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Biomedical subjects

Y Saito

Publications and source records attributed to Y Saito.

At least 19 recordsLinked to original sources

[Split-course radiation therapy in non-small cell lung cancer].

Split-course radiation therapy (Sp-RT) is based on theoretical differences between the kinetics of normal and malignant cells. A rest interval halfway through the course of treatment permits the normal tissues to recover, while the tumor shows vary little repopulation. Indeed, it shows mostly regression, resulting in shrinkage of the radiation field. From 1976 through 1985, 185 patients with localized but inoperable or unresectable (stage I-III) non-small cell carcinoma of the lung completed high-dose definitive RT delivered by continuous-course or split-course irradiation. Forty-seven patients who had large tumors or atelectases of the lung showing slow radioresponsiveness received Sp-RT over 60 Gy at 2 Gy per fraction. Rest periods were two or three weeks long in the interrupted schedules. The 5-year survival rate was 16% in the Sp-RT group and 13% in the continuous RT group. In the 33 patients that had differentiated epidermoid carcinoma with slow responsiveness to irradiation, the radiation fields could be shrunk by Sp-RT to the same extent as in the continuous group. Sp-RT was considered to be useful in the treatment of well-differentiated epidermoid carcinoma of the lung.

Adenocarcinoma

Suppressive effect of carbachol on forskolin-stimulated neurite outgrowth in human neuroblastoma NB-OK1 cells.

We have used human neuroblastoma NB-OK1 cells to investigate the regulation of neurite outgrowth. Carbachol suppressed forskolin-stimulated neurite outgrowth in NB-OK1 cells although forskolin-stimulated cAMP levels were enhanced. The dose-response curve for this suppression was very similar to that for stimulation of inositol monophosphate (IP1) formation and for stimulation of the initial rise of [Ca2+]i elicited by carbachol. Carbachol-mediated changes in neurite outgrowth, IP1 formation and [Ca2+]i displayed high sensitivity for pirenzepine but low sensitivity for AF-DX116. Inhibition of intracellular calcium release with TMB-8 prevented the suppressive effect of carbachol on forskolin-stimulated neurite outgrowth. Hence we describe for the first time a relationship between neurite outgrowth and inositol triphosphate-triggered calcium release mediated by carbachol in the human neuron-derived cell line.

Atropine

Phase II study of cisplatin as a 5-day continuous infusion with vindesine plus recombinant human granulocyte-colony-stimulating factor in the treatment of advanced non-small-cell lung cancer.

A total of 36 patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of 5-day continuous i.v. infusion of cisplatin (25 mg/m2 daily), bolus infusion of vindesine (3 mg/m2) on days 1 and 8, and s.c. injection of recombinant human granulocyte-colony-stimulating factor (2 micrograms/kg daily) on days 6-21. Treatment was repeated every 3-4 weeks. Responding patients with stage IIIA or IIIB disease received chest radiation therapy (50-60 Gy) after this treatment. One complete response and 23 partial responses were observed, for an overall response rate of 66.7% (24/36; 95% confidence limits, 51.3%-82.1%). The median duration of response was 5.7 months and the median overall survival was 10.1 months. WHO grade 3 or 4 leukopenia and neutropenia occurred in 22 (61%) and 27 (75%) patients, respectively, but the mean duration of leukopenia (< 2,000/mm3) and neutropenia (< 1,000/mm3) was 3.4 and 3.5 days, respectively, and there was no instance of life-threatening infection. Thrombocytopenia and anemia of grade 3 or 4 occurred in 28% and 36% of our subjects, respectively. Grade 2 nausea and vomiting occurred in 47% of the patients. Elevated serum creatinine levels (> 1.5 mg/dl) were observed in 3 (8%) of the 36 patients. One patient died of acute renal failure induced by hemorrhage of a gastric ulcer. This regimen is effective in the treatment of NSCLC and further studies of this combination are warranted.

Actuarial Analysis

Phase II study of cisplatin continuous infusion plus vindesine in the treatment of non-small-cell lung cancer.

