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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 523 records · Page 29Linked to original sources

[Clindamycin-2-phosphate in the treatment of respiratory infections and its distribution into pleural effusion].

We treated pneumonia due to anaerobic bacteria, Mycoplasma pneumonia, and other type of pneumonia with clindamycin-2-phosphate (CLDM-P) and studied the distribution of the drug into pleural effusion. The obtained results are summarized as follows. 1. CLDM-P showed excellent effects in all the treated cases of pneumonia due to anaerobic bacteria and Mycoplasma pneumonia. But the success rate was 50% in cases of other type of pneumonia. We suggest that the drug must be used in due consideration of the types of causative bacteria. 2. Five cases which had developed pleural effusions were treated with intravenous drip of CLDM-P 1,200 mg in 200 ml electrolytic solution to see the distribution into pleural effusions. The results showed that the distribution ratio was 9.0% on the average. Peak levels were 1.86-6.07 micrograms/ml and the concentration was as high as 1.28 micrograms/ml on the average 24 hours after administration.

Adolescent↗

[Basal skull metastasis of stomach cancer presenting with Garcin's syndrome--a case report].

A case of 57-year-old man with Garcin's syndrome is reported. By means of upper gastrointestinal endoscopy, this patient proved to have a stomach cancer. He noticed left trigeminal neuralgia for the first time in early Jan. 1986, and when he was referred to our department, his symptoms and signs of left cranial nerve palsy (from 5th to 12th, totally 8 nerves) were complete, although other neurological findings such as long tract signs, cerebellar signs, or papilledema were all negative. Although skull X-ray and basal skull tomography revealed neither bony deformity nor destruction, CT scan and angiography showed suspicious appearance of basal skull invasion of a certain mass. CSF examination revealed no malignant cells or abnormal protein, and sugar content. Exploratory craniotomy for tumor biopsy was performed. Histologically, the tumor had characteristics of anaplastic carcinoma. General survey revealed that he had a stomach cancer which was histologically the same as the basal skull tumor. His general condition became so serious that irradiation to the lesion was not indicated Among many papers reported about Garcin's syndrome, those of basal skull metastasis of stomach cancer are extremely rare. The authors discussed the lesion in comparison with meningeal carcinomatosis involving cranial nerves.

Carcinoma↗

A multivariate study on enzymatic changes in limb muscles and heart muscle of dystrophic mice.

The present study was undertaken to elucidate further the enzymatic changes in dystrophic muscle using multivariate analysis. The activities of 14 kinds of enzymes, including 6 exopeptidases, 4 endopeptidases, beta-N-acetyl-D-glucosaminidase, phosphatase, esterase, and ribonuclease, were examined in forelimb and hindlimb muscles as well as in cardiac muscle of dystrophic mice and their controls. Two principal components identified from the enzymatic spectrum proved to be related especially to aminopeptidases and to serine proteinases, respectively. The enzymatic changes in forelimb muscle were very similar to those in hindlimb muscle when both were compared to those in cardiac muscle. The changes in aminopeptidases were unique to the limb muscles, whereas those of serine proteinases were unique to cardiac muscle of dystrophic mice. In the future, more attention should be focused on the role of exopeptidases in pathogenetic mechanisms of muscular dystrophy, because of the possibility that they play a major role in the initial stage of muscular dystrophy.

Animals↗

Association of primary hyperparathyroidism with myotonic dystrophy in two patients.

In two patients primary hyperparathyroidism developed in association with myotonic dystrophy (MyD). Both patients had solitary adenoma, and the adenomas were surgically removed. After the operation, subjective improvement of muscle weakness was found in one patient. Because parathyroid hormone secretion is regulated by extracellular calcium concentration and because abnormalities in transmembrane calcium transport are thought to play a role in the pathogenesis of MyD, the concurrence of these rather rare disorders in two patients raises the possibility that abnormalities in transmembrane calcium transport may underlie the development of primary hyperparathyroidism in patients with MyD. Although further studies are needed to clarify the possible link between these two disorders, the present study emphasizes the importance of evaluation of parathyroid function in patients with MyD.

Calcium↗

Tumor promoter, TPA, enhances replication of HTLV-III/LAV.

