Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 307 records · Page 17Linked to original sources

PubMed1992

[Evaluation of plasma SC5b-9 (SMAC) in patients with ARDS].

The adult respiratory distress syndrome (ARDS) occurs in patients with various underlying illnesses. It has been suggested that complement activation may play a crucial role in the pathophysiology of ARDS by direct actions of complement fragments and/or by release of mediators including endotoxin, superoxide anion, and arachidonate metabolites. Therefore, complement evaluation was performed in patients with ARDS, with emphasis on SC5b-9 (Membrane Attack Complex). Complement split products, C4d, Bb, and SC5b-9, respectively from the classical, alternative, and terminal complement pathway were measured by enzyme immunoassay (EIA) using respective monoclonal antibodies. Plasma S-protein (vitronectin) concentration was also evaluated by EIA. We could not detect SMAC in normal controls or in a C5-deficient patient with abdominal infection. In contrast, most patients with ARDS and patients at risk showed elevated SMAC, and an increase in the values in association with exacerbation of the disease. However, two patients with ARDS exhibited lower values of SMAC in spite of deterioration and subsequent death. It was suggested that in these two ARDS patients, liver dysfunction may have contributed to the reduced SMAC formation. The finding that S-protein concentration (a MAC inhibitor) in the plasma of these two patients was reduced supports this speculation. It is suggested that simultaneous evaluation of SMAC and S-protein in plasma is helpful in determining the prognosis of critically ill patients.

Adolescent↗

PubMed1992

[Management of airway obstruction using the neodymium-yttrium-aluminium-garnet laser].

The neodymium-yttrium-aluminium-garnet laser (Nd-YAG laser) has proved to be useful therapeutic tool for the management of endobronchial lesions. Between February 1983 and January 1991, 16 patients received endobronchial laser therapy at the Nagasaki University Hospital, 7 patients for tracheal stenosis, and 9 for endobronchial obstruction. In 4 patients with tracheal stenosis, the therapy was performed in an emergency. The type of lesions were lung cancer in 7 patients, thyroid cancer in 3, tracheal tumor (squamous cell carcinoma, and chondrosarcoma) in 2, esophageal cancer in 1, bronchial submucosal tumor in 1, and tracheobronchial tuberculosis in 2. Good symptomatic relief was obtained in 13 patients. One patient died from massive bleeding in the left main stem bronchus. Reobstruction had occurred in 2 patients with cicatricial lesion in right main stem bronchus. In patients with an unresectable malignant lesion, concurrent radiotherapy was needed to prevent the reobstruction.

Aged↗

PubMed1991

Tumor necrosis factor reduces the ACh-induced outward current in identified Aplysia neurons.

Effects of extracellularly applied recombinant human tumor necrosis factor (rhTNF) on the acetylcholine (ACh)-induced K+ current recorded from identified neurons (R9 and R10) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Bath-applied rhTNF (200-500 U/ml) reduced the ACh-induced current in the neurons without affecting the holding current and resting membrane conductance. The suppressing effect of rhTNF on the current was completely reversible. Inhibition by rhTNF was non-competitive. Heat-inactivated rhTNF was without effect. Our results suggest that the immunomodulator TNF can act on the ACh receptor in the nervous system.

Acetylcholine↗

PubMed1991

Clinicopathological study of pulmonary giant cell carcinomas with reference to prognosis of patients.

Giant cell carcinomas of the lung have been notorious in fulminant clinical courses. Thus, this report describes two exceptionally favorable cases among six cases of giant cell carcinoma of the lung. Their histopathological features are a sharply-demarcated tumor of Stage I, absence of vascular permeation of the cancer cells, prominent lymphoid and plasma cell infiltration in the tumor tissue, and lymph follicle formation in the surrounding tissues. Another case with a Stage II tumor showed the same histopathological findings as the above two cases with the exception of lymphatic permeation of the cancer cells. This patient expired about one year after undergoing an operation. As conventional controls, the remaining three cases with Stage III tumors showed an alveolar extension of tumor cells and vascular permeation. There was a fulminant course after the operation. Notwithstanding similar intervals from their clinical onset to operation in the 4 cases other than Cases 4 and 6, their stages showed considerable variations. Hence, each histopathological feature might have substantiated the different clinical courses following the operation. Electron microscopy of three of the cases indicated double-membrane-bound blisters with intermediate junctions in the bizarre giant cells, and cancer cell differentiation toward both glandular and squamous directions.

