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Biomedical subjects

O Katoh

Publications and source records attributed to O Katoh.

At least 91 records · Page 5Linked to original sources

Clinical pharmacology and toxicity of low daily administration of oral etoposide in advanced lung cancer patients.

In this study, pharmacokinetics, clinical effects, and toxicity of daily oral etoposide were studied in 12 patients with advanced lung cancers. Administration schedule was 25 mg/body everyday of a 4-week cycle or 50 mg (25 mg twice)/body for 14 consecutive days of a 4-week cycle. The pharmacokinetic parameters of both groups in serum were as follows: 1) mean peak plasma concentration of 0.91 +/- 0.18 micrograms/mL (25 mg) and 1.24 +/- 0.12 micrograms/mL (25 mg twice); 2) elimination half-lives of 6.48 +/- 1.09 hours (25 mg) and 3.64 +/- 0.27 hours (25 mg twice); and 3) the area under the plasma concentration curve of 7.09 +/- 1.26 micrograms.hr/mL (25 mg) and 8.67 +/- 0.77 micrograms.hr/mL (25 mg twice). There was a significant difference between those two schedules in terms of the plasma concentration and the duration at a low concentration (greater than 1 micrograms/mL) of etoposide. Low daily administration of oral etoposide is shown to be well tolerated and easy on the patient. More studies are needed to study whether prolonged schedules of lower doses of etoposide could result in improved prognosis.

Adenocarcinoma↗

Autocrine and/or paracrine mechanism operate during the growth of human bone marrow fibroblasts.

The growth of human marrow fibroblasts was studied at various plating cell densities. The growth rate of fibroblasts cultured with human plasma derived serum (PDS) increased depending on the cell density plated, whereas fibroblasts cultured with human serum proliferated almost independent of the cell density. Conditioned medium obtained from the culture with PDS at high cell density enhanced the growth of fibroblasts plated at low density, as well as that of fibroblast colony forming cells. Characterization of this conditioned medium showed heat unstable and acid stable peptide factor(s) with high molecular weight (approximately 10(6)) may be responsible for this activity. These results suggest that autocrine and/or paracrine mechanism can operate during the proliferation of marrow fibroblasts, a process thought to be involved in the progression of marrow fibrosis.

Adult↗

[A clinical study of pulmonary tuberculosis in lung cancer patient].

We have reviewed 442 patients with lung cancer. There were 323 male patients with a mean age of 65.8 yr and 119 female patients with a mean age of 66.0 yr. Histological types of lung cancer were squamous cell carcinoma 177 patients (40.0%), adenocarcinoma 167 (37.8%), small cell carcinoma 75 (17.0%), large cell carcinoma 17 (3.8%) and undifferentiated carcinoma 6 (1.4%). When lung cancer was diagnosed, 55 patients (12.5%) showed tuberculous lesions on the initial chest X-ray film. The majority of these tuberculous lesions were old changes, but only one with cavitary lesion was confirmed to be active. Although there was no statistical significance, the incidence of squamous cell carcinoma was higher in the 55 patients with tuberculous lesions than in the remaining 387 patients without ones. In the present study, five patients developed active pulmonary tuberculosis while on a therapy of lung cancer. All of these five patients were male and they had advanced lung cancer on admission. The diagnosis of active tuberculosis was made by autopsy in two patients and by culture--positive after death in two. Only one patient was identified to have active tuberculosis by broncho-alveolar lavage. Three of 5 patients showed old tuberculous lesions on the initial chest X-ray film, but all of five patients showed caseoinfiltrative shadows when active tuberculosis occurred. In addition, the prevalence of active pulmonary tuberculosis was significantly higher in the patients with old tuberculous lesions (5.6%: 3 out of 54 patients) than in those without ones (0.52%: 2 out of 387 patients). Finally, all of the five patients died. The causes of death were lung cancer in three patients, both pulmonary tuberculosis and lung cancer in one and pulmonary tuberculosis in one.

Adenocarcinoma↗

[Clinical studies on ciprofloxacin in chronic respiratory tract infection].

Ciprofloxacin (CPFX), a new pyridone carboxylic acid, was administered orally to the patients with chronic respiratory tract infection and its clinical efficacy and safety were studied in a multicenter open trial. The results and summarized as follows. 1. The efficacy rate for the patients with acute exacerbation as 52.5% (21/40) in 2 week-treatment, and 75.0% (24/32) in 4 week-treatment. 2. The efficacy rate for the patients with chronic phase was 23.1% (6/26) in 2 week-treatment, and 26.9% (7/26) in 4 week-treatment, but acute exacerbation was not observed in any of the patients. 3. CPFX was administered to 6 patients over 60 days for the prophylaxis of acute exacerbation. Only 2 patients had acute exacerbation in 2 and 3 months after the start of the therapy, respectively. 4. Bacteriological eradication rate was high except P. aeruginosa, for which the eradication rate was about 20%. 5. Side effects were observed in 3 patients, and abnormal findings of laboratory tests were observed in 5 patients, though they were not severe. These results show that CPFX is a useful antimicrobial agent for the treatment of chronic respiratory tract infections.

