Therapeutic synergism between low-dose FK 506 and antimetabolites in rat allogeneic heart transplantation.
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Biomedical subjects
Publications and source records attributed to H Miyazawa.
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A 70-year-old male, who suffered from infection by MRSA and Aspergillus of the recurrent large bullae, was operated on cavernostomy for space sterilization. About three months later he underwent muscle plombage with the pedicled latissimus dorsi and serratus anterior flap. These muscles are ideal to place in open wound in the thorax because of the following reasons: These have the ability to eliminate local infection, a sufficient length and volume to obliterate an open cavity. And transposition of these muscles cause minimal functional upper extremity disability. Therefore, we considered that this technic was useful for the case of an infectious intrathoracic cavity with many bronchial fistulas.
A 45-year-old man complaining of bloody sputum was admitted. He had been treated for pulmonary tuberculosis since October 1988. He had bloody sputum in October 1989. His chest X-ray findings showed a cavitary lesion with a thickened and irregular wall in the right upper lobe. Fiberoptic bronchoscopy revealed white nodules on the cavity wall and the biopsy specimen from the nodule yielded a fungus granuloma. Aspergillus fumigatus was cultured from the sputum obtained after the bronchoscopy. Based on these findings, endobronchial aspergillosis and productive aspergilloma on the inner wall of a cavity was diagnosed. He was treated with oral anti-fungal drugs for 4 years. On chest X-ray films taken in June 1993, the cavity had enlarged, and the thickening and irregularity of the cavity wall had disappeared. Transbronchial fiberoptic bronchoscopy within the cavity showed whitish nodules and the cytology specimen obtained from the nodules by brushing yielded fungi, he was treated with oral itraconazol. Six months later, re-examination of the cavity revealed that the wall had become thinner and that the nodules on the inner wall had disappeared. This case illustrates the importance of bronchoscopy, in the diagnosis and evaluation of treatment of productive aspergilloma on the inner wall of a cavity.
A 65-year-old woman was referred to our department because of an abnormal shadow on the chest roentgenogram. The chest roentgenogram showed infiltrative shadows in the right middle and lower lung fields. The chest CT scan showed non-segmental infiltration with a hazy margin and a clear air bronchogram in the right S8 area. A transbronchial aspiration cytology specimen showed atypical lymphocytes, and a transbrochial lung biopsy specimen showed infiltration by atypical lymphocytes. Malignant lymphoma was suspected from the results of the biopsy examination, and a right middle and lower lobectomy was done. The pathological findings showed proliferative atypical lymphocytes in the alveolar and interstitial areas. Malignant lymphoma (diffuse medium cell type by LSG classification) was diagnosed and an immunohistiochemical examination showed monoclonal proliferation of T lymphocytes, which were positive for T lymphocyte surface marker (UCHL-1). Therefore, we believe this was a case of primary pulmonary malignant lymphoma of the T-cell type.
A complementary DNA encoding DNA-dependent ATPase Q1 possessing DNA helicase activity, which is the major DNA-dependent ATPase in human cell extracts, was cloned from a cDNA library of human KB cells. The predicted amino acid sequence has seven consecutive motifs conserved in the RNA and DNA helicase super family and DNA helicase Q1 belongs to DEXH helicase family. A homology search indicated that helicase Q1 had 47% homology in the seven conserved regions with Escherichia coli RecQ protein. Three RNA bands of 4.0, 3.3, and 2.2 kilobases were detected in HeLa cells by Northern blotting. Analysis of the genomic DNA indicated the presence of a homologous gene in mouse cells. The DNA helicase Q1 gene was localized on the short arm of human chromosome 12 at 12p12.
Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 10 normal volunteers with the purpose of measuring rCBF changes related to taste physiology. Discrimination of 0.18% saline from pure water was associated with significantly increased rCBF values in the thalamus, the insular cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the lingual gyrus, the caudate nucleus, and the temporal gyri. The results indicate that rCBF changes in these structures may reflect oral exposure to salt.