Aged↗

PubMed1991

Ionic mechanism of the outward current induced by extracellular ejection of interleukin-1 onto identified neurons of Aplysia.

The ionic mechanism of the effect of extracellularly ejected recombinant human interleukin-1-beta (rhIL-1) on the membrane of identified neurons R9 and R10 of Aplysia was investigated with voltage-clamp, micropressure-ejection, and ion substitution techniques. Micropressure-ejected rhIL-1 caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at its resting potential level (-60 mV) and reejecting rhIL-1 with the same dose produced a slow outward current (I0(IL-1), 20-30 s in duration, 3-5 nA in amplitude) associated with a decrease in input membrane conductance. I0(IL-1) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of I0(IL-1) was approximately +15 mV. I0(IL-1) was sensitive to changes in the external Na+ concentration but not to changes in K+, Ca2+ and Cl- concentrations, and was resistant to tetraethylammonium (5 mM) and 4-aminopyridine (5 mM). Neither perfusion of the neuron with 50 microM tetrodotoxin nor perfusion with 10 mM Co2+ seawater caused any changes in I0(IL-1). I0(IL-1) was partially reduced by 50 microM ouabain. These results suggest that extracellular IL-1 can induce a slow outward current associated with a decrease in Na+ conductance and the immunomodulator IL-1 can act directly on the nervous system as well as on the immune system.

Animals↗

PubMed1991

Gastric hyperacidity and mucosal damage caused by hypothermia correlate with increase in GABA concentrations of the rat brain.

The involvement of brain GABA mechanisms in acid secretion and maintenance of gastric mucosal integrity was studied in the anesthetized rat. Cold exposure lowered the rectal temperature and stimulated acid output in the anesthetized rat. The acid response to cold exposure was completely suppressed by surgical vagotomy. The substantial increase in brain GABA content evoked by pretreatment with aminooxyacetic acid (10 and 20 mg/kg s.c. x 3) significantly potentiated the gastric acid response to the cold exposure stress; suppression of the GABA content induced by semicarbazide (100 mg/kg s.c.) reduced the acid response to cold. Significant correlations were found between the brain GABA contents and the acid secretory activity and also between the GABA contents and the ulcer index of gastric lesions induced by the cold stress. These results indicate that hypothermia evoked by cold exposure stimulates gastric acid secretion and induces gastric lesions through central GABA mechanisms in the rat.

Aminooxyacetic Acid↗

PubMed1991

Analysis of a decreased Na+ conductance by tumor necrosis factor in identified neurons of Aplysia kurodai.

The ionic mechanisms of the effect of extracellularly ejected recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on the membrane of identified neurons R9 and R10 of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion substitution techniques. Micropressure-ejected rhTNF caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at it resting potential level (-60 mV) and reejecting rhTNF-alpha with the same dose produced a slow outward current [Io (TNF)] associated with a decrease in input membrane conductance. Io (TNF) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of Io (TNF) was approximately +10 mV. Ion substitution and pharmacological experiments suggest that Io (TNF) in identified neurons R9 and R10 of A. kurodai is due to a decreased Na+ conductance but not due to an activation of the Na(+)-K+ pump. Our results demonstrate that the immunomodulator TNF can act directly on the nervous system as well as on the immune system.

Animals↗

PubMed1991

Postoperative adjuvant chemotherapy in non-small cell lung cancer: prognostic value of DNA ploidy and post-recurrent survival.

Eighty-six patients with non-small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups. In the adjuvant chemotherapy group, patients received cisplatin-based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2.3 (from 1 to 6 cycles). In this trial, no evidence of improved survival or delayed recurrence was seen in the treated patients. In multivariate analysis of prognostic variables, the most important factor was the pathological stage of the disease and, second, DNA ploidy of the primary tumor. Although histology (squamous vs. non-squamous cell carcinoma) had a trend to influence the survival, it was not a significant factor. A total of 33 patients had recurrences: 17 and 16 patients were in control and adjuvant chemotherapy groups, respectively. Postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group, as determined by the generalized Wilcoxon and log rank tests. Median survival time after recurrence in the control and adjuvant therapy groups was 18.5 and 7.5 months, respectively. These results suggest that DNA ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy. Furthermore, analysis of postrecurrent survival in the adjuvant chemotherapy trial, as well as that of overall and disease-free survivals should be done.

