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Biomedical subjects

S Matsui

Publications and source records attributed to S Matsui.

At least 307 records · Page 17Linked to original sources

Results of kidney transplantation in 25 pediatric patients.

Outcome, long-term prognosis, growth activity and rehabilitation after kidney transplantation were studied in 25 pediatric patients transplanted with a kidney graft from one-haplotype identical parent. Excellent patient and graft survival with low incidences of acute rejection or serious complications could be achieved in this population, as compared with the results of adult recipients. Growth retardations in height and weight were observed in these patients before transplantation, and were significantly correlated with the duration of low or no kidney function. In 12 recipients who were transplanted at ages of younger than 15 years and followed up over two years, a dramatic increase in weight appeared within one year after transplantation and a greater increase in height was exhibited in the second and third year than in the first. Increase in height was significantly greater in those children transplanted at ages of younger than 10 years than in those transplanted at ages of older than 11 years. Catch-up growth was observed in one-third of these children. Retrospectively, there was no difference in the doses of prednisolone given between the two groups of patients with, and without catch-up growth, but the incidence of acute rejection was higher in the group without catch-up growth. Currently, 18 recipients have functioning grafts and 16 (88.9 per cent) of them are in full-time school or working. From these results it is concluded that kidney transplantation is the first feasible manoeuvre for those children with chronic renal failure and it should be performed as soon an possible in order to preserve their growth activity.

Adolescent↗

Effect of cadmium on vitamin D-non-stimulated intestinal calcium absorption in rats.

The present report demonstrates the effect of Cd on intestinal Ca transport and Ca-binding protein in rats adapted to vitamin D repletion and high Ca. There were significant decreases in in vitro intestinal Ca transport in animals exposed to Cd for 2 or 3 months as compared with controls. Ca transport from everted gut sacs of normal rats showed a dose-dependent decrease. 45Ca-binding activity to intestinal mucosa from Cd-exposed rats showed a lower level of decrease than that on control rat mucosa. The typical peak of Cd-binding protein obtained from Sephadex G-100 gel filtration of 109Cd added to mucosal supernatant agreed with results of gel filtration obtained after 45Ca had been added to the same supernatant. Although there were 2 proteins binding Cd or Ca in the intestinal mucosa, with the same molecular weight of 10,000, these proteins were shown to be different, since Cd did not bind with the Ca protein. It was concluded that inhibition of vitamin-D-non-stimulated Ca transport was not caused by Cd bound to Ca-binding protein, but by some other factor.

Animals↗

Efficacy of dibutyryl cyclic AMP in heart failure unresponsive to catecholamines.

The efficacy of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) was evaluated in eight patients with heart failure unresponsive to catecholamine therapy. Seven patients who were hemodynamically at Forrester's hemodynamic subset stage H-IV and had a left ventricular stroke work index (LVSWI) of less than 20 g-m/m2 despite administration of unloading drugs and catecholamines were studied both hemodynamically and clinically. Another patient with dilated cardiomyopathy, in whom invasive hemodynamic monitoring could not be carried out, was studied clinically. The DBcAMP was administered intravenously at a mean (+/- SD) of 0.05 +/- 0.036 mg/kg/min, and hemodynamic measurements were made 63 +/- 37 min after administration. The cardiac index (CI) increased from 1.92 +/- 0.22 to 2.49 +/- 0.59 L/min/m2, and LVSWI from 14 +/- 4.0 to 18 +/- 5.1 g-m/m2, both significantly (CI, P less than 0.01; LVSWI, P less than 0.025). The total systemic vascular resistance index (TSVRI) decreased significantly from 2,746 +/- 427.2 to 2,218 +/- 582.6 dan.sec.cm-5.m2 ( P less than 0.01). The increase in CI was accompanied by a proportional decrease in TSVRI in all patients. Left ventricular function, which was estimated by the relation between pulmonary arterial end-diastolic pressure and LVSWI, was improved in five of seven patients after administration of DBcAMP. Two patients in whom DBcAMP was given intermittently improved clinically and survived. The authors conclude that DBcAMP has powerful vasodilating and mild positive inotropic effects and hence can be useful for treating heart failure unresponsive to catecholamines.

Adolescent↗

[Efficacy of vagotomy on liver regeneration in the prevention of stress ulcer after partial hepatectomy in the cirrhotic rat].

Possible effects of vagotomy (a means of preventing stress ulcers after partial hepatectomy in cirrhotic liver) on liver regeneration were explored. Cirrhosis was induced in rats by means of intraperitoneally administering 4% thioacetamide for 10 consecutive weeks. These rats were subjected to partial hepatectomy (ca. 68% resection) and vagotomy at the same time. Normal rats of consistent age served as controls after receiving hepatectomy. In controls, which received hepatectomy alone, both gastric pH and gastric wall blood flow showed a significant reduction on the third day after surgery. In animals which received both hepatectomy and vagotomy, postoperative reduction in gastric pH was suppressed, but postoperative reduction in gastric wall blood flow was more marked compared to those of controls. In animals which received both hepatectomy and vagotomy, postoperative 3H-thymidine intake and thymidine kinase activity were markedly suppressed compared to controls. In animals which received both hepatectomy and vagotomy, the peak level of mitotic index and the hepatic regeneration rate were markedly suppressed compared to those of controls. The above results indicate that vagotomy is not advantageous to liver regeneration and prevention of stress ulcer after partial hepatectomy in cirrhotic rat because of its potency of inducing marked reduction in gastric wall blood flow and impediment of liver regeneration.

