Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 433 records · Page 24Linked to original sources

PubMed1996

Characterization of yeast sar1 temperature-sensitive mutants, which are defective in protein transport from the endoplasmic reticulum.

SAR1 encodes a low molecular weight GTPase that is essential in the early process of vesicular transport in the secretory pathway. By random and site-directed mutagenesis of the SAR1 gene, we have obtained three temperature-sensitive mutants, N132I, E112K, and D32G. They all show a defect in transport from the endoplasmic reticulum to the Golgi apparatus, and accumulate endoplasmic reticulum membranes at the restrictive temperature. This is consistent with our previous observations in vivo on a galactose-shutoff mutant as well as the in vitro results, and provides powerful tools for further genetic analyses.

Alleles↗

PubMed1996

137Cs concentration in soil samples from an early survey of Hiroshima atomic bomb and cumulative dose estimation from the fallout.

Low background gamma-ray measurement has been performed to determine the 137Cs content in soil samples collected in a very early survey of the Hiroshima atomic bomb. These soil samples were collected just 3 d after the explosion within 5 km from the hypocenter and were not exposed to the global fallout from nuclear weapon tests. Out of 22 samples, 137Cs was detected for 11 samples, and their radioactivities ranged from 0.16-10.6 mBq g-1 at the time of the measurement. A comparison of the 137Cs deposition with the rainfall area within Hiroshima city indicates that the rainfall area was wider than the previously proposed one. Cumulative exposure by the fallout has been estimated to be 0.31 mC kg-1 (0.12 R) in Hiroshima city except for the heavy fallout area and at most 1.0 mC kg-1 (4 R) in the heavy fallout area.

Cesium Radioisotopes↗

PubMed1996

Hodgkin disease occurring in a patient with extremely high serum antibody titers to Epstein-Barr virus--associated antigens without chronic illness.

PURPOSE: We described for the first time a patient with long-lasting, extremely high serum antibody titer against Epstein-Barr virus (EBV) viral capsid antigen and early antigen without clinical symptoms suggestive of active EBV infection; the patient finally developed Hodgkin disease (HD) after 7 years of follow-up. PATIENT AND METHODS: High serum EBV antibody titers were noted at 2 years of age. Immunological evaluation was performed at the age of 7 years. EBV-specific cytotoxic T-lymphocyte activity was normal. None of the other results showed any significant abnormalities except for the abnormal antibody titers against EBV-associated antigens. RESULTS: The patient developed HD at the age of 9 years. In addition, EBV genomes were found in the nuclei of Hodgkin and Reed-Sternberg cells in the lymph node. CONCLUSIONS: This case suggests that (a) a patient with extremely high serum antibody titers against EBV-associated antigens may develop HD after a prolonged period, even though no clinical symptom suggestive of active EBV infection is observed; (b) EBV may play an important role in the occurrence of HD.

Antigens, Viral↗

PubMed1996

Metastatic potential of lymphoma/leukemia cell lines in SCID mice is closely related to expression of CD44.

To investigate whether the lymphocyte homing receptors, adhesion molecules regulating normal lymphocyte traffic, influence the dissemination of lymphoma cells, 24 lymphoma/leukemia cell lines were inoculated into SCID mice subcutaneously, and the correlation between the expression of the adhesion molecules and the metastatic potential of the cell lines was examined. Among the six adhesion molecules examined (LFA-1, ICAM-1, CLA, VLA-4, L-selectin and CD44), L-selectin increased the incidence of lymph node metastasis, and CD44 expression was related to both lymph node and organ (hematogenous) metastasis. A monoclonal antibody to the standard form of CD44 (CD44s), Hermes-3, inhibited the local growth and remote metastasis of CD44+ cell lines. Thus, it is concluded that at least CD44s expression is important in both lymphatic and hematogenous metastasis.

Animals↗

PubMed1996

Multiple small intestinal stromal tumors with skeinoid fibers in association with neurofibromatosis 1 (von Recklinghausen's disease).

