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Biomedical subjects

K Hiura

Publications and source records attributed to K Hiura.

At least 37 records · Page 2Linked to original sources

[A case of Wegener's granulomatosis with a giant solitary pulmonary mass].

A 44-year-old woman was admitted to hospital with a history of high fever, cough, and weight loss. Her chest X-ray film showed a giant solitary pulmonary mass in the left lower lobe. After admission, she developed bilateral eyeache and left exophthalmos. CT film of the head showed a massive lesion in the sinuses. Biopsy specimens obtained from both massive lesions showed either epithelioid granulomas with Langhans' giant cells or necrotising vasculitis. Antineutrophil cytoplasmic antibodies, which have high sensitivity and specificity for active WG, were found. The diagnosis of WG was thus made.

Adult↗

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↗

Effects of 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone and its intermediate metabolites on bone metabolism in vivo and in vitro.

Which intermediate metabolite of 23(S)25(R)-1 alpha,25-(OH)2D3-26,23-lactone causes the unique biological functions of 1 alpha,25-(OH)2D3-26,23-lactone different from that of 1 alpha,25-(OH)2D3 was examined comparatively. The three intermediate metabolites, 1 alpha,25(R)26-(OH)3D3, 1 alpha,23(S)25(R)26-(OH)4D3, and 23(S)25(R)-1 alpha,25-(OH)2D3-26,23-lactol stimulated bone resorption, as 1 alpha,25-(OH)2D3 did, in vitamin D-deficient rats. On the other hand, 1 alpha,25-(OH)2D3-26,23-lactone only inhibited bone resorption. 1 alpha,25-(OH)2D3, 1 alpha,25-(OH)2D3-26,23-lactone and the other three metabolites stimulated MNC formation from hematopoietic blast cells in a manner correlated with their binding affinities for the 1 alpha,25-(OH)2D3 receptor. However, CM obtained from 1 alpha,25-(OH)2D3-26,23-lactone-treated MC3T3-E1 cells inhibited MNC formation, probably by the action of some inhibitory factors elaborated by the cells treated with 1 alpha,25-(OH)2D3-26,23-lactone, whereas CM obtained from 1 alpha,25-(OH)2D3 or other metabolite-treated MC3T3-E1 cells stimulated MNC formation. These facts indicate that only 1 alpha,25-(OH)2D3-26,23-lactone has an inhibitory action of bone resorption and that the lactone ring plays a major part in its expression.

Animals↗

Mouse osteoblastic cells (MC3T3-E1) at different stages of differentiation have opposite effects on osteoclastic cell formation.

Using our new culture system for multinucleate cells (MNCs) that have many characteristics of osteoclasts, we examined the effects of factors produced by osteoblastic cells on osteoclastic cell formation. Conditioned medium (CM) from undifferentiated osteoblastic MC3T3-E1 cells during their growth phase inhibited MNC formation in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Diluted CM (1:81) from differentiated cells obtained after cultivation for more than 20 days stimulated MNC formation, but at lower dilutions inhibited their formation. Dialyzed CM (greater than 2000 mol wt) from the differentiated cells was more stimulatory than undialyzed CM and showed no inhibitory effect on MNC formation. The inhibitory effect was observed with filtered (less than 3000 mol wt) CMs and was specific for osteoblastic cell CM. Prostaglandin E2 (PGE2) was detected in the CM from undifferentiated or differentiated MC3T3-E1 cells at concentrations (317 +/- 66 and 1287 +/- 179 pg/ml, respectively) sufficient to inhibit MNC formation, and this inhibition was partially abolished with CM (at 3-fold dilution) in indomethacin-treated cells (PGE2, less than 20 pg/ml), suggesting PGE2-mediated inhibition of MNC formation and the presence of another factor(s) besides PGE2 that influenced MNC formation. In contrast to day 3 CM plus 1,25-(OH)2D3, day 60 CM plus 1,25-(OH)2D3 induced MNC formation even in the absence of GM-CSF, and this induction was inhibited by an antibody to GM-CSF. Secondary colony formation assays showed the presence of a GM-CSF-like factor in the day 60 CM. These findings indicate that osteoblastic cells are involved in the process of osteoclastic cell formation, with at least two soluble factors produced by osteoblasts, a GM-CSF-like factor, which is stimulatory, and PGE2, which is inhibitory. The effects of CMs also differed depending on the stage of osteoblast differentiation.

