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Biomedical subjects

Y Fukunaga

Publications and source records attributed to Y Fukunaga.

At least 19 recordsLinked to original sources

The changes in body temperature, oxygen consumption, CO2 production and muscle protein turnover rate by selection for body size in Japanese quail, Coturnix coturnix japonica.

1. Body temperature, oxygen consumption, CO2 production and muscle protein degradation rate were measured in the three quail lines selected for body size, a random bred line (RR) and two lines selected for large (LL) or small (SS) body size. 2. The body temperature at 15 weeks of age was highest for small body size line and lowest for large body size line. 3. The body temperature, oxygen consumption and CO2 production of females were significantly higher than that of males. 4. The fractional degradation rate of muscle protein of SS, RR and LL lines were measured as 2.4, 1.6 and 1.2% per day in male, and 2.6, 1.7 and 1.4% per day in female.

Animals

Epizootiological aspects of type 1 and type 4 equine herpesvirus infections among horse populations.

The dissemination of equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) among various horse populations in Japan was investigated through the isolation and typing of virus strains from horses with respiratory diseases. Type specific monoclonal antibody pools were used for the typing of isolates. The 42 strains of EHV-1 and 64 strains of EHV-4 were isolated from 4593 nasal swabs and/or blood plasma samples collected from 3326 horses during a period from 1979 to 1990. All the strains of EHV-1 were isolated from racehorses only and during the winter season exclusively, when the epizootic of respiratory diseases occurred among racehorse populations at two Training Centers of the Japan Racing Association. In contrast, the strains of EHV-4 were isolated from horses irrespective of the season, facility, or horse population; foals and yearlings in breeding farms and our institute, rearing horses in rearing farms, and racehorses. Especially, 4 strains of EHV-4 were isolated from plasma samples containing buffy coat cells. We believe this is the first reported case of EHV-4 cell-associated viremia in the world. All 87 strains isolated from aborted fetuses were identified as EHV-1. The results suggest that EHV-1 is responsible for epizootic respiratory diseases in racehorses in the winter and abortion among mares at the late stage of gestation, and that EHV-4 causes respiratory diseases throughout the year among all horse populations.

Abortion, Veterinary

[Clinical study on responses of the upper esophageal sphincter after subtotal esophagectomy for esophageal cancer].

Responses of the upper esophageal sphincter (UES) to distention of the esophageal wall by use of a balloon catheter were measured in 30 patients after subtotal esophagectomy for esophageal cancer and 33 volunteers with unrelated disorders (control group). Patients were divided into extended dissection group and non-extended dissection group according to the width of lymph node dissection, or palsy group and non-palsy group according to recurrent-laryngeal nerve palsy. The resting upper esophageal sphincter pressure (UESP) and the upper esophageal sphincter contraction (UESC) following UES induced by swallowing were measured after esophageal distention. Neither of UESP nor UESC without distention was significantly different among each group. But those of the extended dissection group and palsy group after esophageal distention were significantly lower values than those of control group. These findings suggest that responses of the UES to distention of esophageal wall are decreased, thus protection against aspiration is probably decreased.

Adult

Pharmacological properties of YM-21095, a potent and highly specific renin inhibitor.

A novel renin inhibitor, YM-21095 [2RS), (3S)-3-[N alpha-[1,4-dioxo-4-morpholino-2-(1-naphthylmethyl)-buthyl]-L- histidil-amino]-4-cyclohexyl-1-[(1-methyl-5-tetrazolyl)thio]-2-but anol), has been synthesized in our laboratories. The aim of this study was to evaluate the pharmacological properties of YM-21095 in in vitro and in vivo experiments. YM-21095 inhibited human renin with an IC50 value of 4.7 x 10(-10) mol/L. YM-21095 was also a potent inhibitor against squirrel monkey renin, but less effective against renins from dog, rabbit, and rat. The effect of YM-21095 is highly specific for renin, since it did not inhibit cathepsin D, pepsin, or angiotensin converting enzyme up to a concentration of 10(-4) mol/L. YM-21095 was resistant to proteolytic actions of the enzymes (pepsin, chymotrypsin, trypsin) and squirrel monkey tissue homogenates (liver, kidney, small intestine). Intravenous infusion of YM-21095 (0.1 to 100 micrograms/kg/min) decreased mean blood pressure and inhibited plasma renin activity in a dose-dependent manner with no effect on heart rate in anesthetized sodium-depleted and sodium-replete squirrel monkeys. The hypotensive effect of YM-21095 in sodium-depleted squirrel monkeys was about ten times as potent as that in sodium-replete squirrel monkeys. Oral administration of YM-21095 to conscious sodium-depleted squirrel monkeys produced dose-related decreases of systolic blood pressure. We conclude that YM-21095 is a potent and highly specific inhibitor of primate renin and produces a blood pressure lowering effect.

