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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 325 records · Page 18Linked to original sources
PubMed1993

Prognostic significance of epidermal growth factor receptor in squamous cell carcinoma of the maxillary sinus.

The expression of epidermal growth factor receptor (EGFR) was determined immunohistochemically in two groups of maxillary sinus squamous cell carcinomas, one with recurrences at the primary site after combination therapy with radiotherapy, chemotherapy and/or surgery and one without local recurrences. Using a four-graded scale (-, +, + +, + + +), 9 of the 10 recurrent carcinomas had a staining intensity and proportion of stained cells of + + or more. A comparable staining intensity was found in 9 of the 18 non-recurrent carcinomas. This difference is statistically significant (Fisher's exact probability test, P < 0.05). These results indicate that an increased expression of EGFR may influence the recurrence rate of squamous cell carcinoma of the maxillary sinus after combined therapy.

Aged↗
PubMed1993

Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small-cell lung cancer.

Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.

Adult↗
PubMed1993

Phase II study of a 72-h concurrent continuous infusion of cisplatin and etoposide in advanced non-small-cell lung cancer.

We conducted a phase II study to evaluate the antitumor activity and safety of concurrent continuous infusion of cisplatin and etoposide in advanced non-small-cell lung cancer (NSCLC). Cisplatin (30 mg/m2 daily) and etoposide (80 mg/m2 daily) were given as a 24-h continuous infusion for 72 h to 48 patients with previously untreated advanced NSCLC. Of the 46 evaluable patients, 9 achieved a partial response, for an overall response rate of 20% (95% confidence interval, 9.4%-33.9%). The median duration of response was 23 weeks. The median duration of survival for all patients was 34.4 weeks. The major toxicity was hematologic. Leukopenia (WHO grade > or = 3) was observed in 22 patients (48%) and thrombocytopenia (WHO grade > or = 3), in 13 patients (28%). In all, 20 patients (43%) experienced severe anemia (WHO grade > or = 3). Nonhematologic toxicity mainly consisted of moderate to severe alopecia in 33 patients (72%) and moderate to severe nausea and vomiting in 25 patients (54%). No significant nephrotoxicity was seen. We conclude that a 72-h concurrent continuous infusion of cisplatin and etoposide does not appear to be active against advanced NSCLC.

Adult↗
PubMed1993

Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats.

Pulmonary clearance and toxicity of cupric oxide (CuO) dusts, which are probably formed in refining and smelting factories, were investigated. Groups of three rats received intratracheal (i.t.) instillation of CuO at a dose of 20 micrograms Cu/rat in time-course experiments (up to 7 days post-instillation). Other groups of three rats received i.t. instillation of CuO at doses of 2.5, 5, 10, 30, 50 and 100 micrograms Cu/rat and were killed at 2 days post-instillation in dose-effect experiments. Intratracheally instilled CuO particles were cleared from the lung with a half-time of 37 h. Copper binding metallothionein (MT) was induced in a dose-dependent manner and detected at 12 h to 3 days post-instillation. Rapid clearance of CuO from the lung and induction of MT at 12 h post-instillation suggest that CuO particles were solubilized and then cleared from the lung. The acute pulmonary toxicity of CuO was evaluated by cytological (numbers of macrophages and polymorphonuclear leukocytes), biochemical and elemental inflammatory indices (lactate dehydrogenase and beta-glucuronidase activities and protein, sulfur, phosphorus and calcium contents) in the bronchoalveolar lavage (BAL) fluid. These inflammatory indices peaked at 12 h to 3 days post-instillation, and increased with dose over the dose range, except for phosphorus content. Dose-effect relationships in BAL inflammatory indicators of CuO-injected (i.t.) groups were compared to those of CuSO4-injected (i.t.) groups. The results of the comparison indicated that there was no significant difference in acute inflammatory potency between CuSO4 (soluble form of Cu) and CuO (insoluble form of Cu) in the rat lung.

Air Pollutants, Occupational↗
PubMed1993

Lung perfusion SPECT in predicting postoperative pulmonary function in lung cancer.

The aim of this prospective study is to evaluate the availability of preoperative perfusion SPECT in predicting postoperative pulmonary function following resection. Twenty-three patients with lung cancer who were candidates for lobectomy were investigated preoperatively with spirometry, x-ray computed tomography and 99mTc macroaggregated albumin SPECT. Their postoperative pulmonary functions were predicted with these examinations. The forced vital capacity and the forced expiratory volume in one second were selected as parameters for overall pulmonary function. The postoperative pulmonary function was predicted by the following formula: Predicted postoperative value = observed preoperative value x percent perfusion of the lung not to be resected. The patients were reinvestigated with spirometry at 3 months and 6 months after lobectomy, and the values obtained were statistically compared with the predicted values. Close relationships were found between predicted and observed forced vital capacity (r = 0.87, p < 0.001), and predicted and observed forced expiratory volume in one second (r = 0.90, p < 0.001). The accurate prediction pulmonary function after lobectomy could be achieved by means of lung perfusion SPECT.

Adenocarcinoma↗
PubMed1993

The sticker-type temperature indicator in digital replantation: simplified application.