We administered chemotherapy consisting of a combination of 5-day continuous intravenous infusion of cisplatin (25 mg/m2/day) plus vindesine (3 mg/m2, as a bolus, on days 1 and 8) to 30 patients with advanced non-small-cell lung cancer (NSCLC) and examined the effectiveness and safety of the treatment. Fifteen patients achieved a partial response, and the overall response rate was 50%, with a median response duration of 30.1 weeks (range 5-108.6 weeks) and a median survival of 39 weeks. Observed side effects were leukopenia (less than 3000/mm3) in 90% of patients (including less than 1000/mm3 in 23%), thrombocytopenia (less than 75000/mm3) in 30%, anemia (hemoglobin less than 9.5 g/dl) in 50%, vomiting in 43%, and alopecia in 77%. Elevated serum creatinine was not seen, and there were no treatment-related deaths. Toxicity was quite acceptable, but hematological toxicity was increased, and treatment was delayed for six patients because of leukopenia. We conclude that this regimen is generally well tolerated in patients with advanced NSCLC. Further studies in which the optimum therapeutic schedule can be made sufficiently safe to reduce leukopenia are needed.

Adult

Intracellular pH regulation in isolated cochlear outer hair cells of the guinea-pig.

1. The intracellular pH (pHi) regulation mechanisms of the outer hair cell (OHC) isolated from the guinea-pig were studied using fluorescence ratio imaging microscopy. 2. The OHC pHi in the resting condition was 7.26 +/- 0.08 (mean +/- S.D., n = 49) when the standard solution buffered with HEPES-Tris was superfused. 3. Exposure to 25 mM-NH4+ in the absence of HCO3- caused biphasic changes in pHi; a transient increase (7.89 +/- 0.14, n = 22) followed by a slow decrease (7.57 +/- 0.12; mean +/- S.D.). Removal of external NH4+ by introducing the N-methyl-D-glucamine (NMDG+) solution in the absence of HCO3- markedly acidified the pHi to 6.38 +/- 0.12 with little pHi recovery. Subsequent application of the standard Na+ solution restored the pHi to the initial value. The recovery was inhibited by 0.5 mM-amiloride but not by 0.3 mM-DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). 4. In the presence of HCO3-, removal of both external NH4+ and Na+ promptly caused an intracellular acidification followed by a pHi recovery. The pHi recovery from an acid load was inhibited by 0.3 mM-DIDS or 10 microM-NPPB (5-nitro-2-(3-phenylpropyl-amino)-benzoate). However, the pHi in the steady state in the presence or absence of HCO3- was not altered by addition of 0.5 mM-amiloride or NMDG+ solution. 5. The intracellular buffering power obtained from the NH4+ exposure and withdrawal was -15.1 +/- 8.7 mM (pH unit)-1 (n = 6) and -14.3 +/- 5.8 mM (pH unit)-1, respectively. 6. Replacement of external Cl- with gluconate in the HCO3- solution increased the pHi from 7.22 +/- 0.12 to 7.51 +/- 0.20 (n = 6), which was inhibited by 0.3 mM-DIDS. Moreover, addition of DIDS to the HCO3- solution increased the pHi by 0.13 +/- 0.08 (n = 8). 7. When the external standard solution buffered with HEPES-Tris was replaced with the HCO3- solution, the basal pHi (7.27 +/- 0.10) was promptly acidified to 6.87 +/- 0.10 then relaxed slowly to 7.00 +/- 0.15 (n = 16). 8. The pHi showed an initial alkalinization and a subsequent slow acidification after the HCO3(-)-free standard solution replaced the HCO3- solution. The slow acidification was inhibited by low external Cl- concentration or by addition of 0.3 mM-DIDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetazolamide

Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide.

To elucidate the ligand-receptor relationship of the natriuretic peptide system, which comprises at least three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and three receptors, the ANP-A receptor or guanylate cyclase-A (GC-A), the ANP-B receptor or guanylate cyclase-B (GC-B), and the clearance receptor (C-receptor), we characterized the receptor preparations from human, bovine, and rat tissues and cultured cells with the aid of the binding assay, Northern blot technique, and the cGMP production method. Using these receptor preparations, we examined the binding affinities of ANP, BNP, and CNP for the C-receptor and their potencies for cGMP production via the ANP-A receptor (GC-A) and the ANP-B receptor (GC-B). These analyses revealed the presence of a marked species difference in the receptor selectivity of the natriuretic peptide family, especially among BNPs. Therefore, we investigated the receptor selectivity of the natriuretic peptide family using the homologous assay system with endogenous ligands and receptors of the same species. The rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats. The rank order of potency for cGMP production via the ANP-A receptor (GC-A) was ANP greater than or equal to BNP much greater than CNP, but that via the ANP-B receptor (GC-B) was CNP greater than ANP greater than or equal to BNP. These findings on the receptor selectivity of the natriuretic peptide family provide a new insight into the understanding of the physiological and clinical implications of the natriuretic peptide system.

Animals

A case of pulmonary hyalinizing granuloma.

