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N Hara

Publications and source records attributed to N Hara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of tumor-associated antigen RCAS1 correlates significantly with poor prognosis in nonsmall cell lung carcinoma.

BACKGROUND: RCAS1 is a recently discovered antigen molecule expressed on the membrane of cancer cells, and it acts as a ligand for a putative receptor present on immune cells such as T, B and NK cells. It has been suggested that RCAS1 expression is related to the escape of tumors from immune surveillance. In this study, the relation between RCAS1 expression and various clinicopathologic variables, including patient prognosis, was investigated in lung carcinoma through immunohistochemical analysis. METHODS: One hundred two surgically resected nonsmall cell lung carcinoma cases were examined histopathologically by means of the monoclonal antibody 22-1-1, which is specific for RCAS1. The correlation between RCAS1 expression and the clinicopathologic features of patients was evaluated. Moreover, the correlation between RCAS1 expression and the survival of patients was analyzed by the Kaplan-Meier method log-rank test, and multivariate analysis was performed by using the Cox proportional hazard model. RESULTS: The samples of 48 of the 102 lung carcinoma patients (47.1%) were positive for RCAS1. There were significant correlations between RCAS1 expression and either pathologic staging (P = 0.0003) or tumor differentiation (P = 0.0308). The survival time for the RCAS1-positive group was significantly shorter than that for RCAS1-negative group (P < 0.0001). Moreover, multivariate analysis for overall survival revealed that RCAS1 expression was a significantly independent prognostic factor in nonsmall cell lung carcinoma patients. CONCLUSION: These results suggested that RCAS1 expression may play an important role in the immune escape mechanism and that RCAS1 expression may be a good indicator of poor prognosis in patients with nonsmall cell lung carcinoma.

Adult↗
PubMed2001

Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma.

BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.

Adult↗
PubMed2001

Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice.

Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on 1-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

Animals↗
PubMed2001

Localization of post-traumatic trochlear nerve palsy associated with hemorrhage at the subarachnoid space by magnetic resonance imaging.

PURPOSE: To report evaluation of traumatic trochlear nerve palsy using head magnetic resonance imaging. DESIGN: Observational case reports. METHODS: We examined two cases involving trochlear nerve palsy after closed head injury. RESULTS: Using a fluid attenuated inversion recovery pulse sequence, MRI showed a high-intensity lesion consistent with subarachnoid hemorrhage at the trochlear nerve area in the ambient cisterns. CONCLUSION: An impact force directed toward the tentorium can be a mechanism of injury in some post-traumatic trochlear nerve palsies. Fluid attenuated inversion recovery pulse sequence is a sensitive method for detection of abnormalities in cases associated with head injury.

Adolescent↗
PubMed2001

Quantitation of HLA-A*0201 bound tumor associated antigens on a peptide pulsed B cell line.

CTLs recognize 8- to 10-mer peptides on MHC class I molecules. Recent studies have shown that human CTLs kill autologous tumor cells in an HLA-restricted and peptide-specific manner, and that artificial pep- tides can stimulate tumor-specific CTLs both in vitro and in vivo. Accordingly, several human clinical trials using such peptides are ongoing worldwide. In such methods, the amount of peptide-MHC complexes that remain on the cell surface of APCs after peptide administration is crucial, because CTL activation depends on the number of ligated TCRs and co-stimulation. However, it remains uncertain how many peptide-MHC complexes are reconstituted and remain on live cells after peptide administration. We herein examined the binding affinities of five HLA-A*0201 restricted peptides-four TAAs and one HIV antigen-to HLA-A*0201 molecules and their decay rates on a live B cell line using tandem mass spectrometry. Our experiments showed that nearly 10(5) peptide-MHC complexes per cell could be reconstituted on a cell surface by pulsing a high dose of peptide even if the binding affinities were intermediate or low. However, the decay rates observed for these pep- tide-MHC complexes on a B cell line were faster than previously estimated.

Animals↗
PubMed2001

Renal vascular walls in patients with preeclampsia superimposed on essential hypertension.