Administration, Oral

Sex differences in the localization and severity of ferric nitrilotriacetate-induced lipid peroxidation in the mouse kidney.

Male mice are much more susceptible than female mice to acute renal proximal tubular necrosis as well as the carcinogenic effect induced by an iron-chelate, ferric nitrilotriacetate (Fe-NTA). In the present study, iron-promoted lipid peroxidation was analyzed histochemically in frozen kidney sections using cold Schiff's reagent and biochemically by measuring thiobarbituric acid-reactive substance in the kidney. When untreated mouse frozen kidney sections were exposed to ascorbic acid-Fe-NTA (0.8 mM, 0.2 mM and 0.4 mM) in vitro for 40 min and washed, diffuse Schiff positivity was obtained along the proximal tubules, and no sex differences were evident. When non-reduced Fe-NTA (0.2 mM and 0.4 mM) was layered on untreated kidney sections from males, about half of the cortical proximal tubules showed a positive reaction with Schiff's reagent, whereas in females the proximal tubules of the outer stripe of the outer medulla were positive. In an ex vivo study, 30 to 40 min after i.p. injection of Fe-NTA (5 mg Fe/kg), Schiff-positive areas corresponded to those observed in the in vitro non-reduced Fe-NTA study in each sex. However, in males, the positive tubular cells gradually became necrotic, whereas in females the positivity disappeared with time and there was no tubular necrosis. Results of the thiobarbituric acid test were correlated with the above findings. In conclusion, the localization and severity of Fe-NTA-induced lipid peroxidation in the tubules differed between the sexes. We suspect that these results reflect functional heterogeneity in the ability of the tubules to reduce iron.

Animals

Late effects of childhood acute leukemia and its treatment.

Late effects of childhood acute leukemia and its treatment were studied in 776 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.

Adolescent

Effect of viral inoculum size on appearance of clinical signs in equine Getah virus infection.

A study was performed to examine the effect of viral inoculum size on the appearance of clinical signs in equine Getah virus (GV) infection by intramuscular inoculation with 10(1.3) to 10(6.3) TCID50 of the MI-110 strain in 6 experimental horses. When inoculated with more than 10(3.3) TCID50 of the virus, every horse developed pyrexia, edema in the hind legs, serous nasal discharge, lymphopenia and viremia in the relatively early stage of disease. On the other hand, enlargement of the submandibular lymph node was observed only in horses inoculated with 10(5.3) and 10(6.3) TCID50 of the virus, while typical eruptions were developed in every horse inoculated with 10(4.3) TCID50 or less. These results demonstrated that the appearance of clinical signs in equine GV infection was dependent on viral inoculum size. Besides, it was assumed to be rare chance that eruptions and enlargement of the submandibular lymph node were developed simultaneously in a horse.

Alphavirus

Intranasal infection of Getah virus in experimental horses.

Aerosol transmission in equine Getah virus (GV) infection was examined by intranasal inoculation with 10(3.0) to 10(7.0) TCID50 of the MI-110 strain in 7 experimental horses. The establishment of intranasal infection of GV was confirmed in all these horses by detecting serum neutralizing antibody against the MI-110 strain. Horses inoculated with more than 10(4.0) TCID50 of the virus manifested mild pyrexia, eruptions, serous nasal discharge, lymphopenia or monocytosis. Viremia ranging from 10(1.0) to 10(3.5) TCID50/0.2 ml occurred in horses inoculated with 10(5.0) TCID50, or more. Virus recovery from the nasal cavity was observed only in horses inoculated with 10(7.0) TCID50, and the viral titers recorded were 10(3.0) TICD50/ml or less. From these results, it is assumed that GV disseminated from the nasal cavity of naturally infected horses, except for intranasal infection with a lot of the virus, is probably very low in titer. So it seems to be rare that GV in natural cycles is spread from horse to horse by aerosol transmission.