The incubation of Molt-4/HTLV-III cells, human T-lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV)-producer cell line, with more than 0.5 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 2 to 4 days stimulated virus-induced cell killing which resulted in a high production of HTLV-III/LAV. TPA significantly increased the number of plaque-forming viruses released from the cultures as well as viral RNA content. Interestingly, MT-4 cells freshly infected with HTLV-III/LAV treated for 4 days with 0.125 to 2.0 ng/ml of TPA were found to retain the capacity to grow, because TPA inhibited the induction of the virus-specific antigens and cytopathic effects. In contrast to the situation in infected MT-4 cells in liquid cultures, the addition of 0.125 and 0.25 ng/ml of TPA into agarose medium induced large plaques, suggesting that TPA basically enhanced the production of the virus from one infected MT-4 cell. Taken together, the data suggest that TPA enhances the replication of HTLV/III/LAV. These assay systems are shown to be useful for analyzing the induction or suppression of a virus infection by many drugs and other factors in vitro.

Antigens, Viral↗

Two sulfur-containing ansamycin antibiotics from Streptomyces albolongus.

Two sulfur-containing ansamycin antibiotics were isolated from the culture broth of Streptomyces albolongus C-46366; the major one was identical with awamycin and the minor one was a new ansamycin antibiotic, ansathiazin. Their structures were elucidated from their reactions and spectroscopic analyses. These antibiotics were active against gram-positive bacteria, acid-fast bacteria and a protozoan.

Anti-Bacterial Agents↗

Preliminary crystallographic study of a ribulose-1,5-bisphosphate carboxylase-oxygenase from Chromatium vinosum.

Crystals of a ribulose-1,5-bisphosphate carboxylase-oxygenase from Chromatium vinosum were obtained with the hanging-drop vapor diffusion technique, using polyethylene glycol 4000 as precipitant. The crystal belongs to the cubic system, space group I432, with unit cell dimension a = 245.9 A. An asymmetric unit includes one-quarter (L2S2, L: large subunit, S: small subunit) of a hexadecameric molecule (L8S8, 544,000 Mr), which is located on the crystallographic point symmetry 222 or 4. The crystal diffracts to at least 3.0 A resolution.

Chromatium↗

Sensitive assay for neutralizing antibodies against AIDS-related viruses (HTLV-III/LAV).

A sensitive assay for neutralizing antibodies (NA) against AIDS-related viruses (HTLV-III and LAV) was developed, using human T-cell lymphotropic virus type-I (HTLV-I)-bearing and HTLV-III-susceptible MT-4 cells. NA to HTLV-III in 21 patients with acquired immune deficiency syndrome (AIDS), 10 individuals with AIDS-related complex (ARC), 20 healthy male homosexuals, and 10 healthy male controls were titrated. Antibodies to HTLV-III were also detected by indirect immunofluorescence (IF). The assay was sensitive up to a dilution of 1:10 000. Sera from patients with AIDS showed a geometric mean titer (GMT) of NA of 1:475, whereas much higher GMTs (1:1318 and 1:1009) were observed in patients with ARC and healthy male homosexuals, respectively. Moreover, titers of NA significantly correlated with the levels of anti-HTLV-III antibodies detected by IF.

Antibodies, Viral↗

Recombinant human interferon gamma suppresses HTLV-III replication in vitro.

Effect of human interferon gamma (rINF gamma) on HTLV-III replication was evaluated quantitatively via a novel infection system using HTLV-I-carrying MT-4 cells. Treatment of HTLV-III-infected MT-4 cells with different concentrations (I-1,000 U/ml) of rINF gamma, which did not affect the growth or viability of uninfected cells, significantly blocked the appearance of immunofluorescent antigens of HTLV-III and the virus-induced cytopathic effect in a dose-dependent manner. A plaque assay was applied to measure the exact amount of viral particles released from HTLV-III-infected MT-4 cultures either untreated or treated with rINF gamma after infection. The number of plaques per dish decreased with increasing drug concentrations. About 50% and 80% of HTLV-III replication were inhibited by the addition of 100 and 1,000 U/ml of rINF gamma, respectively. The effects of INF were observed by day 5 of incubation with the chemical. However, longer treatment of cells with rINF gamma permitted a gradual increase in viral replication. Re-addition of fresh INF into cultures did not change this pattern significantly.

Antigens, Viral↗

[Examination of the fine interstitial changes of pneumoconiosis with high resolution computed tomography (HR-CT)].

