Biomedical subjects
Publications and source records attributed to N Hara.
A rare case of intraosseous well-differentiated osteosarcoma in a 9-year-old boy arising in the rib is reported. A bone scintiscan was found to be useful in accurately diagnosing this lesion as malignant tumor, because plain films and CT scan seemed to indicate a benign tumorous condition.
A patient with a schwannoma of the intrathoracic vagus nerve is presented. The tumor invaded the trachea and caused dyspnea. It was successfully excised by a segmental resection of the trachea with end-to-end anastomosis. This instance of an intrathoracic vagus tumor invading the trachea is, as far as we know, the first reported in the world.
In mouse peritoneal macrophages, alpha 1-adrenoceptor stimulation evokes a Ca(2+)-dependent K+ current [Io(Adr)][Hara et al. (1991) Pflügers Arch 419:371-379]. The roles of D-myo-inositol 1,4,5-trisphosphate (InsP3) and a GTP-binding protein (G protein) in Io(Adr) were investigated with tight-seal whole-cell recordings and fura-2 fluorescence measurements. Intracellular injection of InsP3 (5-50 microM) evoked transient outward currents [Io(InsP3)] with or without damped oscillations in membrane currents at -40 mV. Dialysis with 0.2 mM guanosine 5'-[3-thio]triphosphate (GTP[gamma S], a poorly hydrolysable GTP analogue) at -40 mV activated oscillatory outward currents or a slowly developing steady current on which such oscillations were superimposed after a delay of 10-90 s. Io(InsP3) and the GTP[gamma S]-induced current [Io(GTP[gamma S])] were accompanied by an increase in conductance. Reversal potentials of both responses closely depended on the extracellular K+ concentration. Fura-2 measurements revealed that Io(InsP3) and Io(GTP[gamma S]) result from a rise in intracellular free Ca2+ concentration ([Ca2+]i). Removal of extracellular Ca2+ did not abolish Io(InsP3) and Io(GTP[gamma S]). Both were blocked by bath-applied charybdotoxin. Intracellular D-myo-inositol 1,3,4,5-tetrakisphosphate (InsP4, 50 microM) did not evoke any responses, whereas D-myo-inositol 2,4,5-trisphosphate [InsP3(2,4,5), 20 microM] elicited an outward current at -40 mV. Io(InsP3) was completely blocked by prior dialysis with the InsP3 receptor antagonist heparin (5 mg/ml). Inclusion of guanosine 5'-[2-thiol] diphosphate (GDP[beta S], 2 mM) or heparin (5 mg/ml) together with GTP[gamma S] in the patch pipette solution completely blocked Io(GTP[gamma S]). These results indicate that intracellular injection of InsP3 or GTP[gamma S] mimic Io(Adr).(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between adenocarcinomatous and squamous carcinomatous components in 12 surgically resected adenosquamous lung carcinomas was analyzed using DNA flow cytometry. Well-preserved parts of the tumor showing either adenocarcinoma or squamous cell carcinoma were identified on paraffin blocks. The cells obtained from each component were stained with propidium iodide for DNA flow cytometry. In the analysis of DNA flow cytometry, both components in the same tumor were defined as being related to each other when they showed diploidy or when at least one DNA index of abnormal clones between two aneuploid components was identical. According to these criteria, 8 (67%) of the 12 tumors showed a relationship between adenocarcinomatous and squamous carcinomatous components. This suggests that, despite the different phenotypes, both components of some adenosquamous lung carcinomas may share similar biological characteristics.
Activation of the alpha 1-adrenoceptor (alpha 1-AR) in mouse peritoneal macrophages induces a Ca(2+)-dependent K+ current via release of Ca2+ from internal stores [Hara et al. (1991) Pflügers Arch 419: 371-379]. In order to characterize the alpha 1-AR subtype in macrophages, we examined potencies of the alpha 1-AR subtype-selective antagonists against epinephrine-induced increases in intracellular Ca2+ concentration ([Ca2+]i). The Ki values for the alpha 1-AR in macrophages of WB4101, 5-methylurapidil and phentolamine were 0.13 nM, 0.15 nM and 7.0 nM, respectively. (+)-Niguldipine (10 nM) completely blocked the response. Treatment with chloroethylclonidine (CEC) did not abolish the response. These pharmacological properties of the alpha 1-AR in macrophages agree quite well with those of the alpha 1A subtype.
