Biomedical subjects
Publications and source records attributed to K Sone.
The long-term outcome of coronary aneurysm after Kawasaki disease was investigated using dipyridamole-loading angiography in 33 children with coronary aneurysms after Kawasaki disease. Morphologic regression may not accompany functional improvement in the dilated coronary arteries.
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This is a report of two-year-old female monozygotic twins, both having a ventricular septal defect (VSD, Kirklin type II) and accompanying moderate pulmonary hypertension (PH). The two patients underwent a patch closure procedure to repair the VSD at the same time, and their postoperative courses were uneventful. Rubenstein and Weaver have reported the only case of surgical treatment for monozygotic twins having both VSD and PH. Our patients are the second such case of surgical treatment of VSD and PH in monozygotic twins.
In a previous study, we investigated otorhinolaryngological care by the general practitioners in medical rural areas and demonstrated that a close relationship between general practitioners and otorhinolaryngologists was necessary. In the present study, a survey of prefectural health administration's views on otorhinolaryngological care in medical rural areas was performed. A questionnaire for otorhinolaryngological care in medical rural areas was sent to the divisions of health administration in the 47 prefectures of Japan. Of these prefectures, 46 (97.9%) responded. About 80% of respondents have medical rural areas, and the otorhinolaryngological care is inadequate in most areas. General practitioners of internal medicine or surgery are primarily demanded in about 75% of the prefectures. Otorhinolaryngological care in medical rural areas has never been considered in most prefectures. Because the need for otorhinolaryngological medical care will increase, prefectural health administrations need to pay more attention to otorhinolaryngological care in medical rural areas, and a close relationship between general practitioners, otorhinolaryngologists, and the administration should be established.
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Trientine dihydrochloride (trientine) is an alternative medicinal copper chelating agent for patients with Wilson's disease of penicillamine intolerance. We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short-term and long-term administration to Long-Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease. Male rats were given trientine in their drinking water at 1500 ppm for 18 weeks, from 6 weeks to 24 weeks of age in short-term experiment, and 1500 ppm for 27 weeks then 750 ppm for 52 weeks, from 8 to 87 weeks of age in the long-term experiment. Development of hepatitis was observed in the control LEC rats at 18 weeks of age. They had high levels of plasma transaminases (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT]), and on pathological examination, hepatocyte destruction was observed. Histological findings revealed that short-term administration of trientine inhibited the development of hepatitis remarkably. The plasma GOT and GPT levels of treated animals were only slightly higher than those of normal LEA (Long-Evans with agouti coat color) rats, a sibling line of LEC rats. Copper levels in the liver were decreased by a maximum of 50 percent. In the long-term administration of trientine, the incidence of hepatic cell carcinoma (HCC) in the treated rats was 67 percent that of the untreated LEC rats, and the number of HCCs per rat in the treated group was 0.7 +/- 0.5, being significantly lower as compared with 4.7 +/- 3.5 in the untreated rats. Additionally, the development of cholangiofibrosis in LEC rats was completely prevented by long-term administration of the agent. The copper level in the liver of treated rats was reduced by 33 percent at 87 weeks of age. Development of HCC in LEC rats might be partly, but not totally, because of copper accumulation. No effects on the levels of copper, iron, or zinc in the liver of LEA rats was detected, and no adverse effects were detected in either LEC or LEA rats after both short- and long-term administration of trientine in drinking water.
A radioimmunoassay (RIA) system for quantification of bovine beta 2-microglobulin (beta 2-M) in serum and urine was developed. The protein isolated from bovine colostrum showed a single band in SDS-PAGE, and its molecular weight was approximately 11,600. Amino acid sequences for the first 24 residues and the amino acid composition of the protein were in agreement with those in the bovine beta 2-M of previous research works. In an Ouchterlony test, a single precipitation line was formed between the protein and the antiserum made by the protein. From these results, it was confirmed that the protein isolated from the colostrum was pure bovine beta 2-M. For creation of an RIA calibration curve for urine, a urine void of beta 2-M, as much as possible (beta 2-M-free urine), and a PBS were used as diluents. Intraassay (n = 10) and interassay (n = 3) variances were 1.7-4.6% and 7.1-11.5% in the PBS dilute method, and were 1.4-5.1% and 12.3-13.5% in the beta 2-M-free urine dilute method, respectively. Mean recoveries were 160 +/- 19% (mean +/- SD) and 98.4 +/- 7.9% in PBS and beta-M-free urine, respectively. It was found that the method using the beta 2-M-free urine as a diluent was more accurate than using PBS. The beta 2-M concentrations in serum and urine of healthy Holstein cows measured by this RIA system showed a logarithmic normal distribution for urine and a normal distribution for serum. The mean beta 2-M concentrations were 0.0305(+0.04443)(-0.0210) mg/l (Geometric mean +/- S.D., n = 43) in urine and 2.87 +/- 0.45 mg/l (Arithmetic mean +/- S.D., n = 26) in sera. Further, we could not observe the particular tendency of daily variation in urinary beta 2-M concentrations of healthy cows (Holstein, n = 3 x 2 days).