Aerosols

[Usefulness of Roux-Y type bypass operation using pedicled jejunum in unresectable esophageal cancer].

Twelve patients underwent bypass operation for unresectable esophageal cancer in our department in recent 5 years were reviewed. A group of 8 patients who had Roux-Y type bypass operation using pedicled jejunum was compared with a group of 4 patients who had bypass operation using gastric roll. 1) The anastomotic leakage was found in one patients in each group of patients. 2) The operating time and amount of bleeding were significantly less in the patients being used the jejunal pedicle than in the patients being used the gastric roll. 3) No significant difference was found in the possibility of oral uptake and discharge from hospital and postoperative survival period between these two groups. The bypass operation for unresectable esophageal cancer is a riskful operation. But, we found that the Roux-Y type bypass operation using the pedicled jejumun was a safe and uninvasive procedure for a patient with high risk.

Aged

Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice.

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rats and mice. Male animals are much more susceptible than female animals to both effects. Moreover, the distribution of the susceptible proximal tubules is different between male and female animals. The present study investigated the effects of castration and sex hormones on Fe-NTA-induced renal lipid peroxidation. Male and female ddY mice were either left untreated, castrated, and/or treated with testosterone or estriol. Histochemical (reactivity to cold Schiff's reagent) and biochemical (thiobarbituric acid-reactive substance) evaluations were performed 1 h after the i.p. injection of Fe-NTA (5 mg iron/kg). Testosterone treatment and/or oophorectomy increased the Schiff positivity of the renal cortical proximal tubules and the amount of thiobarbituric acid-reactive substance (testosterone-treated female greater than intact female, P less than 0.005; castrated female greater than intact female, P less than 0.1; castrated and testosterone-treated female greater than intact female, P less than 0.005). In contrast, estriol treatment and/or orchiectomy decreased the Schiff positivity of the renal cortical proximal tubules and the amount of thiobarbituric acid-reactive substance (estriol-treated male less than intact male, P less than 0.01; castrated male less than intact male, P less than 0.01; castrated and estriol-treated male less than intact male, P less than 0.005). Estradiol treatment produced similar results to estriol treatment (estradiol-treated male less than intact male, P less than 0.005). Castration and/or administration of the opposite sex hormone reversed the sex difference in the distribution of proximal tubules susceptible to lipid peroxidation. However, the i.v. injection to male mice, 5 min prior to the Fe-NTA treatment, of conjugated estrogen that is promptly excreted via the urine produced no significant effect. Thus, altered metabolic pathways rather than the direct scavenging activity of estrogens seem to be involved in the sex hormone-dependent difference of lipid peroxidation. Genetically determined sex hormone status appears to have influenced the incidence of Fe-NTA-induced renal adenocarcinoma in intact animals.

Acetates

Induction of immune response and protection from equine viral arteritis (EVA) by formalin inactivated-virus vaccine for EVA in horses.

Thirty-nine horses included 3 pregnant mares were examined by inoculating with formalin inactivated-virus vaccine for EVA. Antibody response of horses after one dose vaccination was somewhat poor and 50% effective inoculum dose of the vaccine should be included 10(8.4) pfu of virus before inactivation. After 2 doses given at an interval of 4 weeks, the horses developed such high titer of SN antibody as up to 1:5,120. The SN titer declined rather rapidly, but supplemental administration of the vaccine at an interval of more than 2 months elicited a prompt antibody response and SN titers persisted as 1:80 to 1:320 at 6 months after the administration. Therefore, supplemental administration of the vaccine as booster every 6 months or 1 year would be capable of maintaining high titer of SN antibody. The inactivated-virus vaccine prevented horses from clinical disease of EVA and protected pregnant mares from abortion by challenge exposure with virulent virus. Fifty percent protective dose in SN titer of 1:43 was confirmed by clinical signs and viremia.