Administration, Oral↗

[Clinical significance of serum CA125 in patients with tuberculous pleurisy].

We measured CA125 levels of the sera and pleural effusions in both patients with tuberculous pleurisy (TB) and with benign non-tuberculous pleurisy (non-TB). In all the TB patients, serum CA125 levels were increased (78 to 370 U/ml, mean +/- SD = 167.3 +/- 96.8 U/ml, n = 8), and were significantly higher than those in non-TB patients (167.3 +/- 96.8 U/ml v.s. 36.9 +/- 18.4 U/ml, p less than 0.01). Neoplastic diseases or gynecological disorders were not found in these patients. On the other hand, either CA125 or LDH levels of pleural effusions were not significantly different between these two groups. Although adenosine deaminase (ADA) levels in pleural effusions were also significantly higher in the TB patients (p less than 0.05), there were no correlation between serum CA125 and ADA levels in pleural effusions. Serial measurement of serum CA125 levels in the TB patients revealed that serum CA125 levels were markedly decreased one to two months after anti-tuberculous therapy (172.6 +/- 103.3 U/ml to 23.3 +/- 9.9 U/ml, p less than 0.01). It is suggested that the measurement of serum CA125 in patients with tuberculous pleurisy is useful as an indicator of disease activity.

Adenosine Deaminase↗

Blastic transformation in essential thrombocythemia. In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages.

A 57-year-old man with essential thrombocythemia (ET) developed myelofibrosis, that progressed to a blastic transformation state. The characteristics of the blastic cells were serially studied both morphologically and phenotypically as well as in cell culture. The blastic cells that were first detected in peripheral blood had features of myeloid stem cells with slight differentiation toward megakaryocytic lineage. However, later in the course, most of the blastic cells were immature. During culture in the presence of human plasma-derived serum (PDS), some blastic cells obtained at the initial stage differentiated, mainly to both granulocytes and macrophages morphologically, but later tended to differentiate into both megakaryocytes and macrophages. Finally the blasts appeared to have lost their ability to differentiate morphologically. However, the blasts formed mixed colonies consisting of erythroblasts, granulocytes, macrophages, and immature blasts when cultured in methylcellulose with PHA-leukocyte conditioned medium. In addition, the blastic cells in suspension culture strongly expressed phenotypic features which are characteristic of erythroblasts, in the presence of both PDS and 12-0-tetradecanoylphorbol 13-acetate (TPA), whereas they expressed features of megakaryoblasts in the presence of PDS alone. These results suggest that essential thrombocythemia is of myeloid stem cell origin. This is the first case in the literature in which a clonal evolution in ET has been followed closely, essential events were identified serially, and the blastic cells, which appeared as a result of the progression of ET, were found to have the capability to differentiate toward the three myeloid lineages.

Blast Crisis↗

Molecular biology of the hst-1 gene.

The hst-1 gene (or HSTF1 by human gene nomenclature) was originally identified in our laboratory by an NIH/3T3 focus formation assay using DNA from a human gastric cancer. Sequence analysis predicted the hst-1 product to be a novel growth factor with 30-50% homology with six other heparin-binding growth factors: basic and acidic fibroblast growth factors (FGFs), the int-2 protein, FGF5, the hst-2/FGF6 protein and keratinocyte growth factor (KGF). A recombinant hst-1 protein was synthesized in silkworm cells and found to be a potent heparin-binding mitogen for murine fibroblasts and human vascular endothelial cells. Although hst-1 expression cannot be detected in most cancer cells, including gastric cancers, it is expressed in mouse embryos and in some germ cell tumours. Both hst-1 and int-2 are located on band q13.3 of human chromosome 11 within a distance of 35 kbp; in the mouse genome these two genes are separated by less than 20 kbp. They are differentially transcribed in the F9 mouse teratocarcinoma cell line; hst-1 is expressed in undifferentiated stem cells and int-2 in differentiated endodermal cells. The hst-1 and int-2 genes were coamplified in a variety of cancer cells, most notably in more than 50% of oesophageal cancers.

Amino Acid Sequence↗

Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with myeloproliferative disorders.

Platelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c-sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patients.

Adult↗

K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes.

