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Biomedical subjects

M Iseki

Publications and source records attributed to M Iseki.

70 records · Page 4Linked to original sources

Sequential serum measurements of thyrotropin binding inhibitor immunoglobulin G in transient familial neonatal hypothyroidism.

Infants with transient neonatal hypothyroidism, in whom TSH binding inhibitor immunoglobulin G (IgG) (TBII) were sequentially measured, are described. Their mother had been taking thyroid replacement for hypothyroidism due to nongoitrous autoimmune thyroiditis. IgGs inhibiting TSH binding were detected in maternal sera by radioreceptor assay. These IgGs also inhibited the adenylate cyclase response to TSH in human thyroid membranes. Three infants had frank hypothyroidism immediately after birth, and TBII were detected in two of them. In the two surviving infants, hypothyroidism was transient and improved when TBII disappeared from their sera. The profile of TBII in one patient corresponded to the IgG disappearance curve. These findings suggest that the transient neonatal hypothyroidism reported was caused by transplacental transfer of TBII.

Adenylyl Cyclase Inhibitors↗

Biosynthesis of bicyclomycin. I. Appearance of aerial mycelia negative strains (am-).

The degeneration of bicyclomycin-producing strains of Streptomyces sapporonensis resulted in sharply depressed bicyclomycin formation in a large scale fermentation. Degenerated strains, whose productivities were only 1/30 to 1/100 of normal strains, could not form aerial mycelia on glucose-BENNETT's agar; they were aerial mycelia negative strains (am-). Repeated transfers of culture, treatment of mycelia with acriflavin, mechanical agitation shock on mycelia or higher growth conditions stimulated the degeneration of producing strains, suggesting the involvement of extrachromosomal elements or plasmids in biosynthesis of bicyclomycin. Shake flask fermentation inoculated with a mixture of a normal high-producing strain and a degenerated low-producing strain resulted in sharply depressed bicyclomycin formation in proportion to the increase of low-producing strain added. It appears that the low-producing strain outgrew the high-producing strain.

Acriflavine↗

Biosynthesis of bicyclomycin. II. Biosynthetic conditions and incorporation of radioactive precursors into bicyclomycin by washed mycelium.

The biosynthesis of bicyclomycin by Streptomyces sapporonensis was studied using suspensions of washed mycelium. Nicotinamide and Fe2+ were found to be essential cofactors in the biosynthesis. Production of bicyclomycin was enhanced most effectively in the presence of equal moles of L-leucine and L-isoleucine, which in experiments with radioactively labeled compounds were found to be incorporated into bicyclomycin at equivalent rates. These facts strongly suggest that bicyclomycin biosynthesis involves coupling of equal moles of these two amino acids.

Amino Acids↗

Active groups of bicyclomycin and the reaction with thiols.

The binding of [14C]bicyclomycin to whole cells of E. coli and to the inner membrane proteins was inhibited by dithiothreitol and 2-mercaptoethanol. The reactivity of the drug with the sulfhydryl group was further studied, using methanethiol as a model compound. The kinetics revealed that the reaction was of pseudo-first-order in excess of thiolate anion. Analysis with gas chromatography-mass spectrometry showed that the main product was an adduct of thiol with bicyclomycin in an equal molar ratio. The structure of the adduct was determined by 1H-NMR spectrometry, showing that thiolate attacked the olefinic double bond of the antibiotic. 3'-Acyl derivatives of bicyclomycin did not significantly affect the binding of [14C] bicyclomycin to inner membrane proteins of E. coli. The results suggested that 4,5-double bond hydrocarbons and 3'-hydroxy group of bicyclomycin participate in the binding to E. coli inner membrane proteins, which are presumably the receptors of the antibiotic. The olefinic double bond seems to be the active center of bicyclomycin, reacting with the sulfhydryl group of the receptor protein, although the whole molecular is needed for the activity.

Anti-Bacterial Agents↗

Mechanism of action of bicyclomycin.

Microscopic examination of cultures of Escherichia coli exposed to bicyclomycin revelaed elongated or spheroplast-like cells. At the lethal level, bicyclomycin was shown to inhibit the synthesis of RNA and protein in the growing cells of E. coli 15 THU, whereas DNA and lipid synthesis were not significantly affected. However, the antibiotic did not block RNA and protein synthesis in vitro. Bicyclomycin was observed to inhibit the synthesis of envelope proteins more markedly than that of cytoplasmic proteins. The synthesis of two major envelope proteins was more sensetive to bicyclomycin than that of the other envelope proteins. One (peak I), which was inhibited to the greatest extent, seemed to be identical with a bound form of lipoprotein, and the other (peak V) with a free form of lipoprotein. Bicyclomycin exhibited inhibitory effects on the exclusive biosynthesis of the lipoprotein in histidine-starved cells of E. coli 15 THU. The biosynthesis of the bound form of lipoprotein was more profoundly inhibited by bicyclomycin than that of the free form. These results indicate that the primary action of bicyclomycin may be due to the interference with the biosynthesis of lipoprotein, and its assembly to peptidoglycan.