High resolution CT was performed in 14 patients with fine interstitial changes of pneumoconiosis and Review image was evaluated for the diagnostic accuracy as compared with conventional chest roentgenogram. Of the 14 Patients in the study, 7 were divided category 1 by the ILO U/C classification, 4 were category 2, 3 were category 3. Studies of lung function showed obstructive ventilatory disturbance characterized by moderate reduction in FEV1.0% (58.6 +/- 16.5%) and V25/H (0.34 +/- 0.24 l/sec/m). HR-CT defined more sensitive in the presence of fine lung nodules than conventional X-p, and showed high contrast interfaces provided by the aerated lung. HR-CT was also of value in detecting bulla, bleb, peripleural changes and hilar lymphadenopathy. Radiologic-pathologic correlation was examined on the specimens of transbronchial lung biopsy in 4 patients, and revealed the diagnostic usefullness of HR-CT.

Adult↗

[A case of sarcoidosis with marked bronchial involvement].

Bronchial mucosal biopsy is considered to be a useful procedure for the diagnosis of sarcoidosis in Europe and the USA. However, bronchial involvement of sarcoidosis has seldom been reported in Japan. We report an interesting case of sarcoidosis with marked bronchial changes. A 40-year-old symptom free women visited our hospital to seek a diagnosis concerning a diffuse reticulonodular shadow in her chest X-ray film. Bronchofiberscopy showed multiple nodules, yellow white plaques and hypervascularity of the thickened edematous mucosa with severe stenosis and deformity of the lober or segmental bronchi. Bronchial mucosal biopsy as well as TBLB revealed typical non-caseating epithelioid granulomas. A pulmonary function test showed restrictive ventilatory disturbance with impaired diffusing capacity and small airway dysfunction. After corticosteroid therapy, bronchial mucosal changes disappeared and chest radiological and pulmonary function abnormalities were improved. After reviewing the bronchofiberscopic findings of 11 cases of sarcoidosis, we found bronchial mucosal changes in 8 cases. Bronchial mucosal biopsy should be regarded as an important procedure for the diagnosis of sarcoidosis.

Adult↗

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis. VIII. Genetic polymorphism of cytosol polypeptide with molecular weight of 20,000.

We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 20,000 detected in lymphocytes and erythrocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, and 2-2) of the polypeptide have been identified in a Japanese population. Family studies indicate that the phenotypes are determined by two common alleles at a single autosomal locus. The polypeptide is present in the cytosol of various kinds of cells and is abundant in erythrocytes. The data on a gel filtration of the erythrocyte cytosol proteins on a Sephadex G-100 column suggest that the polypeptide exists as a dimer in cells. In nine out of 79 individuals, the phenotypes of the polypeptide were different from those of glyoxalase 1 (GLO1) which has similar properties in subunit size, cell distribution, and allele frequencies. These data indicate that the polypeptide with mol. wt. of 20,000 is a new polymorphic cellular polypeptide. We propose that the polypeptide be temporarily designated as cytosol polypeptide with mol. wt. of 20,000 (CP20) and that the gene for CP20 be designated as CP20. The gene frequencies of two common alleles (CP20(1) and CP20(2) are 0.955 and 0.045, respectively, in a Japanese population.

Blood Proteins↗

Amplification of the amyE-tmrB region on the chromosome in tunicamycin-resistant cells of Bacillus subtilis.

In a class of tunicamycin-resistant mutants (tmrA7) of Bacillus subtilis, the production of extracellular alpha-amylase is increased by about five fold. The tmrA7 characteristics (tunicamycin resistance and hyperproduction of extracellular alpha-amylase) can be transferred to recipient cells by transformation. In the transformants and the original tmrA7 mutant, typical amplification of the region from 4 kb upstream of the amyE gene to the tmrB gene on the chromosome was detected. The repeating unit, 16 kb in size, repeats tandemly about five and ten times in the mutant and transformants, respectively, and the alpha-amylase production is proportional to the copy number of the amyE gene. Simultaneous amplification of the tmrB gene, which is responsible for tunicamycin resistance in the multicopy state, and the alpha-amylase structural gene (amyE) seems to be the cause of the pleiotropy of the tmrA7 mutation.

Bacillus subtilis↗

Effect of HTLV-III on the macromolecular synthesis in HTLV-I carrying cell line, MT-4.