A case of multiple small intestinal stromal tumors (SIST) with skeinoid fibers of the jejunum arising in a 50 year old male with neurofibromatosis 1 (NF-1) is reported. Seven small tumors of the jejunal wall were incidentally found and excised during an operation for abdominal and retroperitoneal neurofibromas. Histologically, the tumors were composed of uniform spindle-shaped cells with fascicular pattern, almost indistinguishable from the histology in leiomyoma. Periodic acid Schiff stain-positive hyaline globules were observed among the tumor cells. Ultrastructurally, these globules were stromal tangles of curvilinear, fluffy fibrils, consistent with skeinoid fibers. The electron-dense granules, possibly neuro-secretory granules, were found in the cytoplasm of the tumor cells. Immunohistochemically, the tumor cells were positive for vimentin, neuron specific enolase and CD34, but negative for muscle markers and S100 protein. The association of NF-1 and multiple SIST with skeinoid fibers may have clinical implications. The multiple occurrence of SIST with skeinoid fibers seems to be often cited as one of the gastrointestinal manifestations of NF-1. The possible site of origin of SIST with skeinoid fibers in NF-1 may be the enteric autonomic nerve plexus in the small intestinal wall.

Humans↗

PubMed1996

Bladder cancer producing granulocyte colony-stimulating factor: a case report.

A rare case of bladder cancer producing granulocyte colony-stimulating factor (G-CSF) is reported. A 63-year-old man with a progressive, grade 3 transitional cell bladder carcinoma, showed marked leukocytosis (maximum 181,800/mm3) and an elevated serum G-CSF to 131.7 pg/mL. After radical cystectomy and neoadjuvant chemotherapy, the tumor recurred locally. Immunohistochemical examination with monoclonal antibody specific for G-CSF revealed positive staining in the local recurrent tumor. To our knowledge, there have been only seven cases reported of bladder cancer producing G-CSF.

Carcinoma, Transitional Cell↗

PubMed1996

Interleukin 6-receptor expression on human bronchial epithelial cells: regulation by IL-1 and IL-6.

Airway epithelial cells have a potential to participate in regulation of local homeostasis by releasing active compounds including cytokines and growth factors. Several factors such as transforming growth factor-beta and endothelin have been shown to regulate airway epithelial cell functions through an autocrine mechanism. We studied the expression of the specific receptor for a multifunctional cytokine interleukin 6 (IL-6), which is expressed and released by airway epithelial cells. Specific binding assay demonstrated a single set of binding sites on human primary and transformed bronchial epithelial cells. Human interleukin-1alpha (IL-1alpha) increased maximal binding sites to IL-6. Northern blot analysis demonstrated that airway epithelial cells constitutively expressed mRNA for IL-6 receptor (IL-6R), and IL-1alpha and IL-6 itself upregulated IL-6R gene expression. Moreover, exogenously added human recombinant IL-6 had a stimulatory effect on IL-8 release from human bronchial epithelial cells. These results indicated that human bronchial epithelial cells expressed IL-6R, and IL-6 might be involved in the regulation of the epithelial functions via an autocrine as well as a paracrine mechanism.

Analysis of Variance↗

PubMed1996

Dementia characterized by abundant neurofibrillary tangles and scarce senile plaques: a quantitative pathological study.

We report an elderly case who had demonstrated progressive memory disturbance and disorientation for 4 years. The clinical features were indistinguishable from late-onset dementia of the Alzheimer type (DAT). Neuropathologically, however, senile plaques (SPs) were almost absent throughout the brain. In contrast, numerous neurofibrillary tangles (NFTs) were observed in the hippocampus and neighboring regions, with much higher density than age-matched normal controls. The immunohistochemical and ultrastructural properties of the NFTs were identical to those of typical DAT. The present case is histologically different from DAT because of the scarce SPs and indicates that numerous NFTs in the hippocampal region can be formed independently of the existence of SPs.

Aged↗

PubMed1996

Erythropoietin-producing adrenocortical carcinoma.

