Biomedical subjects
Publications and source records attributed to T Hirose.
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The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 micrograms/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 micrograms/ml medium), an inhibitor of 17 alpha-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 micrograms/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 microgram Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.
To evaluate the potential beneficial effect of a thromboxane synthetase inhibitor, OKY-1581, on increased pulmonary vascular permeability in pulmonary microembolization, we have measured the filtration coefficient in the nonembolized lung after unilateral microembolization in dogs. The unilateral microembolization caused marked elevations in pulmonary artery pressure and blood flow to the nonembolized lung, while pulmonary venous pressure in nonembolized lung did not change. The pulmonary vascular resistance in nonembolized lung did not increase significantly. The filtration coefficient (kf) in nonembolized lung increased to 0.14 +/- 0.02 from te base line value of 0.07 +/- 0.01 ml/min/mmHg/100 g at 30 min after microembolization when the initial hemodynamic changes reduced toward the base line value. In OKY-1581 treated dogs, similar hemodynamic changes did not result in the filtration coefficient in nonembolized lung. Platelet aggregagation was also inhibited after microembolization in OKY-1581 treated dogs. Based on these results, we could conclude that OKY-1581 will serve as a potent beneficial protective drug against pulmonary edema by inhibiting the release of thromboxane A2 following microembolization in the pulmonary vascular bed.
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Forty-two patients with pseudovitelliform macular degeneration (VMD) were studied. The macular lesions were yellow in color, appeared as a slight elevation at the level of the retinal pigment epithelium (RPE), were usually 1/4 to 1/2 disc diameter in size and often showed a round or oval shape. Progression occurred over many years, resulting in a circumscribed atrophic area in the RPE. The lesions in VMD were morphologically similar to those seen in Best's vitelliform dystrophy, but the electrooculogram was normal or slightly subnormal in all cases. The average Lp/Dt ratio in 71 eyes tested was 2.16. There were 31 women and 11 men with a median age of 51 years at initial presentation. Family studies did not reveal other affected members. Long-term follow-up (five years or longer) in ten cases showed that useful vision is retained in at least one eye.
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Two oligonucleotides 14-bases long were synthesized, one complementary to rabbit beta-globin DNA (R beta G14A) and the other with the same sequence except for a single base change (T for C) (R beta G14B). Hybridization conditions were established such that R beta G14A would hybridize to globin DNA while R beta G14B would not. We also synthesized a mixture of 13-base long oligonucleotides (R beta G13Mix), representing eight of the possible coding sequences for amino acids 15-19 of rabbit beta-globin. One of the eight is complementary to globin DNA. R beta G13Mix was found to hybridize specifically to globin DNA under conditions where oligonucleotides forming single base pair mismatches do not. Furthermore, R beta G13Mix was shown to hybridize specifically to colonies containing a plasmid with a globin DNA insert. These results are discussed with respect to a general procedure for screening recombinant clones for those containing DNA coding for a protein of known amino acid sequence.
A gene has been constructed which codes for an analog of human proinsulin in which the normal 35-amino acid connecting peptide is replaced by a "mini-C" peptide of six amino acids (Arg-Arg-Gly-Ser-Lys-Arg). The gene, composed of oligonucleotide fragments synthesized by the triester method, was cloned and expressed as a beta-galactosidase hybrid protein. The proinsulin analog was separated from beta-galactosidase by cyanogen bromide cleavage and purified. Controlled disulfide exchange in the S-sulfonate of the analog generated a molecule having high-pressure liquid chromatography (HPLC) and radioimmunoassay (RIA) behavior consistent with a proinsulin-like structure.
The Wagner-Stickler syndrome is a hereditary progressive arthro-ophthalmopathy with an autosomal dominant pattern of inheritance. Affected persons may have a wide variety of ocular, orofacial, and skeletal problems. We examined 22 index patients and 68 of their relatives. Of these 90 persons (41 in the pediatric age group), 70 were found to have the syndrome. We determined the frequency of the various problems and identified several progressive features. We established an approximate age of onset in the group with known retinal disease and in the asymptomatic group identified by family screening. Although the latter group was initially more mildly affected, they were at risk to develop serious ocular problems. Screening all relatives of affected persons for nonocular features of the syndrome should permit early diagnosis in the asymptomatic group and improve the long-term prognosis.
Subtotal open-sky vitrectomy was performed on 50 eyes with severe retinal detachment that developed as a late complication of ocular trauma. The retina was reattached in 32% of the eyes and vision was improved in 50% of the reattached cases. Two cases of giant retinal tear with massive preretinal retraction were successfully treated by suturing the retinal flap of the tear to the choroid. Subtotal open-sky vitrectomy may be helpful in cases in which closed vitrectomy has failed or would be likely to fail.
We have synthesized two sets of 15-base-long oligodeoxyribonucleotides corresponding to all possible coding sequences for a small portion of human beta 2-microglobulin. Labeled oligonucleotides were used as hybridization probes to screen bacterial clones containing cDNA sequences primed with oligo(dT) and inserted into the plasmid vector pBR322. One beta 2-microglobulin cDNA clone was detected in the 535 bacterial plasmid clones that were screened. The clone has been characterized by blotting and nucleotide sequence analysis. The cloned beta 2-microglobulin sequence contains 217 base pairs of the 3' untranslated region of the mRNA and 328 base pairs (97%) of the coding region.