Biomedical subjects
Publications and source records attributed to K Kondo.
We present the first case (to our knowledge) of acetaminophen-induced eosinophilic pneumonia. Although the patient had taken an acetaminophen-containing combination drug, Kinuya-chinnetsu, for only three days, the abnormal shadow on his chest radiograph continued for about a month. Lymphocyte stimulation tests showed that both Kinuya-chinnetsu and acetaminophen induced the proliferation of peripheral blood lymphocytes.
Total hip arthroplasty was performed on 41 patients with rheumatoid arthritis for 43 intracapsular hip fractures from 1971 to 1989. Followup, observation of clinical signs, and radiographs were conducted between one to ten years. Of the 41 patients, 25 had died by the end of the study. Total hip arthroplasty was found to be effective in relieving joint pain, and the walking ability of patients generally recovered to pre-injury status following the operation. Some patients experienced deterioration of the knee and ankle joints due to rheumatoid arthritis, and in such cases there was progressive loss of walking ability. Nevertheless, the function of the hip joint was well preserved, and most patients reported that pain had disappeared and the joint range of motion had returned to normal. In only one case was revision surgery necessary. There was little overall loosening of prostheses, and there were no problems concerning the durability of the artificial joint. The presence, therefore, of femoral neck fractures in patients with rheumatoid arthritis, who are to be encouraged to get out of bed and begin walking as soon as possible, is a strong indication for total hip arthroplasty.
A total of 34 tissue biopsies were collected from nasopharyngeal carcinoma (NPC) patients and 5 controls with non-NPC. Extracted DNA from tissue biopsies were analyzed for presence of specific gene sequences to EBV type A and type B, and HHV-6 by polymerase chain reaction (PCR). The different sequences of EBV type A and B were parts from the highly divergent forms of the EBV nuclear antigen 2 (EBNA 2). The PCR amplified products for EBNA 2A and EBNA 2B were 115 and 119 base pairs respectively whereas that of HHV-6 DNA was 776 base pairs. The results demonstrated that EBV DNA was detected in 32 of 34 cases (94.1%): 28 (82.3%) with type A, 2 (5.9%) with type B, and 2 (5.9%) with both types. EBV DNA of type A could be detected 1 (20%) of 5 controls. HHV-6 DNA was in 5 of 34 samples (14.7%) whereas HHV-6 DNA was not detectable in biopsy tissues from controls. The results show that in the NPC patient group, A type of EBV is predominant. Detection of HHV-6 DNA in patients group only might be resulted from reactivation of a latent infection or association with EBV-induction of NPC.
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Since 1983, 60 patients (60 joints) with acetabular bone loss underwent the total hip reconstruction using frozen femoral head allografts. Every 6 months, antero-posterior view radiographs of bilateral hip joints and sequential 99mTcMDP bone scintigrams were obtained. A CT scan of bilateral hip joints was taken to measure the volume of allograft. Bone incorporation was observed in 52 patients with an average time of 28.2 months. Bone scintigraphy also revealed that the uptake became normal 2-3 years after the revision. Differences in the time necessary for bone incorporation could be attributed to the size of allografts--the larger the volume, the longer the time required (p < 0.01). It was also found that on the side that received a transplant, the allograft was incorporated faster when there was more bone tissue surrounding the missing part of the acetabulum (p < 0.05).
A screening method using serum fructosamine level and the fasting plasma glucose level was used for screening patients with diabetes mellitus. The criteria for positive tests recommended by the Japanese Society of Multiphasic Health Testing and Services were evaluated. It was found that levels for the serum fructosamine of 290 mumol/l or higher (or, for the fasting plasma glucose of 110 mg/dl or higher) agreed with the standard oral glucose tolerance test in identifying patients with diabetes mellitus in 96.7% of cases, and the serum fructosamine test was simpler and less expensive.