A sticker-type skin-surface temperature indicator, commercially available in Japan, has been utilized to monitor temperature changes in replanted digits. In clinical application, the authors evaluated several shortcomings in some of these devices. For example, the 10-mm diameter indicator is too small for numbers to be seen clearly. The 18-mm diameter indicator is too large to patch onto the finger pulp. To improve this device, the authors used only the number 33 from the 18-mm diameter indicator and applied it to several study subjects. Judgments about the circulatory status of the replanted digit can be made on the basis of the indicator color. The 18-mm diameter indicator, now modified to use only the number 33, is in common use for all the authors' digital replantation cases. Clinicians' ability to see critical temperature changes has been markedly improved, even under poor lighting conditions.

Adult↗
PubMed1993

Interaction between pullulanase from Klebsiella pneumoniae and cyclodextrins.

The interaction between pullulanase from Klebsiella pneumoniae and alpha-, beta-, and gamma-cyclodextrins and 6-O-alpha-glucosyl-alpha-cyclodextrin and 6-O-alpha-glucosyl-beta-cyclodextrin was examined by means of inhibition studies of the enzyme activity, UV difference spectroscopy, and flow calorimetry. All the above cyclodextrins were found to be competitive inhibitors, but beta-cyclodextrin and 6-O-alpha-glucosyl-beta-cyclodextrin showed strong inhibition, the inhibitor constants being two orders of magnitude less than those of alpha- and gamma-cyclodextrins. The difference spectra of beta-cyclodextrin were slightly but significantly different from those of the other cyclodextrins, showing blue shift of a few nanometers. Moreover, only beta-cyclodextrin has a positive entropy change upon binding with the enzyme; all the other cyclodextrins have negative values. These results show that the binding mode of beta-cyclodextrin is subtly different from those of alpha- and gamma-cyclodextrins.

Calorimetry↗
PubMed1993

Insulin-like growth factor (IGF)-I stimulates proliferation and migration of mouse ectoplacental cone cells, while IGF-II transforms them into trophoblastic giant cells in vitro.

We examined the effects of a 10.5-day placental extract and various growth factors (insulin-like growth factor [IGF]-1, IGF-II, epidermal growth factor [EGF], basic fibroblast growth factor [b-FGF], and transforming growth factor-alpha [TGF-alpha]) on proliferation, migration, and transformation of mouse ectoplacental cone (EPC) cells in vitro. Both the 10.5-day placental extract and IGF-I increased the surface area of the EPC cell colony and strongly stimulated the uptake of bromodeoxyuridine (Brd-U) as well as the migratory activity of EPC cells on the plastic culture dish. Such effects of 10.5-day placental extract were partly inhibited by the addiction of anti-IGF-I antibody. On the other hand, IGF-II did not significantly affect proliferation and migration of EPC cells, but increased the number of cells having a large nucleus (trophoblastic giant cells; TGCs) per EPC and enlarged the ploidy levels of EPC cells. Histochemical staining with succinyl wheat germ agglutinin (s-WGA), an in situ marker for secondary TGCs on Day 10.5 post coitum revealed that IGF-II or the placental extract induced the expression of s-WGA-binding glycoproteins in the TGCs in vitro. The effects of IGF-II or placental extracts were also inhibited by anti-IGF-II monoclonal antibody. No appreciable effect was found in the EPCs cultured with TGF-alpha, whereas b-FGF and EGF promoted migratory activity of the cells. The present study indicates that IGFs or IGF-like substances may be present in the mouse placenta, that IGF-I may promote the proliferation and migration of EPC cells, and that IGF-II may induce the transformation of EPC cells into TGCs in vitro.

Animals↗
PubMed1993

Marginal eyelid reconstruction with a composite skin-muscle-mucosa graft from the lower lip.

Marginal defects of the eyelid were repaired using skin-muscle-mucosa composite grafts from the lower lip without cartilage support in 2 patients. The method is a simple one-stage procedure and takes little time to perform. Because of the wide contact between the grafts and the recipient sites, grafting was successful. Texture and color match is not too problematic in elderly persons.

Aged↗
PubMed1993

Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary hypertension.

To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg), rats (PH rats, n = 6) were sacrificed. Vehicle-injected rats (n = 6) served as controls. The right ventricular systolic pressure of PH rats [58.0 +/- 4.7 mm Hg (mean +/- SEM)] was significantly higher than that in the vehicle-treated control rats (29.2 +/- 2.1; p < 0.01). Northern blot analysis showed that the expression of ETB-receptor mRNA decreased in the lung of PH rats. The venous plasma concentration of ET-1 measured by a sandwich-enzyme immunoassay was significantly higher in PH rats than in control rats (5.1 +/- 0.7 versus 1.3 +/- 0.2 pg/ml; p < 0.01). The present findings suggest that the expression of ETB-receptor mRNA decreases in the lung of PH rats, which might be closely related to the increase in plasma ET-1 concentration in these rats.

Animals↗
PubMed1993

Ultrastructure and barrier properties of the endolymphatic duct in the guinea pig.

