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Biomedical subjects

K Yamaji

Publications and source records attributed to K Yamaji.

At least 19 recordsLinked to original sources

Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.

Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

Animals

Antibody to annexin V has anti-phospholipid and lupus anticoagulant properties.

Anti-annexin V (anti-ANXV) IgG and lupus anticoagulant (LAC) were both shown to be capable of inducing apoptosis in umbilical vein endothelial cells [Nakamura et al.: Biochem Biophys Res Commun 205:1488-1493, 1994]. In the present study, we have demonstrated that anti-ANXV IgG prolongs the activated partial thromboplastin time and has an affinity for phospholipids in enzyme-linked immunosorbent assay. This indicates overlapping of anti-ANXV and LAC activities, suggesting that ANXV may be involved in the autoimmune mechanism for LAC production.

Animals

Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus.

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-alpha. The sIL-2R levels of 40 asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20 with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.

Carcinoma, Hepatocellular

Relationship of genotype to level of hepatitis C viraemia determined by competitive polymerase chain reaction.

To compare the levels of hepatitis C virus (HCV) viraemia in carriers of the same genotype in various stages of chronic HCV infection, we quantified the amount of HCV RNA by competitive polymerase chain reaction and determined HCV genotype using type-specific primers. The study population included 255 patients with chronic HCV infection (asymptomatic 33, chronic hepatitis 141, liver cirrhosis 50, hepatocellular carcinoma 31). Of these 255, the prevalence of HCV RNA genotype II was 67.8%, genotype III, 17.3% and genotype IV, 14.9%; no genotype I was found. The level of HCV RNA (logarithmic transformed copy numbers per 50 microliters of serum) was significantly higher in subjects of genotype II than in those of genotypes III or IV (mean titre 5.8 +/- 1.0 vs. 5.1 +/- 1.2 and 4.8 +/- 1.1, P < 0.05, respectively). There was no significant difference in the level of HCV RNA between genotypes III and IV. Of 173 patients of genotype II, there were no significant differences between the level of HCV RNA and the stage of liver disease or in the level of HCV RNA by age. Of the 129 with genotype II with a history of blood transfusion, there was no significant difference between the level of HCV RNA of patients with and without a history of transfusion or between that of patients with a history of blood transfusion and the time elapsed since blood transfusion. The level of HCV viraemia depended on the genotype of HCV RNA and did not correlate to age or to the stage of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[An autopsy of an HIV infected patient with dilated cardiomyopathy (DCM)].

A case of a HIV infected 61-year-old bisexual male with dilated cardiomyopathy (DCM) is reported. The death was originally recorded as from undetermined causes, but on autopsy, his heart showed left ventricular dilatation macroscopically, variety in size and vacuolation of cardiomyocyte, partial deciduation of cardiac muscle and diffuse perivascular fibrosis microscopically. These findings were compatible with DCM which was compounded by excessive weight loss. The further data indicated that the etiology of DCM in this case was directly related to the HIV infection.

Cardiomyopathy, Dilated

[Evaluation of immunochromatography assay technique for detection of antibody to hepatitis B surface antigen (HBsAg)].

A new immunochromatography assay (Dainascreen Ausab Dainabot) has been recently introduced for the detection of the presence of antibody to HBsAg. To evaluate the feasibility of using the Dainascreen Ausab, we carried out comparison tests with this method and PHA. In the test of 439 sera from HB vaccinees, inhabitants in Iki Island, Nagasaki Pref., patients with autoimmune diseases and with acute hepatitis B, 154 (31.2%) were positive by Dainascreen Ausab, 145 (29.4%) were positive by PHA and 145 (29.4%) were positive by both Dainascreen Ausab and PHA. Nine (1.8%) were positive by only Dainascreen and there were none positive by only PHA. A good correlation was observed between the titer of the antibody by this method and IMx. The anti-HBs assay by this method was able to be completed within 15 minutes and the procedure was very simple. The results indicate that the sensitivity of Dainascreen is superior to PHA and that it is easy to use.

Chromatography, Thin Layer

Transmission of hepatitis C virus by health care workers in a rural area of Japan.

OBJECTIVE: The prevailing route of hepatitis C virus (HCV) transmission in Japan is unclear, so we expected that a survey of routes of HCV infection in an endemic area might clarify the mode of transmission. METHODS: We screened 2049 inhabitants in an isolated rural village of Fukuoka, Japan using HCV markers. All serum samples were assayed for antibody to HCV (anti-HCV) (ELISA), and anti-HCV-positive samples were assayed for HCV RNA and genotype (polymerase chain reaction). RESULTS: The prevalence of anti-HCV was 19.7% and increased with advancing age, from zero in the under 19 yr of age group to 30.7% in the 60-69 yr of age group. HCV RNA was detected in 82.9% of the anti-HCV-positive inhabitants, and 88.3% of them had genotype II. Anti-HCV was detected in 17.8% of the children of HCV-carrier mothers, similar to the rate (15.4%) for all inhabitants in the 40-49 yr of age group, the same age group for the mean age of the anti-HCV-positive children. Anti-HCV was detected in 34.8% of husbands of female HCV carriers and in 22.2% of wives of male HCV carriers, similar to the rates (36.2% in males and 26.6% in females) for all inhabitants in 60-69 yr of age group, the same age group for the mean ages of carriers' spouses. The prevalence of anti-HCV was the highest in inhabitants of one of three distinct areas of this village where patients had often been injected with insufficiently sterilized syringes and needles for treatment in the same clinic. CONCLUSION: These observations suggest that medical intervention probably played a more important role in the spread of the HCV infection in the village studied than did familial transmission.

