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Biomedical subjects

T Harada

Publications and source records attributed to T Harada.

At least 397 records · Page 22Linked to original sources

Enhanced CD34 expression of sinusoid-like vascular endothelial cells in hepatocellular carcinoma.

The immunohistochemical expression of CD34 (human hematopoietic stem cell and endothelial cell marker) and laminin were studied in chronic liver diseases and hepatocellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous sinusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and laminin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and perinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothelial cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.

Antigens, CD34↗

Myelofibrosis secondary to renal osteodystrophy.

A hemodialyzed women with secondary hyperparathyroidism who recovered well from myelofibrosis after a total parathyroidectomy with autotransplantation of parathyroid tissue to the forearm (PTx) is described. Before the operation, she had received regular transfusions to maintain an adequate hematocrit even under recombinant human erythropoietin (rhEpo) therapy. She showed splenomegaly and leukoerythroblastosis was present in her peripheral blood. A bone marrow biopsy and bone marrow scintigraphy confirmed the diagnosis of myelofibrosis. After PTx, her hematocrit gradually increased without any transfusion. It has been maintained around 35% now 16 months since the operation. Her spleen has also gradually decreased in size. In addition, no leukoerythroblastosis has been found in the peripheral blood. Serial follow-up scintigraphy of bone marrow revealed a decline in extramedullary hematopoiesis. These findings indicated that her myelofibrosis was the result of secondary hyperparathyroidism, and that this complication is potentially reversible if accurate treatment is given. Physicians dealing with the end-stage renal disease should be aware of this complication to avoid additional transfusions.

Alkaline Phosphatase↗

Subfoveal choroidal neovascularization in uveitis.

Only rarely can the development of subretinal foveal or parafoveal neovascularization be observed in patients with chronic uveitis. We report herein the clinical characteristics pertaining to neovascular membranes and the treatment thereof in 3 patients afflicted with either sarcoidosis (2 patients) or Behçet syndrome (1 patient). Peroral steroids contributed to a reduction of neovascular membranes in 1 patient with sarcoidosis. The management of uveitis is mandatory for the prevention of subretinal foveal neovascular membranes.

Anti-Inflammatory Agents↗

Laparoscopic microwave thermotherapy on small renal tumors: experimental studies using implanted VX-2 tumors in rabbits.

OBJECTIVE: To investigate the effectiveness of microwave thermotherapy on implanted renal VX-2 tumors. METHODS: Fifteen rabbits with implanted renal VX-2 tumors were divided into three groups according to the type of therapy: nephrectomy, laparoscopic microwave thermotherapy, and no treatment. Both the anticancer effect and safety were compared among these groups. RESULTS: The survival rate in the laparoscopic microwave thermotherapy group was significantly higher than that in the no-treatment group, and was the same as that in the nephrectomy group. The serum creatinine level did not increase after microwave therapy. CONCLUSION: Laparoscopic microwave thermotherapy may be useful for a nephron-salvaging treatment in small implanted renal VX-2 tumors in rabbits.

Animals↗

Lens luxation in a CD-1 mouse.

Lens luxation was found in a male CD-1 (ICR) mouse. Ophthalmologic examinations revealed conical cornea anterior synechia and corneal neovascularization in the right eye. The lens was dislocated heterocentrically within the posterior chamber. Histologically, anterior lens luxation and adhesion between the iris and cornea were observed.

Animals↗

Plasma enzymic changes in insulin-induced hypoglycemia in experimental rabbits.

In order to elucidate the effects of hypoglycemia on cardiac and skeletal muscle, plasma activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were assessed in rabbits with hypoglycemia induced by i.v. injection of insulin. After hypoglycemia lasting for more than 30 min, the plasma levels of ALT, AST and LDH rose significantly in 4 out of 5 rabbits reaching a peak at 24 hr. The plasma activity of CK rose remarkably and reached a peak at 6 hr after insulin injection in all rabbits. These results suggest prolonged hypoglycemia may cause myocardial and/or skeletal muscle damage, which can be ascertained by measuring plasma activities of the related enzymes.