Animals↗

[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 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↗

Cranial MR imaging in patients with von Recklinghausen's disease (neurofibromatosis type I).

MR imaging was performed for 24 patients with von Recklinghausen's disease. Twenty of the 24 patients showed abnormal findings in MR imaging. In many cases, the lesions were multifocal. In 14 patients small focal areas of increased signal on T2-weighted images were thought to represent heterotopias or hamartomas. Eight patients had optic tract gliomas. Three patients had parenchymal gliomas. In one patient, white matter showed high intensity on T2-weighted images representing delayed myelination. The rate of abnormal findings was higher for MR imaging than CT. MR imaging was found to be an excellent imaging method for known diseases and for detecting lesions in asymptomatic patients.

Adolescent↗

[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↗

Biological activity assessment of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone and its intermediate metabolites in vivo and in vitro.

The biological activity of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone, and three intermediate metabolites of the lactone in vivo and in vitro was comparatively examined. The three intermediate metabolites, 1 alpha,25(R)26(OH)3D3, 1 alpha,23(S)25(R)26(OH)4D3, and 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactol, stimulated increases, as did 1 alpha,25(OH)2D3, in intestinal calcium transport and serum calcium level in vitamin D-deficient rats fed a low-calcium diet. On the other hand, 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone increased the calcium transport but decreased the serum calcium level. 1 alpha,25(OH)2D3,23(S)25(R)-Lactone and the other three metabolites stimulated multinucleate cell formation from hematopoietic blast cells in a manner correlated with their binding affinities for the 1 alpha,25(OH)2D3 receptor. But 23(S)25(R)-lactone did not show any inhibitory effect on the multinucleate cell formation induced by 1 alpha,25(OH)2D3 in contrast to the results obtained from unfractionated marrow cultures. Conditioned medium obtained from 23(S)25(R)-lactone-treated MC3T3-E1 cells inhibited the formation, probably by the action of some inhibitory factors elaborated by the cells treated with the lactone, whereas conditioned medium obtained from 1 alpha,25(OH)2D3 or other metabolite-treated MC3T3-E1 cells stimulated the formation. These findings suggest that 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone might inhibit bone resorption through an inhibition of osteoclastic cell formation and that other vitamin D3 metabolites stimulate bone resorption by development of new osteoclastic cells in addition to indirect osteoclast activation.

Animals↗

[A case of adult T-cell leukemia with diffuse panbronchiolitis].

We have reported an adult T-cell leukemia (ATL) patient with a 3-year history of diffuse panbronchiolitis (DPB). The patient, a 62-year-old woman, had been complaining severe cough and purulent sputa for 2 years. In 1984, she was admitted to Saga Medical School, where her clinical diagnosis, DPB, was made. One year later, it was revealed that she suffered from ATL, confirmed by the presence of ATL cells in peripheral blood and anti-ATLA antibody. This case suggests that ATL may play an important role in the pathogenesis of some DPB patients.

Bronchiolitis↗

Existence of parathyroid hormone binding sites on murine hemopoietic blast cells.

We demonstrated that 125I-labeled human parathyroid hormone (1-34;8,18-Nle,34-Tyr)[[125I]hPTH(1-34)] bound specifically to hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Half-maximal inhibition of binding was achieved at concentrations of unlabeled hPTH(1-34) of about 5 x 10(-9)M. Insulin and hPTH(39-68) did not compete for PTH binding sites. Specific binding of hPTH(1-34) was detected in neither macrophages nor multinucleated cells (MNC's). Furthermore, treatment of hemopoietic blast cells with hPTH(1-34) stimulated MNC formation, and the range of concentrations (10(-10)-10(-8)M) over which hPTH(1-34) caused these effects was similar to that which inhibited the binding of [125I]hPTH(1-34). These findings suggest the presence of a PTH receptor on osteoclast precursors and the direct effect of PTH on them, resulting in osteoclast-mediated bone resorption.

