[TDZ string packs in clinical tests].
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Biomedical subjects
Publications and source records attributed to T Okuda.
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A case of chromophobe adenoma with capsular calcification combined with Rathke's cleft cysts is presented. A 28-year-old woman presented with a seven-year history of amenorrhea. Several months before admission to our department of neurosurgery on November 6, 1982, she developed galactorrhea and difficulty in reading because of visual failure. Neurological examination on admission revealed bitemporal hemianopsia, visual disturbance, left optic atrophy. Plain skull films and CT scan showed suprasellar capsular calcification. The patients hormonal status was assessed pre- and postoperatively. The basal serum prolactin (PRL) level was elevated at 790ng/ml, but other hormone basal plasma levels were within normal limits despite decrease in FSH, LH, The LH, FSH and PRL demonstrated a blunted response to LH-RH (100 micrograms). Both TSH and PRL demonstrated a blunted response to TRH (500 micrograms). The GH showed no response to insulin tolerance test (0.1 U/kg). On November 24, right frontal craniotomy was performed. A grayish bulging mass was noted surrounded by a calcified layer(2-3 mm) in the suprasellar region. When incised this calcified hard layer, showed multi-small cysts with yellow fluid. Under the cyst layer, there was a soft mass which was curetted easily. Histologically, under the ossified layer, there were multi-small cysts, lined by a single layer of ciliated columnar epithelium. The central soft mass was regarded as a chromophobe adenoma with no calcified body. Following partial removal of the tumor, there was prompt improvement in clinical signs and plasma PRL level.(ABSTRACT TRUNCATED AT 250 WORDS)
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The fourth, second and fifth components of mouse complement were purified by a combination of polyethylene glycol precipitation, ion exchange chromatography and gel filtration. The final products were homogeneous on SDS-PAGE, and the activity yields were 8.5% for C4, 32% for C2 and 40% for C5. C4 was composed of three polypeptide chains with mol. wts of 90,000, 78,000 and 32,000. C2 was composed of a single polypeptide chain with a mol. wt. of 115,000 and cleaved by C1s into two fragments with mol. wts of 80,000 and 35,000. The half life of C4b2a was 7 min and was not prolonged by the iodination of C2. C2 activity could not be measured using EAC14hu or EAC14gp cells, but measurement was possible with the use of EAC14mo cells with purified C5 components of mouse complement. C5 was composed of two polypeptide chains with mol. wts of 135,000 and 84,000. This is the first report on the purification of functionally active mouse complement components C4, C2 and C5 from plasma.
The thoracic aorta and basilar artery, in which the incidence of atherosclerosis is known to be different, were examined to elucidate the correlation between the structure of the intercellular cleft junction between adjacent endothelial cells and its permeability to HRP. Tannic acid or HRP in the vessel lumen passed through the intercellular clefts of the thoracic aorta into the subendothelial space, whereas in the basilar artery they were unable to penetrate beyond the tight junction of the intercellular clefts. Freeze-fracture replicas revealed that the tight junctions of the thoracic aorta consisted of one to two junctional strands in most areas of the cleaved planes, with discontinuities in some places, whereas those of the basilar artery consisted of a continuous belt-like meshwork of six anastomosing junctional strands on average. These observations confirm that the structure of endothelial junctions in arteries has a close correlation with the permeability of the intercellular clefts to HRP.
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SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.
A study of the metabolic fate of [14C]SM-1652 after intravenous or intramuscular injection into rats showed that: (i) the elimination of the labeled compound from the blood was the same after intravenous and intramuscular injections; (ii) the radiolabeled drug was distributed rapidly and widely after intravenous administration with the highest concentration in the kidney and the lowest in the brain; (iii) placental transmission was slight, as it was passed into the milk, where the concentration was about 14% that of plasma; (iv) 33 and 67% of the administered radioactivity was excreted in urine and feces, respectively; (v) radioactivity in both urine and bile was ascribable to unaltered SM-1652; and (vi) upon repeated intramuscular injections twice daily, levels of labeled SM-1652 in tissue increased gradually, reaching a plateau at the 11th injection.
