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Biomedical subjects

T Okuno

Publications and source records attributed to T Okuno.

At least 199 records · Page 11Linked to original sources

Clip electrode method for recording eye movements in experimental animals.

Both the guinea pig and squirrel monkey were used in this study. An animal model for inner ear disease was established, and each animal was subjected to vestibular function tests consisting of spontaneous nystagmus recording, positional testing, caloric testing, and optokinetic stimulation testing. Recordings of nystagmus in the guinea pig and squirrel monkey were successfully obtained by using newly devised clip electrodes. A variety of nystagmic patterns in animal models following experimentally created perilymphatic fistula and labyrinthectomy are presented in this study.

Animals↗

Immunosuppressive dose of azathioprine inhibits replication of human cytomegalovirus in vitro.

Azathioprine (Aza) was found to have anti-human cytomegalovirus (HCMV) activity in vitro at concentrations used for immunosuppression therapy. The dose of Aza for 50% plaque reduction was 0.592 micrograms ml for HCMV in human embryonic lung (HEL) cells, but those of Aza for 50% plaque reduction for herpes simplex virus (HSV) and varicella-zoster virus were more than 20 micrograms/ml. The dose of Aza for 50% reduction of the HCMV yield in infected cells was 0.25 micrograms/ml, while that for 50% reduction of the HSV yield in infected cells was more than 50 micrograms/ml. The dose of Aza for 50% growth inhibition of HEL cells was 30 micrograms/ml, and 50.7 and 120 times greater than the doses for 50% reduction of the plaque formation and the yield of HCMV, respectively. Thus Aza was found to have a strong anti-HCMV activity at concentrations used for immunosuppression. When HCMV infected cells were treated with cyclosporine (CsA: 0.2 microgram/ml) and prednisolone (Pred: 0.3 microgram/ml) simultaneously with Aza, the doses of Aza for 50% reduction of plaque formation and the yield of HCMV were 0.73 and 0.32 micrograms/ml, respectively. Thus an inhibitory effect of Aza was also observed in HCMV-infected cells treated with CsA and Pred at their concentrations used for immunosuppression. Maintenance of an anti-HCMV dose of Aza in combination with CsA and Pred might establish not only satisfactory immunosuppression but also suppression of HCMV infection in transplant recipients.

Antiviral Agents↗

2',5' Oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during interferon treatment of chronic non-A, non-B hepatitis.

The 2'-5' oligoadenylate synthetase (2-5 AS) activity of peripheral blood mononuclear cells and serum was measured in 23 patients with chronic non-A, non-B hepatitis during interferon therapy, 16 of whom were found to have antibody to hepatitis C virus (anti-HCV). Patients received a daily dose of either 1 million, 3 million or 6 million units of human interferon-alpha or -beta for 4 to 6 weeks. Before treatment, the 2-5 AS activity was not significantly different from that in normal control subjects or patients with chronic hepatitis B. However, during treatment the 2-5 AS activity increased 2- to 41-fold from the initial level. Alanine aminotransferase (ALT) levels normalized promptly after the start of treatment in 15 (65.2%) of the 23 patients, but remained elevated in the remaining 8 (34.8%). Six (40%) of the 15 patients showed consistently normal ALT levels for 6 to 30 months after the end of treatment. There was no significant difference between the responders and non-responders in the pattern of change of 2-5 AS activity, but pretreatment activity levels in peripheral blood mononuclear cells were significantly higher (P less than 0.001) in the patients whose ALT levels did not normalize during treatment. The frequency of patients with a positive anti-HCV was significantly higher (P less than 0.05) in the group in which ALT levels normalized. Therefore, these findings suggest that the pretreatment 2-5 AS activity and the detection of anti-HCV may be useful parameters for predicting the response to interferon therapy.

2',5'-Oligoadenylate Synthetase↗

Detection of 2',5' oligoadenylate synthetase activity in acute viral hepatitis with special reference to histologic features in the acute stage.

