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T Harada

Publications and source records attributed to T Harada.

At least 451 records · Page 25Linked to original sources

Changes in circulating immune complex and charge distribution with upper respiratory tract inflammation in IgA nephropathy.

The circulating IgA class immune complex (IgA-IC) and its charge distribution, at the appearance of macroscopic hematuria and after tonsillectomy in patients with IgA nephropathy, were investigated in the present study. 3.5% polyethylene glycol precipitate (3.5% PEG-IgA) was used for IgA-IC detection and isoelectric focusing for its charge distribution. The level of IgA in 3.5% PEG-IgA, principally IgA1, and the proportion of anionic 3.5% PEG-IgA (isoelectric point, pl, 4.8-5.6) were significantly elevated in episodes of macroscopic hematuria with upper respiratory tract inflammation and with the appearance of macroscopic hematuria 1 day after tonsillectomy. Therefore, an increase in anionic IgA-IC (pl 4.8-5.6), principally IgA1, and the tonsils were considered to be concerned with the mechanism involved in the appearance of macroscopic hematuria.

Adult↗

The time course of myosin light-chain phosphorylation in blood-induced vasospasm.

The phosphorylation of an M(r) 20,000 myosin light chain (MLC20) promotes the generation of contractile force through actin-myosin adenosine triphosphatase in most agonist-mediated vascular smooth muscle cell contraction. However, the role of calcium-mediated contractile processes in sustained arterial narrowing after subarachnoid hemorrhage remains unknown. In a femoral artery model of vasospasm, whole blood was applied to arteries in 54 rats for periods of 2 to 10 days; the contralateral artery treated with platelet-rich plasma served as matched control. During the early stage of vasospasm (Days 2-5), in the media of arteries exposed to blood, MLC20 phosphorylation (including diphosphorylated forms) increased significantly (30-38%; P < 0.05); total medial MLC20 during this interval was comparable to that in controls. After 5 days, however, total MLC20 decreased markedly (> 90%; P < 0.01) compared with controls; phosphorylated MLC20 was undetectable during this interval. MLC20-mediated contractile processes may be prominent in the early stages of arterial narrowing after subarachnoid hemorrhage; later stages are associated with the loss of MLC20 and the possible persistence of arterial narrowing by other mechanisms.

Animals↗

Antioxidant and iron-chelating agents in cerebral vasospasm.

Prior work in our laboratory showed that the perivascular application of deferoxamine (an antioxidant and iron-chelating agent) inhibited delayed arterial narrowing after chronic blood exposure in a rat femoral artery model of vasospasm. To determine which of these mechanisms was operant in vasospasm, we compared deferoxamine with two agents (ascorbic acid and U74389F) that have antioxidant but not iron-chelating capacity. For the systemic application of drugs in 23 rats, whole blood encased in a silastic cuff was applied to the right femoral artery of each rat; whole-blood serum (lacking erythrocytes) was similarly applied to the left femoral artery. Deferoxamine (30 mg/kg/d), ascorbic acid (1000 mg/kg/d), U74389F (30 mg/kg/d), or pH-matched control vehicle was administered three times daily by intraperitoneal injection for 7 days. After exposure to whole blood, arteries treated with intraperitoneal vehicle showed an 85% reduction in the lumen, compared with vessels exposed to erythrocyte-free serum (P < 0.001). Intraperitoneal ascorbic acid and U74389F produced moderate amelioration in arterial narrowing (53 and 61% decrease, respectively, in the lumen versus controls; P < 0.05 versus vehicle); deferoxamine had no significant effect when administered intraperitoneally. To test the efficacy of these agents by the perivascular application of drugs, whole blood was applied to both femoral arteries in each of 25 rats. Solutions of deferoxamine (10 mg/ml), ascorbic acid (50 or 100 mg/ml), or U74389F (15 or 30 mg/ml) were directly applied to the perivascular thrombus surrounding the femoral arteries, compared with vehicle applied to contralateral vessels. The perivascular application of 50 mg of ascorbic acid (36% reduction, P < 0.05), 100 mg of ascorbic acid (31% reduction, P < 0.01), or 10 mg of deferoxamine (41% reduction, P < 0.05) significantly inhibited arterial narrowing, compared with vehicle. The application of U74389F at a dose of 15 or 30 mg directly into the perivascular thrombus produced nonsignificant reduction in arterial narrowing. These data suggest that mechanisms other than direct iron toxicity, such as generation of cytotoxic free radicals, may play an important role in cerebral vasospasm. In addition, the route of administration and concentration of drugs in the perivascular region adjacent to the thrombus may be critical to their efficacy.

Animals↗

[The effects of long-term intake of restricted calcium, vitamin D, and vitamin E and cadmium-added diets on various organs and bones of mice: a histological and the roentgenological study].