Several yeast strains belonging to genus Candida were found to selectively hydrogenate l-sorbose with enantiomeric specificity, yielding optically pure l-iditol in the culture broth. The most active strain, isolated from a commercial lemon, was identified as Candida intermedia, which produced 50 g of l-iditol per liter from 150 g of l-sorbose per liter during a 5-day fermentation period (35% yield).
N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine, a synthetic muramyl dipeptide analog, stimulated the production of the third component of complement (C3) in mice. The serum concentration of C3 was elevated significantly by subcutaneous treatment with a single dose (10 to 100 micrograms per mouse) of the adjuvant 24 h before assay of the serum. Thereafter, the concentration decreased gradually with time and returned to the normal level on day 4 to 5. Immunoelectrophoretic analysis of the serum revealed that the decrease in serum C3 could not be accounted for by the cleavage to C3a and C3b. By intermittent treatment with the adjuvant on every fifth day, a significant increase in serum C3 was repeated. However, no continuous retention of the serum level of C3 was established even during continuous treatment with the adjuvant once a day for 10 consecutive days. Instead, in this case, the level of C3 increased repeatedly at almost 5-day intervals.
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There are two methods for hemolytic titration of C4. One is a method using EAClgp, oxyC2hu and EDTA-Cgp (E-C method) and the other using EAClgp, oxyC2hu and C4Dgp (C4D method). The C4 titers obtained by these two methods differed depending on whether the C4 exists in plasma or in serum. In the case of Ssh strain, serum C4 activity assayed by the E-C method was higher than that by the C4D method, while plasma C4 activity assayed by the E-C method was lower than that by the C4D method. It was hypothesized that these results would occur from the difference in the state of C4 molecule present in serum or plasma. From chromatographic analysis, it was apparent that the C4 molecule in serum existed in at least four different molecular states; free C4 molecule with low Ss antigenicity, hemolytically inactive Ss protein, active C4 with high molecular weight and low Ss antigenicity, and inactive Ss protein with high molecular weight. Their expression of Ss antigen and the hemolytic C4 activity were different, and each type of C4 molecule behaved differently in the assay of the two methods. Furthermore an important role of mouse C5 in the hemolytic assay of mouse C4 is discussed.
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The influence of the chirality of the 7-acyl side chain and of various N-acyl moieties (A-CO-) on the in vitro activity of 7 beta-[2-acylamino-2-(4-hydroxyphenyl)acetamido ]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acids (6) was investigated. A cephalosporin having a 7-acyl side chain of S-configuration (6r) was only weakly active against Staphylococcus aureus and Klebsiella pneumoniae and was inactive against the other species tested. Among the various N-acyl moieties in the cephalosporins having a 7-acyl side chain of the R-configuration, the 4-hydroxypyridine-3-carbonyl moiety, unsubstituted or substituted with 5-bromo and/or 6-alkyl groups and the 4-hydroxy-1,5-naphthyridine-3-carbonyl moiety, unsubstituted or substituted with a 6-methyl and a 6-methoxy group gave the most active compounds. N-Ethylation of the 4-hydroxy-1,5-naphthyridine-3-carbonyl derivative and the 4-hydroxypyridine-3-carbonyl derivative (6p, 6q) resulted in a decrease of the in vitro activity.
The influence of various 3-substituents on the antibacterial activity of 7 beta-[D-2-(4-hydroxy-6-methylpyridine-3-carbonylamino)-2-(4-hydroxyphenyl) acetamido]ceph-3-em-4-carboxylic acids (III) was investigated. Introduction of an acidic substituent, such as a sulfo or a carboxyl group, to a 3-(1-methyl-1H-tetrazolyl)thiomethyl substituent (IIIf--i) resulted in a marked loss of activity against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Enterobacter aerogenes, in contrast to an in crease of activity against Proteus mirabilis. Displacement of the acetoxy group of IIIb with pyridines (IIIm--p) enhanced the activity against P. aeruginosa and E. aerogenes: their activity against those strains were superior to that of the cephalosporin IIId having a 3-(1-methyl-1H-tetrazolyl)thiomethyl substituent. As a result of extensive studies in addition to the study of in vitro activity in this series, 7 beta-[D-2-(4-hydroxy-6-methylpyridine-3-carbonylamino)-2-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, code No. SM-1652, cefpiramide (generic name), was selected as a candidate for further biological and clinical investigations.