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Biomedical subjects

S Hiraga

Publications and source records attributed to S Hiraga.

At least 163 records · Page 9Linked to original sources

[Study on changes in plasma platinum concentrations after administration of CDDP to maintenance hemodialysis patients].

Changes in plasma platinum concentration after administration of CDDP were studied in six patients on maintenance hemodialysis with malignancies. Plasma exchange was carried out on three patients for the purpose of plasmapheresis. A therapeutic dose of 51 mg/m2 of CDDP was administered to each patient without any severe adverse reactions. Plasma platinum concentration was measured by atomic absorption spectrophotometry, and the decay curve of the agent showed a biphasic pattern with an initial steep alpha phase and an ensuing mild beta phase in both hemodialysis patients and normal controls. As these patterns showed no renal excretion of CDDP, it was suggested that the uptake of CDDP into tissue was one of the main causes of the steep alpha phase. In patients given plasma exchange one or two hours after the beginning of CDDP administration, the reduction rates of plasma platinum were 74.7-61.7%, but the collection rate of the agent in the exchanged plasma was only 22.2-7.5%. These results indicated that the uptake of CDDP into tissue might occur rapidly within a few hours after CDDP administration.

Adult↗

Increases in brain tumor and cerebral blood flow by blood-perfluorochemical emulsion (Fluosol-DA) exchange.

It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]iodoantipyrine (IAP) and quantitative autoradiographic techniques. The exchange transfusion was performed in two groups of awake animals breathing 100% oxygen: (a) complete blood-PFC exchange, hematocrit 4%; and (b) partial blood-PFC exchange, hematocrit 20-25%. The tissue/blood partition coefficient for IAP was determined in a separate set of experiments under identical conditions and was used in calculating blood flow. Cerebral blood flow increased approximately 2-fold following complete blood-PFC exchange and 1.5-fold by the partial exchange. A similar 1.5-fold increase in flow was measured in intraparenchymal tumors following partial exchange; however, a flow increase was not identified in the meningeal extension of the tumors. The increase in cerebral blood flow is consistent with an autoregulatory response of the central nervous system vasculature to maintain an adequate supply of oxygen to central nervous system tissue. Presumably, the increase in blood flow to the intracerebral tumor reflects the autoregulatory response of the host tissue. The effect of blood-PFC exchange on blood flow and drug delivery to tumor may depend on the particular tumor and its site of growth (host tissue). The tissue/blood partition coefficient for IAP increased from 0.8 to 1.0 and 1.4 following partial and complete blood-PFC exchange, respectively. This change in the partition coefficient reflects the change in the intravascular fraction of IAP that is bound to plasma proteins. The enhanced therapeutic effect that has been reported in some experimental tumor models may result from a higher tissue/blood equilibrium distribution ratio (due to reduced plasma protein binding) resulting in a higher tissue exposure to certain drugs following PFC administration.

Animals↗

Partitioning of the F plasmid: overproduction of an essential protein for partition inhibits plasmid maintenance.

Multicopy plasmids carrying the sopB gene of the F plasmid inhibit stable inheritance of a coexisting mini-F plasmid. This incompatibility, termed IncG, is found to be caused by excess amounts of the SopB protein, which is essential for accurate partitioning of plasmid DNA molecules into daughter cells. A sopB-carrying multicopy plasmid that shows the IncG+ phenotype was mutagenized in vitro and IncG negative mutant plasmids were isolated. Among these amber and missense mutants of sopB, mutants with a low plasmid copy number and a mutant in the Shine-Dalgarno sequence for translation of the SopB protein were obtained. These results demonstrate that the IncG phenotype is caused by the SopB protein, and that the incompatibility is expressed only when the protein is overproduced. This suggests that the protein must be kept at appropriate concentrations to ensure stable maintenance of the plasmid.

Bacterial Proteins↗

Attempts to increase intratumoral blood flow in the rat solid Walker 256 tumor by the use of the perfluorocarbon emulsion fluosol-DA.

We have examined the effect of the perfluorocarbon emulsion, Fluosol-DA 20% (FDA), on blood flow in rats bearing an advanced solid Walker 256 tumor implanted s.c. Blood-FDA exchange in unanesthetized rats maintained under 100% oxygen was accomplished by simultaneous arterial withdrawal and i.v. infusion until the hematocrit was less than 4%. Control rats were maintained under 100% oxygen but did not undergo any exchange. Regional blood flow studies in tumors of control and FDA-exchanged rats were performed using [14C]iodoantipyrine and quantitative autoradiography. FDA-blood exchange did not increase flow to the whole tumor. Similarly, the pattern of regional flow within the tumor, which was determined in histologically distinct areas--including dense and normocellular, necrotic and peripheral zones invading into muscle and connective tissue--was not substantially altered. Flow to cerebral tissue was increased two-fold, although flow to normal tissues including temporalis muscle, skin and diaphragm was not altered. These results show that FDA-blood exchange does not enhance vascular flow in solid Walker 256 tumor implanted s.c. in the rat.