This study was performed to clarify the relationship between changes in contractile proteins in renal vascular walls and the prognosis of hypertension during pregnancy. Twenty preeclamptic patients underwent renal biopsies after delivery and were divided into the following three groups: group I, patients with persistent hypertension after delivery (n = 7; mean age, 34.8 +/- 1.4 years [SE]); group II, patients who became normotensive after delivery and hypertensive again during follow-up (n = 5; mean age, 34.8 +/- 1.6 years), and group III, patients who became normotensive after delivery (n = 8; mean age, 28.0 +/- 1.0 years). We also examined age-matched healthy controls (group IV; n = 7; mean age, 34.9 +/- 1.5 years). Renal biopsy specimens were immunohistochemically stained by the avidin-biotinylated peroxidase complex method using antimonoclonal smooth muscle cell myosin heavy chain isoform antibodies (SM-1, SM-2) and antimonoclonal alpha-smooth muscle cell actin antibody (actin). We estimated and semiquantitatively scored the degree of staining in each section. In interlobular arteries, SM-1, SM-2, and actin staining in group I were significantly reduced compared with group IV (SM-1, SM-2, P: < 0.05; actin, P: < 0.01). In afferent arterioles (Afs), SM-1, SM-2, and actin staining were reduced in group I. SM-2 staining in group I was significantly reduced compared with the other three groups (versus group II, P: < 0.05; versus groups III and IV, P: < 0.01). These findings suggest that phenotypic changes in vascular smooth muscle cells (especially the disappearance of SM-2 in Afs) reflect the stage of underlying essential hypertension and can predict from the change in hypertension during pregnancy whether it will persist after delivery.

Actins↗
PubMed2001

Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor.

Caspases have been implicated in the effector process of apoptosis in several systems including the Fas-Fas ligand pathway. We previously demonstrated that excessive apoptosis of lung epithelial cells and the Fas-Fas ligand pathway were essential in the pathogenesis of bleomycin-induced pneumopathy in mice. Therefore, the purpose of this study was to investigate whether a caspase inhibitor could prevent the development of this model. The expression of caspase-1 and caspase-3 was upregulated on lung epithelial cells, alveolar macrophages, and infiltrating inflammatory cells in this model. We demonstrated that a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, decreased the caspase-1- and caspase-3-like activity, the number of apoptotic cells, the pathological grade of lung inflammation and fibrosis, and the hydroxyproline content in lung tissues in this model. We conclude that caspase inhibitors could be a new therapeutic approach against lung injury and pulmonary fibrosis.

Administration, Inhalation↗
PubMed2001

PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways.

Goblet cell metaplasia is an important morphological feature in the airways of patients with chronic airway diseases; however, the precise mechanisms that cause this feature are unknown. We investigated the role of endogenous platelet-activating factor (PAF) in airway goblet cell metaplasia induced by cigarette smoke in vivo. Guinea pigs were exposed repeatedly to cigarette smoke for 14 consecutive days. The number of goblet cells in each trachea was determined with Alcian blue-periodic acid-Schiff staining. Differential cell counts and PAF levels in bronchoalveolar lavage fluid were also evaluated. Cigarette smoke exposure significantly increased the number of goblet cells. Eosinophils, neutrophils, and PAF levels in bronchoalveolar lavage fluid were also significantly increased after cigarette smoke. Treatment with a specific PAF receptor antagonist, E-6123, significantly attenuated the increases in the number of airway goblet cells, eosinophils, and neutrophils observed after cigarette smoke exposure. These results suggest that endogenous PAF may play a key role in goblet cell metaplasia induced by cigarette smoke and that potential roles exist for inhibitors of PAF receptor in the treatment of hypersecretory airway diseases.

Animals↗
PubMed2001

Attenuation of bleomycin-induced pneumopathy in mice by monoclonal antibody to interleukin-12.

We previously demonstrated essential roles of the Fas-Fas ligand (FasL) pathway in bleomycin-induced pneumopathy in mice. T lymphocytes and natural killer cells express FasL on activation and use it as a cytotoxic effector molecule. Because interleukin (IL)-12 is known to play a critical role in cell-mediated immunity, we investigated whether anti-IL-12 antibody treatment suppresses the development of this model. The anti-IL-12 antibody treatment decreased the number of apoptotic cells and the degree of inflammation and fibrosis in lung tissue. The results of RT-PCR showed that IL-12p40, IL-12 receptor (R) beta2, interferon-gamma, tumor necrosis factor-alpha and FasL mRNAs were upregulated after bleomycin instillation. The upregulation of FasL, IL-12Rbeta2, and tumor necrosis factor-alpha mRNA expression in lung tissue was suppressed by anti-IL-12 antibody treatment. The results of enzyme-linked immunosorbent assay showed that the levels of IL-12p40, but not of IL-12p70, were increased in lung tissue after bleomycin instillation. Although the increase in IL-12Rbeta2 mRNA levels suggests that the T helper type 1 cell response may participate in lung injury, the increase in IL-12p40 supports T helper type 2 cell predominance in the fibrotic process of this model. The administration of anti-IL-12 antibody could be a novel therapy against lung injury and pulmonary fibrosis.