We measured the sequential changes in 2',5' oligoadenylate synthetase activity in 21 patients with acute viral hepatitis (5 with type A, 6 with type B, and 10 with type non-A, non-B hepatitis) by radioimmunoassay. Liver biopsies were performed during the acute phase in all patients. Among patients with acute hepatitis A and B, the 2',5' oligoadenylate synthetase levels were transiently elevated at the time of the peak alanine aminotransferase level in the patients in whom a liver biopsy showed acute hepatitis or non-specific reactive hepatitis. Of 10 patients with acute non-A, non-B hepatitis, 4 showed a similar 2',5' oligoadenylate synthetase activity pattern and liver histology to those observed in acute hepatitis A and B. In the remaining 6, the 2',5' oligoadenylate synthetase levels remained elevated for 3.5 to 6 months while the alanine aminotransferase was elevated. Liver biopsy in these patients showed chronic hepatitis. Persistent detection of raised 2',5' oligoadenylate synthetase activity levels during the acute stage of non-A, non-B hepatitis may thus be an indicator of progression of the disease.

2',5'-Oligoadenylate Synthetase↗

MELAS of infantile onset: mitochondrial angiopathy or cytopathy?

An 83-day-old male infant had convulsions, hypertrophic cardiomyopathy, and lactic acidosis. Cranial computed tomography revealed low-density areas in both parieto-occipital lobes and in the left temporal lobe. Muscle biopsy did not reveal ragged-red fibers, but abnormal mitochondria were found in the capillary endothelial cells as well as in the muscle fibers. At 5 months of age, the patient developed purpura on the soles and palms. Skin biopsy showed degeneration of the endothelial cells with abnormal mitochondria in the arterioles and capillaries. Myelinated nerves in the skin had vacuolated axons with swollen mitochondria, and their myelin sheaths showed vacuolation. At 9 months of age, he died of heart failure, and autopsy revealed abnormal mitochondria in the myocardium but not in the coronary vessels. Our findings indicate that the symptoms of the mitochondrial encephalopathy, myopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome cannot be fully explained by the mitochondrial angiopathy alone.

Acidosis, Lactic↗

Congenital myotonic dystrophy with progressive edema and hypoproteinemia.

We report a patient with congenital myotonic dystrophy who had progressive edema and hypoproteinemia. An atrioseptal defect and patent ductus arteriosus were noted and were considered to be the cause of the right heart failure and edema. Although urinary protein levels were minimal, infusion of albumin did not improve the hypoproteinemia. Administration of dexamethasone increased the serum protein level, but the edema was not ameliorated. Autopsy revealed a slight lymphatic dilation in the small intestine, suggesting protein-losing enteropathy.

Autopsy↗

GABAergic innervation in cerebral blood vessels: an immunohistochemical demonstration of L-glutamic acid decarboxylase and GABA transaminase.

The presence of GABAergic innervation in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). Both GAD and GABA-T immunoreactivities were found to be associated with large bundles and single fibers in the adventitial layer of arteries examined. The density and distribution pattern of both GAD- and GABA-T-immunoreactive fibers were found to be comparable at most regions examined. Both fibers were found to be most dense in the anterior cerebral artery and its adjacent part of the circle of Willis. Several peripheral arteries were found to receive very sparse or no GAD- and GABA-T-immunoreactive fibers. Superior cervical ganglionectomy did not appreciably affect the distribution of both fibers. Cold-storage denervation, however, resulted in a drastic decrease in both fibers. At ultrastructural levels, both GAD- and GABA-T-immunoreactive nerve profiles were found to be very close to the smooth muscle cells. These results demonstrate the presence of a potentially functional GABAergic innervation in cerebral circulation. On few occasions, GAD immunoreactivities were also found in some endothelial cells, suggesting that a nonneuronal GABA system may also be present in cerebral arteries.

4-Aminobutyrate Transaminase↗

Thermal effect of infra-red radiation on the eye: a study based on a model.