A case of pulmonary hyalinizing granuloma was presented. The patient was a 37-year-old male who was found to have abnormal chest roentgenograms showing multiple pulmonary nodules taken at the annual chest mass survey in October 1989. The largest nodule measured 35 mm in diameter. He was asymptomatic. No definite diagnosis was established either by brushing cytology, biopsy through bronchoscopy or percutaneous needle biopsy. No abnormalities were found in the GI tract, the urogenital system or the bone. Brain CT indicated an iso-density area surrounded by low density in the left fronto-parietal region. Two nodules of the lingula removed by open lung biopsy revealed a homogeneous cut surface. Histological diagnosis was pulmonary hyalinizing granuloma, consisting of hyalinized collagen fibers and bundles infiltrated with chronic inflammatory cells. No therapeutic effect was recognized with prednisolone. Craniotomy was performed and the brain lesion was removed. Anaplastic astrocytoma was the diagnosis. The brain lesion had no etiological correlation with pulmonary hyalinizing granuloma. Pulmonary hyalinizing granuloma itself is a rare benign disease with no specific therapy and is important in the differential diagnosis of lung diseases showing multiple pulmonary nodules.

Adult

An improved method of bronchial stump closure for prevention of bronchopleural fistula in pulmonary resection.

We performed 880 pulmonary resections from January 1982 to June 1988 using Sweet's procedure for closure of the bronchial stump, in which 39 patients (4.4%) developed bronchial fistulas. Bronchoscopic studies showed that bronchopleural fistulas were located mainly at the corner of the stump. This indicates that the corner is the point with the highest tension when Sweet's procedure is employed. In some cases, stumps were injured by suture materials, resulting in bronchopleural fistulas. Since July 1988, bronchial stumps have been closed by using two pairs of teflon pledgets with additional interrupted sutures. From July 1988 to April 1990, 288 patients were treated by this new method, and only one of them developed bronchopleural fistula. This new method prevents injury of the stump by suture material and reduces the tension at the bronchial stump for a long time. Thus, pulmonary resections can be safely employed even after anti-cancer chemotherapy and/or radiation therapy.

Bronchi

Intracranial extension of an orbital pseudotumor accompanied by internal carotid artery occlusion--case report.

A rare case of histologically verified orbital pseudotumor with intracranial extension in a 33-year-old male is reported. Preoperative radiographs showed the mass extending beyond the orbit and involving the bilateral cavernous sinuses. The intracranial lesion at biopsy surrounded the right internal carotid artery above the right cavernous sinus. Cerebral angiography showed complete occlusion of the cervical portion of the right internal carotid artery. Possibly, multiple lesions had extended contiguously through the venous system around the cavernous sinus, with subsequent involvement of the internal carotid artery. This case suggests that orbital pseudotumor may not be a separate clinical entity, but a part of the syndrome caused by inflammation of the venous system around the cavernous sinus.

Adult

Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats.

The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level.

Adipose Tissue

Interleukin 2 and tumor necrosis factor alpha are complementary for proliferation of the hematopoietic stem cell line LyD9.

We have shown that tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL-2) are complementary for stimulation of growth of the hematopoietic stem cell line, LyD9. Neither TNF alpha nor IL-2 alone could stimulate the proliferation of LyD9 cells even after pre-incubation with these growth factors. The number of high-affinity IL-2 receptors on LyD9 cells did not increase after incubation with IL-2 and TNF alpha. These results suggest that the proliferative response of LyD9 by TNF alpha and IL-2 is not mediated by receptor inducing activities. We used the induction of the proto-oncogenes c-myc and c-pim to characterize the proliferative stimulation by IL-2 and TNF alpha. Northern blot analysis revealed that the simultaneous addition of IL-2 and TNF alpha was more efficient than IL-2 alone for c-myc mRNA induction. However, the addition of TNF alpha and IL-2 could not increase c-pim mRNA more than the level induced by IL-2 alone. The results indicate that the two growth factors complement each other by transducing different types of growth signal.

Blotting, Northern

Atherosclerosis from a viewpoint of arterial wall cell function: relation to vitamin E.

Vitamin E affects many key events in atheromatous lesions. Inhibition of EC injury and platelet aggregation was already reported. Foam cell formation must be inhibited according to the data presented by us and other speakers. However, effects on cell proliferation of SMC are paradoxical. The in vivo effects will be dependent on the effective concentration of vitamin E in the loci.

Animals

[An immunohistological study of normal parotid gland].