Adult

Lupus anticoagulant autoantibody induces apoptosis in umbilical vein endothelial cells: involvement of annexin V.

The effects of lupus anticoagulant (LAC) on cultured human umbilical vein endothelial cells were studied. All five monoclonal antibodies from a patient with systemic lupus erythematosus (SLE), as well as plasma samples with LAC activity from six SLE patients, induced apoptosis. Anti-annexin V IgG also induced apoptosis. Since monoclonal antibodies and plasma from SLE patients had an affinity for annexin V, an endothelial apoptosis pathway mediated by annexin V was suggested as the molecular pathogenesis of the hemostatic derangement associated with LAC.

Animals

Large scale production and characterization of lyophilized pyridoxalated hemoglobin-polyoxyethylene (PHP).

Lyophilized PHP as an oxygen carrier is prepared from outdated red cell and dicarboxymethylated polyoxyethylene. In order to apply PHP for a clinical use, a large scale production of high quality PHP has been studied. We have set up a 20 L scale production flow of PHP88. The product was tested to confirm the quality and lot-to-lot consistency. The blood group specific materials were weakly positive in stroma-free hemoglobin (SFH), however, were found negative in the PHP of this scale. The amount of phosphatidylethanolamine (PE) in purified SFH and PHP88 reconstituted solution was 0.19 +/- 0.04 and 0.03 +/- 0.01 ppm, respectively. Contamination of viruses such as HBV and Non A non B hepatitis virus could not be observed in the final product. Elimination and inactivation of HIV was validated through a spike test. The characterizations of the final products in 20 L scale were done through MW, P50, Hill coefficient, viscosity, and molecular weight distribution by SDS-PAGE and batch to batch consistency was also confirmed. The results show that production process is appropriate to eliminate the blood group materials, PE and virus, and produce PHP of high quality. Lyophilized PHP88 can be produced by addition of maltose and can be stored over 1 year.

Biotechnology

A comparison of the perceived and the ECG measured heart rate during cycle ergometer, treadmill and stairmill exercise before and after perceived heart rate training.

The ability to perceive exercise heart rate before and after training was tested in six young male university students, perceptions of heart rate being compared with ECG monitored heart rates during cycle ergometry, treadmill running and stairmill climbing. Between initial and final tests, subjects undertook 13 weeks of running training (2 h/day, 3-4 days/week), and during this period they compared their perceptions of heart rate with values observed on watch-type wrist-mounted pulse monitors. Individual initial perceptions showed only a moderate correlation with ECG values. This correspondence was improved as perceptions were compared with measured heart rates over the course of training, significantly so for the mode of exercise most similar to that adopted in the training sessions (treadmill running at a heart rate of 140 beats/min). The final accuracy of perceptions at a heart rate of 140 beats/min (error 8-9 beats/min during treadmill running) compared favourably with the accuracy of either pulse counting or the traditional rating of perceived exertion as commonly observed in the exercising public. This suggests that there may be an application for perceived heart rates in regulating the intensity of prescribed exercise.

Adult

Large bullous eruption in patients with ulcerative colitis.

Oligocentric large bullous eruptions in two patients with ulcerative colitis were reported. Such bullae were similar to those seen in drug-induced coma, and those described as drug eruption due to high dose frusemide. However, neither narcotic drugs nor frusemide had been given in either case. The bullae were cured after the administration of corticosteroid and/or salazosulfapyridine with a course paralleling that of the ulcerative colitis. Thus the bullae seem to be a cutaneous manifestation of ulcerative colitis.

Adult

Increase in the concentration of immunoreactive endothelin in human pregnancy.