Aged↗

PubMed1991

Influence of surgical resection before and after chemotherapy on survival in small cell lung cancer.

We attempted to define the role of surgery in the treatment of small cell lung cancer (SCLC). Of 81 patients with clinically localized SCLC, 36 underwent surgical resection: 19 underwent initial resection with postoperative chemotherapy, while the remaining 17 were treated initially with chemotherapy, then resection. The remaining 45 patients were treated with a combination of chemotherapy and radiotherapy. The 5-year survival for the 36 surgical patients was 38%; median survival time (MST) was 33 months. Nineteen patients treated with postoperative chemotherapy showed a 42% 5-year survival, while 17 patients treated with preoperative chemotherapy showed a 33% 5-year survival. This difference was not significant. However, stage III survival tended to be better in patients with preoperative chemotherapy (MST, 29 months) than in those who had had postoperative chemotherapy only (MST, 17 months). Although survival of the 45 nonsurgical patients was poor, stage I and II patients, or those with complete remission showed a 25% 5-year survival with an MST of 33 months, and a 21% 5-year survival with an MST of 25 months, respectively. We thus concluded that initial resection combined with postoperative chemotherapy is beneficial for patients with stage I, and probably stage II disease. For resectable stage III, particularly in patients with N2 disease, adjuvant resection after chemotherapy may be a favorable choice in the management of SCLC. For advanced stage III, complete remission by chemotherapy should be attempted in combination with radiotherapy.

Aged↗

PubMed1991

The activation of Ca(2+)-dependent K+ conductance by adrenaline in mouse peritoneal macrophages.

Responses to adrenaline in mouse peritoneal macrophages were investigated with perforated and cell-attached patch-clamp recording, and with a combination of the perforated-patch recording and fura-2 fluorescence measurements. Extracellularly applied adrenaline induced a transient outward current (4-10 s in duration, 100-500 pA in amplitude) at -40 mV associated with a marked increase in conductance. The adrenaline-induced current [Io (Adr)] reversed polarity near -80 mV. The reversal potential depended distinctly on the external K+ concentration but not on external Cl- concentration. Removal of external Ca2+ did not affect Io(Adr) within 2-4 min but subsequent responses to adrenaline were progressively depressed. In contrast, treatment with an intracellular Ca2+ chelator, the acetoxymethyl ester of 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid completely abolished Io(Adr). Furthermore, Io(Adr) was blocked by bath-applied quinidine and charybdotoxin, but not by tetraethylammonium or apamin. Extracellular application of an alpha 1-adrenoceptor agonist phenylephrine and of noradrenaline mimicked Io(Adr). On the other hand, Io(Adr) was antagonized by a non-selective alpha-adrenoceptor antagonist phentolamine (0.2 microM) and an alpha 1-adrenoceptor antagonist prazosin (0.2 microM), but was not affected by an alpha 2-adrenoceptor antagonist yohimbine (1 microM) or a beta-adrenoceptor antagonist propranolol (1 microM). Cell-attached single-channel recordings with the pipette solution containing 145 mM KCl revealed the activation of single-channel currents with a conductance of 40 pS during application of adrenaline outside the patch. Parallel measurements of membrane current and fura-2 fluorescence in the same cell demonstrated a correlation between the rise in [Ca2+]i and an increase in K+ conductance. Therefore, it is concluded that adrenaline activates a Ca(2+)-dependent K+ conductance by release of Ca2+ from internal stores through an activation of an alpha 1-adrenoceptor.

Animals↗

PubMed1991

Giant extrathoracic hematoma after thoracoplasty--a case report.

A rare case of an extrathoracic giant hematoma developing after a thoracoplasty in a 67 year old man is presented herein. The patient underwent a right thoracoplasty without removal of plombage and a left thoracoplasty with removal of plombage for tuberculosis of the bilateral upper lobes 27 and 24 years prior to presentation, respectively. He presented to us in May, 1987, with a subscapular tumor which had been growing over the last 5 years. A giant tumor, measuring 23 x 17 x 12 cm and weighing 2585 g was successfully removed and the patient has since been well without any evidence of recurrence.

Aged↗

PubMed1991

DNA ploidy patterns of tumors diagnosed as metachronous or recurrent lung cancers.