Cytoskeletal proteins from each epithelial component of the parotid gland were studied immunohistologically using monospecific monoclonal antibodies, and we obtained several interesting results: 1) The expression of vimentin, S-100 protein and GFAP were essentially unrecognizable. 2) The expression of alpha-actin was recognized only in myoepithelial cells, and was negative in other tissues. 3) The expression of CK-3, CK-6, CK-7, CK-8 and CK-18 was commonly recognized in both acinal and ductal cells. 4) The expression of CK-13 and CK-19 was recognized in ductal cells, but was negative in acinal cells. 5) We propose that the characteristic cell be referred to as a "duct satellite cell", as it comprises part of the intercalated duct and is sporadically localized around striated and layer ducts. 6) These duct satellite cells express all subclasses of cytokeratin observed in myoepithelial, acinal and ductal cells. 7) The duct satellite cells observed in this study are most likely to correspond to the undifferentiated reserve cells described in "bicellular theory", and we speculate that all epithelial tissues of the parotid gland originate from these cells.

Actins

[A case of neuro-Behçet's disease with hemorrhagic brain stem lesion detected by MRI].

A 45-year-old woman complained of fever, arthralgia and left hemiparesis. She had suffered from recurrent oral aphthous ulcers, genital ulcers, uveitis and erythema nodosum. Laboratory examination demonstrated pleocytosis in the cerebrospinal fluid. MRI showed foci of high signal intensity on the T2-weighted images in the right pontine base, surrounded by a rim of low signal intensity suggestive of small hemorrhages. Following steroid therapy, these symptoms diminished and abnormal findings in brain MRI improved. This MRI findings may be due to hemosiderin deposition at recent stage resulting hemorrhages in foci of acute inflammation stage. We would like to emphasize that MRI are useful to evaluate the lesion of neuro-Behçet's disease and some lesions may behave like hemorrhages.

Behcet Syndrome

[Morphometrical analysis of non-cancerous liver tissue with special reference to clinicopathological features of hepatocellular carcinoma].

This study was undertaken to investigate the relationship between morphometrical characteristics of noncancerous liver tissues and clinicopathological features of hepatocellular carcinoma (HCC) in 89 cases which underwent either hepatectomy (n = 56) or autopsy (n = 33). Using Automatic Image Analyzer (IBAS-2), we determined interstitial ratio (IR) of the non-cancerous liver tissues as a morphological parameter in all cases. In addition, mean values of area (MA), maximal diameter, and shape factor of pseudolobules were determined in the cirrhotic patients. IR in cases with main tumors smaller than 3 cm was higher than that in cases with tumors larger than 3 cm (23.5 +/- 6.7% vs 18.5 +/- 8.9% mean +/- SD: p less than 0.01), and IR in cases with histologically proven intrahepatic metastases (im positive) was also higher as compared to im negative cases (17.5 +/- 9.0% vs 21.3 +/- 8.0%; p less than 0.05). Among the other parameters determined in the cirrhotics, MA was higher in cases with tumors larger than 3 cm than in cases with smaller tumors (2.54 +/- 1.87 mm2 vs 1.78 +/- 1.01 mm2; p less than 0.05), and MA was higher in im positive cases as compared to im negatives (2.67 +/- 1.91 mm2 vs 1.67 +/- 0.96 mm2; p less than 0.01). These data indicated that non-cancerous liver tissue has a close relation not only to the carcinogenesis but to subsequent tumor growth and progression of HCC.

Adult

Effects of changes in sodium electrochemical potential gradient on p-aminohippurate transport in newt kidney.

1. The relation between p-aminohippurate uptake and the electrochemical potential gradient of Na+ (delta muNa+) across the peritubular membrane was examined in newt (Triturus pyrrhogaster) kidney. The delta muNa+ was modified by changing cellular Na+ concentration and/or lowering the electrical potential difference across the peritubular membrane (peritubular membrane potential) 2. Elevation of external K+ concentration or addition of alanine at 40 mM to the medium decreased the delta muNa+ mainly through the depolarization of the cells. Addition of 1 mM ouabain resulted in a decrease in the peritubular membrane potential and increase in cellular Na+ concentration, thus decrease in the delta muNa+. 3. p-Aminohippurate uptake decreased in proportion to the decrease in the delta muNa+ under all experimental conditions, indicating that the maintenance of the delta muNa+ is required for p-aminohippurate transport. 4. All three different experimental conditions, high medium K+ concentration, 40 mM alanine or 1 mM ouabain, increased the apparent Michaelis constant, Kt, without affecting the maximal uptake rate, V, for p-aminohippurate. These results suggests that the delta muNa+, largely the peritubular membrane potential, may affect the association and/or dissociation of p-aminohippurate and Na+ at both interfaces of the peritubular membrane of the proximal tubular cells.

Alanine