To investigate the function of a basic and neutral amino acid transporter-like protein (rBAT) which is a candidate gene for cystinuria, we analysed the rBAT gene in cystinuric patients. Patient 1 is a compound heterozygote with mutations in the rBAT gene causing a glutamine-to-lysine transition at amino acid 268, and a threonine-to-alanine transition at amino acid 341, who inherited these alleles from his mother (E268K) and father (T341A), respectively. Injection of T341A and E268K mutant cRNAs into oocytes decreased transport activity to 53.9% and 62.5% of control (L-cystine transport activity in oocytes injected with wild-type rBAT cRNA), respectively. Co-injection of E268K and T341A into oocytes strongly decreased amino acid transport activity to 28% of control. On the other hand, co-injection of wild-type and mutant rBAT did not decrease transport activity. Furthermore, immunological studies have demonstrated that the reduction of amino acid transport is not due to a decrease in the amount of rBAT protein expressed in oocyte membranes. These results indicate that mutations in the rBAT gene are crucial disease-causing lesions in cystinuria. In addition, co-injection experiments suggest that rBAT may function as a transport activator or regulatory subunit by homo- or hetero-multimer complex formation.
Recent studies suggest that the jejunal/kidney-type facilitative glucose transporter (GLUT5) functions as a high-affinity D-fructose transporter. However, its precise role in the small intestine is not clear. In an attempt to identify the fructose transporter in the small intestine, we measured fructose uptake in Xenopus oocytes expressing jejunal mRNA from five species (rat, mouse, rabbit, hamster and guinea-pig). Only jejunal mRNA from the rabbit significantly increased fructose uptake. We also cloned a rabbit GLUT5 cDNA from a jejunal library The predicted amino acid sequence of the 487-residue rabbit GLUT5 showed 72.3 and 67.1% identity with human and rat GLUT5 respectively. Northern-blot analysis revealed GLUT5 transcripts in rabbit duodenum, jejunum and, to a lesser extent, kidney. After separation of rabbit jejunal mRNA on a sucrose density gradient, the fractions that conferred D-fructose transport activity in oocytes also hybridized with rabbit GLUT5 cDNA. Hybrid depletion of jejunal mRNA with a GLUT5 antisense oligonucleotide markedly inhibited the mRNA-induced fructose uptake in oocytes. Immunoblot analysis indicated that GLUT5 (49 kDa) is located in the brush-border membrane of rabbit intestinal epithelial cells. Xenopus oocytes injected with rabbit GLUT5 cRNA exhibited fructose uptake activity with a Km of 11 mM for D-fructose. D-Fructose transport by GLUT5 was significantly inhibited by D-glucose and D-galactose. D-Fructose uptake in brush-border membrane vesicles shows a Km similar to that of GLUT5, but was not inhibited by D-glucose or D-galactose. Finally, cytochalasin B photolabelled a 49 kDa protein in rabbit brush-border-membrane preparations that was immunoprecipitated by antibodies to GLUT5. Our results suggest that GLUT5 functions as a fructose transporter in rabbit small intestine. However, biochemical properties of fructose transport in Xenopus oocytes injected with GLUT5 cRNA differed from those in rabbit jejunal vesicles.
In 1991, a new psychological selection procedure was employed during the selection of Japanese Space Station astronauts. It was based on international selection criteria developed by an international psychological/psychiatric working group. A total of 372 individuals--fewer than expected--submitted applications for Space Station astronaut in Japan. Of the applicants, 233 were given several psychological written tests [Anxiety Scale, Performance Test, General Aptitude Test Battery, and Environmental Adjustment Test Battery (EATB)] in Phase I of the selection. Forty-five applicants went on to take the General Aptitude Test Battery (GATB), Human Assessment Method (a group test), a semi-structured psychological interview and an intelligence test in Phase II of the selection. All applicants were found to be highly intelligent. Interestingly, an unexpectedly large number of candidates were disqualified by the newly developed EATB. Assessment of individual functioning in a group (the Human Assessment Method) resulted in no applicant being ranked in either the "qualified with reservation" (QR) or "disqualified" (DQ) category. Much has been learned from this initial application of psychological "select-in" testing, but further efforts are needed to improve both psychological criteria and evaluation methods and to determine their reliability and validity.
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From a drug delivery system using silicone gel, the amount of Ofloxacin (OFLX) released or transferred to a wound and blood was measured over 2 weeks. From three types of silicone gel containing 2, 0.2 and 0.02% OFLX respectively, levels from that with 2% OFLX were highest, approximately two to five times higher than that with 0.02% OFLX. Statistically significant differences were found between the three types (P < 0.01, Student's t-test). When used in partial thickness skin wounds on rats, only an extremely small amount of OFLX was detected in the serum, being higher under gel containing 2% OFLX. In a clinical study, however, no drug was detected either in the blood or the wound after 1 week.
Using 60 Hirosaki hairless rats, the relationship between the time of starting topical administration of Prostaglandin E1 using silicone gel and flap survival rate is described. Compared to control groups, beginning the administration of PGE1 at 0 (P < 0.01) and 3 h (P < 0.05) after flap elevation resulted in an increased flap survival area (Student's t-test). However, in groups in which PGE1 administration was begun at 6, 9 and 12 h after flap elevation, no statistically significant differences could be detected.
A study has been undertaken to investigate Prostaglandin E1 administration procedure for improving flap survival. Whether the drug was administered continuously or transcutaneously using a silicone gel drug delivery system; or was topically injected into the critical zone of the flap; or was intraperitoneally administered intermittently over an hour after surgery a statistically significant improvement of flap survival occurred (P < 0.01, Student's t-test). However, no improvement of flap survival was seen when the drug was administered only once intraperitoneally immediately after flap elevation, although administered doses of the drug in those rats was equal to the doses in the rats which received intermittent administration of the drug intraperitoneally over an hour after surgery.
We have developed a simple and reproducible method employing chemiluminescence to measure oxygen-derived free radicals generated in oxygenated myocardium. Isolated perfused rat hearts were frozen in liquid nitrogen during the control perfusion (non-ischemia), after 30 min of global ischemia (ischemia), or after 20 min of reperfusion following 30-min global ischemia (reperfusion). The frozen hearts were ground to a fine powder and then oxygenated by mixing with phosphate-buffered saline (PBS) (pH 7.4 and PO2 183-194 mmHg) containing lucigenin. The mixed solution was injected into a chemiluminescence detection flow cell. The chemiluminescence intensity increased in relation to the lucigenin and myocardium contents of the test solution. However, it was not affected by the temperature of PBS in the range of 25 degrees C to 50 degrees C. The chemiluminescence intensity of ischemic myocardium was 2.5 times larger than that of non-ischemic or reperfused myocardium (P < 0.01). Recombinant human superoxide dismutase (r-h-SOD) reduced dose-dependently the chemiluminescence intensity induced by oxygenation of ischemic myocardium, while chemically inactivated r-h-SOD did not.
We analyzed total and ionized calcium concentrations in gallbladder bile of 34 humans in four groups: 8 patients with no gallstone, 11 gallstone patients treated with no gallstone dissolution agents, 8 gallstone patients treated with chenodeoxycholic acid (CDCA) and 7 gallstone patients treated with ursodeoxycholic acid (UDCA). We found that total calcium level ranged from 1.40 to 8.01 mmol/liter, closely related to total bile acid concentration (r = 0.759). However, ionized calcium level was maintained in a narrow range of 0.25 to 1.23 mmol/liter and had no relation to total bile acid concentration. UDCA-rich bile showed relatively high level of ionized calcium. We performed ultrafiltration of bile with cut-off molecular weight 1,000 to investigate the interaction between biliary calcium and bile acid aggregates. The proportion of ultrafiltrated bile acid level to that in original bile in the UDCA group was statistically higher than the other groups. Relatively large percentage of smaller bile acid aggregates in UDCA-rich bile may impair its calcium solubility.