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N Hara

Publications and source records attributed to N Hara.

At least 109 records · Page 6Linked to original sources
PubMed1999

Role of neutrophil elastase in ozone-induced airway responses in guinea-pigs.

Ozone-induced airway hyperresponsiveness occurs concurrently with neutrophilic inflammation and epithelial injury in various species including humans. The mechanism of neutrophil-induced airway hyperresponsiveness, however, has not yet been fully clarified. Neutrophil elastase (NE) is a multipotent protease released from activated neutrophils, which may play a role in ozone-induced airway hyperresponsiveness. In order to address this issue, the effects of ONO-5046, a specific NE inhibitor, were investigated in ozone-exposed guinea-pigs. Awake animals were exposed to ozone at 3 parts per million for 2 h, airway responsiveness to acetylcholine (ACh) measured and examination of bronchoalveolar lavage fluid (BALF) performed. Ozone exposure increased airway responsiveness to both inhaled and intravenous ACh, the concentration of NE in BALF and the number of neutrophils and airway epithelial cells in BALF. Although pretreatment with ONO-5046 (200 mg x kg(-1), i.p.) had no effect on these changes immediately after the exposure, it significantly inhibited airway hyperresponsiveness to inhaled ACh, whilst decreasing the number of neutrophils and epithelial cells in BALF 3-5 h after the exposure. In contrast, ONO-5046 showed no significant effect on airway hyperresponsiveness to intravenous ACh at any time. These results suggest that neutrophil elastase contributes to ozone-induced airway hyperresponsiveness developing during the hours after exposure, presumably by means of inducing epithelial injury.

Acetylcholine↗
PubMed1999

[Preventive effect of prostaglandin E1 on cisplatin-induced nephrotoxicity].

In order to prevent the nephrotoxicity induced by cisplatin (CDDP), prostaglandin E1 (PGE1) was administered intravenously after anticancer chemotherapy to six patients with lung cancer. All patients underwent two courses of multi-drug chemotherapy with the same regimen including a single administration of 80 mg/m2 CDDP. From the 7th day of the 2nd course of chemotherapy, 120 micrograms PGE1 had been administered for five days. During the two courses of chemotherapy, serum creatinine, blood urea nitrogen, creatinine clearance (Ccr), 24-h excretions of beta 2-microglobulin (beta 2-MG) and N-acetylglucosaminidase (NAG) in urine were measured every week in all patients. The mean value of Ccr was higher in the 2nd course than in the control course (65 ml/min vs. 74 ml/min). The 24-h excretions of beta 2-MG and NAG were also reduced in the 2nd course. Out of six patients, only one was complicated by mild phlebitis at the PGE1 infusion site. From these results it was suggested that PGE1 was effective for prevention of CDDP nephrotoxicity.

Aged↗
PubMed1999

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

Adult↗
PubMed1999

[A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer].

Paraneoplastic cerebellar degeneration (PCD) is a clinical syndrome and known to be occasionally associated with small cell carcinoma of the lung (SCLC). PCD usually affects patients before the cancer is evident. The disorder evolves subacutely, and causes severe pancerebellar dysfunction. In this paper, we report a case of PCD associated with SCLC. A 65-year-old man presenting with 2 weeks of progressive vertigo, gait ataxia, and speech disturbance, was readmitted to our hospital. He had earlier been given a diagnosis of SCLC, oat cell carcinoma, and had undergone high-dose chemotherapy with peripheral blood stem cell transplantation during his first admission. Following that treatment regimen, the tumor disappeared completely and the patient had been in remission. Based on neurological findings and the presence of anti-neuronal antibodies a diagnosis of PCD was made. Although cyclophosphamide (500 mg/m2) was administered, the patient experienced no relief of his cerebellar ataxia. Six months afer readmission, he died of cardiac tamponade due to malignant pericarditis. A histological examination at autopsy found few Purkinje cells and a proliferation of Bergmann's astrocytes in the cerebellar cortex. These findings were consistent with the diagnosis of PCD.

Aged↗
PubMed1999

[Horner's syndrome in a patient with diffuse malignant pleural mesothelioma].

A 63-year-old man was admitted to our hospital because of left back pain and dysesthesia in his left arm. On physical examination, the patient had ptosis, myosis, and anhydrosis on the left side, suggesting Horner's syndrome. A chest computed tomographic scan disclosed a mass lesion adjoining to the left posterior mediastinum. Although the mass lesion showed a slight decrease in size after the systemic administration of corticosteroids, no further improvement was obtained. Open chest examination revealed extended thickening of the parietal pleura with massive involvement of the upper thoracic sympathetic trunk. The diagnosis was malignant mesothelioma of sarcomatous type. Horner's syndrome is a rare but possible complication in the clinical course of malignant pleural mesothelioma.