A 62-year-old Japanese male with an erythropoietin-producing adrenocortical carcinoma is presented. The elevated erythropoietin level and erythrocytosis returned to normal after surgical removal of a huge left adrenal tumor weighing 1,580 g. A histopathological diagnosis of adrenocortical carcinoma was made. Despite adjuvant combined chemotherapy, the patient died of lung and liver metastases 3.5 months after operation. Although the possibility that the elevated plasma erythropoietin level and erythrocytosis resulted from local kidney hypoxia, caused by pressure from the huge adrenal tumor, cannot be completely neglected, the positive cytoplasmatic evidence of immunoreactive erythropoietin in the carcinoma cells and the detection of a high erythropoietin level in the tumor extract on radioimmunoassay confirmed that this is a very rare case of erythropoietin-producing adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

PubMed1996

Molecular cloning and characterization of human cardiac homeobox gene CSX1.

Accumulating evidence has suggested that homeo-domain-containing proteins play critical roles in regulating the tissue-specific gene expression essential for tissue differentiation and in determining the temporal and spatial patterns of development. In order to elucidate the mechanisms of human heart development, we have isolated a human homologue of the murine cardiac homeobox gene Csx (also called Nkx-2.5) and denoted it as CSX1. The amino acid sequence of the CSX1 homeodomain is 100% and 67% identical to that of murine Csx/Nkx-2.5 and Drosophila tinman, respectively. CSX1 has at least three isoforms generated by an alternative splicing mechanism. One of these isoforms (CSX1a) encodes a protein of approximately 35 kD that possesses the homeodomain, whereas the other two (CSX1b and CSX1c) encode a truncated protein of approximately 12 kD that is identical to the CSX1a protein at the amino-terminal 112 amino acids but lacks the homeodomain. Northern blot analysis showed that CSX1 transcripts are abundantly expressed in both fetal and adult hearts, but no signal was detected in other human tissues examined. Amplification of each isoform by reverse transcriptase-polymerase chain reaction revealed that all of the three isoforms are expressed in fetal and adult hearts and that the homeobox-containing isoform CSX1a is most abundant. The homeodomain-containing protein encoded by CSX1a binds to Csx/Nkx-2.5 binding sequences and transactivates the sequence-containing luciferase reporter gene. Unexpectedly, the homeodomain-lacking protein encoded by CSX1b also transactivates the reporter gene, although CSX1b does not bind to the Csx/Nkx-2.5 binding sequences. The highly conserved homeodomain sequence in evolution and the restricted expression in the heart suggest that CSX1 plays an important role in the development and differentiation of the human heart and that there may be two different mechanisms in transcriptional regulation by the CSX1 protein, homeodomain-dependent and -independent mechanisms.

Base Sequence↗

PubMed1996

Immunosuppression in organ transplantation.

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant, performed by Hume et al. (1952), there has been an elusive search for agents that can render the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ, while sparing non-specific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes: chemical (pharmaceutical), biological (immunological), physical (radiological) and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, ciclosporin, azathioprine and FK506 have been epoch-making discoveries at each stage in the history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and/or B cells by inhibiting cytokine synthesis (ciclosporin, FK506), cytokine action (rapamycin), or cell differentiation (15-deoxyspergualin) pathways, rather than to act on immune systems in a non-selective fashion. At the present time, however, there is no single panacea. To achieve the maximum preventive and therapeutic effects with the minimum toxicity, two or more immunosuppressive drugs are used appropriately in combination, taking the mechanisms of action of each into consideration.

Adrenal Cortex Hormones↗

PubMed1996

Extensive pulmonary metastases in malignant pleural mesothelioma. A rare clinical and radiographic presentation.

We report a case of malignant pleural mesothelioma in a patient who presented with pleural effusion and reticulonodular shadow on chest radiograph. Pulmonary metastases were diagnosed by transbronchial lung biopsy specimen and the patient died of extensive pulmonary metastases. This pattern of clinical and radiographic presentation is seldom reported for malignant pleural mesothelioma.

Humans↗

PubMed1996

Importance of diffuse aspiration bronchiolitis caused by chronic occult aspiration in the elderly.

Diffuse aspiration bronchiolitis (DAB) is a new term that we proposed to define a clinical entity that is characterized by a chronic inflammation of bronchioles caused by recurrent aspiration of foreign particles. In the present study, a total of 4,880 consecutive autopsies were reviewed and we found 31 patients with DAB (0.64%). To investigate the clinicopathologic features of DAB, the 23 patients with DAB (age, 81.2 +/- 6.2 years [mean +/- SD]), from whom clinical information was available, had their features compared to those of 40 randomly selected patients with aspiration pneumonia (age, 81.9 +/- 8.3 years [mean +/- SD]). Oropharyngeal dysphagia was observed in half of the patients with DAB, and two thirds of patients with DAB were bedridden. The onset of DAB was more insidious than aspiration pneumonia, and in half of the patients with DAB episodes of aspiration were unrecognized. Neurologic disorders (52.2%) and dementia (47.8%) were common associated diseases. Most patients with DAB showed signs of bronchorrhea, bronchospasm, and dyspnea. The macroscopic appearance of the cut surface of DAB lung showed diffusely scattered miliary yellowish nodules that resembled those of diffuse panbronchiolitis (DPB). Histologic findings of DAB were characterized by localization of chronic mural inflammation with foreign body reaction in bronchioles. Recurrence of small amounts of aspiration might play a role in the pathogenesis of DAB. In view of possible therapeutic intervention, we emphasized the importance of recognizing this entity and differentiating DAB from pulmonary diseases associated with bronchospasm in the elderly, in particular, late-onset asthma and DPB.

Aged↗

PubMed1996

Pathogenesis of drug-induced gingival overgrowth. A review of studies in the rat model.

Drug-induced gingival overgrowth is a side effect associated principally with 3 types of drugs: anticonvulsant (phenytoin), immunosuppressant (cyclosporine A), and various calcium channel blockers (nifedipine, verapamil, diltiazem). In this review, we describe the features of phenytoin-, cyclosporine A- and nifedipine-induced gingival overgrowth in rats and discuss factors influencing the onset and severity of these disorders. There are several features common to the gingival overgrowth induced by these drugs: 1) gingival overgrowth is more conspicuous in the buccal than in the lingual gingiva and less severe in the maxilla than in the mandible; 2) once the blood concentration of the drug reaches a certain level as a result of increasing the dose, the incidence of gingival overgrowth is 100% and its severity is dependent on the blood level, the most severe overgrowth being induced by cyclosporine A; 3) the duration of drug administration for maximal gingival overgrowth to develop is about 40 days; 4) the gingival overgrowth regresses spontaneously after discontinuing the drug; 5) accumulation of dental plaque is not essential for the onset of overgrowth, but plays a role in its severity; and 6) more severe overgrowth is induced in young than in old rats. Furthermore, male rats are more susceptible than females to nifedipine-induced gingival overgrowth. These results suggest that drug-induced gingival overgrowth in rats is dependent on the oral drug dose, blood drug level, age, and sex and that preexisting gingival inflammation is a factor relevant to its severity. Since these factors have also been suggested to be important determinants for human drug-induced gingival overgrowth, the rat model may prove valuable in the future for elucidating the molecular pathogenesis of the disorder.

Age Factors↗

PubMed1996

[Renal toxicity of prulifloxacin (NM441) in rats].

Renal toxicity of prulifloxacin, a new antibacterial agent, was investigated in rats of both sexes. The animals were given prulifloxacin orally for 28 days at a dose of 3000 mg/kg. Tubular nephrosis in which crystalline substances appeared primarily within tubules was observed from the second day of administration, and a large number of brown circular crystals were found in the urinary sediment from the first day of administration. Electron microscopic observation revealed a close resemblance of the ultrastructural characteristics between the intratubular crystalline substance and the urinary brown circular crystal, and the tubules were occasionally occluded by the crystalline substances. Infrared spectral analysis and X-ray microanalysis indicated that the brown circular crystal consisted of NM394, an active metabolite of prulifloxacin. These results suggested that NM394, which was filtered into the primary urine, may be precipitated as crystals on the process of water reabsorption in the tubules. And then most of the crystals would be washed out as crystalluria particles, and some of crystals retained and caused the obstructive uropathy.