Following rat heterotopic heart allotransplantation, low to lethal doses of the antimetabolites mizoribine (MIZ), RS-61443 (RS), and AZA were given alone or in combination with subtherapeutic doses of FK506 (0.04 mg/kg/day) for 14 days after transplantation. With the median effect analysis of Chou and Kahan for quantitative drug interactions, substantial therapeutic synergism was demonstrated between FK506 and non-toxic doses of MIZ (2.5, 5, and 10 mg/kg/day) or AZA (5, 30, and 45 mg/kg/day), which was particularly evident with the lowest dose MIZ (2.5 mg/kg/day). When FK506 was used in combination with MIZ or AZA but not with RS, the maximum effect (peak median graft survival) was enhanced significantly from 15 days (MIZ alone) to 26 days (P < 0.05), and from 19 days (AZA alone) to 32 days (P < 0.01). In contrast, RS interacted with FK506 no more than additively. Although RS was the most powerful single antimetabolite, the best overall survival was obtained by combining AZA and FK506. The addition of FK506 did not significantly increase the percent mortality and LD50 of the antimetabolites.
DNA polymerase alpha is a key enzyme in eukaryotic chromosomal DNA replication. tsFT20 is a temperature-sensitive mutant cell line derived from mouse mammary carcinoma FM3A cells, and the cells contain heat-labile DNA polymerase alpha and are arrested at the S phase at the nonpermissive temperature. We isolated cDNA of the catalytic subunit of DNA polymerase alpha from tsFT20 cells. DNA sequence analysis revealed that the cDNA from tsFT20 has a single mutation, a cytosine to thymine substitution that changes amino acid 1180 from serine to phenylalanine. We have also shown that tsFT20 cells could be rescued by transfection with the wild-type cDNA. These results demonstrate that the point mutation in the gene of DNA polymerase alpha causes the temperature-sensitive phenotype of tsFT20 cells and provide additional evidence that DNA polymerase alpha is essential for chromosomal replication in mammalian cells. We also detected mutation sites in one spontaneous and six N-methyl-N'-nitro-N-nitrosoguanidine-induced growth revertants of tsFT20 cells by single strand conformation polymorphism analyses and direct sequencing. All revertant cell lines had a second point mutation adjacent to the first mutation site in tsFT20 cells.
We evaluated the removal of a cat major allergen (Fel d I) from futons (Japanese bedding) with the use of a large-sized home washing machine. Before and after washing a futon that had been used in a home with a cat, a small amount of cotton was collected from the futon and Fel d I was extracted from the cotton. The levels of Fel d I were assayed by a sandwich enzyme-linked immunosorbent assay (ELISA). We found that washing reduced the Fel d I level in futons by more than 95%. In conclusion, washing of futons is an effective method for elimination of their cat allergens.
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To evaluate the role of allergens from Periplaneta fuliginosa, which is the most predominant cockroach species in homes in Tokyo areas, for asthma sensitization, we measured specific IgE antibodies to two cockroaches, P. fuliginosa and Blattella germanica, and to a mite, Dermatophagoides farinae, in 171 sera from children with asthma by Pharmacia's CAP system. We found that 16% of the sera had anti-P. fuliginosa IgE, whereas 9.9% had anti-B. germanica and 85% anti-D. farinae IgE. Further, we measured the levels of Per f I (Per a I equivalent) allergen in the house dust from living room, kitchen and bedding. We detected the allergen in eight of ten homes. The Per a I equivalent levels in kitchen were higher than in other sites, but they were much lower than Der I and Der II as Dermatophagoides allergens.
During the period of eight years from 1985 to 1992 we had sixteen patients (pulmonary tuberculosis: 6, atypical mycobacteriosis: 10) who had been under the treatment for tuberculosis and on whom home oxygen therapy (HOT) was started. Of sixteen patients twelve had history of antituberculous therapy in the past. There were nine chronic active or persistently sputum positive patients of whom three were pulmonary tuberculosis and six atypical mycobacteriosis. The duration of illness was long in these patients and it was more than ten years in tuberculosis patients. Four cases died, two cases of pulmonary tuberculosis died from hemoptysis, and two cases of atypical mycobacteriosis died from respiratory failure.