Animals↗

[Pharmacokinetics in neonates and infants following administration of amikacin].

Sixteen neonates (at ages of 8 to 28 days) and 8 infants (at ages of 35 days to 1 year), who were in need of treatment with amikacin sulfate, were subjected to the present study. The drug was administered by intramuscular route (1.39 to 3.13 mg/kg) or by intravenous drip infusion over a 30 to 60 minutes period (2.94 to 6.00 mg/kg). Blood levels and urinary excretion of the drug were investigated with these subjects. The blood levels were also analyzed according to pharmacokinetic models. 1. When the drug was administered intramuscularly to neonates at average doses of 1.49 and 2.96 mg/kg and to infants at average doses of 2.97 mg/kg peak levels of 2.74, 6.53 and 8.55 micrograms/ml, respectively, were attained at 30 minutes after dosing. 2. When the drug was administered to neonates at average doses of 3.01 and 5.89 mg/kg by intravenous drip infusion over a 30 to 60 minutes period and to infants at average doses of 2.97 and 6.00 mg/kg in the same manner, peak levels of 7.70, 20.9, 9.40 and 23.0 micrograms/ml, respectively, were attained at the end of the intravenous drip infusion. 3. Urinary levels and recovery rates tended to increase with ages of these subjects. Urinary recovery rates for the neonates and the infants were 41.0 and 58.9%, respectively, on the average. 4. From a pharmacokinetic analysis of blood levels of the drug, it was concluded that, in any of the subjects who received the drug intramuscularly or by intravenous drip infusion, it would be possible to use the one-compartment open model. In the subjects who received the drug by intravenous drip infusion, however, it was determined the two-compartment open model would be the choice. 5. In the neonates and the infants, whose blood levels were analyzed according to the one-compartment open model, Ka values averaged 7.51 and 6.62 hr-1, respectively, with respective average Kel values of 0.32 and 0.66 hr-1. Average Vd values obtained were 0.36 and 0.26 L/kg, respectively. There was a negative correlation between the Vd values and the ages of the subjects, while there was a positive correlation between the Kel values and the ages. 6. Appropriate conditions for administering the drug by intravenous drip infusion to neonates and infants at ages of more than 1 week were investigated taking observed blood levels and achieved peak levels and trough levels calculated using the one-compartment open model into account.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Substrate recognition of isopeptidase: specific cleavage of the epsilon-(alpha-glycyl)lysine linkage in ubiquitin-protein conjugates.

The structural chromatin protein A24 (uH2A) is a conjugate of histone H2A and a non-histone protein, ubiquitin. Eukaryotic cells contain an enzyme, generically termed isopeptidase, which can cleave A24 stoichiometrically into H2A and ubiquitin in vitro. Isopeptidase, free of proteinase activity, has been partially purified from calf thymus by ion-exchange chromatography, gel filtration and affinity chromatography, and analyzed for its substate specificity. There are three major types of isopeptide bonds besides the epsilon-(alpha-glycyl)lysine bond between H2A and ubiquitin; namely, the disulfide bridge, the aldol and aldimide bonds and the epsilon-(gamma-glutamyl)lysine crosslink. Under conditions where A24 was completely cleaved into H2A and ubiquitin, none of these naturally occurring isopeptide bonds was cleaved by isopeptidase. Furthermore, the bonds formed in vitro by transglutaminase reaction between casein and putrescine, through the gamma-NH2 of glutamine residue and the NH2 of putrescine, were not cleaved by the enzyme. The enzyme also failed to cleave the glycyl-lysyl and other orthodox peptide linkages within proteins. Among various proteins examined, the substrates for isopeptidase reaction were confined to conjugates between ubiquitin and other proteins, formed through epsilon-(alpha-glycyl)lysine bonds. Since ubiquitin released by isopeptidase is re-usable for an ATP-dependent conjugation with other proteins, its carboxyl terminal -Gly-Gly-COOH most likely is preserved intact, and is not blocked. These results suggest that isopeptidase specifically recognizes and cleaves the epsilon-(alpha-glycyl)lysine bond. A possible biological significance of this enzyme is discussed.

Animals↗

N-band proteins of nucleolar organizers: chromosomal mapping, subnucleolar localization and rDNA binding.