We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor alpha beta-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.
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A 57-year-old man with lung squamous cell carcinoma revealed hypercalcemia, hypophosphoremia, elevation of nephrogenous cAMP and metabolic alkalosis. Serum parathyroid hormone (PTH) and 1,25(OH)2D3 concentrations were not elevated. These findings were consistent with those in humoral hypercalcemia of malignancy (HHM). PTH-related peptide (PTHrP) concentrations were determined using N- and C-terminal specific radioimmunoassays (PTHrP-N, PTHrP-C), and elevation of both PTHrP-N and PTHrP-C concentrations in the serum was noted (PTHrP-N, 27 pmol/liter (normal < 5); PTHrP-C, 1408 pmol/liter (normal < 50)). High concentration of PTHrP (946 pmol/liter for PTHrP-N and 5983 pmol/liter for PTHrP-C) was also found in the pleural fluid obtained at autopsy. Immunohistochemical study, using paraffin-embedded sections of the tumor tissue obtained at autopsy, revealed numerous PTHrP-positive cells and expression of PTHrP gene was confirmed by Northern blot analysis. These findings indicate that PTHrP, produced in the tumor tissue, was secreted into the blood stream, which caused HHM in the patient. Gel permeation chromatography of the serum and pleural fluid revealed several peaks of both PTHrP-N and PTHrP-C. Molecular forms of PTHrP-N were larger than those of PTHrP-C in the serum as well as pleural fluid. These findings indicate that multiple forms of PTHrP molecules are present in the serum and pleural fluid. Granulocytosis was also noted in the patient. However, granulocyte- and granulocyte macrophage-colony stimulating factor were not detected in the serum, and the mechanism of the granulocytosis in the patient was unclear.
Incubation of [27-13C]-3 alpha, 7 alpha, 12 alpha-trihydroxycoprost-24-en-26-oic acid with rat liver homogenate followed by 13C-NMR analysis of the incubation product has resulted in the identification of [26-13C]-27-nor-3 alpha, 7 alpha, 12 alpha-trihydroxycoprostan-24-one, supporting the idea that the substrate has been metabolized into 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-oxocoprostan-26-oic acid CoA derivative.
Qualitative and quantitative analyses showed that there was iron (Fe) in a blackish lesion removed from a cat with severe corneal sequestration. Chromatic compound did not extract. The Fe content of the lesion was about 100 times higher than that of a normal cornea, as measured by X-ray fluorescence. Results of other chemical analyses indicated that the Fe in the blackish cornea was not derived from blood in the neovascularized limbus.
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Incubation of glutathione, containing 35S-glutathione (GSH), and leukotriene (LTA4) in the presence of LTC4 synthase produced 35S-LTC4. The LTC4 was ether extracted and detected by ultraviolet absorbance (280 nm) after reverse phase-high performance liquid chromatography (RP-HPLC) separation. The 35S-LTC4 was quantitated by scintillation counting. LTC4 production increased in a dose-dependent manner for GSH concentrations from 10(-8) to 10(-2) M. On the contrary, the 35S detected in the ether phase and the 35S-LTC4 recovered from RP-HPLC decreased inversely with the concentration of unlabeled GSH added but did not with the addition of L-cysteine. This decrease in 35S-LTC4 production versus increased GSH levels results from a direct competition between unlabeled GSH and 35S-GSH reacting with the LTA4. Incubation of GSH (0.5 mM), containing 35S-GSH (0.3 uCi, 10 nM) and LTA4 (10 microM) with LTC4 synthase produced 35S-LTC4 at a linear rate over 5 min. The 35S-LTC4 increased in proportion to the LTC4 synthase added. Therefore, we have demonstrated that LTC4 synthase activity can be monitored by a simple radioassay procedure that measures 35S counts in ether extracts from incubation mixtures. This reliable and rapid assay procedure promises to facilitate characterization and purification of LTC4 synthase, a membrane-bound GSH S-transferase of unique specificity.
We report a case of right phrenic nerve paralysis caused accidentally by compression after internal carotid artery puncture. Postoperatively she received respiratory management and conservative treatment after extubation. Cases of phrenic nerve paralysis following cardiac surgery have been reported, but paralysis as a complication of internal jugular vein cannulation by anterior approach is rare.
