J and K were readily converted by the intact cells of the parent strain to milbemycins alpha 1 and alpha 3, respectively. Physico-chemical characterization and the bioconversion studies revealed that milbemycins J and K were new antibiotics having the 16-membered macrocyclic lactone with a 6,6-membered spiroketal ring system.

Anti-Bacterial Agents↗
PubMed1983

Milbemycins, a new family of macrolide antibiotics. Structure determination of milbemycins D, E, F, G, H, J and K.

The milbemycins, a group of potent, broad-spectrum antiparasitic and pesticidal agents, are architecturally novel antibiotics of 16-membered macrocyclic lactone. Seven new milbemycin analogues designed as milbemycins D, E, F, G, H, J and K were isolated from the fermentation broth of the mutant strain of Streptomyces hygroscopicus subsp. aureolacrimosus. The structural determination of these new components was made mainly by comparing with mass spectra, and 1H and 13C NMR spectra of milbemycin alpha- and beta-series previously published from our laboratory. Milbemycins D, E, F, G and H have characteristically an isopropyl side chain at C-25 which differs from the known milbemycin family bearing methyl or ethyl group at C-25. Milbemycins J and K possess a ketone group at C-5 instead of a hydroxyl or methoxy group. Apart from X-ray crystallography, the R-configuration of the hydroxyl group at C-5 could be best explained both by application of CD allylic benzoate method to the n-N, N-dimethylaminobenzoate of milbemycin D and by comparison of the specific rotation of milbemycin D itself and its acetate with the epimeric isomers at C-5.

Anti-Bacterial Agents↗
PubMed1983

Milbemycins, a new family of macrolide antibiotics. Studies on the biosynthesis of milbemycins alpha 2, alpha 4 and D using 13C labeled precursors.

The biosynthetic origins of the carbon skeleton of milbemycins alpha 2, alpha 4 and D were studied. 13C Labeled antibiotics, milbemycins alpha 2, alpha 4 and D, were isolated from the culture broth of Streptomyces hygroscopicus subsp. aureolacrimosus strain Au-3 after feeding [1-13C]acetate, [1-13C]-propionate, [3-13C]propionate, [1-13C]isobutyrate, DL-[2-13C]valine and L-[methyl-13C]methionine, and 13C NMR spectra of the antibiotics thus obtained were measured. It was revealed that the carbon skeleton, except for carbon 25, of milbemycins alpha 2, alpha 4 and D are derived from seven acetate units and five propionate units. It was also shown that the methyl, ethyl and isopropyl groups at carbon 25 in milbemycins alpha 2, alpha 4 and D are derived from acetate, propionate and isobutyrate or DL-valine, respectively, and the methyl carbon of the methoxy group at carbon 5 in milbemycins alpha 2 and alpha 4 was enriched by L-[methyl-13C]methionine.

Acetates↗
PubMed1983

Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki.

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.

Adult↗
PubMed1982

Fine structural studies of ciliary processes after treatment with cholera toxin or its B subunit.

Delivery of 2 micrograms of cholera toxin (CT), a specific, irreversible activator of adenyl cyclase, via the blood causes dilation of capillaries and stromal edema of the ciliary processes. These morphologic changes occur within 3 h, are maximal at 12 to 24 h, then gradually return to normal by 72 h. In the late phase of hypotony, ultrastructural changes in the ciliary epithelia, similar to Greeff vesicles, are due to a "paracentesis effect" from hypotony, caused by decreased aqueous flow through the eye. Delivery of 2 micrograms of the B subunit of CT (Sub-B) causes very mild capillary dilation and stromal edema of ciliary processes. These changes reach their peak at 3 h, then return to normal at 24 h. No significant damage occurred to the pigmented or non-pigmented epithelium with either agent. No hemorrhage, invasion of inflammatory cells or appearance of fibrin exudates in the ciliary processes could be detected.

Animals↗
PubMed1982

Ultracytochemistry of cholera-toxin binding sites in ciliary processes.

Cholera toxin reduces the rate of aqueous humor in concentrations (10-11M) that do not disturb the morphology of the aqueous-humor forming epithelial cells of the ciliary processes of the rabbit eye. The search for an endogenous mediator of aqueous-humor formation comparable to cholera toxin in its mode of operation prompted us to map the distribution of cell surface receptors for cholera toxin in the ciliary processes of the eyes of rabbits. Cytochemical studies were carried out with the use of conjugates of cholera toxin to fluorescein isothiocyanate (CT-FITC) and to horseradish peroxidase (CT-HRP), and of the B subunit of cholera toxin to horseradish peroxidase (B-HRP). Multiple fluorescent CT-FITC binding sites were observed on the outer nonpigmented epithelial layer near the crests of the processes. Processes incubated with CT-HRP in vitro showed surface staining of 30-40% of the nonpigmented epithelial cells. A prominent reaction product was observed along the basal and lateral plasma membranes of these cells. In vivo studies carried out after arterial infusion of B-HRP showed a reproducible dense reaction product between the apical surfaces of the pigmented epithelium (PE) and of the nonpigmented epithelium (NPE) facing each other. Aggregations of reaction product were observed with the electron microscope in the extracellular space between the apices of PE and NPE. The apical plasma membrane of the endothelium of the blood vessels near the crests of the ciliary processes was stained after either in vivo or in vitro exposure to peroxidase conjugates. These findings indicate that the cell-surface receptors which mediate the action of cholera toxin on aqueous humor formation are very likely localized in the apical plasma membranes of the epithelium of the ciliary processes.

Animals↗
PubMed1981

Extrusion of lysosomal bodies from apical mouse retinal pigment epithelium.

The retinal pigment epithelium (RPE) of 1- 24-month-old CF-1 mice was examined by both light and electron microscopy. Measurement of the area occupied by lysosomal bodies was carried out using a semiautomatic quantitative picture analyzing system (Kontron-EKO). Accumulation of lysosomal bodies in the apical RPE cytoplasm was the most characteristic feature in eyes over 12 months of age. The relative volume of lysosomal bodies to each RPE cytoplasm was maximal in 24-month-old mice RPE, approximately three times that of 3-month-old mice. Complicated lysosomal bodies and small lysosomal bodies were also observed in the dilated microvilli, in the apices of the apical RPE cytoplasm and in the subretinal spaces in eyes over 18 months of age. The passway and extrusive mechanism of lysosomal bodies are discussed.

Animals↗
PubMed1981

Intraocular pressure and aqueous flow are decreased by cholera toxin.

Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2-fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood-aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP.

Adenylyl Cyclases↗