[Drug-induced interstitial pneumonitis].
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Biomedical subjects
Publications and source records attributed to M Kido.
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We examined the DNA from 12 patients with ovarian tumors (four benign germ cell tumors, one malignant germ cell tumor, one benign common epithelial tumor and six common epithelial carcinomas) for the allele loss on chromosome 17 using 12 probes for hypervariable loci. At THH59 loss of heterozygosity (LOH) was detected in three benign germ cell tumors and two epithelial carcinomas. At a more distal locus, KKA35, LOH was detected in three benign germ cell tumors and one epithelial carcinoma.
A considerable number of gastric cancers derive from stomach mucosa where chronic atrophic gastritis is severe and extensive. Based on the fact that the serum pepsinogen levels provide a precise measure of the extent of chronic atrophic gastritis, we have devised a mass screening method involving serum pepsinogen measurement to identify subjects at high risk of gastric cancer. In 1991, we screened 4,647 workers (male: 4,113, female: 534, mean age: 49.0 years) at a Japanese company using this method. Out of 875 subjects (18.8%) with a serum pepsinogen I level of less than 50 micrograms/liter and a pepsinogen I/II ratio of less than 3.0, 676 subjects (14.5%) were selected for further investigation by endoscopy. This led to the detection of four subjects (0.086%) with gastric cancer (three in an early stage) and four subjects with adenoma. The cancer detection rate of this new screening method was comparable, and in some respects superior, to that of the traditional barium X-ray screening. Since the incidence of test-positive subjects was as low as 10% amongst subjects aged less than 40, this screening method appears to be especially useful for screening of younger generations. The new method is less expensive than the traditional barium X-ray and subjects experience little discomfort. Further, many serum samples can be quickly measured simultaneously. The results of this study have indicated that serum pepsinogen screening provides a valuable method for detecting gastric cancers.
The objective of this study was to evaluate the combined effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor (TNF) by alveolar macrophages. Rats were exposed to cigarette smoke in vivo, and production of TNF by alveolar macrophages was measured in the presence of mineral fibres in vitro. For smoke exposure, rats were divided into two groups. Five were exposed to a daily concentration of 10 mg/m3 of cigarette smoke for an eight hour period, and five rats (controls) were not exposed to smoke. Bronchoalveolar lavage was performed after exposure to smoke and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibres on a microplate for 24 hours. Activity of TNF in the supernatant was determined by the L-929 fibroblast cell bioassay. When alveolar macrophages were not stimulated by mineral fibres, production of TNF by rats exposed to smoke and unexposed rats was essentially the same. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibres, production of TNF by alveolar macrophages from rats exposed to smoke was higher than that by alveolar macrophages from unexposed rats. The findings suggest that cigarette smoke and mineral fibres have a synergistic effect on TNF production by alveolar macrophages.
To determine the factors that predispose the patient with lung cancer to develop terminal pulmonary infections, we reviewed the case records and autopsy data of 304 patients who died of lung cancer in the Kyushu University Hospital between 1976 and 1990. The incidence of mycobacterial infection was significantly higher among those treated with antineoplastic therapy and corticosteroids (group 3) than in those who received antineoplastic therapy alone (group 2). The incidence of nonbacterial infection did not differ significantly between the two groups. In some group 3 patients, the administration of corticosteroids for relatively short periods (less than one month) led to fatal mycobacterial infection. Among those patients with lymphocytopenia, the incidence of fatal mycobacterial infection was significantly higher in group 3 than in group 2, whereas the incidence of fatal nonbacterial infection was not. In group 3, the incidence of fatal mycobacterial and nonbacterial infections did not differ significantly among those with and without lymphocytopenia. Thus, in patients with lung cancer who were receiving antineoplastic treatment, corticosteroids were more closely associated with the development and exacerbation of mycobacterial infection than was lymphocytopenia. The influence of corticosteroids on the development of nonbacterial infection was not more marked than that of lymphocytopenia. The incidence of common bacterial infections was no higher among those patients who received no antineoplastic treatment or corticosteroid (group 1), group 2, and group 3. Therefore, the local and systemic effects of the lung cancer itself are likely more important in predisposing the patient to bacterial infections than are either antineoplastic agents or corticosteroids.