Horner Syndrome↗
PubMed1999

[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer].

The combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2. The maximum tolerated dose (MTD) and the recommended dose was determined with Continual Reassessment Method. For each dose level, 6 cases, 3 cases and 6 cases were registered respectively and all 15 cases were evaluable. In the dose level 3 with 1,000 mg/m2 of gemcitabine and 80 mg/m2 of cisplatin, grade 4 neutropenia was observed as DLT in 3 out of 6 cases, thus dose level 3 was considered as MTD and the recommended dose. Major adverse events were leukopenia, neutropenia, nausea/vomiting and anorexia. The incidence of such adverse events seemed to be dose-dependent and especially the grade of neutropenia seemed to be more serious as the dose increased. Also, the grade of liver function tests abnormal seemed to be more serious as the dose increased but the incidence as well as the grade did not have tendency of dose-dependent in another events including renal function tests abnormal. On the other hand, as to the efficacy PR was observed in 4 out of 15 cases. Based upon the results, it is necessary to discuss further the efficacy in the recommended dose in the combination therapy of gemcitabine and cisplatin.

Adenocarcinoma↗
PubMed1999

[Effect of PCBs on mouse lung tumorigenesis induced by 1-nitropyrene: a preliminary report].

We have analyzed the effect of polychlorinated biphenyls (PCB, Kanechlor-400) on 1-nitropyrene (1-NP) induced lung tumor. Male A/J mice (6 weeks old) were used for the experiment. A total of 2.5 mg/kg PCB was administered intraperitoneally (PCB group), a total of 0.38 mmol/kg 1-NP was administered intraperitoneally for 17 times (1-NP group), PCB was administered followed by i.p. injection of 1-NP (PCB + 1-NP group), and only vehicle was administered (control group). The lung lesions induced were examined 18 weeks after the final treatment with 1-NP or vehicle. In control group, no neoplastic lesion in the lung was induced. In PCB group, only one lesion with adenoma was induced. In 1-NP group, various kinds of lung neoplastic lesions including hyperplasia, adenoma and adenocarcinoma were induced. In PCB + 1-NP group, both the number and size of tumors induced were significantly more than those in 1-NP group. In addition, the number of adenocarcinoma formed was more in PCB + 1-NP group than in 1-NP group. Each lesion was microdissected to collect and analyze DNA of the targeted tissue. K-ras gene mutation was detected in part of adenoma lesions and all the carcinoma lesions. The mutation was found in either 1-NP or PCB + 1-NP group, but not in control and PCB group. The pattern of K-ras mutation was CAA to CGA in codon 61 or GGT to GAT in codon 12. There was no difference in the pattern of K-ras mutation despite of the pretreatment with PCB. Although the present data are from small sample size, it was suggested that PCB may promote (but not initiate) 1-NP induced lung tumorigenesis, and may not induce K-ras mutation directly in the experimental system.

Adenocarcinoma↗
PubMed1999

[Cancer and thromboembolism].

Thromboembolism is the most common complication in patients with malignant diseases. The recent studies have indicated that the pathogenesis of thromboembolism in cancer is associated with the hemostatic alternations induced by cancer cells and cancer-stimulated mononuclear cells: injury to the endothelial lining of blood vessels, activation of blood coagulation and depression of anticoagulant function. Although thromboembolism is generally observed in patients with advanced cancer, it may occur in patients with occult cancer. In the treatment of thromboembolism, the administration of low molecular heparin has been introduced recently, in addition to the immediate and intensive treatment of cancer.

Humans↗
PubMed1999

[Diffuse idiopathic skeletal hyperostosis with fibrobullous change in upper lung lobes and dyspnea due to limitation of thoracic cage].

A 48-year-old man was admitted to our hospital because of shortness of breath and abnormal shadows on chest roentgenograms. Although he had been given a diagnosis of ankylosing spondylitis (AS) at the onset of his symptoms, a diagnosis of diffuse idiopathic skeletal hyperostosis (DISH) was made by our orthopedics department on the basis of bone X-ray findings. Spirograms demonstrated a restrictive pattern and residual volume was increased. Total lung capacity and respiratory muscle function were normal, suggesting that the abnormal spirogram findings were due to decreased thoracic cage compliance. Chest roentgenograms and computed tomographic scans showed apical fibrobullous changes in both lungs, similar to those observed in AS. To our knowledge, this is the first case of DISH with pulmonary involvement to be reported to date. The pulmonary manifestations were similar to those of AS, and it was speculated that they were due to limitation of the thoracic cage.