The ultrastructure and barrier properties of the endolymphatic duct (ED) were examined by light and electron microscopy. ED epithelial cells were classified into two types: type I and type II duct cells. The type I duct cells were cuboidal or low columnar and were characterized by a convex apical surface and a few basal processes. The type II duct cells were squamous and were characterized by a flat apical and basal membrane, many small vesicles and a number of small pits along the basal membranes. After electrophoretic horseradish peroxidase (HRP) injection into the ED lumen, no HRP uptake into ED epithelial cells of either type was observed. There was no reaction product either in the lateral intercellular spaces beyond the tight junctions between ED epithelial cells or in ED subepithelial tissues. The ED epithelial cells were considered to play no active role in apical macromolecular absorption and to be impermeable to intraluminal macromolecules.

Absorption↗
PubMed1993

Glomerular growth in the remnant kidney after a contralateral nephrectomy.

A unilateral nephrectomy enhances growth or weight gain in the remaining kidney, although it is not known whether the mechanism involves the division of glomerular cells. We have isolated glomeruli from the remnant kidney at different time intervals after a nephrectomy and measured the percentage of cells in the G1, G2 + M and S phases by flow cytometry. All the steady-state glomerular cells remained in G1 phase, while a significant percentage had progressed into the S phase by 4 h after the uninephrectomy. The rise in the number of cells in the S phase gradually decreased to control values by 48 h, during which time the number of cells in both G1 and G2 + M phases increased concomitantly. Neither DNA nor RNA content per glomeruli was altered by 4 and 24 h after uninephrectomy. The data suggest an early division of the glomerular cells in the remnant kidney after a contralateral nephrectomy.

Animals↗
PubMed1993

Autoimmune haemolytic anaemia, Sjögren's syndrome and idiopathic thrombocytopenic purpura in a patient with sarcoidosis.

A unique occurrence of sarcoidosis autoimmune haemolytic anaemia (AIHA), Sjögren's syndrome and idiopathic thrombocytopenic purpura (ITP) in the same patient is reported. Although the occurrence of autoimmune disease with sarcoidosis is well known, a case in which several of these diseases coexist with sarcoidosis is rare. We present a man with longstanding sarcoidosis who developed AIHA. Sjögren's syndrome and ITP. This case report seems to be the first case in which three autoimmune diseases were accompanied by sarcoidosis in 1 patient.

Adult↗
PubMed1993

Immunohistochemical localization of carbonic anhydrase in the endolymphatic sac of the mouse and guinea pig.

The localization of carbonic anhydrase (CA) in mouse and guinea pig endolymphatic sac (ES) was determined by immunohistochemistry. In the distal and intermediate portions of the ES of both species, epithelial cells reacted with anti-CA antiserum. All epithelial cells in the distal portion stained for CA. In the intermediate portion, immunoreactivity was prominent in about half the epithelial cells, but less intense in the remaining epithelial cells. The proximal portion of the ES lacked immunoreactivity. CA may play a crucial role in ES electrolyte transport.

Animals↗
PubMed1993

Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension.

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

Animals↗
PubMed1993

Phase I clinical and pharmacokinetic study of a 14-day infusion of etoposide in patients with lung cancer.

PURPOSE: A phase I study was conducted to determine the maximum-tolerated dose (MTD) of a 14-day continuous infusion of etoposide, and to evaluate the pharmacokinetics in patients with lung cancer. PATIENTS AND METHODS: Etoposide was administered continuously through a central venous catheter using a pump. The starting dose level was 300 mg/m2 over 14 days, with dose escalations of 100 mg/m2 over 14 days until unacceptable toxicities occurred. Pharmacokinetic studies were performed in all patients. RESULTS: Twenty-one patients, 20 with non-small-cell lung cancer and one with refractory small-cell lung cancer, received 37 courses. No World Health Organization (WHO) grade III or greater toxicity occurred at doses up to 400 mg/m2 over 14 days. At 700 mg/m2 over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving fractions of leukocytes (r = -.64, P = .001) and platelets (r = -.68, P < .001). The leukocyte count at the termination of chemotherapy predicted the nadir count (r = .93, P < .001). CONCLUSION: Steady blood levels of etoposide were maintained for prolonged periods, during 14-day continuous infusions. Leukocytopenia and stomatitis were dose-limiting. Nadir counts and surviving fractions of leukocytes were predicted by the leukocyte count at the end of chemotherapy and the concentration of etoposide, respectively. The recommended dose for phase II trials is 600 mg/m2 over 14 days.

Adult↗
PubMed1993

Effect of FK409, a novel nitric oxide donor, on acute experimental myocardial ischemia.

The anti-ischemic heart effect of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]- 5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 micrograms/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocardiograms. Glyceryl trinitrate (GTN; 10, 32 micrograms/kg) or dipyridamole (1000 micrograms/kg) failed to suppress the ST-segment elevation, although continuous i.v. infusion of GTN (32, 100 micrograms/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100 micrograms/kg) and intraduodenal (i.d., 100, 1000 micrograms/kg) injections, while GTN (100 micrograms/kg, i.v.; 1000 micrograms/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 microgram/kg/min, i.v.) and GTN (10 micrograms/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10(-10)-4.6 x 10(-7) M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.

Animals↗