Animals↗

Molecular cloning of a human apoC-III variant: Thr 74----Ala 74 mutation prevents O-glycosylation.

Apolipoprotein C-III (apoC-III) is a major protein of very low density lipoprotein (VLDL). The apoC-III polypeptide contains a carbohydrate chain containing galactosamine, galactose, and sialic acid attached in O-linkage to a threonine residue at position 74. We have cloned the apoC-III gene from a subject whose serum contained unusually high amounts of apoC-III lacking the carbohydrate moiety (C-III-0). DNA sequence analysis of the cloned gene revealed a single nucleotide substitution (A----G) that encodes an alanine at position 74 instead of the normal threonine. As a result of this amino acid replacement, the mutant apoC-III polypeptide is not glycosylated. The mutation in the apoC-III gene creates a novel AluI site that permits diagnosis of the change by Southern blotting of genomic DNA.

Alanine↗

[A case of giant obsolete hydrocele testis].

A 58-year-old man visited the urological clinic in Prefectural Tohkamachi Hospital with complaint of swelling of bilateral scrotal contents. He had no history of fever, pain or difficulty of urination. Physical examination revealed a giant mass of adult-head size in right scrotum and left inguinal hernia of fist growth. Surgical extirpation of the right scrotal mass and left inguinal herniorrhaphy was performed and the mass was diagnosed as obsolete hydrocele testis and weighed 1,600 g. The excised hydrocele sac showed marked thickening and dark brown pus amounted to about 1,400 ml, which was negative in bacterial culture. Histological examination revealed partial deposits of cholesterol and calcification in tunica vaginalis with extremely atrophic testis and destructive spermatogenesis. The findings suggested the existence of long-term infection in hydrocele testis. The etiology and pathogenesis of this disease is discussed.

Calcinosis↗

Pharmacological actions of dopamine sulfoconjugate on cardiovascular system.

Pharmacological actions of dopamine 4-sulfate on the cardiovascular systems were examined and compared with those of dopamine. Dopamine 4-sulfate, used in the present study, was minimally contaminated with dopamine (less than 0.02%). Dopamine 4-sulfate at doses ranging from 0.1 to 1 mumol/kg did not elicit any appreciable changes in systemic blood pressure and heart rate of anesthetized rabbits. Contractile activity and heart rate of isolated perfused rat heart were also unaffected by the agent. Dopamine 4-sulfate at concentrations of 1 and 0.3 mM, reduced a significant contraction of isolated rabbit renal and femoral arteries, respectively, but not in the aorta. The extent of the increase in tension development induced by 1 mM dopamine 4-sulfate in the femoral artery, was almost similar to that induced by 3 microM dopamine. The maximal tension development induced by 1 mM dopamine 4-sulfate in the femoral artery occurred more slowly than that induced by 3 microM dopamine. Furthermore, dopamine 4-sulfate-induced increase in tension development, like that of dopamine itself, was inhibited by 0.3 microM phentolamine and 0.1 microM haloperidol. Any appreciable conversion of dopamine 4-sulfate into dopamine was not seen in the medium of the organ bath in vitro during the experiment. The results suggest that dopamine sulfoconjugate exerts little effect on the cardiovascular system and, if any, induces a constriction of some vascular beds without conversion into dopamine.

Animals↗

Clinical reports on plasma exchange in the Kidney Center, Tokai University School of Medicine.

There were 72 patients (19 with hepatic failure, 10 with fulminant hepatitis, eight with paraquat poisoning, eight with rheumatoid arthritis, five with myasthenia gravis, four with hyperlipidemia, four with systemic arteriosclerosis including brain infarction, three with pemphigus vulgaris, two with multiple myeloma, two with systemic lupus erythematosus, two cases non-specific Ig-G antibody, two cases medication with an anticancer drug, one with multiple sclerosis, one with Crohn's disease with amyloid kidney and one with chronic myeloblastic leukemia) treated by plasma exchange in the Kidney Center, Tokai University School of Medicine from Jan. 1983 to Dec. 1986. We performed plasma exchange using fresh frozen plasma in 40 cases and Lactate-Ringer's solution containing albumin (4.0-5.0%) in 20 cases as the replacement fluid. In 17 cases, we performed double filtration plasma exchange with the recycle system and no replacement fluid. Although PE therapy did not constitute a basic therapy for hyperlipidemia, pemphigus vulgaris, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus, it was effective in relieving severe clinical symptoms. At the present time, conventional plasma exchange does not improve the survival rate of patients with hepatic failure and fulminant hepatitis. Developments of a new artificial liver support apparatus and identity of many toxic substances in hepatic failure are necessary. No hypotension, hypovolemic shock or other significant complications were experienced.