Alanine Transaminase↗

Intraglomerular C3 synthesis in human kidney detected by in situ hybridization.

Complements 3 and 4 are known to be synthesized in diseased renal tissue and the mRNA of these complements has been demonstrated, using polymerase chain reaction, in renal biopsies from nephritic patients. However, the types of cells producing the complements in intact renal tissue have not been defined. To identify the renal cellular components involved in complement synthesis, we analyzed the expression of C3 mRNA in renal tissues from patients with immune-complex glomerulonephritis by a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide. Renal tissues from 15 patients with immunoglobulin (Ig) A nephropathy (IgAN), five with lupus nephritis (LN), and five with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidney with tumors served as normal controls. C3 mRNA was detected in mesangial cells, glomerular epithelial cells, and Bowman's capsule in IgAN and LN. In the interstitium, some tubules and some infiltrating mononuclear cells were positively stained for C3 mRNA. C3 mRNA was not detected in MCNS and control tissues. Our results confirm that the glomerular resident cells can synthesize C3 in immune-mediated glomerulonephritis and suggest that locally synthesized complement may be involved in tissue injury in glomerulonephritis.

Biopsy↗

Pancreaticopleural fistula visualized by computed tomographic scan combined with endoscopic retrograde pancreatography.

We report a case with left pleural effusion caused by a pancreaticopleural fistula, which was formed between a small pseudocyst in the pancreatic body and the posterior mediastinal side of left costophrenic recess. The patient, a 66-year-old male with an alcohol drinking habit, had cough and chest pain but no symptoms or signs suggestive of abdominal pathology. In this case, computed tomographic scan performed immediately after endoscopic retrograde pancreatography was very useful not only in demonstrating the presence of the pancreatic internal fistula but in clarifying its anatomical relation to the surrounding organs.

Aged↗

Patterns of hearing recovery in idiopathic sudden sensorineural hearing loss.

Patterns of hearing recovery in idiopathic sudden sensorineural hearing loss (ISSNHL) during the initial stage of treatment were examined in 51 patients who showed significant recovery. By plotting average hearing threshold level or degree of average hearing improvement against number of days after the first examination, a pattern of recovery was seen for each patient, and the superimposed patterns of hearing recovery were examined as a whole and in groups. The results indicated that most patients showed either initial rapid recovery reaching a plateau or a very gradual and slow recovery. In a small number of patients, the pattern of rapid recovery appeared somewhat delayed. Further analysis by grouping the patients revealed that initial rapid recovery was frequently observed in the groups which showed smaller degree of hearing loss at the first examination, greater degree of hearing improvement overall, and smaller degree of hearing loss once stable. The results of this study appear to indicate that patterns of recovery at the initial stage of ISSNHL reflect the prognosis to a certain degree.

Adolescent↗

Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma.

The authors investigated the role of somatic mutations of the neurofibromatosis type 2 (NF2) gene in sporadic meningioma. Neurofibromatosis 2 is a dominantly inherited familial tumor syndrome predisposing affected patients to a variety of central nervous system tumors including vestibular schwannoma and meningioma. Neurofibromatosis type 2 is caused by germline mutations in the NF2 tumor suppressor gene. In addition, the authors and others have reported that somatic NF2 gene mutations occur frequently in nonfamilial vestibular schwannoma. In this study, molecular genetic analysis was performed on 23 nonfamilial meningiomas. Paired DNA samples extracted from the blood and tumors of the patients were analyzed for loss of heterozygosity (LOH) in the region of the NF2 gene on chromosome 22 using closely linked DNA markers. The NF2 gene mutations were sought by single-stranded conformation polymorphism analysis and DNA sequencing. Fourteen (61%) of 23 meningiomas showed LOH in the region of the NF2 gene on chromosome 22. Somatic NF2 gene mutations were detected in eight meningiomas (35%) after screening all 17 exons. All tumors with NF2 gene mutations showed simultaneous chromosome 22 LOH. Review of the histopathological findings of the cases studied did not demonstrate any predominance of genetic abnormalities in a particular histological type of meningioma. These results are compatible with the hypothesis that the NF2 gene acts as a tumor suppressor and that its inactivation is important in the pathogenesis of sporadic meningioma.