Animals↗

[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↗

[Rapid and complete hematopoietic reconstitution following peripheral blood stem cell autotransplantation in a child with T cell acute lymphoblastic leukemia].

Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3-4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203 X 10(4) CFU-GM/kg body weight was reinfused to the patient following marrow-ablative chemotherapy (MCNU 600 mg/m2, cytosine arabinoside 6 g/m2, etoposide 300 mg/m2, cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5 X 10(9)/l by day + 7 and platelet count reached 20 X 10(9)/l by day + 9. Thereafter, white blood cell count continued to increase and reached a maximum of 38 X 10(9)/l on day + 14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

[A pancreatico-bronchial fistula with right hydropneumothorax].

A 39-year-old heavy drinker was admitted to Saga Medical School Hospital on February 21th, 1987. He had suffered from dyspnea, chest pain and lumbago three weeks prior to admission. His chest X-ray showed right hydropneumothorax and right lower lobe atelectasis and his CT scan showed a cystic lesion in the mediastinum. His laboratory data showed a high level of amylase in serum, urine and pleural effusion. A fistula connecting the pancreas to right pleural cavity was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP). In addition, bronchoscopy showed complete obstruction of the right lower bronchus (B7). These bronchoscopic findings and hydropneumothorax on his chest X-ray suggested the leakage of pancreas juice through the pancreatico-pleural fistula injured the lung tissue directly and produced a bronchopleural fistula. In this case, hyperalimentation and drug therapy using protease inhibitor resulted in successful closure of the fistula and reexpansion of the collapsed lung.

Adult↗

Generation of osteoclasts from isolated hematopoietic progenitor cells.

A variety of studies have shown that osteoclasts originate from bone marrow, but their exact progenitors and differentiation pathway remain unclear. The treatment of mice with a high dose of 5-fluorouracil (5-FU) results in an enrichment for primitive hematopoietic progenitors; using this procedure, we prepared a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro. When spleen cells from mice pretreated in vivo with 5-FU were cultured in the presence of methylcellulose medium containing recombinant interleukin-3 (rIL-3), small colonies consisting of blast cells with little sign of differentiation developed on day 7 of culture. We lifted these blast colonies, pooled them, and replated them as secondary methylcellulose cultures in the presence of rIL-3 and erythropoietin. Approximately 60% of the cells formed colonies comprising various combinations of neutrophils, macrophages, eosinophils, mast cells, megakaryocytes, and erythroblasts. We replated such blast cells into microtiter wells and cultured them in the presence of rIL-3 (100 U/mL) or recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) (100 U/mL) plus 1.25(OH)2D3 (10(-7) mol/L). Multinucleated cells appeared from day 14 of culture and approximately 100 giant cells per well were scored on day 21 of culture. Parathyroid hormone (1 U/mL) also induced the multinucleated cell formation. May-Grunwald-Giemsa staining revealed the large cells containing many nuclei in their cytoplasm, which is characteristic of bone-resorbing cells or osteoclasts. These cells showed a tartrate-resistant acid phosphatase (TRAP) activity. Calcitonin caused a striking shape change in these cells and suppressed the formation of multinucleated cells. Moreover, electron microscopy shows that these cells were able to resorb fetal calvariae. In the presence of r granulocyte-colony stimulating factor, r macrophage-colony stimulating factor, or r interleukin-6 plus 1.25(OH)2D3, formation of TRAP-positive multinucleated cells was lower compared with the support of rIL-3 or rGM-CSF. Mature macrophages collected from colonies did not form the multinucleated cells as described above, even in the presence of rIL-3 and 1.25(OH)2D3. Moreover, to exclude the possibility that osteoclasts generated from non-blast cells, we performed a cloning experiment from one isolated blast cell and demonstrated that single cells differentiate into osteoclasts or macrophages in the presence of rIL-3 with or without 1.25(OH)2D3. This system will provide a useful model for further analysis of osteoclast formation in vitro.

Animals↗