The ribosomal DNA(rDNA)-containing chromatin in eukaryotes forms a unique architecture called the "secondary constriction" or "nucleolus organiser region (NOR)" on mitotic chromosomes. To gain more insight into non-histone chromosomal proteins (NHCP), termed "N-band proteins", that are specifically associated with the NOR in a wide variety of eukaryotes, we attempted to: identify the NHCP responsible for N-band staining; determine their stoichiometry; map them on metaphase chromosomes; determine their subnucleolar localization and examine their possible ability to bind rDNA. Based on several criteria, including chromosomal localization, solubility, association with chromatin, and intra-nuclear localization, two of the nucleolus-rich NHCP, termed component B of mol.wt 55,000 and component C of mol.wt. 41,000, were tentatively identified as N-band proteins. Immunological studies using a polyclonal, monospecific antibody raised against component C show that this protein is in fact associated with the chromosomal telomeres where NORs are located. In nucleoli, N-band proteins appear to be compartmentalized into a structure that probably corresponds to fibrillar components. Both components B and C are among several NHCPs that showed, under in vitro conditions, a strong affinity for rDNA cloned in lambda phage but not for calf thymus genomic DNA or phage vector DNA. The antibody against component C effectively suppressed in vitro transcription by RNA polymerase I in nucleoli and nucleolar chromatin. Component C appears to exist in the nucleus at 3.75-5.13 X 10(3) copies per rDNA unit or 0.09-0.13 copy per nucleotide. These findings support the hypothesis that the NOR is a chromosomal site, architecturally not only unique but also different from other chromatin regions in that constituent DNA, i.e., rDNA, is organized in a specific manner by interacting with specific NHCP, i.e., N-band proteins.

Animals↗

Improved outcome of renal transplantation with cyclosporine compared with azathioprine--experience in 33 recipients followed for over one year.

Long-term clinical aspects after kidney transplantation using cyclosporine (CsA) were studied in 33 patients who received kidney grafts from one haplotype identical living related donor and who were followed for at least one year. Both actual graft and patient survival rates were 97 per cent at one year. Incidence and severity of acute rejection were reduced to a greater extent in patients treated with CsA than in patients treated with azathioprine (AZ). The incidence of infections was low, and no serious bacterial infection occurred in these 33 patients. In 17 of 33 patients with a deteriorative graft function caused by intractable nephrotoxicity, CsA was converted to AZ. The mean serum creatinine level of converted patients was significantly higher than that of patients maintained with CsA at each time when a dose of CsA was stepwise reduced from 14 mg/kg/day to 6 mg/kg/day. Conversion to AZ improved graft function dramatically, although it resulted in reversible acute rejections in 4 patients. CsA induced hepatotoxicity occurred in 10 patients, but in all normal liver function was restored with decrease in the dose. The potent immunosuppressive effect of CsA compensates for its side effects. However, CsA should be converted to AZ when the chronic nephrotoxicity persists at a late stage of post-transplantation.

Adolescent↗

Characterization of experimental ischemic brain edema utilizing proton nuclear magnetic resonance imaging.

Correlations between T1 and T2 relaxation times and water and electrolyte content in the normal and ischemic rat and gerbil brains were studied by means of both nuclear magnetic resonance (NMR) spectroscopic and imaging methods. In the spectroscopic experiment on excised rat brains, T1 was linearly dependent on tissue water content and T2 was prolonged in edematous tissue to a greater extent than expected by an increase in water content, showing that T2 possesses a greater sensitivity for edema identification and localization. Changes in Na+ and K+ content of the tissue mattered little in the prolongation of relaxation times. Serial NMR imaging of gerbil brains insulted with permanent hemispheric ischemia offered early lesion detection in T1- and especially T2-weighted images (detection as soon as 30 min after insult). The progressive nature of lesions was also imaged. Calculated T1 and T2 relaxation times in regions of interest correlated excellently with tissue water content (r = 0.892 and 0.744 for T1 and T2, respectively). As a result, detection of cerebral ischemia utilizing NMR imaging was strongly dependent on a change in tissue water content. The different nature of T1 and T2 relaxation times was also observed.

Animals↗

The active immunoglobulin kappa chain gene is packaged by non-ubiquitin-conjugated nucleosomes.

To elucidate the molecular features of active chromatin, we have mapped, by two-dimensional electrophoresis, the protein composition of nucleosomes that package the immunoglobulin kappa chain gene of mouse plasmacytoma cells. Nucleoprotein particles that possess the active kappa chain gene comigrate with bulk mononucleosomes that contain high mobility group proteins HMG-14 or -17 but lack histone H1. High electrophoretic resolution of the underlying core particles, after removal of ubiquitin by isopeptidase treatment, reveals that these nucleosomes are nonubiquitinated, even though they coincidently migrate with bulk ubiquitinated particles. This distinctive electrophoretic behavior may be correlated with the presence of histone H2A.X. Nucleosomes exhibiting these unusual properties appear to span at least 10 kilobases, in both transcribed and nontranscribed regions, suggesting that mechanisms independent of transcription exist to initiate, maintain, and propagate a common chromatin phenotype over long distances along the kappa chain locus.

Animals↗