We report three cases of pulmonary cryptococcosis in which one community acquired and two nosocomial infections were suspected. Clinical studies were focused on histological and immunological diagnosis and antifungal chemotherapy. The first case was initially suspected of having primary cryptococcosis. The second case was first suspected to have BOOP on the basis of clinical and radiological findings. The third was initially suspected of having lung cancer because of an enlarging mass lesion in fibrotic lung and elevated tumor markers. All cases were treated with antifungal agents. Two cases were treated with fluconazole alone, the other case with fluconazole and 5-fluorocytosine. In all cases, the abnormal shadows on chest X-ray demonstrated 50 to 90 percent improvement within 6 months, and cryptococcal antigen in the serum decreased. There were no side effects from the drugs.
We report two cases of pulmonary lymphangioleiomyomatosis with recurrent spontaneous pneumothorax. The cases were diagnosed by open lung biopsy. Case 1 was a 38-year-old woman, whose chest X-ray showed linear and reticular shadows. Lung tissue was negative for hormone receptors. She was treated with tamoxifen, but developed allergic symptoms. Her condition gradually deteriorated despite oxygen and progesterone therapy. Case 2 was a 41-year-old woman, whose chest X-ray showed a reticular shadows and slight overinflation. Hormone receptors were not examined, but the disease did not progress with oxygen, progesterone and GnRH agonist (Sprecur) therapy.
A 61-year-old man was admitted to our hospital on October 8, 1991 because of abnormal shadows on chest X-ray at annual checkup at his company. Chest X-ray and CT on admission showed diffuse reticular shadows in bilateral lower lung fields and a nodular opacity approximately 10 mm in diameter in the right lower lung. Since transbronchial lung biopsy was not diagnostic, an open lung biopsy was performed on October 28, 1991. The lung specimens showed diffuse pulmonary fibrosis compatible with usual interstitial pneumonia and an intrapulmonary lymph node containing silicotic nodules. Only 29 cases (including the present case) of intrapulmonary lymph nodes have been reported. Although the causes of intrapulmonary lymph nodes are not clear, smoking is considered to play an important role in the development of pulmonary lymphoid tissue. In our case, the intrapulmonary lymph node contained silicotic nodules. Only several case have been reported to have silicotic nodules in the lymph nodes. As suggested by Kradin, they may be induced by relatively low levels of exposure to dust. Our case also had pulmonary fibrosis (IIP), and is the first reported case of intrapulmonary lymph node associated with IIP. Although it is difficult to determine these two diseases occurred coincidently or not, it is possible that a low level of dust exposure may have contributed to both silicotic nodules in the lymph node and IIP.
We tried to make a well-characterized bacterial protein function in mammalian cell nuclei. For this purpose we chose Escherichia coli RecA protein and fused its carboxy terminus to the nuclear location signal of SV40 large T-antigen by oligonucleotide-dependent modification of the gene. When injected into the cytoplasm, the modified RecA protein (T-RecA for the T-antigen signal) accumulated efficiently in the nuclei, whereas the wild-type RecA protein remained in the cytoplasm. The T-RecA protein retained its original in vivo activity, judging from the finding that uv-sensitive bacteria (recA- E. coli) became uv-resistant on transformation with the T-recA plasmid as well as the recA plasmid. For expression of the T-recA gene in mammalian cells, the 5' region was replaced by the chicken beta-actin promoter and Kozak's initiation signal. A high level of expression was observed when Chinese hamster ovary (CHO-K1) cells were transfected with this plasmid. Indirect immunofluorescence examination revealed that the T-RecA protein in nuclei of mammalian cells bound to chromatin.
Mouse lung tumors were induced in C57BL/6J(female) x A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors.