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Biomedical subjects

Y Saito

Publications and source records attributed to Y Saito.

At least 19 recordsLinked to original sources

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

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

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

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

Systemic hyalinosis (juvenile hyaline fibromatosis). Ultrastructure of the hyaline with particular reference to the cross-banded structure.

Systematic hyalinosis (juvenile hyaline fibromatosis) is characterized by hyalinized skin lesions. Electron microscopic examination of a hyalinized skin tumor from a 19-year-old man with this syndrome revealed that the hyaline was composed of ruthenium red-positive ultrastructures (granules, filaments, and a kind of cross-banded structure), indicating the presence of glycosamino-glycan or glycoprotein, and a small number of thin collagen fibrils. Using a new ruthenium red staining method combined with an enzymatic digestion procedure, it was demonstrated that the cross-banded structure and granules consisted of chondroitin sulfate-proteoglycan and/or glycoprotein, and that the cross-banded structure is probably a noncollageneous aggregate of the granules attached to the parallel-arranged filaments of hyaluronic acid-like nature.

Adult

Selective effects of membrane sterol depletion on surface function thymidine and 3-O-methyl-D-glucose transport in a sterol auxotroph.

Using a sterol-specific auxotroph of LM cells (mouse fibroblasts), we obtained cells with progressively lower sterol contents. 3-O-Methylglucose and thymidine were shown to enter the cells by saturable as well as by nonsaturable processes and it was possible to measure these processes separately at various stages of sterol depletion. Sterol depletion inhibited the saturable as well as the nonsaturable components for both 3-O-methylglucose and thymidine uptake. The extent of inhibition of the saturable process was much more than that of the nonsaturable component at any stage of the sterol depletion. Furthermore, in the course of progressive sterol depletion the saturable component of 3-O-methylglucose or thymidine uptake was inhibited well before the nonsaturable process. Sterol depletion produced reductions in the Vmax values but no change in the Km values for the saturable uptake of these two substrates. The depletion of cellular sterol to 75% resulted in 70% and 90% reduction of the saturable uptake of 3-O-methylglucose and thymidine, respectively, and 30% and 50% reduction of the nonsaturable uptake of 3-O-methylglucose and thymidine, respectively. DNA and protein synthesis, however, were not affected at all when the saturable component of thymidine uptake was inhibited by 50% demonstrating that the observed decrease of transport activity was selective and not a reflection of a gross alteration in cellular physiology.

Biological Transport, Active

Effect of sterol depletion on LM cell sterol mutants. Changes in the lipid composition of the plasma membrane and their effects on 3-O-methlglucose transport.

With the use of two sterol biosynthetic mutants, LM cells with various sterol levels were obtained after extended periods of growth with suboptimal sterol concentrations. As was found in the preceding paper, sterol depletion resulted in reduction of the apparent Vmax values for 3-O-methylglucose transport with no change in the apparent Km values. Analysis of the lipid compositions of isolated plasma membranes and crude endoplasmic reticulum membranes showed that depletion of the cellular sterol levels led to a reduction in the sterol content of both membranes. Furthermore, there were significant changes in the fatty acid composition of the phospholipids of both membranes. The amount of 18:1 of the plasma membrane phospholipids increased dramatically accompanied by a marked decrease in 16:0. The loss of transport activity could be reproduced in vitro by removing cholesterol from cells with the use of liposomes containing phosphatidylcholine. Furthermore, activity was restored to normal values when the cells were subsequently incubated with liposomes composed of phospholipids plus cholesterol. These findings indicate that 1) an inter-relation exists between the fatty acyl group structure of phospholipids and the sterol content of LM cell membranes which may serve to maintain membrane function and 2) that the reversible inactivation of a surface membrane transport system is directly related to reversible changes in the properties of membrane lipid.

Biological Transport, Active

The estimation of conduction velocity in human skeletal muscle in situ with surface electrodes.

In the present study new methods were developed for estimation of conduction velocity using surface electrodes. The subjects were 4 healthy male volunteers, aged 23-29 years. EMGs were recorded from m. biceps brachii by several surface electrodes and a fine-wire bipolar electrode during weak isometric contraction with the elbow positioned at 90 degrees. Surface electrodes, 8 mm in diameter, were spaced along the course of muscle fibers at 20 mm intervals, while the bipolar fine-wire electrode was inserted in the middle of the muscle. The EMGs recorded on the magnetic tape were analyzed through a mini-computer system (ATAC-2300). Triggering a signal averager by spike potentials of single motor unit recorded by the inserted electrode, the average contribution of the single motor unit to the surface EMG could be extracted. The conduction velocity in m. biceps brachii determined from the averaged waves of each surface electrode was 4.6 +/- 0.5 m/sec (mean +/- S.D.). The conduction velocity estimated from the cross-correlation analysis between the EMGs of two different surface electrodes agreed well with the value obtained by the averaging technique mentioned above.

Action Potentials

Studies of cholesterol esterase in rat arterial wall.

Cholesterol esterase activity was estimated in homogenates of rat arterial wall using radioactive cholesteryl oleate incorporated into phospholipid vesicles as a substrate. The labeled oleic acid was separated from the ester by addition of benzene-chloroform-methanol mixture. Under these conditions, two pH optima were found at about 4.5 and 7.5. Most of the activities at pH 4.5 and 7.5 were found in the lysosomal and microsomal fraction, respectively. No enzyme activity was detected when the substrate vesicles were prepared with phosphatidylethanolamine or sphingomyelin, but the activity was higher when the substrate vesicles were prepared with phosphatidylserine and highest when they were prepared with phosphatidylcholine. The relationship between enzyme regulation and lipid deposition in the arterial wall is discussed.

Animals

Comparison of efficacy of amoxapine and imipramine in a multi-clinic double-blind study using the WHO schedule for a standard assessment of patients with depressive disorders.

A multi-clinic double-blind controlled study on amoxapine in comparison with imipramine, using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders, was performed and the data were analyzed with 111 patients. The assessment of severity of illness and overall improvement indicated clearly the superiority of the antidepressive effect of amoxapine to that of imipramine. The onset of antidepressive effect of amoxapine was clearly more rapid than that of imipramine, and in more than half of the patients in the amoxapine group the improvement was seen within four days following the drug administration. Amoxapine was superior to imipramine in terms of safety and usefulness. The side-effects due to amoxapine appeared less frequently and were less serious than with imipramine. The difference between amoxapine and imipramine was especially remarkable for hypotensive effect. The antidepressive effect of amoxaphine was superior to that of imipramine for almost all symptoms and signs. Amoxapine displayed an especially remarkable effect on psychomotor retardation, depressive feeling, anxiety and tension, somatic complaints and sleep disturbance.

Amoxapine

Acidic glycosaminoglycans in human esophagus tissue.

The constitution of acidic glycosaminoglycans (AGAG) in the normal human esophagi which were obtained at autopsy from 13 female subjects, from 30 to 59 years old, was biochemically analyzed by the procedures such as resin chromatographic separation, electrophoretic characterization in 3 buffer systems and enzymic assay with chondroitinases and hyaluronidase. The main AGAG was hyaluronic acid which amounts to a half of total AGAG, followed by heparan sulfates and dermatan sulfate one fifth of total AGAG each, and small amounts of chondroitin-4- and -6-sulfates and oversulfated chondroitin sulfate. Heparin was not detected. A possible role of the esophageal AGAG was discussed.

Adult

Effects of pantetheine on cholesteryl ester synthesis in the arterial wall of rats on high cholesterol diet.

Increase of acyl-CoA synthesis was observed when extracts of rat arterial wall were incubated with pantetheine [D-bis-(N-pantothenyl-beta-aminoethyl)-disulfide]. Cholesteryl ester synthesis from palmitate in the arterial wall extract in vitro was higher with arteries from rats on high cholesterol diet than with those from rats on normal diet, but the synthesis was reduced in the arteries of rats on high cholesterol diet with pantetheine. Triglyceride synthesis was higher with arterial wall extracts of rats on high cholesterol diet than with preparations from rats on normal diet and was not reduced with those of rats on high cholesterol diet plus pantetheine. The value of the effects of pantetheine on lipid metabolism in the prevention of atherosclerosis is pointed out.

Acyl Coenzyme A

Postural variations in nasal resistance and symptomatology in allergic rhinitis.

Variations in nasal resistance (NR) which was induced by positional change of the head were examined in 15 normal subjects and 15 patients with allergic rhinitis. Nasal symptoms were also observed in 15 patients and nasal symptom scores were calculated. Concerning the postural variations of NR, patients with allergic rhinitis showed much more remarkable change than normal subjects. Nasal symptom scores of all patients decreased after nasal insufflation of Beclomethasone Dipropionate for 2 weeks. Coincidence between improvement in postural variations of NR and that of nasal symptom score was not always seen in each patient. However, as a mean value of 15 patients, postural variations of NR improved after nasal insufflation of Beclomethasone Dipropionate.

Adult