In a study of 1040 patients undergoing cardiac surgery at The Osaka Medical College Hospital from 1984 through 1991, we analyzed the correlation between a variety of preoperative and operative parameters and the risk of postoperative sternal wound infection, as well as the efficacy of various therapeutic method for this condition. Sternal infection or mediastinitis developed after cardiac surgery in 31 patients (3.0%). As the risk factors for wound infections, age, diabetes mellitus, reexploration, duration of cardiopulmonary bypass and use of bilateral internal thoracic artery grafting were listed. Application of pectoral muscle flaps significantly led to shorten a duration between diagnosis of infection and hospital discharge, and increased survival rate, than the other treating methods such as debridement or irrigation. We conclude that bilateral internal thoracic artery grafts should not be used in the cases with diabetes, and closure with pectoral muscle flaps is effective for sternal infection and mediastinitis.
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The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.
The effect of exercise on strength and chemical composition of rat femur bone was examined. Ten 5-week-old rats were forced to exercise on a treadmill with a running speed of 20 m/min at set time intervals for a 4-week period. Another 10 rats were kept idle as controls. After exercising, bending tests of the rat femur bones were carried out, and the content ratios of Sr to Ca, Sr/Ca, were measured by energy-dispersive fluorescent X-ray analysis and EPMA line analysis. The strength of the exercise group was greater than that of the control group. The ratio, Sr/Ca, of the exercise group showed a tendency to increase compared to that of the control group. It is clear that the chemical composition of bone varies with the degree of exercise, and that the bone becomes strengthened at the same time.
A P element (PE)-induced Drosophila melanogaster mutation, hari, affects the formation of the bristle mechanosensory organ in the adult fly. In this mutation, the site of PE insertion is in the first intron of the gene (CycA) encoding cyclin A (CycA). In order to analyze the hari mutant at the molecular level, we cloned and sequenced the cDNA and genomic DNA encoding CycA. CycA has seven exons and six introns, and its transcription unit spans 6 kb. All exon-intron junctions are compatible with the GT/AG consensus. Results of primer extension analysis and RNase protection assay indicate that CycA has major and minor transcription start points (tsp). To our knowledge, this is the first report on the CycA genomic sequence from a multicellular organism.
We have identified a yeast gene encoding a protein structurally similar to mammalian nucleolin. The gene was previously cloned as a cold shock-inducible gene and found to be identical to yeast NSR1 gene, which encodes a protein that has been reported to bind sequences required for nuclear localization of protein. The carboxyl-terminal half of NSR1, consisting of two tandemly repeated putative RNA-binding domains and a glycine/arginine-rich domain, has 37% amino acid sequence identity with the same part of mammalian nucleolin, while no sequence similarities are found between their amino-terminal regions. Although a null mutation of the NSR1 gene was not lethal, it caused a severe defect on growth. Pulse-labeling analysis revealed that the nsr1 strain had reduced levels of 18 S rRNA and accumulated 35 S pre-rRNA compared with the wild-type strain. The level of 25 S rRNA was also slightly reduced in the nsr1 strain. Pulse-chase labeling experiments showed slow processing of 35 S pre-rRNA and impaired methylation of 18 S rRNA. The ratio of 40 S to 60 S ribosomal subunits in the nsr1 strain is significantly reduced and is consistent with impaired synthesis of 18 S rRNA. The results indicate that NSR1 is involved in pre-rRNA processing and ribosome biosynthesis in yeast.
Yeast NSR1 protein is structurally related to mammalian nucleolin and is involved in ribosome synthesis as described in the preceding paper (Kondo, K., and Inouye, M. (1992) J. Biol. Chem. 267, 16252-16258). We report here the regulation of NSR1 gene expression and the effect of nsr1 deletion on growth and pre-rRNA processing after cold shock. A basal level of the transcript was detected at 30 degrees C only in exponentially growing cells and increased approximately 3-fold after cold shock to 10 degrees C. NSR1 protein level also increased about 3-fold after the shock. The nsr1 deletion caused a severe growth defect at low temperatures as well as a long growth lag after temperature shift from 30 to 10 degrees C. Northern hybridization analysis demonstrated that cold shock led to a rapid decrease in the amounts of 27 S, 20 S, and 7 S rRNA precursors in the nsr1 strain, although at 30 degrees C a major defect was observed only in 20 S pre-rRNA synthesis. Pulse-chase labeling of rRNA showed that pre-rRNA processing in the nsr1 strain was greatly impaired after cold shock. These results demonstrate that the NSR1 protein is required for normal pre-rRNA processing and cell growth in yeast when cells are exposed to abrupt temperature drop.
The reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis and sequencing were used to examine p53 gene alterations in 18 surgical specimens of primary lung cancers obtained in Japan. Somatic mutations resulting in amino acid changes were found in eight of the 18 cases (44%). Seven missense mutations were located in amino acid-conserved domains or their vicinities (codons 110 to 307). Most mutations were found at G-C pairs, suggesting that specific carcinogens are involved in the etiology of lung cancer. The p53 mutations showed a significant association with a history of smoking (P = 0.0294). We suggest that the p53 mutations may be associated with smoking-induced lung carcinogenesis.
S-Nitrosothiols (S-nitrosocysteine, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine), which belong to the group of endothelium-derived relaxing factors (EDRFs), caused decreases of cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured rat vascular smooth muscle cells (VSMCs). The endothelin-1 (ET-1)-induced sustained increase of [Ca2+]i in rat VSMCs was completely abolished by preaddition of at least an equal molar quantity of S-nitrosocysteine (Cys-SNO). Also exposure of VSMCs to a mixture of Cys-SNO and ET-1 at the same time resulted in the transient increase only. These results suggest that S-nitrosothiols may have no significant effect on ET-1-induced Ca2+ release from intracellular stores via inositol 1,4,5-triphosphate production but do affect Ca2+ influx through Ca2+ channels in the plasma membrane.
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The gene for D-aminopeptidase (dap) has been isolated from the bacterium Ochrobactrum anthropi SCRC C1-38 [Asano, Y., Nakazawa, A., Kato, Y., & Kondo, K. (1989) J. Biol. Chem. 264, 14233-14239] and its nucleotide sequence determined. An expression plasmid pC138DP (4.5 kb) was constructed by placing the gene downstream of the lac promoter of pUC19. The amount of the enzyme in the cell-free extract of Escherichia coli JM109/pC138DP was elevated to 288,000 units/L of culture, which is about 3600-fold over that of O. anthropi SCRC C1-38. The enzyme comprised about 30% of the total extractable cellular protein. The gene consisted of an open reading frame of 1560 nucleotides which specifies a protein of Mr 57,257. The deduced amino acid sequence of the enzyme showed that it is related to carboxypeptidase DD, beta-lactamases, and penicillin-binding proteins. Seven mutants of the enzyme were generated by site-specific mutagenesis to explore the roles of the residues of interest, around the sequence Ser61-Xaa-Xaa-Lys64, where Xaa is any amino acid, since the identical sequences also appear in the penicillin-recognizing peptide hydrolases with Ser at the active sites. The mutant enzymes expressed in E. coli were purified to homogeneity and kinetically characterized. Replacements of the site at Ser61 and Lys64 yielded mutants showing significantly reduced Vmax values, while most of the Km values remained unchanged. Changes at Cys60, which is adjacent to the likely active center Ser61, to Ser and Gly resulted in the production of enzyme less sensitive to PCMB, with almost unaltered Vmax/Km values. The enzyme appears to be a serine peptidase rather than a thiol one. The inhibition by PCMB in the wild-type enzyme may have been caused by a formation of a mercaptide bond between Cys 60 and PCMB. Considering that D-aminopeptidase, carboxypeptidase DD (a penicillin-binding protein), and beta-lactamase have a common feature in recognizing peptides containing D-amino acid and that the former two catalyze transpeptidation reactions with substrates containing D-alanyl-D-alanine moieties, we propose that the enzyme is a new member of the "penicillin-recognizing enzymes". We showed that the enzyme is actually inhibited by beta-lactam compounds, such as 6-APA, 7-ACA, benzylpenicillin, and ampicillin, although they are not the substrate for the enzyme. The relationship between the primary structures and the reactions catalyzed by D-aminopeptidase and other serine hydrolases beta-lactamases and carboxypeptidase DD is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)