Diagnosis, Differential↗
PubMed1999

Extended resection of the pulmonary artery and the aorta for primary lung cancer. Report of a case.

We report a case of squamous cell carcinoma of the lung in which a left pneumonectomy combined resection of the pulmonary artery and aorta was performed using a cardiopulmonary bypass. The bifurcation of the pulmonary artery was repaired with a pericardial patch and the descending aorta was replaced with an artificial vessel Eleven months later, the patient underwent dissection of the contralateral mediastinal lymph nodes because of a recurrence of the disease. Even though pulmonary metastases have again recently appeared, he is alive and doing well two years after operation. To obtain a better prognosis in cases demonstrating an involvement of the bifurcation of pulmonary artery, more effective combined treatment still needs to be developed.

Adult↗
PubMed1999

[Clinical experiences and problems with home medical treatment in an orthopedic clinic].

Twenty-five patients who received home medical treatment were reviewed. There were 11 males and 14 females, with a mean age of 77 years. In an orthopedic clinic, it is difficult to secure the time for to visit a patient's home. Another problem for doctor is that the medical fee for home treatment is very low. To promote home treatment by orthopedists, it is important to secure the time to visit a patient's home, to improve the fees for home treatment, and to establish a connection with a visiting nurse care station and visiting rehabilitation workers.

Aged↗
PubMed1999

[Pulmonary radiation injury manifested by signs of bronchiolitis obliterans with organizing pneumonia after postoperative breast cancer radiotherapy].

A 67-year-old woman underwent surgery for cancer of both breasts (right: mastectomy, left: conserving surgery), and received 60 Gy radiation to the left postoperative breast. Three months later, cough and fever developed. A chest radiograph demonstrated infiltrative shadows in the left lung field. Transbronchial lung biopsy specimens disclosed organizing exudates in the alveolar spaces and bronchioles. After treatment with prednisolone, the clinical symptoms and radiographic infiltrates disappeared. This was a case of pulmonary radiation injury pathologically manifested by signs of bronchiolitis obliterans with organizing pneumonia.

Aged↗
PubMed1998

Analysis of environmental carcinogens associated with the incidence of lung cancer.

It is presumed that carcinogens present in human lungs contribute to the incidence of lung cancer. Most of the carcinogens are inhaled in lung alveoli with particulate matter through the respiratory tract. On the basis of chemical analysis of 256 lung specimens with carcinomas resected in the period 1991 1996, the concentration of 1-nitropyrene (1-NP) was 19.7+/-10.5 pg/g of dry weight, and that of the dinitropyrenes (DNP) was 3.50+/-0.14-6.26+/-1.76. In addition, 2-nitrofluoranthene (NF) and 3-NF were detected at a higher level of 38.6+/-17.2 and 39.1+/-14.2, respectively, pg/g of dry weight. Concentrations of benzo[a]pyrene, benzo[e]pyrene, benzo[k]fluoranthene and benzo[ghi]perylene in 37 specimens collected in the period 1991 1996, were in the range of 138+/-82-399+/-220 pg/g of dry weight. No difference was found in the concentration of chemicals deposited in lung specimens from patients with lung cancer and tuberculosis as a control. By following the prognosis of 112 patients with carcinomas, we found that the deposition of 1-NP, 1,3-DNP, and 3-NF in lung tissues influenced their 5-year-survival after determination of chemicals. Lung specimens were divided into two groups of higher and lower chemical concentrations at the levels of 18 pg/g for 1-NP, 15 for 1,3-DNP, and 35 for 3-NF, and the findings were statistically analyzed by adjusting for age, gender, smoking status and cell type. The 5-year-survival of patients was markedly lower in the higher concentration group than the lower group.

Adult↗
PubMed1998

Role of adrenergic nervous system in cigarette smoke-induced bronchoconstriction in guinea pigs.