Animals

Renal tissue and urinary kallikrein activity in two-kidney, one-clip hypertensive rats.

Renal tissue and urinary kallikrein activity were studied to assess the role of the renal kallikrein-kinin system in two-kidney, one-clip hypertensive rats. Body weight, urine volume, systolic blood pressure and urinary kallikrein activity were measured in 11 hypertensive rats and 6 normotensive rats 1, 4, 8 and 12 weeks after clipping or sham operation. The hypertensive rats used in the present study had systolic blood pressures of over 180 mm Hg 12 weeks after the operation and presented polyuria with a reduction in weight gain, which placed them in the malignant hypertension category. Urinary kallikrein activity in hypertensive rats significantly decreased from 21.7 +/- 13.3 nkat/day at 1 week to 11.6 +/- 5.5 nkat/day at 12 weeks after clipping (p less than 0.05), while urinary kallikrein activity in normotensive rats significantly increased from 23.6 +/- 8.9 nkat/day at 1 week to 43.7 +/- 16.2 nkat/day at 4 weeks after the sham operation. Significant differences were observed in urinary kallikrein activity between hypertensive rats and normotensive rats 4 and 12 weeks after the operation (p less than 0.05). Renal tissue kallikrein activity from bilaterally nephrectomized kidneys was investigated 12 weeks after the operation. No significant difference in tissue kallikrein activity was found between the two kidneys of the hypertensive rats. However, tissue kallikrein activity was significantly lower in the contralateral kidney of hypertensive rats as compared to the same kidney of normotensive rats (2.13 +/- 0.73 nkat/g in hypertensive rats vs. 3.05 +/- 0.69 nkat/g in normotensive rats, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[A study of granular lymphocytes (GL) in children and young adults].

In this study, we investigate the percentage and absolute number of granular lymphocytes (GL) in venous blood smears and the percentage of CD16+ and CD57+ lymphocytes in the peripheral venous blood of 91 healthy controls (1 to 29 years old) and 168 patients with various diseases (1 month to 36 years old). GL were morphologically classified into four subsets: large-sized lymphocytes with large granules (LL-LG), large-sized lymphocytes with small granules (LL-SG), medium-sized lymphocytes with large granules (ML-LG) and medium-sized lymphocytes with small granules (ML-SG). The results were as follows: 1) In the controls, the percentage of GL in total lymphocytes was 10.0 +/- 6.2% (mean +/- 1SD). Therefore its normal value was below 22.4% (mean +/- 2SD). The absolute count of GL was 320.7 +/- 221.0/mm3. The percentages of LL-LG, LL-SG, ML-LG and ML-SG in total lymphocytes were 1.7 +/- 2.2%, 2.3 +/- 2.8%, 2.6 +/- 2.3% and 3.4 +/- 2.7%, respectively. 2) In flow cytometric studies, the percentage of CD16+ in the controls was 10.2 +/- 6.7%; CD57+, 8.2 +/- 5.1%; CD57+ CD16+, 4.2 +/- 3.3%; CD57+ CD16-, 4.0 +/- 2.8%; CD57- CD16+, 6.4 +/- 4.8%. The distribution patterns of lymphocytes by two-color analysis with FITC-labelled anti-CD16 and PE-labelled anti-CD57 monoclonal antibodies in the controls were classified into four groups. 3) Only seven of the 168 patients exhibited significantly high percentage of GL in total lymphocytes. They consisted of 4 splenectomized patients and 3 patients with pancytopenia, two of whom had pancytopenia complicated by immunoglobulin deficiency. Five of the 7 patients also had markedly high percentage of CD16+ and/or CD57+ lymphocytes. In these 5 patients, the ratios of four subsets of GL and the distribution patterns of lymphocytes with CD16 and CD57 surface antigens were different from the patient to patient and those for controls.

Adolescent

Clinical courses and treatment of splenic artery aneurysms--report of 3 cases and review of literatures in Japan.