The toxic effects of long-term administration of cadmium (Cd) on the kidneys, liver, and hind leg bones were studied histologically and roentgenologically in 29-day-old female ICR-strain mice separated into groups variously fed 1) a commercial (calcium [1.17%], vitamin D [220IU/100g], vitamin E [10mg/100g]) diet, 2) a low Ca (0.18% diet, 3) a low Ca and low D (50IU/100g) diet, and 4) a low Ca, low D and low E (5mg/100g) diet. Though the levels of vitamin D and vitamin E were designed to be low in each diet, their amounts fulfilled the nutritional requirements. Three subgroups in each category were fed Cd at dietary concentrations of 0, 20 or 40 ppm. After 12, 18 or 24 months on these diets the mice were sacrificed. 1) In the groups fed the commercial diet containing Cd, prominent swelling of the glomerulus and thickening of the basement membrane of glomerulus were observed. This did not occur in the groups fed the commercial diet without Cd. 2) In the groups fed the Cd-added low-Ca diet the following findings were more prominent compared with the low-Ca diet group. In the kidneys, swelling of the glomerulus, hyaline casts in tubular lumina and cellular infiltration of the interstitial tissue were present. In the liver, cellular infiltration on the interstitial tissue were present. In the liver, cellular infiltration of the interstitial tissue occurred. In the hind leg bones, thinning of trabeculae and ossification of the Achilles's tendon were seen. 3) In the Cd-added low-Ca, D diet groups, there was atrophy of glomerulus, thickening of basement membrane of glomerulus, and atrophy of tubular epithelial cells in the kidneys, while in the liver, binuclate cells, anisonucleosis and enlargement of Kupffer cells were seen. In the hind leg bones, thinning of the cortex and trabeculae were present. All of these findings were more prominent in this group than in the low-Ca, group. 4) In the Cd-added low-Ca, D, E, diet groups subjects the following findings were more prominent than in the low-Ca, D, E, diet group. In the kidneys, there was swelling of glomerulus and in the liver, there were binuclate cells, anisonucleosis, and cellular infiltration into interstitial tissue. In the hind leg bones, thinning of the cortex and trabeculae, a decrease of cartilage cells and a decrease of osteocytes were seen. These histological and roentgenological changes were seen to increase in a dose-dependent manner with the amount of dietary Cd.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[The effects of long-term intake of restricted calcium, vitamin D, vitamin E and cadmium-added diets on the skeletal muscles of mice: an enzyme histochemical study].

To clarify the effect of chronic cadmium exposure on muscles, 29-day-old female ICR strain mice were separated into 7 groups and various diets were given to each group. Group I a commercial diet (Intact), Group II a diet low in calcium and low in vitamin D, Group III a diet low in Ca, low in D and low in vitamin E, Group IV a low in Ca, low in D and 20ppm cadmium-added diet, Group V a low in Ca, low in D and 40ppm Cd diet, Group VI a low in Ca, low in D, low in E and 20ppm Cd diet and Group VII a low in Ca, low in D, low in E and 40ppm Cd diet. The levels of vitamin D and vitamin E were designed to be low in each diet but their amounts fulfilled the minimum nutritional requirements. The experimental period was long, ranging from 29 days to 24 months. Using a microscope, two skeletal muscles, the soleus (red muscle) and the gastrocnemius (white muscle) of mice with chronic Cd effects were observed after staining with H. E. and analyzed after enzyme histochemical reaction to ATPase. Using ATPase stain, type I muscle fibers were distinguished from type II muscle fibers. The long-term effects of cadmium. 1) Comparisons among groups II, IV and V. After 18 months it was found in group IV that myopathic muscle damage (increased random variation of fiber size [Size] and widening of interstitial tissue [Widening]) were more prominent that in group II. In group V myopathic muscle damage (Size and Widening) and type II atrophy were more prominent that in group IV. At 24 months it was found in group IV that myopathic muscle damage (Size, internal nuclei [IN] and Widening) and type I and type II atrophy were more prominent than in group II. In group V myopathic muscle damage (Size, IN and Widening) and type I and type II atrophy were more prominent than in group IV. 2) Comparisons among group III, VI and VII.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

jun-B gene expression in rat retinal cells following focal retinal injury.

We examined jun-B gene expression in the rat retina after a focal retinal injury by in situ hybridization. 30 min after producing a penetrating retinal wound, the retina showed the expression of jun-B mRNA intensively in the inner nuclear layer (INL) and relatively sparsely in the ganglion cell layer. The double-labeled retina by immunocytochemistry and in situ hybridization demonstrated that jun-B mRNA within the INL surrounded S-100 protein immunoreactive cytoplasm in the middle sublayer of the INL. These results suggest that the jun-B expression is induced mainly in Müller cells following retinal damage.