The relationship between the first tumor and the second tumor resected in 8 patients with non-small cell lung cancer was analyzed using deoxyribonucleic acid (DNA) flow cytometry. Of the 8 patients, 6 were clinically diagnosed as having metachronous lung cancers and 2, local recurrent tumors. The mean interval between operations in patients with metachronous lung cancers was 62 months (range, 15 to 128 months). Both tumors showed the same histology in 4 patients and a different histology in 2. In the 2 patients with local recurrent tumors, the interval between operations was 9 months and 39 months. In the analysis of DNA flow cytometry of the first and second tumors in the same patient, the tumors were defined as independent of each other when one tumor showed diploidy and the other, aneuploidy, or when each DNA index of abnormal clones between two aneuploid tumors was different. When both tumors showed diploidy or when at least one DNA index of abnormal clones between two aneuploid tumors was identical, the tumors were defined to be related to each other. According to these criteria, in 5 (83%) of the 6 patients clinically diagnosed as having metachronous lung cancers, the second tumor was classified as independent of the first tumor. On the other hand, in the 2 patients clinically diagnosed as having recurrent tumors, the second tumor was judged to be related to the first tumor. These data suggest that DNA flow cytometric analysis of tumors may be of value in the diagnosis of metachronous lung cancers.

Adenocarcinoma↗

PubMed1991

Long-term survivors in resected and nonresected small cell lung cancer.

Long-term survival (greater than or equal to 3 years) was evaluated in 164 patients with small cell lung cancer (SCLC). Thirty-seven patients underwent surgical resection, and 127 did not. All but one resected patient received combination chemotherapy. Of the 20 (12%) long-term survivors, 13 (35%) were resected, and 7 (6%) were not. Eleven of these resected patients had pathologically confirmed stage I disease. All of the 7 nonresected patients achieved complete remission by treatment, 6 of these having presented with limited disease. In addition, all patients received thoracic irradiation combined with chemotherapy. Two of the 20 patients who survived beyond 3 years developed a second malignancy 11.3 and 12 years, respectively, after initial treatment for SCLC. In conclusion, surgical resection for stage I, and probably stage II SCLC followed by chemotherapy may be an appropriate therapeutic approach. For advanced limited disease, thoracic irradiation, in addition to chemotherapy, seems to improve long-term survival.

Adult↗

PubMed1991

GABAA and GABAB-receptor agonists evoked vagal nerve efferent transmission in the rat.

The effect of GABA agonists on vagal efferent activity was studied in anesthetized rats. PCPGABA, a GABAB agonist (4 and 8 mg/kg, s.c.), markedly activated the neural efferent discharge of the vagus. Muscimol, a GABAA agonist (0.1 and 0.3 mg/kg, i.v.), also facilitated vagal activity. Both agonists caused significant gastric acid hyperacidity. Bicuculline (0.25 mg/kg, i.v.) or picrotoxin (0.5 mg/kg, i.v.) given 10 min prior to each agonist had no effect on the frequency of vagal nerve firing elicited by PCPGABA (4 mg/kg, s.c.) or muscimol (0.3 mg/kg, i.v.). Pretreatment with scopolamine (0.25 mg/kg, i.v.) abolished PCPGABA stimulated vagal activity and gastric acid secretion. Methscopolamine (0.25 mg/kg, i.v.) inhibited only the hyperacidity evoked by PCPGABA, but not vagal activation. These results suggest that PCPGABA and muscimol may cause gastric acid secretion through central cholinergic descending mechanisms that are resistant to GABAA and GABAB antagonists.

Acetylcholine↗

PubMed1991

Appearance of thrombosis-inducing activity in the plasma of patients undergoing pulmonary resection.

Thrombosis-inducing activity (TIA) was detected in the peripheral blood of patients with lung cancer who had undergone pulmonary resection. TIA was examined by intravenously injecting plasma from the patients into BALB/c mice. The plasma containing TIA induced multiple thromboses in the lung and caused the mice to die 3 to 30 minutes after injection. The subjects were 19 patients whose plasma contained no TIA before operation. TIA was detected in 5.3 percent (1/19) on the first postoperative day (POD), 47.4 percent (9/19) on the seventh POD, 47.1 percent (8/17) on the 14th POD, 26.7 percent (4/15) on the 21st POD, and 20 percent (2/10) on the 28th POD. Plasma fibrinogen levels and peripheral platelet counts increased postoperatively and reached a maximum on the seventh and 14th POD, respectively. Peripheral blood with TIA had a significant elevation of plasma fibrinogen levels and platelet counts as compared to that without TIA. These observations suggest that TIA is present in blood in a hypercoagulable state in patients after pulmonary resection. Since tumor necrosis factor and interleukin 1 are known to induce hypercoagulable states both in vitro and in vivo, we tried to determine whether it was possible to detect both cytokines in blood indicated as hypercoagulable state by the presence of TIA. They did not, however, reach detectable levels in the blood.