A resection of pulmonary metastases from colorectal cancer was performed in 27 patients. The cumulative 5-year survival after thoracotomy was 41.1%. Patients with either one or two metastases had a significantly better survival, with a 5-year survival of 54.3%, than did those with a greater degree of metastases (p < 0.01). Other factors including the disease-free interval, size of metastases, type of pulmonary resection, and stage of primary cancer had no apparent influence on post-thoracotomy survival. Furthermore, the presence of controlled hepatic metastases had no adverse effect on survival and did not seem to contraindicate pulmonary resection. The lung and primary colorectal region were the major sites of recurrence. Therefore, the primary colorectal site should be explored thoroughly and the number of metastases should be carefully considered when pulmonary resection is considered for metastatic colorectal cancer.
A 62 year old man treated with carbamazepine for 3 months developed eczema and acute interstitial pneumonitis. A lymphocyte-stimulation test was reactive to carbamazepine. Withdrawal of the drug resulted in prompt improvement. Only 10 cases of this type of drug-induced lung disease have previously been reported.
A combination chemotherapy of cisplatin and UFT was administered to fourteen patients with unresectable non-small cell lung cancer. To determine the maximum safety dose of UFT combined with CDDP (80 mg/m2), patients were assigned to three groups as follows: step 1: UFT (400 mg/m2) from day 1 to day 14; step 2: from day 1 to day 21; step 3: from day 1 to day 28. Cisplatin was administered on day 8 in each group. Myelosuppression with grade 3-4 and gastrointestinal toxicity of grade 3 were observed in one and two patients, respectively. The other toxicity was mild. There was no difference in the degree of toxicity among the three groups. The response rate of twelve evaluable patients was 50%; CR 0, PR 6, NC 4 and PD 2. Thus, chemotherapy using cisplatin 80 mg/m2 with daily administration of UFT 400 mg/m2 was considered to be well tolerated and effective in the treatment of non-small cell lung cancer.
We have developed an intraoperative intrapleural treatment with the use of distilled water combined with cisplatin for carcinomatous pleuritis found at thoracotomy in patients with non-small-cell lung cancer. In the in vitro experiment, three different cell lines were used as a model of malignant pleural effusion. Cell growth was examined after a 3-day culture, which was preceded by exposure of the cells to cisplatin in either phosphate-buffered saline solution or distilled water for 1/2 to 5 minutes. The growth inhibition of tumor cells after hypotonic cisplatin treatment was significantly greater than after treatment with saline solution and cisplatin. Tumor that was obtained by resection of non-small-cell lung cancer was used as a model to demonstrate decreased viability of the tumor after exposure to hypotonic cisplatin. The viability of the tumor in a 6-day culture, preceded by exposure to hypotonic cisplatin (50 micrograms/ml) for 10 minutes, was markedly decreased. Intraoperative intrapleural hypotonic cisplatin was instilled in seven patients with pleural carcinomatosis without side effects and with control of pleural dissemination and pleural effusion for 6 to 29 months.
We attempted to clarify whether the T factor of the TNM staging system should be viewed as a predominant prognostic factor in patients with pathologic stage I non-small-cell lung cancer when analyzed together with various histopathologic factors and deoxyribonucleic acid ploidy pattern of tumors. We studied 151 patients who were in this stage. Histopathologic factors used in the analysis were as follows: histologic cell type (squamous or nonsquamous cell carcinoma), grade of differentiation, and tumor invasion of visceral pleura and vessels. Deoxyribonucleic acid ploidy pattern of tumors was analyzed by flow cytometry, and the tumors were classified as diploid or aneuploid tumors. Significant prognostic factors (p < 0.05) that were demonstrated by univariate analysis of survival curves were as follows: (1) T1 versus T2; (2) well versus moderately or poorly differentiated tumor; (3) the absence versus presence of tumor exposed on pleura, (4) artery invasion, (5) lymphatic vessel invasion; and (6) diploid versus aneuploid tumor. Multivariate prognostic factor analysis showed the grade of differentiation and deoxyribonucleic acid ploidy pattern to be predominant prognostic factors. The T2 tumor group had significantly more cases with tumor invasion of lymphatic vessels that did the T1 tumor group and included 18 cases with tumor exposed on pleura. When these two factors were excluded from multivariate analysis, the T factor was marginally significant (p = 0.08). These observations suggest that the T factor is not necessarily a predominant prognostic factor in pathologic stage I non-small-cell lung cancer.