Anti-Bacterial Agents↗

Freeze-fracture study of the site of attachment of Cryptosporidium muris in gastric glands.

The mode and organization of the attachment site of Cryptosporidium muris to gastric glands of stomach were investigated by the freeze-fracture method. Cryptosporidium muris was enveloped by a double membrane, of host plasma membrane origin, which formed the parasitophorous vacuole. The outer membrane of the double membrane was continuous with host plasma membrane, while the inner membrane was connected with the anterior part of the parasite plasma membrane at the annular ring. The density of intramembranous particles (IMP) was severely altered at the above two junctures. The parasitophorous outer membrane showed low IMP-density when compared to the host plasma membrane, although both membranes were continuous at the dense band. The inner membrane had few IMP, whereas the parasite plasma membrane showed numerous IMP, although both membranes were continuous at the annular ring. The size of dense band and annular ring was similar in diameter. The feeder organelle was clearly visible as membrane folds in freeze-fracture and some of them were connected with small vesicles of cytoplasm, indicating that the feeder organelle may play an important role for incorporation of nutrients from the host cell.

Animals↗

Heterogeneous distribution of membrane cholesterol at the attachment site of Cryptosporidium muris to host cells.

Distribution of membrane cholesterol at the attachment site of Cryptosporidium muris was investigated by freeze-fracture cytochemistry using a polyene antibiotic filipin. Since the host plasma membrane enveloped C. muris, the inner and outer membranes were continuous with the parasite plasma membrane at the annular ring and with host membrane at the dense band, respectively. Although many filipin-cholesterol complexes were observed on the plasma membrane of host cells and parasites, a line showing no complexes was evident at the above two membrane junctures. These observations indicate that parasitic infection of C. muris altered the organization of membrane cholesterol.

Animals↗

Heterotopic gastric mucosa in intrahepatic bile duct, presenting with hemobilia: a case report.

We present a 66-year-old man with unique heterotopic gastric mucosa in the intrahepatic bile duct causing hemobilia. Endoscopic retrograde cholangiography showed irregular stenosis of the left intrahepatic bile duct, and a provisional diagnosis of cholangiocarcinoma was made. Therefore, partial hepatic lobectomy and cholecystectomy were performed. Histological examination of the liver showed the presence of ectopic gastric mucosa in the intrahepatic bile duct containing mucous glands with parietal and chief cells and bile. Heterotopic gastric mucosa in the intrahepatic bile duct is a rare cause of hemobilia.

Aged↗

Chemotherapeutic effect of azithromycin and lasalocid on Cryptosporidium infection in mice.

Prednisolone-immunosuppressed mice (ICR, 7-wk-old female) were each inoculated with 1 x 10(5) oocysts of Cryptosporidium parvum. Medication with azithromycin (400 mg/kg/day) or lasalocid (64, or 128 mg/kg/day) was started 13 h after inoculation and continued for 3 days. The number of oocysts discharged by each mouse was calculated on days 4-12 post-inoculation. Compared with non-medicated controls, oocyst production by the medicated mice was markedly reduced; some mice did not discharge oocysts and the remaining mice discharged less than 1/100 the number of oocysts of the control mice. These results indicate that both azithromycin and lasalocid have prophylactic or therapeutic activity against Cryptosporidium.

Animals↗

Freeze-fracture studies of Cryptosporidium muris.

The attachment site of Cryptosporidium muris to host cells was investigated using the freeze-fracture method. Cryptosporidium muris was enveloped by a double membrane of host plasma membrane origin, which formed the parasitophorous vacuole. The outer membrane of the double membrane was continuous with the host plasma membrane at the dense band, while the inner membrane was connected with the anterior part of the parasite plasma membrane at the annular ring. The density of intramembranous particles (IMP) was dramatically altered at the above two junctures. The outer parasitophorous membrane showed low IMP-density as compared to the host plasma membrane, although both membranes were continuous. The inner parasitophorous membrane had few IMP, whereas the parasite plasma membrane showed numerous IMP. When the attachment sites of parasites and host cells were fractured, circular-shaped fractured faces were observed on both sites of the parasite and host cell. These exposed faces corresponded to the dense bands and were very similar in size in each parasite.

Animals↗