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Biomedical subjects

K Nagao

Publications and source records attributed to K Nagao.

At least 127 records · Page 7Linked to original sources

Rheumatoid arthritis associated with renal amyloidosis and crescentic glomerulonephritis.

A 43-year-old woman with rheumatoid arthritis (RA), renal amyloidosis and crescentic glomerulonephritis had severe abdominal pain, melena and progressive renal failure. Autopsy findings revealed vasculitis of small and middle size of vessels and there was a deposition of amyloid in the small intestines. Although there were no findings of vasculitis in the kidney, amyloid deposition was noticed and 70-80% of glomeruli showed a crescentic formation. No immunological abnormality was found in glomeruli. Although the immunological mechanisms of crescentic glomerulonephritis were not necessarily eliminated, amyloid deposition may play a role in crescent formation.

Acute Kidney Injury↗

1513-DMIa and 1513-DMIb, DNA methyltransferase inhibitors produced by Streptomyces sp. strain No. 1513.

Two new methyltransferase inhibitors were isolated from the culture filtrate of Streptomyces sp. strain No. 1513 and named 1513-DMIa and 1513-DMIb. 1513-DMIa and 1513-DMIb were distinguished in certain properties from DMI-1, DMI-2, DMI-3 and DMI-4 previously reported. The molecular weight of 1513-DMIa and 1513-DMIb were estimated to be 576 and 8400 from the results of FAB-MS and gel filtration, respectively. The inhibitory activities of 1513-DMIa and 1513-DMIb were shown to be pH- and temperature-dependent and both inhibited M. EcoRI in an uncompetitive manner with respect to DNA or S-adenosylmethionine (SAM).

Chromatography, Gel↗

[Normal term delivery after adrenalectomy for Cushing syndrome in a pregnant patient--a case report].

This is a case of a 29-year-old female. She visited our hospital with the chief complaint of swelling of the legs and abdominal bloating at the 10th week of pregnancy. Edema and central obesity were observed in the lower extremities. Hematological and biochemical tests revealed hypokalemia. Gynecologically, she was normal. Elevated blood cortisol levels were identified on the hormonal tests, which suggested the existence of Cushing's syndrome. Ultrasound revealed the presence of a tumor in the left adrenal gland, and she was referred to our department for surgery. On September 13, 1994, left adrenalectomy was performed in a right lateral position under inhalation anesthesia and epidural anesthesia. Adjuvand steroid therapy was initiated during surgery and the blood cortisol levels were normalized within 2 months. She delivered a baby girl weighing 2,722 g at the 40th week of pregnancy via a normal transvaginal delivery. Pregnancy rarely occurs in patients with Cushing's syndrome. We think she was the first case in Japan who had normal 40th week transvaginal delivery after adrenalectomy during pregnancy. We present a description of our case here with reference to the relevant literature.

Adrenalectomy↗

Fattiviracin A1, a novel antiviral agent produced by Streptomyces microflavus strain No. 2445. II. Biological properties.

Fattiviracin A1, showed potent antiviral activities against herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), influenza A virus and human immunodeficiency virus type 1 (HIV-1). It showed no cytotoxicity against Vero cells. Fattiviracin A1 exhibited no significant antibacterial or antifungal activities. Treatment of HSV-1 with fattiviracin A1 decreased its infectivity to Vero cells. The mechanism of its antiviral activity may be due to inactivation of the viral particles and inhibition of viral entry into host cells.

Animals↗

Topostatin, a novel inhibitor of topoisomerases I and II produced by Thermomonospora alba strain No. 1520. I. Taxonomy, fermentation, isolation and biological activities.

A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. Topostatin inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I, and also inhibited the relaxation of supercoiled pBR322 DNA and decatenation of kinetoplast DNA by human placenta topoisomerase II. Topostatin had neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The inhibitor exhibited growth inhibitory activity against the tumor cells (SNB-75 and SNB-78) of central nervous system, but did not exhibit any antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and fungi.

Antineoplastic Agents↗

Topostatin, a novel inhibitor of Topoisomerases I and II produced by Thermomonospora alba strain No. 1520. II. Physico-chemical properties and structure elucidation.

Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of Thermononospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and II, and it has neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The molecular formula of topostatin was determined as C36H58N4O11S based on the FAB-MS analyses, and the structure was elucidated to be a novel 14-membered ring containing peptide and terpenoid by various NMR spectroscopies.

Enzyme Inhibitors↗

[Prognostic effect of PyNPase (pyrimidine nucleoside phosphorylase) activity in breast cancer].