Upon infection of human T-cell leukemia virus type I (HTLV-I)-carrying human T-cell lines such as MT-4, HTLV-III, a probable etiologic agent of acquired immune deficiency syndrome (AIDS) caused fast and strong cytopathic effects leading ultimately to the death of the cells. Such effects were preceded by the rapid induction of HTLV-III antigens. Cell lines not infected with HTLV-I could, however, be subcultured after infection with HTLV-III, although they were also positive for HTLV-III antigens. To understand this cytopathogenicity of HTLV-III in HTLV-I bearing cells, macromolecular synthesis, including DNA synthesis and total protein synthesis, and also IL-2 receptor expression were investigated kinetically. In infected MT-4 cells DNA synthesis was markedly inhibited by HTLV-III after the HTLV-III antigen synthesis became evident. This inhibition occurred before cell damage was detected in terms of viable cell-growth, but after induction of HTLV-III antigen. Puromycin, at 40 micrograms/ml, caused no toxic changes in MT-4 cells over 3 days but prevented viral antigen synthesis and virus-induced cytopathic effect. Protein synthesis and IL-2 receptor expression were also inhibited at 4 and 5 days post infection. The degree of the effects and their kinetics suggest that they are the secondary effects of cytotoxicity by HTLV-III infection.

Cell Line↗

Pulmonary angiitis with atypical lymphoreticular infiltrates in Wiskott-Aldrich syndrome: possible relationship of lymphomatoid granulomatosis and EBV infection.

We describe a 12-year-old boy with Wiskott-Aldrich syndrome who developed a pulmonary vasculitis associated with lymphoreticular proliferation, consistent with the histological and clinical diagnosis of lymphomatoid granulomatosis. The lesions were responsive to cyclophosphamide and steroids. The patient has had severely depressed immune function and was shown to have abnormal Epstein-Barr virus (EBV)-specific cellular and humoral immune responses. Lymph nodes obtained at autopsy were positive for EBV genome. In this patient, reactivated EBV infection resulting from impaired immune surveillance of the virus may have been responsible for the development of this paraneoplastic disorder.

Child↗

In-vitro infection of chronic lymphocytic leukemia cells by Epstein-Barr virus (EBV).

We sought to determine the potential of infecting lymphoid cells from patients with chronic leukemia (CLL) with Epstein-Barr virus (EBV) by testing for EBV receptors (EBVR) by flow cytometry, assessing for infectability of these cells by culturing with B95-8-derived virus, and staining for EB nuclear-associated antigens (EBNA) at various times post-infection. EBVR were present on 54-91% of lymphoid cells in seven cases of CLL and on 46% of prolymphocytic leukemia cells. Dynamic changes regarding EBNA positivity, morphology, and viability occurred post-infection with the virus. On day 2 only a few EBNA-positive lymphoblasts were observed. On days 11-21 positivity increased from 2 to 34% of cells. Simultaneously, the viable cell number declined to approximately 1/10th of original number. A significant proportion of the EBNA-positive cells corresponded to the original CLL cells. In 3 of 7 cases of CLL a Pan T-cell phenotype was demonstrated by Leu-1 monoclonal antibody testing. The infected cells did not react with two monoclonal antibodies, EBV-CS 1 and 4, which react with B-cell lymphoblastoid cell lines (B-LCL). Moreover, the B-LCL derived at 1-2 months post-infection of CLL cells did not express the Leu-1 antigen, but expressed EBV-CS 1 or 4 defined antigens. In the prolymphocytic leukemia, 64% of the cells showed EBNA positivity on day 7 and giant cells with huge round or multiple nuclei appeared which were EBNA-positive. CLL and prolymphocytic leukemia cells can be infected as demonstrated by EBNA-positivity. This infection does not lead to immediate transformation, but evokes lymphoblast and multinucleated giant cell production prior to the death of cells.

Aged↗

Establishment of a high production system for AIDS retroviruses with a human T-leukemic cell line Molt-4.

A cell culture system was developed for the continuous and efficient production of acquired immune deficiency syndrome (AIDS) retrovirus. After infection of a human T-cell line Molt-4 with HTLV-III and LAV the cells grow permanently and produce large amounts of virus continuously. The yields of production of virus were assessed either with reverse transcriptase activity or a newly established biological quantitation assay of active virus. The amounts of virus with this cell system were much higher than those of the H9 cell system. This procedure enabled us first to compare the two viral isolates HTLV-III and LAV directly in the same cell line. Establishment of the culture system, allowing efficient production of AIDS retroviruses, provides a useful tool for the isolation of the virus from patients with AIDS and for more basic research, such as the mechanisms of immune destruction caused by the virus leading to the occurrence of various malignancies.

Cell Line↗