DNA fragments amplified in a stomach cancer-derived cell line, KATO-III, were previously identified by the in-gel DNA renaturation method, and a 0.2-kilobase-pair fragment of the amplified sequence was subsequently cloned. By genomic walking, a portion of the exon of the gene flanking this 0.2-kilobase-pair fragment was cloned, and the gene was designated as K-sam (KATO-III cell-derived stomach cancer amplified gene). The K-sam cDNAs, corresponding to the 3.5-kilobase K-sam mRNA, were cloned from the KATO-III cells. Sequence analysis revealed that this gene coded for 682 amino acid residues that satisfied the characteristics of the receptor tyrosine kinase. The K-sam gene had significant homologies with bek, FLG, and chicken basic fibroblast growth factor receptor gene. The K-sam gene was amplified in KATO-III cells with the major transcript of 3.5-kilobases in size. This gene was also expressed in some other stomach cancer cells, a small cell lung cancer, and germ cell tumors.

Amino Acid Sequence↗

Fibroblast colony-forming cells with high sensitivity to serum mitogen(s) exist in bone marrow of patients with chronic myelocytic leukemia.

Marrow fibroblast colony formation was studied in patients with myeloproliferative disorders, using human serum or platelet-derived growth factor plus plasma-derived serum as growth-stimulating factors. Colony numbers negatively correlated with the patient's age, but were not different from those of controls. However, both maximum and average cell numbers per colony were significantly increased in patients with chronic myelocytic leukemia (CML) as compared to controls. These results suggest that fibroblast colony-forming cells with high sensitivity to human serum mitogen(s) exist in a CML bone marrow. These may possibly be involved in one of the mechanism concerned with promoting fibrosis in this disease.

Adult↗

[A case of pulmonary nocardiosis associated with middle lobe atelectasis].

Pulmonary nocardiosis is a rare disease. We reported a case of pulmonary nocardiosis associated with middle lobe atelectasis. A 66-year-old female was admitted to Saga Medical School Hospital with complaints of fever, productive cough and hemosputum. Nocardia asteroides was isolated from her sputum and bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim (ST) improved her symptoms and Nocardia asteroides were rapidly eliminated from her sputum. However, she had severe side effects of ST: toxic dermatitis, granulocytopenia and liver dysfunction, whereupon administration of ST was stopped. About two weeks later, Nocardia asteroides appeared again in her sputum. Either netilmicin (NTL) or minocycline (MINO) given consecutively could not eliminate Nocardia asteroides from her sputa. Subsequently a combination therapy of OFLX administration and gentamicin inhalation was tried. This treatment improved her symptoms and eradicated Nocardia asteroides from her sputa completely. In vitro study, ST, MINO and aminoglycosides showed good susceptibility against Nocardia asteroides. In this case, it was revealed that GM inhalation therapy is also very useful for pulmonary Nocardiosis.

Aged↗

[A case of Pasteurella multocida infection in bronchiectasis].

Pasteurella multocide (P. multocida), a small gram-negative bacillus, has been known to be the causative agent of hemorrhagic septicemia in animals. P. multocida infection in human was reported as skin abscess and/or septicemia after an animal bit or scratch. Pulmonary infections of P. multocida have been developed in the patients with chronic pulmonary diseases such as bronchiectasis. In Japan, however, P. multocida respiratory tract infections are rare. In this report, a 80-year-old female with bronchiectasis was admitted on August, 1985. She had a productive cough, hemosputum, and a low grade fever. The chest X-P on admission showed an atelectasis of the left middle lobe and severe bronchiectatic changes of the left lower lobe. P. multocida was isolated from her sputa. The chemotherapy of CTM resulted in clinical improvement. On May 1988, she complained of a productive cough and a low grade fever again. P. multocida was isolated from the sputum on several occasions in significant numbers (1 x 10(8)/ml). Recently, the cases of the chronic respiratory diseases have been increasing. We think, P. multocida is important and should be considered as a pathogen in the care of chronic pulmonary diseases.

Aged↗

Recurrent bleeding after arterial embolization in patients with hemoptysis.

Thirty-three patients with hemoptysis caused by nonmalignant diseases underwent arterial embolization. In seven (21.2 percent) of 33 patients, hemoptysis recurred after initial embolization in a follow-up period ranging from one day to four years. Although there was no difference in age and daily quantity of bleeding among patients with and without recurrences, those with mycetoma suffered the highest recurrence of bleeding after initial embolization (three [75 percent] of four patients). In the initial arteriograms of the seven patients were found six cases of markedly increased vascularity, three of increased vascularity in the bilateral lung, and three of nonbronchial systemic arterial supply to the diseased lung. Of six patients who received reexamination at the time of recurrent bleeding, the arteriogram demonstrated recanalization of previously embolized artery in five and revascularization by collateral circulation in five. In addition, hemoptysis recurred in three (60 percent) of five patients after second embolization and in one (50 percent) of two after third embolization. Four patients underwent surgical therapy: two after the initial embolization, one after the second, and one after the third, and these patients had no recurrence. While arterial embolization as initial treatment of hemoptysis is a highly useful procedure, this is a palliative procedure and potential for recurrence of hemoptysis exists as the lesion that has initially caused hemoptysis is not cured by the embolization. We emphasize that a combination therapy of repeated embolization and surgery will probably improve the efficacy of treatment of recurrent bleeding after initial embolization.