Maternal plasma concentrations of immunoreactive endothelin (ir-ET) during pregnancy, labour and after birth were measured by radioimmunoassay. Concentrations of ir-ET in the umbilical artery, umbilical vein, amniotic fluid and neonatal urine were also examined. The mean (+/- S.E.M.) plasma ir-ET concentration in early pregnancy (4-7 weeks) was 13.7 +/- 0.5 pmol/l, which was significantly higher than that in non-pregnant women (5.9 +/- 0.3 pmol/l). During pregnancy, plasma ir-ET concentrations gradually decreased to a minimum of 11.5 +/- 0.4 pmol/l in weeks 20-23, and then increased again towards term (12.5 +/- 0.4 pmol/l after 36 weeks of pregnancy). In women undergoing vaginal delivery, the mean plasma ir-ET concentration (17.1 +/- 0.7 pmol/l) increased significantly, compared with that in late pregnancy. After delivery, the plasma ir-ET concentration decreased abruptly to 4.0 +/- 0.2 pmol/l on the first day. Plasma ir-ET concentrations in umbilical vessels were significantly higher than those in maternal plasma. In addition, concentrations in the umbilical artery were significantly higher than those in the umbilical vein in cases of vaginal delivery. Concentrations of ir-ET in amniotic fluid were much higher than those in maternal or fetal plasma. ir-ET concentrations in neonatal urine on day 1 after birth were below the detection limit (less than 0.1 pmol/l) by radioimmunoassay in 70% of the cases examined but on day 5 after birth ir-ET was present at measurable concentrations in all cases. It is suggested that endothelin may act as a circulating hormone during pregnancy and labour in both maternal and fetal circulations.

Amniotic Fluid

Giant solitary sebaceous gland hyperplasia on the frontal region.

A case of a 39-year-old Japanese woman with a dome-shaped elevated nodule on the frontal region of the scalp is reported. Our case is very similar both clinically and histologically to that of 'giant solitary sebaceous gland hyperplasia' described by Kudoh et al. in 1988.

Adult

Oxygen uptake and heart rate responses to treadmill and water running.

The relationship between heart rate (HR) and oxygen uptake (VO2) was assessed during treadmill running and during running-like motions in water without ground support. Athletes self-selected easy, moderate and hard efforts during water running. While there was a linear relationship between HR and VO2 in both exercise conditions, there was considerable between-subject variability of the slope and intercept of the linear regressions. These data are taken to indicate that HR for a given VO2 during water compared to land running is influenced in large part by the skill of the athlete in the water running activity.

Adult

The effect of citrate loading on exercise performance, acid-base balance and metabolism.

Nine subjects (VO2max 65 +/- 2 ml.kg-1.min-1, mean +/- SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g.kg-1 body mass) or a sodium chloride placebo (P, 0.045 g.kg-1 body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% VO2max, followed by exercise to exhaustion at 95% VO2max. Pre-exercise arterialized-venous [H+] was lower in C (36.2 +/- 0.5 nmol.l-1; pH 7.44) than P (39.4 +/- 0.4 nmol.l-1; pH 7.40); the plasma [H+] remained lower and [HCO3-] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% VO2max was similar in C (310 +/- 69 s) and P (313 +/- 74 s). Cardiorespiratory variables (ventilation, VO2, VCO2, heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195 +/- 19 mumol.l-1; P, 81 +/- 7 mumol.l-1) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% VO2max. Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.

Acid-Base Equilibrium

Establishment of a human dermatofibrosarcoma protuberans cell line: cytological characteristics.

We established a dermatofibrosarcoma protuberans (DFSP) cell line derived from a DFSP tumor from a 69-year-old female. The population doubling time of the cells was about 45 hours. The cells were mostly round, although a few triangular or spindle-shaped cells were also found. They could not be transplanted into nude mice. These cells had some histiocyte characteristics which are not observed in fibroblasts: 1) Electron microscopically, there were more lysosomes and phagolysosomes than in fibroblasts. Dense bodies and myelin figures derived from lysosomes were also observed. 2) Staining with acid phosphatase (ACPase), esterase, and alpha-1-antitrypsin was positive. 3) The cells had C3 receptors but no Fc receptors. However, there were two differences between DFSP cells in the established line and those in the early stages: in the former, the capacity for immunophagocytosis (Fc receptors and phagocytosis of Candida albicans) and collagen synthesis were almost entirely absent.

Aged

A new resuscitation fluid "stabilized hemoglobin" preparation and characteristics.

A new oxygen carrier for use as a blood substitute was prepared and characterized in vitro. Pyridoxylated hemoglobin, which was obtained by the reaction of human hemoglobin with pyridoxal-5-phosphate, was modified by alpha-carboxymethyl, omega-carboxymethoxyl polyoxyethylene (POE) of the molecular weight 3600 daltons. In order to eliminate viruses and nucleic acids possibly contaminated, the hemoglobin solution was purified by ultrafiltration with a membrane of the nominal molecular weight limit 300 Kdaltons. Furthermore POE conjugated pyridoxylated hemoglobin was treated with 20% ethanol to inactivate viruses. A concentration of hemoglobin, which is incorporated in the conjugate, of the final product was fixed at 6% to make normovolemic exchange transfusion possible. In consideration of the stability during transporting and storage, lyophilized product was selected as a final form ("Stabilized Hemoglobin"). "Stabilized hemoglobin" could be stored in a refrigerator over one year within the acceptable methemoglobin increase. (15%) Viscosity of Stabilized Hemoglobin solution was determined at 2.4 centipoise and is almost half of whole blood and therefore this will be useful not only in resuscitation but also in improvement of microcirculation.

Blood Substitutes