Cataracts occur frequently among workers who deal with hot material such as molten glass or steel, as a result of exposure to intense infra-red radiation (i.r.) emitted from it. To investigate this hazard, a theoretical model of the human eye being exposed to i.r. was developed, and the temperature distributions within it were calculated. It is suggested that i.r. cataracts in the workplace result from the generation of heat by absorption of i.r. in the cornea and heat conduction to the lens. The threshold i.r. irradiances for cataract formation were determined from the relationship between the incident irradiance and the lens temperature, and were in the range 163-178 mW cm-2 for long-term exposures (greater than about 5 min) under normal conditions. However, these values may be reduced by 50% for workers who perform heavy work at a high ambient temperature. It may be possible to set i.r. exposure limits in the workplace based on these threshold data.

Cataract↗

Physicochemical characterization of human herpesvirus 6 infectivity.

Infectivity of human herpesvirus 6 (HHV-6) was physicochemically characterized. Virus particles were excreted from infected cord blood mononuclear cells into the culture supernatant at a concentration of 10(8) to 10(9) virus particles/ml. The virus particle/infectivity ratio of HHV-6 in the culture supernatant was approximately 10(3):1 and that in the sonicated infected cells was 10(4):1. Infectivity was stable below 37 degrees C and at neutral pH (7.0 to 8.5). These fundamental data may be useful for serological and biological research on HHV-6.

Cells, Cultured↗

Infectivity of plasmids containing brome mosaic virus cDNA linked to the cauliflower mosaic virus 35S RNA promoter.

Full-length biologically active cDNAs of brome mosaic virus genomic RNAs 1, 2 and 3 were constructed by joining cDNA fragments. The cDNAs were constructed so that, at the 5' ends, unique SnaBI sites were present at the site of initiation of transcription. The cDNAs were inserted between a modified cauliflower mosaic virus (CaMV) 35S RNA promoter and terminator regions derived from CaMV DNA, and cloned into pUC18. When a mixture of the plasmid DNAs was inoculated onto Chenopodium hybridum leaves, local lesions appeared 5 to 6 days later. However, no symptoms appeared in similarly inoculated barley plants. Plasmid cDNAs with extra sequences at the 5' end were infectious but RNAs transcribed from cDNAs with similar sequences were not.

Base Sequence↗

Latent human herpesvirus 6 infection of human monocytes/macrophages.

Human herpesvirus 6 (HHV-6) DNA was detected in peripheral blood from exanthem subitum patients during the acute and convalescent phases of infection using the polymerase chain reaction. Although DNA could be detected in non-adherent and adherent mononuclear cells during the acute phase, it was detected predominantly in adherent cells during the convalescent phase; furthermore, viral DNA was found in adherent cells of healthy adults. When adherent mononuclear cells were cultured in vitro, virus was found to replicate well in differentiated cells cultured for 7 days in vitro before infection. When cells were cultured for more than 1 month, no detectable antigen and no evidence of virus growth was observed, but viral DNA could be detected. These apparently latently infected monocytes were treated with phorbol ester, after which virus could be recovered from the cultures. Therefore, we have developed an in vitro latency system for HHV-6; our results suggest that HHV-6 may latently infect monocytes in vivo and in vitro and that it may be reactivated in cells by some factors.

Adult↗

Water and electrolyte balance in the vascular space during graded exercise in humans.

We analyzed the changes in water content and electrolyte concentrations in the vascular space during graded exercise of short duration. Six male volunteers exercised on a cycle ergometer at 20 degrees C (relative humidity = 30%) as exercise intensity was increased stepwise until voluntary exhaustion. Blood samples were collected at exercise intensities of 29, 56, 70, and 95% of maximum aerobic power (VO2max). A curvilinear relationship between exercise intensity and Na+ concentration in plasma ([Na+]p) was observed. [Na+]p significantly increased at 70% VO2max and at 95% VO2max was approximately 8 meq/kgH2O higher than control. The change in lactate concentration in plasma ([Lac-]p) was closely correlated with the change in [Na+]p (delta[Na+]p = 0.687 delta[Lac-]p + 1.79, r = 0.99). The change in [Lac-]p was also inversely correlated with the change in HCO3- concentration in plasma (delta[HCO3-]p = -0.761 delta[Lac-]p + 0.22, r = -1.00). At an exercise intensity of 95% VO2max, 60% of the increase in plasma osmolality (Posmol) was accounted for by an increase in [Na+]p. These results suggest that lactic acid released into the vascular space from active skeletal muscles reacts with [HCO3-]p to produce CO2 gas and Lac-. The data raise the intriguing notion that increase in [Na+]p during exercise may be caused by elevated Lac-.