Adult↗

Utility of angiograms in patients with catamenial hemoptysis.

Pulmonary endometriosis is the likely cause in patients with hemoptysis during menses. While we describe two cases of catamenial hemoptysis, which were localized with chest CT scanning, angiograms revealed normal appearance. We suggest that angiograms may have little value in the evaluation of patients with pulmonary endometriosis.

Adult↗

Transforming growth factor-beta regulates growth as well as collagen and fibronectin synthesis of human marrow fibroblasts.

Three growth factors present in platelets, namely platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF), have been implicated in the pathogenesis of bone marrow fibrosis frequently associated with myeloproliferative disorders. In this study, regulation of the proliferation, as well as collagen and fibronectin synthesis from marrow fibroblasts by TGF-beta was investigated. TGF-beta alone at high plating density stimulated the proliferation of cells at low concentrations, but rather showed inhibition at high concentrations in both MPD patients and control subjects. In the presence of PDGF, which has been confirmed to be a main growth factor for marrow fibroblasts, low concentration of TGF-beta inhibited the proliferation at low cell density, but there was no inhibition at high cell density. The synthesis of both type I and type III procollagen was enhanced by high concentrations of TGF-beta in both MPD patients and control subjects, while PDGF or EGF showed no effect. The fibronectin synthesis was also enhanced by TGF-beta, but not by PDGF or EGF. These results suggest that growth and stromal protein synthesis of fibroblasts causing marrow fibrosis are regulated by TGF-beta as well as PDGF and EGF, when these factors are released or leaked from platelets or megakaryocytes into marrow environment in MPD patients.

Adult↗

[A study of neutrophil functions in patients with chronic respiratory tract diseases].

We tested blood neutrophil functions in the patients with chronic respiratory tract diseases to study the mechanism of susceptibility to bacterial infections. Peripheral blood neutrophils were obtained from 15 healthy subjects and 14 patients including diffuse panbronchiolitis, bronchiectasis, chronic emphysema and chronic bronchitis. Seven patients suffered from the chronic P. aeruginosa infection. Firstly, neutrophil chemotaxis was determined by the method of Boyden Chamber assays using FMLP as a neutrophil chemoattractant. The number of migrated neutrophils were 239.2 +/- 65.6 cells/50 HPF in the patients group and 256.6 +/- 49.0 cells/50 HPF in the control group. Secondly, neutrophil phagocytosis against P. aeruginosa, E. coli and K. pneumoniae was determined by phagocytic activity (PA) and phagocytic index (PI). PA against each bacteria was 44.1 +/- 13.2% (P. aeruginosa), 44.8 +/- 12.3% (E. coli) and 35.8 +/- 13.6% (K. pneumoniae) in the patients group and 42.3 +/- 10.6% (P. aeruginosa), 43.0 +/- 11.9% (E. coli) and 36.3 +/- 16.0% (K. pneumoniae) in the control group. PI against each bacteria was 2.2 +/- 0.6 (P. aeruginosa), 2.1 +/- 0.3 (E. coli) and 2.6 +/- 0.9 (K. pneumoniae) in the patients group and 2.2 +/- 0.6 (P. aeruginosa), 2.2 +/- 0.4 (E. coli) and 2.5 +/- 0.6 (K. pneumoniae) in the control group. Thirdly, neutrophil bacteriocidal activity was determined by superoxide production and intracellular killing efficiency. Superoxide produced from OPZ-triggered neutrophils was 17.8 +/- 6.5 nmol/3.5 X 10(6) cells/20 min in the patients group and 20.2 +/- 5.8 nmol/3.5 X 10(6) cells/20 min in the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Respiratory failure due to vocal cord dyskinesia in olivo-ponto-cerebellar atrophy.

We present a case of OPCA with severe respiratory failure due to vocal cord dyskinesia. This vocal cord dyskinesia was found by fiberoptic bronchoscopy and confirmed by laryngeal electromyogram. Tracheal fenestration and drug therapy of haloperidol were successful for clinical improvement. To our knowledge, this is the first report of vocal cord dyskinesia in OPCA. We emphasized that OPCA could complicate vocal cord dyskinesia, causing severe respiratory failure.

Bronchoscopy↗