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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 397 records · Page 22Linked to original sources

[Mycoplasma pneumoniae pneumonia with diffuse nodular shadows and right hilar lymphadenopathy].

A 51-year-old man was admitted to our hospital because of fever, a productive cough, and dyspnea. His chest X-ray film revealed diffuse reticulonodular shadows and right hilar lymphadenopathy. A chest CT scan revealed thickened bronchial walls and diffuse centriacinar or centrilobular nodular shadows. Serologic testing provided conclusive evidence of Mycoplasma pneumoniae infection. The diffuse pattern and hilar lymphadenopathy on chest X-ray films are uncommon in this disease, and they caused some uncertainty regarding the correct diagnosis. M. pneumoniae attaches to cells of the respiratory tract and produces a locally acting cytotoxin. Immunologic mechanisms have been shown to play an important role in the pathogenesis of pneumonia. This case suggests that immunologic mechanisms are an important factor in diffuse lung lesions.

Humans↗

Angiosarcoma of the scalp associated with renal transplantation.

A case of cutaneous angiosarcoma occurring in a 51-year-old male renal transplant patient is reported. Multiple violaceous nodules surrounded by poorly demarcated red to purple discoloration were found on his scalp. Immunosuppressants consisting of azathioprine and prednisolone had been administered during the 12-year period since the renal transplantation. We diagnosed the lesion clinically as a cutaneous angiosarcoma and performed a wide surgical excision. The histopathological findings confirmed the diagnosis and showed tumour cells in the peripheral margin. Postoperatively, the patient started immunotherapy with systemic administration of recombinant interleukin-2 (rIL-2), but he refused to continue it because of the acute rejection of the transplanted kidney induced by the rIL-2. Instead he received radiation therapy (total 7000 rad) of the scalp. Although no recurrence was noticed for 15 months after the completion of radiation, he died due to lung metastasis from angiosarcoma. We review the seven cases, including ours, of angiosarcoma after renal transplantation that are reported in detail in the literature.

Fatal Outcome↗

[Antigenic epitopes recognized by autoantibodies to calpastatin in patients with rheumatoid arthritis and their clinical significance].

We have previously described that novel autoantibodies to calpastatin (endogenous inhibitor for calcium-dependent neutral protease, calpain) were detected in patients with rheumatoid arthritis (RA) and other disorders. Since calpain is thought to mediate inflammatory process and cartilage destruction, autoantibodies to its inhibitor protein, calpastatin, may be involved in the pathogenic mechanism of rheumatoid arthritis. In the present study, we analyzed antigenic epitopes reactive with autoantibodies to calpastatin and their clinical correlation. cDNA encoding the C-terminal 178 amino acids of human calpastatin (RA-6) was digested by restriction enzymes and ligated in to pEX expression vectors. These recombinant plasmids were tranfected into E. coli POP2136 and screened by colony blots using RA sera containing anticalpastatin antibodies and a mouse monoclonal antibody. RA patient sera recognized the C-terminus of domain IV (epitope C1 ; aa. 647-673) and C-terminus of domain III (epitope C2 ; aa. 496-571), whereas the mouse monoclonal antibody recognized an entirely different region containing the calpain-binding site (epitope B2 ; aa. 572-625). To evaluate epitope reactivity of patient autoantibodies, 15 RA sera containing anti-calpastatin were reacted with epitope fusion proteins. In immunoblotting, most RA sera recognized either C1 or C2 epitopes (67% and 40%, respectively), and only one patient recognized both epitopes. B2 epitope a more progressed and sever state of arthritis than those not reacting with C1. These results suggests that anti-calpastatin antibodies may play a role in the pathogenic mechanisms of RA and their epitope reactivity may be important for disease progression.

Adult↗

[A case of successfully treated fungal tricuspid infective endocarditis with repeated pulmonary embolism].

A case of successfully treated fungal tricuspid infective endocarditis with repeated pulmonary embolism is reported. A 60-year-old man had received along term intravenous hyperalimentation for the treatment of the complication after hepatopancreatoduodenectomy, associated with Candida sepsis. He was once discharged, successfully treated with antifungal agents. But he was readmitted to our hospital due to fever, cough and chest pain. Blood culture revealed Candida tropicalis. Pulmonary scintigraphy and angiography revealed multiple infarcts of the right lung, and echocardiography showed vegetation on the tricuspid valve. Because of exacerbation of shortness of breath, tricuspid valvuloplasty and thromboembolectomy in the pulmonary arteries was performed. Postoperative course was uneventful and he had a marked improvement of dyspnea after operation.

Candidiasis↗

[Diversion of the inferior vena cava into the left atrium after repair of atrial septal defect with partial anomalous pulmonary venous drainage].

An 11-year-old female had operative repair of atrial septal defect associated with partial anomalous pulmonary venous drainage by direct suture at 6-year-old. Postoperatively, cyanosis and nodal bradycardia were noted by physical exercise. During 5 years thereafter, the symptoms were gradually aggravated accompanying. Cardiac catheterization revealed diversion of the inferior vena cava into the left atrium. Oxygen sampling showed right to left shunt of 22% at the atrial level. At reoperation, orifice of the inferior vena cava into the right atrium became narrow 5 mm in diameter. After enlargement of the orifice, the atrial septum was created with a Gore-Tex patch to redirect the inferior vena cava to the right atrium. Post operative course was uneventful with disappearance of the cyanosis. The patient is up and well now 9 years after reoperation.

Child↗

Long-term prognosis of renal transplant surviving for over 10 yr, and clinical, renal and rehabilitation features of 20-yr successes.

Long-term mortality and morbidity was evaluated in 267 patients with a minimum follow-up of 10 yr and the physical status, graft function and quality of life in 15 patients with a functioning graft surviving for over 20 yr were reviewed. Actual patient and graft survival rates were 80.2% and 51.1% at 10 yr (n = 267) and 56.4% and 32.7% at 20 yr (n = 55), respectively. Although the rate of graft failure due to rejection was 4 times higher than that of patient death within 10 yr, it decreased to the level of patient death in the second decade. Dominant causes of death in patients with graft surviving for over 10 yr were hepatic failure due to viral hepatitis and malignancies. In 15 patients with graft currently surviving beyond 20 yr, while all patients have excellent graft function, malignancy occurred in 5, viral hepatitis in 3, aseptic necrosis in 3, and diabetes mellitus in one patient. No patient has suffered cardiovascular complications. Despite a high rate of morbidity, they show a satisfying status of rehabilitation (full time working 11/ 15, 73.3%). In order to attain more improved QOL in patients with long-term surviving renal transplant, close follow-up aiming at diminution of complications is required throughout the period after transplantation.

Adult↗

[A case of hepatic arterial infusion chemotherapy for multiple liver metastasis from breast cancer].

A 52-year-old woman underwent Auchinclass' operation for breast cancer. The histological type was papillotubular carcinoma. One year and 5 months after operation, multiple liver tumors were found on the CT scan and multiple bone metastasis on MRI. The former were treated by hepatic artery infusion chemotherapy with epirubicin and 5-FU using a subcutaneous implanted pump and the latter by 50 Gy irradiation. The patient began to complain of abdominal pain and discomfort after hepatic artery infusion, so all treatment was discontinued. Six months later the patient died of respiratory failure due to pleural dissemination. No liver mass was detected, and bone metastasis was not changed in section tissues. This suggested that the therapy for a breast cancer patient with distant metastasis must be considered according to the region of recurrence.

Adenocarcinoma↗

Autoregulation of human cardiac homeobox gene CSX1: mediation by the enhancer element in the first intron.

Csx/Nkx-2.5 is a murine homeobox gene expressed predominantly in cardiocytes and their progenitor cells. The highly lineage-restricted expression pattern of Csx/Nkx-2.5 gene suggests the existence of a positive autoregulatory loop in the transcriptional regulation of Csx/Nkx-2.5. The first intron of CSX1, a human homolog of Csx/Nkx-2.5 gene, had two potential CSX1-binding sequences. Activity of the CSX1 minimal promoter in cultured cardiac myocytes was significantly increased by placing the 3' half of the CSX1 first intron downstream of the reporter gene, suggesting that this region functions as a positive enhancer element. Transient transfection experiments in nonmuscle cells demonstrated that the reporter construct containing the CSX1 minimal promoter and the 3' half of the CSX1 first intron was strongly transactivated by overexpression of CSX1, whereas the CSX1 minimal promoter alone was not. Together these results suggest that the highly lineage-restricted expression of CSX1 is accomplished by autoactivation, which may be mediated by the enhancer element in the first intron.

Animals↗

Detection of H3+ in interstellar space.