Aged↗

PubMed1991

[Surgical indication for T1N2 disease: comparison of survival among resected T1N2, T2 N2 and non-resected T1 (M0) disease].

Based on the outcome of 28 patients with pathologically confirmed T1N2 disease who underwent surgical resection, we evaluated surgical indication for this stage. Twenty three patients underwent complete resection and 5 patients incomplete resection. The histologic type of tumor was adenocarcinoma in 20 patients and squamous cell carcinoma in 8 patients. The 5-year survival rate was 22% for all resected patients and 28% for completely resected patients. These survival rates were better than those (16% and 23%, respectively) in patients with T2N2 disease. However, there was no significant difference of survival among incompletely resected T1 N2, and non-resected T1 (M0) patients. Although 9 of 28 T1N2 patients survival more than 3 years, all but one patient underwent complete resection of tumor and had clinical N0 or N1 before surgery. In conclusion, surgery should be indicated only for patients with completely resectable tumor, even in T1N2 disease.

Adult↗

PubMed1991

[Assessment of a phase III trial of adjuvant chemotherapy in resected lung cancer: an imbalance of surgical results among cooperative institutions].

Many investigators have studied the benefit of adjuvant chemotherapy (AC) in resected lung cancer. However, its benefit is still controversial, except for small cell lung cancer. In the present study, we discussed problems in the preparation of a phase III trial of AC in resected lung cancer. Since a phase III trial requires generally large sample sizes for a short period, a multicenter approach is frequently necessary. However, there are several problems in the preparation of such trial. Firstly, we found that survival for resected lung cancer was considerably different among institutions. Overall 5-year survival for 279 resected N2 disease collected from 7 major institutions was 23%. The 5-year survival for each institution, however, ranged from 7 to 41%. This difference is probably caused by the fact that surgical indication, an ability in operation and postoperative care are different among institutions. Secondly, the number of patients enrolled in the trial spread widely among cooperative institutions. In a phase III trial of AC for resected stage III A patients, 209 patients were collected from 25 institutions. The number of patients enrolled from individual institutions ranged from 0 to 25. Only 5 institutions were possible to enter more than 10 evaluable patients on the trial. Recently, a phase III trial of neoadjuvant therapy was carried out in stage III A (T1-2N2) patients at 5 major institutions. Patients were treated initially with 2 cycles of chemotherapy (CDDP + VDS + MMC), followed by surgical resection. Of 22 resected patients, 4 who underwent extended pneumonectomy, happened to die postoperatively only in one institution. This also shows an imbalance of surgical results among cooperative institutions. In conclusion, we consider that it is particularly important to select institutions without an imbalance of surgical results in a phase III trial.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Synchronous lung cancers defined by deoxyribonucleic acid flow cytometry.

When two pulmonary tumors are seen simultaneously in patients with lung cancer, it always raises a question as to whether the lesions are synchronous lung cancers or lung cancer with intrapulmonary metastasis. To settle this issue, we used deoxyribonucleic acid flow cytometry. Deoxyribonucleic acid ploidy patterns of tumors were able to be analyzed in 14 patients with two simultaneous pulmonary tumors resected by operation. These two tumors, with completely different patterns of deoxyribonucleic acid ploidy, were defined as synchronous lung cancers. Tumors were defined as lung cancer with intrapulmonary metastasis when both tumors showed diploidy or when at least one deoxyribonucleic acid index of abnormal clones between two aneuploid tumors was the same or almost identical. Tumors of the five patients with stage I disease were classified as synchronous lung cancers according to the criteria involving deoxyribonucleic acid flow cytometry. Both tumors were adenocarcinomas in four patients and large-cell and squamous cell carcinomas in one. Both tumors in four patients were located in the same lobe but different segments. All but one patient with different histologic types are alive without recurrence from 24 to 100 months after operation. Tumors of the nine patients with stage III disease in whom intrapulmonary metastasis was clinically suspected were classified as lung cancer with intrapulmonary metastasis according to the criteria. These data suggest that deoxyribonucleic acid flow cytometry of tumors may have diagnostic value in determining synchronous lung cancers.

Adult↗