Animals↗

Proteolytic activity of NS3 serine proteinase of hepatitis C virus efficiently expressed in Escherichia coli.

The serine proteinase of hepatitis C virus (HCV) non-structural protein NS3 was efficiently expressed in an active form as a fused protein with oligohistidine in Escherichia coli. The recombinant fusion protein was purified to near homogeneity by affinity chromatography on a metal chelation column. Trans-cleavage activity of this protein was investigated by using the substrate NS5 protein expressed in insect cells. The purified serine proteinase trans-cleaved the partially purified NS5 protein. In contrast, the NS3 proteins with mutations at the proposed catalytic site, Ser1165 or His1083, lost the trans-cleavage activity. Analysis of the authentic enzyme and variants with site-directed mutations provides a useful tool for understanding the structure-function relationship of the NS3 serine proteinase. We then developed an in vivo trans-cleavage assay system by coexpression of the NS3 proteinase and the NS5 substrate in E coli, and examined the effect of known inhibitors of serine proteinase. Inhibition of its proteolytic activity by N-p-tosyl-L-lysine chloromethyl ketone (TLCK) was observed, but only at high concentrations. The in vitro and in vivo trans-cleavage assays for NS3 serine proteinase will facilitate efficient testing for inhibitors of the replication of HCV and specific treatment for hepatitis C.

Baculoviridae↗

[Detection and localization of enlarged parathyroid glands in patients with hyperparathyroidism using 99mTc-methoxyisobutylisonitrile (MIBI): a study of subtraction scintigraphy with 99mTc-pertechnetate].

In this study we investigated the detectability of abnormal parathyroid gland(s) by 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy in patients with hyperparathyroidism. The subjects were 6 patients with primary hyperparathyroidism (PHP) with a single adenoma and 13 patients with renal hyperparathyroidism (RHP) on chronic maintenance hemodialysis. The imaging data of 99mTc-pertechnetate were subtracted from those of 99mTc-MIBI (MIBI-Tc), and number and location of the positive images on scintigrams were compared with those obtained by conventional scintigraphy using 201Tl-Cl and 99mTc-pertechnetate (Tl-Tc). All of the patients underwent surgery, and the number and location of the abnormal parathyroid glands were confirmed. The number of resected parathyroid glands were 6 in PHP and 52 in RHP. The detectability of MIBI-Tc was 83.3% in PHP and 51.9% in RHP, while that of Tl-Tc was 100% and 44.2%, respectively. Although no statistically significant difference in the detectability was found between MIBI-Tc and Tl-Tc, the number of false positives with MIBI-Tc was less than that with Tl-Tc. The detectability of MIBI-Tc depended on the size of the parathyroid gland. The maximal diameter and weight of the smallest parathyroid gland detected were 15 mm and 290 mg in PHP, and 9 mm and 50 mg in RHP. The existence of the thyroid gland did not reduce the detectability of MIBI-Tc. In conclusion, MIBI-Tc was clinically very useful for the detection of abnormal parathyroid glands in patients with hyperparathyroidism.

Adult↗

Congenital hypothyroidism: assessment with ultrasound.

PURPOSE: To determine the clinical utility of cervical ultrasound in patients suspected of having congenital hypothyroidism. METHODS: Thirty-seven patients with suspected congenital hypothyroidism underwent ultrasound and scintigraphic evaluation of the thyroid anatomy, morphology, and function. The ultrasound findings and laboratory data were compared with the standard-of-reference scintigraphic findings and laboratory data for diagnosing specific causes in those patients, and prognosis was correlated with the ultrasound findings. RESULTS: Ultrasound was not reliable for detecting ectopia (n = 8) or differentiating ectopia from aplasia (n = 1). Ultrasound showed ectopia in six (four in the mouth floor and two in the tongue base) of eight cases (75% sensitivity). Ultrasound did not show one ectopia in the floor of mouth because its echogenicity was similar to that of surrounding tissues. A second ectopia, in the hypopharynx, was missed because of hindrance of the laryngeal air. Radioactive iodine uptake and scintigraphy was required for the patients with enlarged glands in the normal place to differentiate dyshormonogenesis from other categories. Specific causes were diagnosed correctly with ultrasound findings and laboratory data alone in all of the 20 patients who had hemiaplasia or small or normal-size glands in the normal location. Incidences of heterogeneity and hypoechogenicity of the thyroid gland in patients with prolonged clinical course (whose replacement therapy or follow-up extended for more than 1 year) were significantly higher than those in patients with short clinical course. CONCLUSION: Ultra-sound can obviate the need for scintigraphy in more than half (54%) of patients with possible congenital hypothyroidism. Ultrasound has a potential to predict prognosis of these patients.