Animals↗
PubMed2001

N-omega-nitro-L-arginine methyl ester increases airway responsiveness to serotonin but not to acetylcholine in cats in vivo.

BACKGROUND: We previously reported that N(omega)-nitro-L-arginine methyl ester (L-NAME) enhances airway responsiveness to inhaled serotonin in cats treated with atropine and propranolol. OBJECTIVE: To further elucidate the role of nitric oxide (NO) in airway responsiveness, we investigated whether L-NAME induces airway hyperresponsiveness to serotonin and acetylcholine (ACh) in animals with intact innervation. METHODS: Cats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.), and mechanically ventilated. To assess airway responsiveness, we measured increase in total pulmonary resistance (RL) produced by delivering serotonin or ACh aerosol to the airway, and determined PC200 (the concentration which caused a 200% increase in RL). RESULTS: The following results were obtained: (1) Airway responsiveness to serotonin was significantly enhanced by the administration of L-NAME (100 mg/kg) in animals treated with atropine and propranolol. (2) Airway responsiveness to serotonin was also significantly enhanced by L- NAME in animals with intact innervation. (3) In contrast, airway responsiveness to ACh was not changed by the addition of L-NAME in cats with intact innervation. CONCLUSION: These results suggest that NO modulates nonspecific airway responsiveness in animals with intact innervation, presumably by a reflex mechanism.

Acetylcholine↗
PubMed2001

KL-6, surfactant protein A and D in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis.

BACKGROUND: KL-6, and surfactant protein A (SP-A) and surfactant protein D (SP-D) derived from alveolar type II cells and/or bronchiolar epithelial cells have been reported to be useful markers for interstitial lung diseases. OBJECTIVE: The aim of this study was to measure the levels of these molecules in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis to investigate their relationship with other markers of inflammatory activity. METHODS: We measured KL-6, SP-A and SP-D levels in BALF from patients with pulmonary sarcoidosis using an ELISA. RESULTS: KL-6 and SP-D, but not SP-A levels were significantly increased in pulmonary sarcoidosis compared with controls. KL-6, SP-A and SP-D levels were significantly correlated with each other. KL-6 and SP-D levels were relatively and significantly correlated with the percentage of lymphocytes in BALF. KL-6, SP-D, but not SP-A levels were significantly correlated with the concentration of albumin in BALF. There was no significant correlation between KL-6, SP-A, or SP-D levels and chest X-ray findings, angiotensin-converting enzyme levels, or CD4/CD8 ratio in BALF. CONCLUSIONS: We conclude that KL-6 and SP-D levels in BALF were increased in pulmonary sarcoidosis. Since these markers are specifically derived from epithelial cells, it is considered that KL-6 and SP-D levels are reflecting damage or release of these markers from epithelial cells due to the inflammatory response.

Adult↗
PubMed2001

Upregulation of Fas-signalling molecules in lung epithelial cells from patients with idiopathic pulmonary fibrosis.

The caspase cascade is an executioner of apoptosis, mediated by Fas. Fas-associating protein with death domain (FADD) interacts with Fas and initiates apoptosis through activating caspase-8. It has previously been demonstrated that the Fas-Fas ligand pathway may be involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate Fas-signalling molecules in epithelial cells in IPF. The immunohistochemistry for FADD and caspase-1 and -3 and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabelling (TUNEL) methods were performed in lung tissues from 10 patients with IPF obtained by thoracoscopic biopsy and in seven normal lung parenchyma specimens. The induction of caspases expression and activation by Fas-ligation on lung epithelial cell line A549 was also investigated. The immunoreactivity grade for FADD and caspase-1 and -3, and positive signals for TUNEL were significantly increased in epithelial cells of IPF compared with controls. Fas-ligation induced upregulation of caspase-1 and -3 expression in the nucleus and cytoplasm in A549 cells. Procaspase-1, -3, and -8 were activated in apoptotic cells, but not in viable cells. Although direct measurement of the caspase activity in lung epithelial cells of idiopathic pulmonary fibrosis could not be made, these results suggest that the Fas-signalling pathway is upregulated in lung epithelial cells of idiopathic pulmonary fibrosis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Nitric oxide buffers renal medullary vasoconstriction induced by prostaglandins synthesis blockade.