The H3+ ion is widely believed to play an important role in interstellar chemistry, by initiating the chains of reactions that lead to the production of many of the complex molecular species observed in the interstellar medium. The presence of H3+ in the interstellar medium was first suggested in 1961, and its infrared spectrum was measured in the laboratory in 1980. But attempts to detect it in interstellar space have hitherto proved unsuccessful. Here we report the detection of H3+ absorption in the spectra of two molecular clouds. Although the present results do not permit an accurate determination of the H3+ abundances, these ions appear nevertheless to be present in sufficient quantities to drive much of the chemistry in molecular clouds. It should soon be possible to obtain more accurate measurements, and thus better quantify the role of ion-neutral reactions in the chemical evolution of molecular clouds.

Extraterrestrial Environment↗

Signaling pathways and survival effects of BDNF and NT-3 on cultured cerebellar granule cells.

We investigated the signaling pathways exerted by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in relation to their survival-promoting effects on dissociated cultures of cerebellar granule cells prepared from postnatal 9-day-old rats. Granule neuron survival in culture was supported by BDNF, but not significantly by either nerve growth factor (NGF) or NT-3. BDNF and NT-3 resulted in not only the respective autophosphorylation of the Trk receptors, TrkB or TrkC, but also tyrosine phosphorylation of SHC, a protein involved in controlling p21ras activity, and phosphatidylinositol-3' (PI-3') kinase. NGF does not result in TrkA phosphorylation. In parallel, c-fos was induced within 30 min, in response to BDNF and NT-3. NT-3 induced the phosphorylation of these proteins to a lesser extent than BDNF. BDNF also induced the tyrosine phosphorylation of phospholipase C gamma (PLC gamma), but the NT-3-induced one was not detected. We postulate that no survival promotion by NT-3 is due to lesser level of trkC expression and of the NT-3-induced signaling in the cultured cerebellar granule neurons. Wortmannin, a specific inhibitor of PI-3' inhibited the BDNF effect on neuronal survival. PI-3' kinase-dependent pathways might be involved in the promotion of cerebellar granule cell survival by BDNF.

Adaptor Proteins, Signal Transducing↗

Expression of cyclin A decreases during neuronal apoptosis in cultured rat cerebellar granule neurons.

Cultured cerebellar granule neurons died in an apoptotic manner when the K+ concentration in culture medium was lowered to the normal level (5 mM) after maturation of cells with a high concentration of K+ (26 mM). The changes in expression of 14 cell cycle-related genes in this CNS apoptosis model were analyzed by quantitative RT-PCR. Most of the genes analyzed were stable during apoptosis. The expression of cyclin A mRNA, however, transiently decreased 1 h after the induction of apoptosis, and recovered within 3 h to above the basal level. In this system, the level of cyclin D1, which has been reported to be up-regulated in apoptosis of NGF-deprived cultured sympathetic neurons, did not change. These results suggest that the molecular mechanisms in these two apoptosis models are different. To determine cyclin A protein level, we used an immunostaining method. The number of cyclin A-positive neurons decreased during apoptosis. Moreover, the numbers of MAP2- and cdk2-positive neurons also decreased in a similar manner. Taken together, these results suggest that there is a relationship between apoptosis and cell cycle, and that morphological changes during apoptosis result from cytoskeletal structure degradation.

Age Factors↗

Cloning and sequencing of cDNA encoding 4-aminobenzoate hydroxylase from Agaricus bisporus.

A cDNA clone encoding 4-aminobenzoate hydroxylase (EC 1.14.13.27) has been isolated using a probe prepared by PCR on the basis of partially determined amino acid sequences of the enzyme. The cDNA contained 1380-base pair open reading frame encoding 460 amino acid residues (M(r) 50974), 14-base pair 5'-untranslated region and 123-base pair 3'-untranslated region including a poly(A) tail of 20 nucleotides. All of the partially determined amino acid sequences were shown to be included in the deduced amino acid sequence. Homology analyses showed that the two regions on the enzyme share other flavoproteins such as salicylate hydroxylase and p-hydroxybenzoate hydroxylase.

Adenosine Diphosphate↗

Inhibition of peripheral interleukin-1 beta-induced hyperalgesia by the intracerebroventricular administration of diclofenac and alpha-melanocyte-stimulating hormone.