The goal of this study was to clarify the role of the adrenergic nervous system in bronchoconstriction induced by exposure to cigarette smoke in guinea pigs. Artificially ventilated animals were exposed to 160 puffs of smoke for 8 min. Bronchoconstriction was assessed as a percentage of the baseline total pulmonary resistance (RL). The effects of pretreatment with phentolamine (0.1 mg/kg, i.v.), propranolol (1 mg/kg, i.v.), and/or atropine (1 mg/kg, i.v.) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction. Phentolamine, an alpha-adrenoceptor antagonist, significantly inhibited cigarette smoke-induced bronchoconstriction, while propranolol, a beta-adrenoceptor antagonist, significantly enhanced it. Combined use of these compounds further enhanced the bronchoconstriction. All of modulations of the bronchoconstriction by adrenoceptor antagonists were completely abolished by pretreatment with atropine. Phentolamine and/or propranolol had no effect on the bronchoconstriction induced by inhaled acetylcholine. Pretreatment with yohimbine (0.5 mg/kg, i.v.), a selective alpha2-adrenoceptor antagonist, showed modulatory effects similar to those of phentolamine on cigarette smoke-induced bronchoconstriction. These results suggest that cigarette smoke-induced bronchoconstriction is regulated by the prejunctional modulation of the cholinergic system via alpha- and beta-adrenoceptors. This mechanism may be modulated by the autoregulation of adrenergic nerves via the alpha2-autoreceptor.

Acetylcholine↗
PubMed1998

Effects of epinastine hydrochloride on cholinergic neuro-effector transmission in canine tracheal smooth muscle.

We determined the effects of epinastine hydrochloride, an anti-asthmatic drug, on cholinergic neuro-effector transmission in canine trachea. Isometric tension of tracheal strips was measured in the presence of indomethacin and propranolol. Epinastine (10(-6) M) significantly suppressed the contraction evoked by electrical field stimulation, but had no effect on the acetylcholine-evoked contraction. An L-type Ca2+ channel blocker, nicardipine, did not suppress the electrical field stimulation-induced smooth muscle contraction and did not alter the inhibitory effect of epinastine. An N-type Ca2+ channel blocker, omega-conotoxin, suppressed the electrical field stimulation-induced contraction in a dose-dependent manner, and in a subthreshold/intermediate concentration abolished the inhibitory effect of epinastine. These findings indicate that epinastine exerts prejunctional inhibitory effects on airway smooth muscle of dogs, presumably by inhibiting acetylcholine release from vagal nerve terminals, and suggest that this effect is mediated by N-type Ca2+ channels.

Animals↗
PubMed1998

Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic.

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis using a mouse dorsal air sac model. The inhibitory effect of roxithromycin was dose-dependent and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. However, at concentrations of up to 50 microM, roxithromycin had no effect on lung cancer cells and human vascular endothelial cell growth and lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Roxithromycin at concentrations greater than 20 microM inhibited endothelial cell migration and tube formation.

Animals↗
PubMed1998

Granulocyte-macrophage-colony stimulating factor stimulates tumor invasiveness in squamous cell lung carcinoma.

BACKGROUND: Bronchial epithelial cells produce a significant amount of granulocyte-macrophage-colony stimulating factor (GM-CSF), which is believed to mediate both the host defense and inflammation. Recently, GM-CSF has been demonstrated to be produced by several tumor cells and also to be associated with tumor growth and metastasis. In the current study, the authors investigated the biologic role of GM-CSF produced by squamous cell lung carcinoma. METHODS: The production of GM-CSF from 17 human lung carcinoma cell lines was determined by an enzyme-linked immunoabsorbent assay. In vitro invasiveness was investigated by using a Biocoat Matrigel (Collaborative Biomedical Products, Bedford, MA) precoated invasion chamber. The activity of the matrix metalloproteinases (MMPs) were examined by gelatin zymography. The expression of GM-CSF in 113 cases of resected nonsmall cell lung carcinoma was analyzed immunohistochemically, and the association between the expression of GM-CSF and clinicopathologic features was investigated. RESULTS: The production of GM-CSF by squamous cell carcinoma cell lines was closely related to the in vitro invasiveness and MMP activity of the cancer cells. Recombinant GM-CSF stimulated the invasiveness of less invasive LK-2 and LC-1 cells in a dose-dependent manner, and this stimulation was abrogated by the neutralizing anti-GM-CSF antibody. Furthermore, anti-GM-CSF antibody decreased the invasiveness of highly invasive EBC-1 and NCI-H157 cells. GM-CSF also increased the MMP activity of LK-2 and LC-1 cells. Of 113 resected nonsmall cell lung carcinomas, 30 of 71 squamous cell carcinomas (42.3%), and 24 of 42 adenocarcinomas (57.1%) stained positively for GM-CSF. The expression of GM-CSF in squamous cell carcinomas was associated with the local invasion by the primary tumor. CONCLUSIONS: These results suggest that the production of GM-CSF is involved in both the in vitro invasiveness and the local progression of squamous cell carcinoma of the lung.

Carcinoma, Squamous Cell↗