We have treated three cases of splenic artery aneurysms recently, so we reported them with a review of 181 cases in Japan. All three cases are women and have characteristic clinical courses and pathogenesis in each to which we performed a reasonable operation so that they could be saved. First one is a ruptured case. So we performed ligation of the splenic artery from inside the aneurysm under 9 min.'s clamp of the aorta. Second one was pointed out the splenic artery aneurysm during admission for cholecystectomy, so we performed splenectomy and aneurysmectomy, and after that we reconstructed the splenic artery with end-to-end anastomosis. Third one suffered from splenomegaly and portal hypertension. We performed splenectomy with the aneurysm. From the clinical and pathological findings, we concluded that an aneurysm in our first case was associated with arterial dysplasia, second with hemodynamic changes in parous women, and third with portal hypertension. Aneurysms of the splenic artery have been rarely reported until recently, when developments in diagnostic procedures made their discovery easier. We have diagnosed splenic artery aneurysm in three patients preoperatively. The clinical symptoms and operative procedure was different in each case, and are reported here. We demonstrated the summary of our three cases of that at Table 1.

Aneurysm

[Electrocardiogram in pulmonary heart disease--clinical evaluation of right chest leads].

A clinical study was made to evaluate the usefulness of electrocardiograms in right precordial leads (V3r or V4R) for the diagnosis of cardiac complications among patients with chronic pulmonary disease. Walsh and colleagues reported that the change of direction in the terminal vector of QRS loop in the vector cardiogram is useful for the evaluation of chronic pulmonary heart disease. They showed that the terminal vectors of QRS loops tend to deviate to the right and/or posterior direction in the early stage of chronic pulmonary heart disease. We utilized the electrocardiograms in the right precordial leads to detect the second R waves, which are thought to reflect the terminal vectors of QRS loops in the vectorcardiograms. When the electrocardiograms in the right precordial leads were compared, the second R waves in leads V3R or V4R were more frequently observed among patients with chronic pulmonary heart disease than those without. However, in the same two groups, the frequency of second R waves in leads V5R or V6R didn't differ. We conclude that the second R waves in leads V3R or V4R in a patient with chronic lung disease suggest the presence of chronic pulmonary heart disease as a complication.

Adult

Increased density of ecto 5' nucleotidase antigen on leukemic T cells from patients with cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.

Malignant CD4+ T cells in adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphoma (CTCL) express a number of cell surface molecules that are upregulated on normal T cells activated by foreign antigen. In this report we describe an interesting exception to the parallel phenotypic features of activated T cells and malignant CD4+ T cells. A monoclonal antibody (MoAb; termed 27.2) that was raised to HTLV-1+, CD4+25+ leukemic T cells stained weakly 25% of peripheral T cells, including approximately 50% of CD8+ T cells and 20% of CD4+ T cells. Flow cytometry analysis indicated that the surface density of the 27.2 antigen was unchanged or diminished when normal T cells were activated by antigen. However, 3/4 Sezary cases and 4/8 cases of ATL had relatively high densities of the 27.2 antigen. Immunoprecipitation and sodium dodecylsulfate polyacrylamide gel electrophoresis of the NP-40-solubilized membranes of surface-iodinated ATL cells indicated that MoAb 27.2 reacted with a 75 Kd molecule. The size and distribution of the 27.2 antigen on T cell subsets suggested that it might be the enzyme ecto-5' nucleotidase (NT), a phosphatidylinositol-linked enzyme that catalyzes dephosphorylation of monophosphate nucleotides to their respective nucleosides. This was confirmed by demonstrating that lymphocyte ecto-5'NT activity was blocked partially and inhibited completely by preincubating cells with MoAb 27.2 for 1 hour at 4 degrees C and 24 hours at 37 degrees C, respectively. When used with a second MoAb (27.1) to a novel T cell activation antigen found on all CTCL and ATL leukemias examined, 27.2 was found to discriminate between normal and leukemic T cells in two patients with ATL. These studies suggest that ecto-5'NT has diagnostic value in T cell malignancies and may be aberrantly expressed in some cases of ATL and CTCL.

5'-Nucleotidase