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This report is a case study of miliary tuberculosis that was induced when adrenocorticosteroid treatment for tuberculosis of the wrist was given because of a mistaken diagnosis of rheumatoid arthritis. An 85-year-old man was admitted to a hospital with a fever and chest pains. Since an examination of the chest X-ray revealed fine nodules throughout both lungs and a sputum smear tested positive for acid-fast bacilli, he was transferred to our hospital. The patient had a three-year history of pain in his left wrist joint. He had swelling on the dorsal aspect of his left wrist for 1 1/2 years, and had been diagnosed as having rheumatoid arthritis. Prednisolone had been administered in dosages of 5 mg per day for two months and 5 mg every other day for four months prior to admission. Upon admission to the hospital, an X-ray examination of the wrist revealed marked destruction of the left carpal bones. Smears of fluid aspirated from the swelling showed acid-fast bacilli, and cultures grew M. tuberculosis. He was treated with INH, RFP and SM, however, he had complications of tuberculous spondylitis and renal tuberculosis, and died nine months after admission.
A case of pulmonary eosinophilic granuloma confirmed by transbronchial lung biopsy (TBLB) is reported. A 63-year-old man was admitted to our hospital complaining of productive cough and exertional dyspnea. Chest roentgenogram and computed tomography showed bilateral linear and reticular shadows predominantly in the upper and middle lung fields. TBLB was performed and the specimens showed granulomatous lesions consisting of histiocytes with infiltration of eosinophils. Histiocytes were positive for S-100 protein by immunohistochemistry. He was diagnosed as having pulmonary eosinophilic granuloma. In the diagnosis of pulmonary eosinophilic granuloma, open lung biopsy is useful, but TBLB is also useful for diagnosis in the active or early stage of this disease.
We investigated the relationship between the amounts of Cry j I in house dust and airborne Cryptomeria japonica pollen in the same location. Cry j I was still detected in house dust collected two weeks after airborne C. japonica pollen had disappeared. Disappearance of Cry j I in house dust coincided with the disappearance of symptoms in the C. japonica pollinosis patients who lived in the same area. Airborne Cupressaceae pollen appeared during the latter half of the C. japonica pollen season. Disappearance of Cupressaceae pollen did not coincided with the disappearance of the symptoms in C. japonica pollinosis patients. Therefore, some symptoms of C. japonica pollinosis patients after C. japonica pollen disappeared from the air may be caused by pollen which had attached to clothes and been brought indoors.
The regional cerebral blood flow (rCBF) was measured with positron emission tomography in eight normal volunteers with the purpose of measuring rCBF changes related to the comprehension of an unfamiliar spoken languages. When attempting to comprehend the meaning of words, the left hemisphere showed dominant increases in rCBF, however, when subjects attempted to evaluate the emotional tone of the same spoken passage, relatively large increases in rCBF more found in the right hemisphere. The results indicate that there may be several different auditory representations of language which involve both left and right hemispheres, both of which may contribute to the overall comprehension of spoken language.
The DNA polymerase alpha-primase complex purified from mouse FM3A cells is composed of four polypeptides with molecular masses of 180, 68, 54, and 46 kDa. The largest subunit has DNA polymerase activity, the two smallest subunits have DNA primase activity, and the function of the 68-kDa subunit is unknown. We have isolated the cDNAs of the four subunits by low stringency hybridization and reverse transcription polymerase chain reaction and determined their nucleotide sequences. The predicted amino acid sequence of the 180-kDa subunit shows 88, 38, 34, and 32% identity to those of the catalytic subunits of human, Drosophila melanogaster, Schizosaccharomyces pombe, and Saccharomyces cerevisiae DNA polymerase alpha, respectively, and contains seven regions whose orders and sequences are highly conserved among viral and other eukaryotic DNA polymerases. The deduced amino acid sequence of the 68-kDa subunit shows 25% identity to that of the 73-kDa subunit of D. melanogaster DNA polymerase alpha-primase, shows no significant sequence similarity to any other protein in the data bases, but contains a potential phosphorylation site(s) for cdc2 kinase. The amino acid sequence of the 54-kDa subunit shows 32% identity to that of the large subunit of S. cerevisiae DNA primase. During activation of quiescent Swiss mouse 3T3 cells to proliferate, the levels of mRNA of the four subunits of the DNA polymerase alpha-primase complex increased before DNA synthesis. In growing mouse FM3A cells, the transcripts of the four subunits are present throughout the cell cycle and increase slightly prior to the S phase.