To clarify the clinical significance of PyNPase (Pyrimidine Nucleoside Phosphorylase)/ PD-ECGF activity in breast cancer, we examined the possible correlation of PyNPase activity to clinicopathological features and prognosis in 195 patients with primary breast cancer between January 1992 through December 1993. The mean PyNPase activity of primary breast cancer, assayed by ELISA method, was 140.6 U/ml, which was between that of benign breast disease (18.2) and recurrent tumors (270.9). In histological type of breast cancer, tumors with solid-tubular carcinoma had significantly higher levels of PyNPase activity. The activity of ER negative or aneuploid tumors was higher than that of ER positive or diploid tumors, respectively. And there was a significant relationship between PyNPase activity and proliferative activity determined by S-phase fraction (SPF) or DNA polymerase alpha. These findings suggested that PyNPase activity was associated with the degree of malignancy. As regards prognosis, in lower SPF (< 16%) group, patients with higher PyNPase activity had significantly lower disease--free survival rates, whereas those with higher activity had a favorable prognosis in the higher SPF (> or = 16%) group. The contradiction might be explained by the possibility that 5-FU derivatives were effective only in patients with high SPF and PyNPase activity, as all patients were treated by a regimen containing 5-FU derivatives. We suggest that PyNPase activity is associated with progression and proliferation of breast cancer, and that it may be useful for prediction of prognosis and therapeutic efficacy of 5-FU derivatives.

Adult↗

[Koch's phenomenon after BCG vaccination and the two-step tuberculin test in elementary school children].

In Japan, BCG vaccination, which covers more than 90% of infants, has been given according to the national immunization policy. Moreover, first-grade children in elementary school are screened with tuberculin skin test, and those who show negative reaction in the Japanese standard, i.e. size of erythema less than 10 mm, are re-vaccinated with BCG according to the Tuberculosis Prevention Law. However, since the incidence of tuberculosis among children below age 14 is as low as 1.5/100,000 in Japan, it is time to reconsider the BCG vaccination policy. As the first step to assess the efficiency of the present program, we observed the occurrence of Koch's phenomenon after BCG vaccination in elementary school children in Chiba City in 1995 and 1996, and we introduced the two-step tuberculin test to elementary school children in 1997. Among 180 BCG vaccinated children in 1995 and 1996, 168 (93.3%) had been vaccinated by 4-year of age. We could follow local reaction of BCG re-vaccination and observed Koch's phenomenon in 117 (69.6%, 95% C.I. of 62.7-76.6%). Among 92 tuberculin negative children in 1997, 85 (92.4%) had been vaccinated by 4-year of age. In the two-step tuberculin test program of 85 initial negative-reactors, 63 (74.1%, 95% C.I. of 64.8-83.4%) turned to positive by the second test. Those results suggest that more than 69% of tuberculin-negative school children who were vaccinated previously maintained immunity with BCG. Our studies raised a problem of the current BCG re-vaccination policy that depends on the result of tuberculin test. Due to the discrepancy between tuberculin allergy and immunity in tuberculosis, many school children may be given BCG vaccination unnecessarily. Taking into consideration the incidence of tuberculosis in children, discontinuation of BCG re-vaccination policy at elementary school entrance should be considered.

BCG Vaccine↗

[Two cases of spontaneous hemopeumothorax].

We experienced two cases of spontaneous hemopeumothorax. One case was a 17-year-old male with a complaint of back pain. A chest tube for rapid pleural evacuation disclosed hemorrhage as much as 3,000 ml, with drainage volume being gradually decreased. He needed about two month's admission because of complication of pyothorax. The other case was a 46-year-old male with a complaint of chest pain. Chest X-P gave the diagnosis of right hemopeumothorax. Thirty minutes later, he became shock, and five hours later, we performed an emergency intervention of video-assisted thoracoscopic surgery (VATS). Bleeding site of a funicular structure from the parietal pleura was stopped by clipping, with excellent postoperative results. Spontaneous hemopeumothorax is often indicated for early surgical intervention because of association with a high risk of hemorrhagic shock. In such a case, VATS is very helpful.

Adolescent↗

[The issues of emergency medical system in patients with prehospital cardiac arrest complicating acute coronary syndrome in Japan].

Each year approximately 30,000 persons in Japan experience prehospital cardiac arrest complicating acute coronary syndrome, and about 96 percent of them die. The majority of these sudden cardiac deaths are the result of fatal arrhythmias that often can be stopped by rapid initial medical care. In Tokyo, however, the first responder to provide cardiopulmonary resuscitation are about 10 percent, the successful defibrillation rate by Japanese paramedics who are not authorized advanced cardiac life support (ACLS) with drugs are about 15 percent and there are very few cardiologists who have been engaged in ACLS and initial management of suspected acute coronary syndrome in the emergency department. Therefore, each community emergency medical system should develop a plan to provide rapid initial medical care to patients with cardiac arrest (those with and without acute coronary syndrome).