Adult↗

Intercostal-to-pulmonary arterial anastomosis, complicated by high-output heart failure: case report.

A patient who had high-output heart failure resulting from anastomosis of the intercostal and bronchial arteries to the right pulmonary artery is reported. The patient was a fifty-one year-old man who was admitted to our hospital with left heart failure. A radionuclide angiocardiogram revealed blood flow from the aorta to the right pulmonary artery. A descending aortogram revealed abnormally dilated right intercostal and bronchial arteries, which formed the anastomosis. The right pulmonary artery was visualized via that anastomosis. Tuberculous pleurisy in the patient's history was considered to be the cause of the anastomosis. The therapeutic procedure used was embolization via a catheter for the anastomosis, but most anastomoses could not be embolized. The present report is considered the first on anastomosis of the intercostal artery to the pulmonary artery to the extent that high-output heart failure occurs.

Arteries↗

Non-Menkes-type copper deficiency with regression, lactic acidosis, and granulocytopenia.

A 2-year-old girl with granulocytopenia developed fever followed by truncal ataxia and progressive neurologic regression. CT demonstrated symmetric low-density areas in the cerebral white matter. Sural nerve biopsy revealed axonal degeneration. Blood lactate levels were high, and serum levels of copper and ceruloplasmin and urinary excretion of copper were low. Cultured skin fibroblasts showed normal copper uptake. Treatment with oral copper administration normalized serum copper and ceruloplasmin levels, blood lactate levels, and granulocyte count. However, copper levels in the CSF were still low, and the patient showed no clinical improvement. We speculated that copper transport across the intestinal wall and across the blood-brain barrier was impaired.

Acidosis, Lactic↗

[Exposure of workers to electric and magnetic fields from radiofrequency dielectric heaters to process polyvinyl chloride material].

Exposure of workers to electric and magnetic fields from radiofrequency dielectric heaters (RF heaters) to process polyvinyl chloride material was surveyed. Measurements of electric and magnetic field strengths were made in 10 workers operating 7 RF heaters at 3 plants in Japan. Six of the RF heaters are of the sewing machine type and the other is of the shuttle tray type. In all the RF heaters surveyed the nominal frequency of the radiofrequency generator was 40 MHz, and therefore electric and magnetic field from these are assumed to oscillate at the same frequency. The power output ranged from 0.83 W to 1.8 W for the sewing machine type and was 2.4 W for this shuttle tray type. Measurements were made at about 5 cm from the surface of the hand, eye, chest, waist, knee and foot of each worker. The meter readings were converted to equivalent plane wave power density and corrected for duty cycle (0.073 to 0.27). It was found that all the workers surveyed were exposed to electric and magnetic field strengths greater than the TLV recommended by ACGIH (1 mW/cm2). For the hand, eye, chest, waist, knee and foot of the worker, 95%, 63%, 32%, 47% and 36% and 27% of the measured field strengths exceeded the TLV, respectively. Especially for the sewing machine type RF heaters, electric fields at the hand and eye were extremely strong. Thus, for the hand, 100%, 75% and 38% of the measured electric field strengths exceeded the TLV, ten times the TLV, and one hundred times the TLV, respectively, and for the eye, 88% and 25% exceeded the TLV and ten times the TLV, respectively. No correlation was observed between power output of the RF heaters and measured electric and magnetic field strengths at any anatomical site of the worker.

Chemical Industry↗

Complete sacral agenesis--a case report.

We report a case of a girl with complete sacral agenesis associated with arthrogrypotic-like deformity. This case demonstrates that a posterior knee release and braces following operation are effective treatment for knee-flexion contractures. Accordingly it is suggested that a supracondylar osteotomy is not required for mild or moderate recurrence of knee-flexion contractures.

Contracture↗