Congenital Hypothyroidism↗

A case of nephrotic syndrome associated with ischemic colitis exhibiting thickening of the colon wall.

The patient was a 54-year-old male with proteinuria, which was first noted in 1984. Recently, the patient experienced aggravation of the proteinuria, which resulted in nephrotic syndrome. Renal biopsy revealed findings compatible with membranous nephropathy. While being treated with prednisolone (30 mg/day), the patient experienced intense abdominal pain of sudden onset, diarrhea, and melena. A tumor was demonstrated by abdominal ultrasonography and CT scan. A diagnosis of ischemic colitis was made by colonoscopy. FDP and fibrinogen levels were elevated, and abnormalities of the coagulation and fibrinolytic factors were found at the onset of the symptoms.

Colitis, Ischemic↗

A case of acute renal failure due to ethylene glycol intoxication.

We describe an 18-year-old man with acute renal failure due to inadvertent ingestion of antifreeze that contained ethylene glycol (EG). A relatively small amount of EG was ingested, but nausea and vomiting were observed soon after ingestion. During admission to a local hospital, consciousness became impaired and generalized convulsion was noted. He was transferred to our hospital because of rapid deterioration of renal function. Emergency hemodialysis was begun. The patient underwent one treatment session of hemodialysis each day, for a total of 8 hemodialytic sessions before his renal function recovered. Examination of the renal biopsy specimen revealed degeneration of the renal tubular epithelium and presence of intratubular calcium oxalate crystals. The clinical features of the patient were mild except for acute renal failure. These findings suggest that even a small amount of EG will have toxic effects on the kidney.

Acute Kidney Injury↗

[Relationship between impaired blood pressure control and multiple system involvement in chronic alcoholics].

Chronic ethyl alcohol (ethanol) abuse is associated with different types of neurological involvement. Impaired blood pressure control such as in hypertension and/or orthostatic hypotension is a known autonomic dysfunction in chronic alcoholics. Although abstinence appears to improve blood pressure, the precise mechanisms underlying the effects of alcohol remain unknown. We suspected that abnormal blood pressure might influence the outcome of alcohol-related neurological symptoms. We therefore reviewed the alcohol history of 28 male patients admitted to our hospital with multiple system involvement. No family history of spinocerebellar degeneration was found. All of the patients had a history of chronic alcohol abuse. The duration of alcohol abuse in 28 patients was 28.8 + 11.2 yrs. Daily ethanol consumption was less than 83 ml in 6 patients between 83 ml and 138 ml in 11 and more than 138 ml in 11. We assessed the relationship between impaired blood pressure control, clinical characteristics, and outcome after abstinence for a period ranging from 30 days to 6 years in 22 chronic alcoholics who had drunk more than 83 ml/day. All of the patients had various types of autonomic dysfunction, and a high incidence of impaired blood pressure control and decreased CVR-R were noted. The symptoms improved or even completely resolved after cessation of alcohol consumption, however, 8 of the 22 patients in our study reached a plateau and have permanent symptoms. Patients with no improvement as a result of abstinence had a long history of excessive drinking. Brain CT/MRI, SPECT and P300 studies were conducted. SPECT and P300 were performed in both the supine and standing position in 5 and 7 patients, respectively. Five patients who had severe orthostatic hypotension with syncope were found to have cerebrovascular lesions on MRI. Changes in P300 amplitude and/or distribution and latency were noted after a fall in blood pressure. Although the etiology of impaired blood pressure control in alcoholics remains unknown, we believe that abnormal blood pressure affects the outcome of alcohol-related neurological symptoms.

Adult↗

C-fos gene expression in rat retinal cells after focal retinal injury.

PURPOSE: To examine the expression of c-fos proto-oncogene in the rat retina after focal retinal injury. METHODS: A penetrating wound was made by pushing a 22-gauge hypodermic needle through the retina into the vitreous. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using anti-S100 protein antibody. RESULTS: Thirty minutes after the penetrating wound, c-fos mRNA was expressed in the inner nuclear layer (INL) and the ganglion cell layer (GCL) of the retina. Immunocytochemistry before in situ hybridization demonstrated c-fos mRNA surrounding the S-100 protein immunoreactive cytoplasm in the middle layer of the INL. CONCLUSIONS: Focal retinal injury of the rat retina induced the expression of c-fos mRNA in retinal cells. In the INL, it is suggested that the major cells that express c-fos mRNA after focal retinal injury were the Müller cells. These results suggest that c-fos may be involved in the transcription in the Müller cells after injury to the retina.

Animals↗