Acute Disease↗

Expression of E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma: an immunohistochemical study.

Bronchioloalveolar carcinoma (BAC) has features distinct from those of conventional pulmonary adenocarcinoma (CPA) in terms of its characteristic growth pattern along alveolar walls and intrapulmonary metastasis via the aerogenous route. We speculated, therefore, that BAC might differ from CPA in its capacity for cell-to-cell or cell-to-basement membrane adhesion. E-cadherin (E-CD), one of the most important elements of epithelial integrity molecules, is related to tumor metastasis in various organs. Differences of E-CD and associated catenin expressions between BAC and CPA, however, have not been elucidated. We examined the expression of E-CD and alpha-, beta- and gamma-catenin immunohistochemically in 18 BACs (9 mucinous, 7 nonmucinous, and 2 sclerosing) in comparison with CPAs, all of which were well-differentiated adenocarcinomas. In addition, we analyzed the correlation between the expression of these cell adhesion molecules and the presence of intrapulmonary metastasis, histologic subtypes, and cell proliferation activity. Clinicopathologically, we observed intrapulmonary metastases in 4 of the 18 BACs and none of the CPAs. In 14 of the 18 BACs, more than one-half of the tumor cells expressed E-CD, and the E-CD expression level was significantly higher in the BACs than in the CPAs. In addition, all of the BACs exhibited preserved membranous staining for E-CD, whereas in 5 of the 14 CPAs, the expression pattern was disorganized cytoplasmic staining; the difference was statistically significant. The Ki-67 labeling index was significantly lower in the BACs than in the CPAs. There were no appreciable differences in E-CD expression among the BAC subtypes. E-CD expression was significantly lower in the BACs with intrapulmonary metastasis than in the BACs without intrapulmonary metastasis. These findings indicated to us that BAC was distinct from CPA in terms of proliferation activity and expression of certain adhesion molecules and that E-CD downregulation was associated with a tendency toward intrapulmonary metastasis.

Adenocarcinoma↗

[Tuberculosis in respiratory system--tracheo-bronchial tuberculosis, pulmonary tuberculosis, tuberculous pleurisy and thoracic empyema].

Tuberculosis in respiratory system is most common in mycobacterial infections. Eighty percent of the patients with pulmonary tuberculosis visit hospital because of the respiratory symptoms, and only 10% of them were discovered by chest X-ray mass screening. In order to confirm respiratory tuberculosis, various methods to obtain specimens for mycobacterial examination have been carried out; hypertonic saline nebulizing for sputum expectoration, trans-bronchoscopic biopsy, percutaneous needle aspiration, and so on. The recent development of imaging modalities including CT, MRI, and ultrasonogram have been much contributed to the improvement of diagnosis of pleural tuberculosis. Basically, the main treatment for respiratory tuberculosis is chemotherapy except chronic tuberculous thoracic empyema. The initial chemotherapy regimen should be chosen among the three arms; [INH + RFP + PZA + EB (or SM)] x 2-->[INH + RFP] x 6, [INH + RFP + EB (or SM)] x 6-->[INH + RFP] x 3-6, and [INH + RFP] x 6-9. The sputum positive patient is recommended to have the chemotherapy regimen including PZA. In the patients with tracheo-bronchial tuberculosis an attention should be paid for the airway narrowing or obstruction during and after the scheduled chemotherapy. For a part of patients with tuberculous pleurisy and thoracic empyema, a surgical treatment must be indicated.

Empyema, Tuberculous↗

Fission yeast Cut2 required for anaphase has two destruction boxes.

The fission yeast Schizosaccharomyces pombe cut2(+) gene is essential for sister chromatid separation. Cut2 protein, which locates in the interphase nucleus and along the metaphase spindle, disappears in anaphase with the same timing as mitotic cyclin destruction. This proteolysis depends on the APC (Anaphase-Promoting Complex)-cyclosome which contains ubiquitin ligase activity. The N-terminus of Cut2 contains two stretches similar to the mitotic cyclin destruction box. We show that both sequences (33RAPLGSTKQ and 52RTVLGGKST) serve as destruction boxes and are required for in vitro polyubiquitination and proteolysis. Cut2 with doubly mutated destruction boxes inhibits anaphase, whereas Cut2 with singly mutated boxes can suppress cut2 mutations. Strong expression of the N-terminal 73 residues containing the destruction boxes leads to the accumulation of endogenous cyclin and Cut2, and arrests cells in metaphase, whereas the same fragment with the mutated boxes does not. Cut2 proteolysis occurs in vitro using Xenopus mitotic extracts in the presence of functional destruction boxes. Furthermore, Cut2 is polyubiquitinated in an in vitro system using HeLa extracts, and this polyubiquitination requires the destruction boxes.