The aim of this study was to examine whether nitric oxide (NO) buffers the renal medullary vasoconstriction induced by a prostaglandins (PG) synthesis inhibitor. Daily blood pressure measurements were made with implanted catheters and changes in cortical blood flow (CBF) and medullary blood flow (MBF) were determined by implanted optical fibers and laser-Doppler flow measurement techniques in conscious rats. Sodium and water balance were also determined. Infusion of meclofenamate, a nonisozyme-specific cyclooxygenase (COX) inhibitor, at 5 microg/kg/min over 4 consecutive days (n=12 rats) elicited a transitory increase (p<0.05) in mean arterial pressure (MAP) and a transitory decrease (p<0.05) in MBF and sodium excretion without altering CBF. In contrast, the simultaneous infusion of meclofenamate and N(G)-nitro-L-arginine methyl ester (L-NAME, 0.8 microg/kg/min), a NO synthesis inhibitor, over 4 consecutive days (n=12) produced a continuous increase (p<0.01) in MAP and a continuous decrease (p<0.05) in MBF and sodium excretion without altering CBF. The results of this study suggest that the renal medullary vasoconstrictor effects and sodium retention induced by meclofenamate are enhanced by a subpressor dose of L-NAME, and that NO may buffer the renal medullary vasoconstriction induced by the blockade of PG synthesis in conscious rats.

Animals↗
PubMed2001

Acute interstitial pneumonia induced by ONO-1078 (pranlukast), a leukotriene receptor antagonist.

A 62-year-old woman treated with pranlukast for 2 months developed interstitial pneumonitis with a high fever. A lymphocyte stimulation test was reactive to pranlukast. Her clinical symptoms improved with discontinuation of pranlukast and administration of systemic corticosteroid. To our knowledge, this is the first reported case of drug-induced lung disease involving a leukotriene. The steps that can be taken to promptly reach a diagnosis and to successfully treat this life-threatening condition are described.

Acute Disease↗
PubMed2001

Molecular mechanisms of pulmonary fibrosis and current treatment.

Pulmonary fibrosis is a common response to various insults or injuries to the lung. Although there are various initiating factors or causes, the terminal stages are characterized by proliferation and progressive accumulation of connective tissue replacing normal functional parenchyma. The pathogenesis of pulmonary fibrosis includes endothelial and epithelial cell injury, production of inflammatory cells and their mediators, and fibroblast activation. Conventional therapy consisting of glucocorticoids or cytotoxic drugs is usually ineffective in preventing progression of the disease. Further understanding of the molecular mechanisms of endothelial and epithelial cell injury, inflammatory reaction, fibroblast proliferation, collagen deposition and lung repair, should lead to the development of effective treatments against pulmonary fibrosis. Accordingly, this review summarizes recent progress made in understanding the molecular mechanisms of pulmonary fibrosis. A detailed discussion is presented regarding each of the potential new therapies which have emerged from the animal models of pulmonary fibrosis and which have been developed through advances in cellular and molecular biology.

Animals↗
PubMed2001

[The effect of pregnancy on the long-term renal function in lupus nephritis patients].

Pregnancy is an important consideration in the treatment of patients with lupus nephritis(LN), particularly because the disease predominantly affects females of childbearing age. Forty-two patients were studied retrospectively to investigate whether delivery adversely affects the natural course of renal function in patients with LN. The patients were divided into two groups(patients with delivery during the follow-up period: Group I, n = 11; patients who were not pregnant: Group II, n = 28; excluding 3 patients with abortion). Group I and II profiles at the beginning of the follow-up were as follows: age(years): 26.7 +/- 5.0(mean +/- SD) and 30.5 +/- 8.4; S-Cr(mg/dl): 0.86 +/- 0.27 and 1.05 +/- 0.52, respectively; urinary protein(g/day): 2.42 +/- 3.05 and 3.37 +/- 4.08; follow-up period(months): 144 +/- 65.2 and 98.7 +/- 68.0; WHO IV LN was 27%(3/11) in Group I and 61%(17/28) in Group II. The activity of SLE in Group I disappeared before gestation, except for one case, and no patients experienced recurrence during pregnancy or after delivery. Delivery did not adversely affect the long-term prognosis of renal function in the three patients with WHO IV LN in Group I. The changes in the renal function between Groups I and II during the follow-up period were not significantly different (delta 1/Cr/dl/mg/months: -0.00066 +/- 0.00356 in Group I, 0.00636 +/- 0.02889 in Group II). Renal deterioration was observed in only one case (9%) in Group I (the patient had persistent proteinuria of over 2 g/day throughout the clinical course and started hemodialysis 12 years after delivery), and in 3 cases(11%) in Group II at the end of follow-up. The renal survival rate did not significantly differ between the two groups. We concluded that delivery does not adversely affect the long-term prognosis of patients with LN that is clinically controlled through treatment.

Adolescent↗