The present study was undertaken to investigate whether or not the endogeneous mechanisms in the brain can modulate the changes in nociception produced by peripherally-administered interleukin-1 beta (IL-1 beta) in rats. We administered diclofenac and alpha-melanocyte-stimulating hormone (alpha-MSH) into the lateral cerebroventricle (LCV) 10 min before the intraperitoneal (i.p.) injection of recombinant human IL-1 beta (rhIL-1 beta, 1 ng/kg-100 ng/kg) and then observed the changes in nociception using a hot-plate test. The i.p. injection of rhIL-1 beta (10 ng/kg and 100 ng/kg) reduced the paw-withdrawal latency without affecting the colonic temperature. The maximal reduction in the paw-withdrawal latency was observed 30 min after the i.p. injection of rhIL-1 beta at 100 ng/kg. The rhIL-1 beta (100 ng/kg)-induced hyperalgesia was inhibited by the LCV injection of both diclofenac (1 ng) and alpha-MSH (100 ng). The LCV injection of either diclofenac (1 ng) or alpha-MSH (100 ng) was found to have no effect on nociception by itself. These findings therefore suggest that the hyperalgesia induced by peripheral IL-1 beta can be modulated by a cyclooxygenase pathway of the arachidonate and alpha-MSH in the brain.

Animals↗

Oxygen-induced apoptosis in PC12 cells with special reference to the role of Bcl-2.

We previously reported that PC12h cells are killed by a high oxygen atmosphere. In this study, we further characterized this oxygen-induced cell death and found apoptotic features, as follows. Firstly, chromatin condensation was observed in cells cultured in a 50% O2 atmosphere. Secondly, cycloheximide and cordycepin, protein and RNA synthesis inhibitors, respectively, prevented the oxygen-induced cell death in PC12h cells, suggesting that it is mediated by an intracellular death program. Thirdly, NGF, CPT-cAMP and depolarization by high potassium medium also effectively inhibited this apoptotic cell death in PC12h cells. The effect of high K+ is thought to be mediated by the influx of Ca2+ into cells through voltage-dependent Ca2+ channels, because nifedipine, an L-type Ca2+ channel blocker, inhibited the effect of high K+. In addition, since the oxygen-induced apoptosis was blocked by the antioxidant vitamin E, this oxygen toxicity is suggested to be mediated by reactive oxygen species. To further characterize this oxygen-induced apoptosis at the molecular level, we used PC12 cells overexpressing the proto-oncogene bcl-2. Although a large number of PC12 cells transfected with the control vector died in a 50% O2 atmosphere within 6 days, bcl-2-transfected PC12 cells survived and proliferated. These findings suggested that our system using PC12 cells will be a useful model with which to analyze the molecular mechanisms of apoptosis induced by oxidative stress in neuronal cells.

Animals↗

Retrograde labelling in vivo of vagus nerve nucleus in rat by carbocyanine dye.

To elucidate the patterns of visceral innervation of the vagus nerve in rats, we labelled the severed efferent path at the level of the neck in vivo by applying a solution of 0.1% carbocyanine dye DiI/100% ethanol. Two weeks after dye application, horizontal sections of the brain stem were analysed quantitatively under an epifluorescence microscope. Particles of DiI were present in neuronal cell bodies and the cellular processes in the dorsal motor nucleus (DmoX) of the vagal nerve and nucleus ambiguus (Nam). Approximately 80% of DiI-labelled cells were located in the DmoX whereas 16% were in the Nam. The rest of the labelled cells were in the vicinity of the central canal. The DiI labelling technique appears to be a useful new technique for quantitative analysis of central neurones sending visceral efferents.

Animals↗

Vitamin B6 deficiency accelerates metabolic turnover of cystathionase in rat liver.

Although most of cystathionase was found to exist as an inactive apoenzyme in the liver of vitamin B6-deficient rats, the concentrations of the immunoreactive enzyme protein were virtually the same for control and vitamin B6-deficient livers. Under vitamin B6 deficiency, however, the rate of synthesis of cystathionase, measured by incorporation of labeled amino acid into the immunoprecipitated enzyme, was increased severalfold due to an increased level of cystathionase mRNA. Western blot analysis of lysosomal proteins showed that the amount of cystathionase in the lysosomes from the liver of vitamin B6-deficient rats was also increased severalfold. This observation suggests that lysosomes specifically recognize the apocystathionase for sequestration in preference to the holoenzyme. The present study provides the molecular basis for dual roles of vitamin B6 in controlling the metabolic turnover of cystathionase; it regulates synthesis of the enzyme by modulating the expression of cystathionase gene, and it regulates degradation of the enzyme by different susceptibilities of apo- and holoenzymes to lysosomal proteolysis.

Animals↗