Anaphase↗

Intracytoplasmic inclusion bodies of the substantia nigra in myotonic dystrophy. Immunohistochemical observations.

We recently reported a significantly higher incidence of intracytoplasmic inclusion bodies (IIBs) of the substantia nigra in patients with myotonic dystrophy (MyD) than in age-matched controls. The changes are, per se, not specific, since a small percentage of disease and normal controls also showed similar inclusions. To elucidate the pathological significance of the inclusion in MyD, we studied immunohistochemical characteristics of IIBs of the substantia nigra in eight patients with MyD. Many IIBs showed moderately intense immunoreactivity for ubiquitin, microtubule-associated protein (MAP) 1 and MAP 2. However, the IIBs did not react with any of the following: anti-neurofilament protein antibodies (Abs) (68, 160 and 200 kDa), anti-neuron-specific enolase antibody (Ab), anti-tau Ab, anti-tubulin Abs (alpha and beta), anti-paired helical filament Ab, anti-actin Ab, anti-phosphorylated epitope of neurofilaments Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-glial fibrillary acidic protein Ab. Our results suggest that IIBs of the substantia nigra in MyD are related to an alteration of neuronal cytoskeleton metabolism affecting microtubular proteins in conjunction with activation of ubiquitin proteolytic systems.

Aged↗

Chromosomal rearrangement t(11;22) in extraskeletal Ewing's sarcoma and primitive neuroectodermal tumour analysed by fluorescence in situ hybridization using paraffin-embedded tissue.

The clonal chromosomal rearrangement t(11;22) has been reported by karyotypic analysis to be specific for Ewing's sarcoma of bone and soft tissue origin as well as primitive neuroectodermal tumour. In this report, immunohistological analysis of MIC 2 expression and fluorescence in situ hybridization (FISH) were performed using paraffin-embedded tissues. We examined t(11;22) in the nuclei isolated from two Ewing's sarcomas, four primitive neuroectodermal tumours, and three neuroblastomas, which served as negative controls by FISH with an alpha-satellite DNA probe for chromosome 11, a chromosome 22 marker probe, and whole chromosome painting probes for both chromosomes 11 and 22. Both cases of Ewing's sarcoma and the four primitive neuroectodermal tumour specimens were immunoreactive for MIC 2. Both Ewing's sarcomas and three of the four primitive neuroectodermal tumours contained the tumour-specific t(11;22), but the three neuroblastomas did not show this translocation. Based on the cytogenetic results and on the immunohistological investigation of MIC 2 expression, Ewing's sarcoma is suggested to be related closely to primitive neuroectodermal tumour. FISH is a useful aid in determining the tumour type of Ewing's sarcoma and putative related tumours.

12E7 Antigen↗

Phalangeal intraosseous well-differentiated osteosarcoma of the hand.

A case of intraosseous well-differentiated osteosarcoma in one phalanx of the hand is reported. A 78-year-old man noticed swelling in the little finger of his right hand approximately 7 years before referral. Imaging disclosed a tumour with a "ground glass" appearance and irregular mottled calcification occupying almost all of the phalanx marrow and suggested slight invasion into the soft tissue. Open biopsy suggested a diagnosis of well-differentiated fibroblastic osteosarcoma. The finger and its metacarpal bone were amputated and a tumour measuring 3.5 x 2.2 x 2.0 cm and with an indistinct soft tissue margin was found in the bone marrow. Histologically, the tumour was composed of fibroblastic cells with few mitoses, and neoplastic bone formation was apparent. Although the tumour appeared to be a fibrous dysplasia, the presence of nuclear atypia, hypercellularity, and the absence of a typical woven bone pattern in addition to the soft tissue invasion indicated otherwise. Ultrastructural examination showed focal myofibroblastic differentiation, and immunohistochemistry revealed smooth muscle actin, vimentin, osteocalcin, osteonectin and MIBI in the tumour cells. This ultrastructural and immunohistochemical study is believed to be the first detailed report of an intraosseous well-differentiated osteosarcoma of phalangeal bone.

Actins↗