Administration, Oral↗

PubMed1996

[Acute myocardial infarction and silent myocardial ischemia in the elderly--clinical features and effectiveness of therapy in an era of coronary intervention].

To elucidate the clinical features of acute myocardial infarction (AMI) and post-MI silent myocardial ischemia (SMI) in the elderly, and efficacy of therapy in an era of coronary intervention, a total of 10,607 patients with AMI who were enrolled in a multicenter survey between 1982 and 1992 were examined. The elderly had a higher ratio of females, noncardiac illness, atypical symptoms at the onset of AMI, severe pump failure at admission, cardiac rupture and multivessel disease. Hospital mortality was markedly higher in patients > or = 75 years, and it was 4-fold compared with patients < 65 years. In the last 5 years, the rate of application of coronary angiography and primary PTCA significantly increased even in the very elderly. In contrast, use of thrombolysis highly diminished. Hospital mortality declined (14.6 vs 11.9%, p < 0.001) in every age group compared with the first 5 years, although it was higher in the elderly even in the last 5 years. Investigation of 642 survivors after AMI admitted to one hospital showed that the elderly had a higher incidence of SMI and post-MI angina compared with the non-elderly. Clinical features of SMI were similar in both groups. However, medical treatment was more prevalent and recurrence of MI and cardiac death during follow-up (average 27 months) were more frequent in the elderly. In this retrospective study, characteristics of AMI and SMI, and effectiveness and limitation of therapy in the elderly were clearly demonstrated. It was evident that hospital mortality of the elderly had improved, although it was still higher than the non-elderly.

Aged↗

PubMed1996

Increased success of blind nasotracheal intubation through the use of nasogastric tubes as a guide.

We were able to improve the success rate of blind nasotracheal intubation by using nasogastric tubes as a guide during intubation, first, for passing the endotracheal tube through the nasal cavity, and second, passing it from the pharynx to the larynx. By adding both sedation by modified neuroleptanalgesia (NLA) and topical and transtracheal administration of lidocaine, our technique became safer and smoother. We have completed 36 cases without accident, with an average time for intubation of 8.25 min. The Rüsh spiral tube was thought to be the most suited to this form of intubation because of the 90 degrees cut of its tip, its high-volume cuff, and its flexibility in all directions. These features are useful for hearing breath sounds, raising the tip of the tube by inflation of the cuff, and advancing the tube in a turning motion.

Anesthesia, Dental↗

PubMed1996

[Resection and reconstruction of full thickness chest wall].

Nine patients underwent full thickness chest wall resection and reconstruction in our department between January 1981 and December 1994. There were chest wall recurrence of breast cancer in 5 cases, primary chest wall chondrosarcoma in 2, primary chest wall malignant fibrous histiocytoma in 1 and metastatic sternal renal cell carcinoma in 1. Seven of 9 cases underwent partial sternal resection. Sizes of chest wall defects were from 10 x 7 cm to 15 x 14 cm. In eight cases of 9, chest wall reconstruction was by double Marlex mesh repairs and various flaps (major pectoral muscle in 3, major pectoral myocutaneous flap in 2, latissimus dorsi myocutaneous flap in 1 and pedicled omentum in 1). The last case underwent repair with rectus abdominis myocutaneous flap without mesh. There was no operative death. Postoperative complications occurred in 4 patients: partial skin necrosis in 2, skin dehiscence in 1 and respiratory failure in 1. Eight cases are alive now from 9 months to 14 years and 8 months after chest wall reconstruction. One patient with metastatic renal cell carcinoma died of recurrence 3 years after operation. Full thickness chest wall resection and reconstruction is a safe operation and may provide a long-term survival.

Aged↗