Chromosomes, Human, Pair 22↗

[Hearing acuity in the elderly in Japan].

In Japan, the elderly population has progressively increased. It is therefore expected that various social services for the elderly will be demanded. As most of the elderly have hearing impairment due to presbycusis, it is difficult to communicate smoothly with them. To provide the various social services, it is necessary to investigate hearing acuity in the elderly. Accordingly, the Hearing Research Group, which belongs to the Research Project on Aging and Health in the Ministry of Health and Welfare of Japan, investigated the hearing acuity of people 65 years old, or more. One thousand one hundred ninety two subjects were divided into five groups, Group A consisted of 170 males and 216 females between 65 and 69 years old, Group B, 186 males and 158 females between 70 and 74; Group C, 147 males and 140 females between 75 and 79; Group D, 63 males and 61 females between 80 and 84; and Group E, 29 males and 22 females 85 years old or more. We examined the 175 subjects 80 years old or more. Therefore, it is considered that this study could indicate the present condition of hearing acuity of the elderly of Japan. The average hearing levels measured at seven frequencies (125, 250 and 500Hz, and 1, 2, 4, and 8KHz) were 35.0dB in group A, 42.1 in group B, 46.1 in group C, 52.1 in group D, and 55.6 in group E. There were no differences in the average hearing level between males and females in any group. The audiogram pattern indicated a gradually descending curve in most subjects in all groups. The average speech discrimination rate was 75.4% in group A, 70% in group B, 63.8% in group C, 59.7% in group D, and 52.1% in group E. The percentage of subjects showing a short increment sensitivity index of more than 70% was 45.2% in group A, 49.3% in group B, 47.9% in group C, 51.6% in group D, and 59.7% in group D. In conclusion, hearing loss due to aging tended to be more progressive at higher frequencies while hearing acuity of frequencies covering normal speech was preserved. However, the speech discrimination rate decreased relative to changes in the pure tone hearing level. It was considered that the pathology of hearing loss due to aging begins with retrocochlear changes and cochlear factors are added to retrocochlear changes with aging.

Aged↗

Differential distribution of CaM kinases and induction of c-fos expression by flashing and sustained light in rat retinal cells.

PURPOSE: To examine the expression of c-fos proto-oncogene and phosphorylation of cAMP responsive element binding (CREB) protein in the rat retina after changes in the light-dark condition. METHODS: Rats were exposed to both steady light and flashing light and were killed at the end of light exposure. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using phosphoSer-133 specific CREB antiserum, anti-calcium calmodulin dependent protein (CaM) kinase II, and anti-CaM kinase IV. RESULTS: c-fos mRNA was expressed in the outer half of the inner nuclear layer (INL) and in the ganglion cell layer (GCL) after 30 minutes of sustained light. After 30 minutes of flashing light, c-fos expression also was detected in the inner border of the INL. Phosphorylated CREB immunoreactive nuclei had similar distribution after steady and flashing light. Both CaM kinase II and CaM kinase IV, which phosphorylate CREB at Ser 133 in vitro, were expressed in the GCL and in the INL. CaM kinase II, however, was localized in the inner border of the INL, whereas CaM kinase IV was distributed in the outer half of the INL. CONCLUSIONS: These results suggest that the differential expression of c-fos mRNA induced by flashing and sustained light may reflect the CREB phosphorylation by CaM kinases in a different subpopulation of retinal cells.

Animals↗

Detection of cytokine mRNA-expressing cells in peripheral blood of patients with IgA nephropathy using non-radioactive in situ hybridization.