Adult↗

Structure and function of the F plasmid genes essential for partitioning.

The F plasmid in Escherichia coli has its own partition mechanism controlled by the sopA and sopB genes, and by the cis-acting sopC region. The DNA sequence of the entire partition region and its flanking regions is described here. Two large open reading frames coding for 43,700 Mr and 35,400 Mr proteins correspond to sopA and sopB, respectively. The sopB reading frame is located immediately downstream from the sopA reading frame. Twelve 43 base-pair direct repeats exist in the sopC region without any spacer regions, and one pair of seven base-pair inverted repeats exists in each of the direct repeats. Analysis of deletions in the sopC region showed that the direct repeats play an important role in plasmid partition and IncD incompatibility. IncG incompatibility is exhibited by pBR322 derivatives carrying the sopB gene alone. When compared with the partition genes parA and parB of plasmid P1, homology in amino acid sequence was found between the SopA protein of F and the ParA protein of P1, and also between SopB protein of F and ParB protein of P1. In addition, homology was found between Rep proteins of F and P1.

Amino Acid Sequence↗

F plasmid ccd mechanism in Escherichia coli.

The ccd mechanism specified by the ccdA and ccdB genes of the mini-F plasmid determines fate of plasmid-free segregants in Escherichia coli (Jaffé et al., J. Bacteriol. 163:841-849, 1985). The killing function in plasmid-free segregants by the ccd mechanism did not affect cell growth of coexisting cells in the same culture. Elongated cells and anucleate cells caused by the ccd mechanism were clearly detected by flow cytometry in cultures of bacterial strains harboring Ccd+ Sop- mini-F plasmids defective in partitioning. This indicates that the defect in correct partitioning of plasmid DNA molecules into daughter cells also induces the ccd mechanism to operate.

Bacterial Proteins↗

[Studies on gamma-glutamyl transpeptidase (gamma-GTP) in seminal plasma].

The significance of gamma-GTP (gamma-glutamyl transpeptidase) in seminal plasma was examined by measuring the gamma-GTP activity in ejaculate, seminal plasma, prostatic secretion, testis, epididymis, vas deferens, prostate and sperm. The gamma-GTP activity was measured spectrophotometrically (405 nm) using L-gamma-glutamyl-p-nitroanilide as a substrate. One unit of enzyme activity was defined as the amount liberating 1 mumol of p-nitroaniline per min. The mean gamma-GTP activity was 9,094 +/- 4,351 mU/ml in ejaculate and 7,487 +/- 4,286 mU/ml in seminal plasma of 76 men visiting the infertility clinic. There is a positive correlation between gamma-GTP activity in ejaculate and in seminal plasma. The gamma-GTP activity was 15,044 +/- 6,422 mU/ml in prostatic secretion and twice as high as the activity in seminal plasma. There was no significant correlation between gamma-GTP activity in seminal plasma and volume of ejaculate, sperm density or sperm motility. The gamma-GTP activity in testicular tissues was 72 +/- 25 mU/mg protein except for two cases in which its activity was not detected (3 years old; retentio testis, 71 years old; prostatic carcinoma, was administered with hormonal medicine). The gamma-GTP activity in prostatic tissues was 133 +/- 68 mU/mg protein. The relationship between the gamma-GTP activity in testicular tissues and Johnsen's mean score count. Judging from the present results together with the previous reports of Rosalki et al (1977) and Simon et al (1978) the prostate seemed to be the major source of gamma-GTP in human semen.

Epididymis↗

[Neurogenic bladder with pituitary adenoma: report of two cases].

Two cases of neurogenic bladder with pituitary adenoma are reported. The pituitary adenomas produced excessive GH (growth hormone). The etiology of the neurogenic bladder was not identified by X-ray examination or any other tests. Urodynamic study, however, indicated a functional cause of neurogenic bladder. Case 1 was a 55-year-old male, who had a relatively small pituitary adenoma with mild symptoms. Urologically, there was complete urinary retention. Cystometrogram showed a flaccid pattern, detrusor-sphincter dyssynergia in sphincter-EMG and ice water test was negative. Case 2 was a 67-year-old female, who had a large pituitary adenoma and severe symptoms. Cystometrogram showed an almost normal pattern, however, there was detrusor-sphincter dyssynergia and ice water test was negative. We suggested that the neuropeptide takes some part in the pathophysiologic cause of neurogenic bladder.

Adenoma↗