IgA nephropathy (IgA-N) is considered to be an immune-mediated disorder and several immunological abnormalities have been observed. In the present study, we optimized non-radioactive in situ hybridization and applied this technique to evaluate the degree of expression of various cytokine mRNAs in peripheral blood mononuclear cells (PBMC) taken from patients with IgA-N on cytospin preparation. Using this method, together with image analysis, we examined the expression of mRNA in cells which secrete cytokines, such as IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-6. The expression of these mRNAs was clearly observed in monocytes and lymphocytes at a single-cell level. Compared with healthy adults, the expression of IL-4 mRNA, IL-5 mRNA and IL-6 mRNA, but not IL-2 mRNA or IFN-gamma mRNA, was significantly enhanced. Our results indicate that non-radioactive in situ hybridization method is a powerful technique for analysis of cytokine mRNAs in PBMC at a cellular level. Our results also suggest that mRNA expression of IL-4, IL-5 and IL-6, produced by Th2 cells, is increased in patients with IgA-N. The abnormal regulatory process involved in cytokine expression may play an important immunopathologic role in IgA-N.

Adult↗

Cone-associated c-fos gene expression in the light-damaged rat retina.

PURPOSE: To examine whether light-controlled c-fos gene expression is mediated by a cone specific pathway in the rat retina. METHODS: To produce a cone-rich retina, rats were placed under continuous lighting for 21 days. The illuminance in the cages ranged from 1200 to 2000 lux. The presence of cones was determined by peanut agglutinin and rods by the monoclonal antibody 1-E7. The presence of c-fos transcripts in the retinas was analyzed by in situ hybridization using single-stranded RNA probes. RESULTS: After long-term exposure to continuous light, the 1-E7 immunoreactivity was not detected in the outer nuclear layer. The cone photoreceptors and cells in the ganglion cell (GCL) and inner nuclear layers (INL) survived. In normal retinas, there was strong hybridization for c-fos expression in the GCL and the INL 30 minutes after the onset of the light cycle. Light-damaged retinas also showed hybridization in the GCL but not in the INL under the same light regime. CONCLUSIONS: These results suggest that c-fos gene expression can be controlled through a cone specific pathway in the retina.

Animals↗

[Prolonged QTc intervals in Parkinson's disease--relation to sudden death and autonomic dysfunction].

Sudden death has been reported in Parkinson's disease (PD), but the cause of death has not been fully clarified. A prolonged QT interval on the electrocardiogram (ECG) of patients without cardiac dysfunction is an independent risk factor for sudden death regardless of etiology. QT prolongation is believed to be related to cardiac autonomic dysfunction. We suspected that QTc intervals, as well as QT intervals, might be related to the clinical characteristics of PD and to the function of the autonomic nervous system in PD and also postulated a relationship between QTc prolongation and sudden death in PD. We investigated the QTc intervals on the ECGs of 48 PD patients (20 males 28 females) aged 64.5 +/- 9.4 years and 44 controls aged 60.0 +/- 8.2 years, and excluded patients with heart disease. QTc intervals were determined by using ECG-8210, ECAPS12 (Nihon-Kohden). The autonomic nervous system was evaluated by measuring CVR-R and performing orthostatic tests. Since the autonomic nervous system is considered to play an important role in the mechanism of diurnal blood pressure variation (DBPV), we assessed DBPV in 19 PD patients by determining blood pressure automatically every 30 minutes for 24 hours with an ambulatory blood pressure monitor (90202, Space Lab). QTc intervals were significantly longer in the PD patients (412 +/- 26 msec) than in the controls (401 +/- 14 msec) (p < 0.02, t-test). QTc prolongation was significantly correlated with severity according to Hoehn and Yahr stage (r = 0.509, p < 0.001), orthostatic hypotension, and decreased CVR-R ratio but not with duration of PD or treatment. The incidence of QTc prolongation was higher in the PD patients with non-dipper type DBPV than in those with the dipper type. Two of the PD patients died suddenly. Their QTc intervals a year before their death were 451 msec and 470 msec, respectively, suggesting that cardiac dysautonomia may have been involved in the cause of their death. These findings suggest that cardiac autonomic dysfunction is related to the severity of PD, and that it may predispose such patients to cardiac disorders including sudden cardiac death.

Adult↗