Search PubMed⌕ Search

Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 703 records · Page 39Linked to original sources

Combination chemotherapy with cisplatin and peplomycin in squamous cell carcinoma of the head and neck.

Ninety-three patients with head and neck cancer were treated with combined cisplatin-peplomycin chemotherapy (CP therapy). Cisplatin (CDDP) 50 mg/m2 i.v. (intravenous) or i.a. (intraarterial) over 2 hr was given with hydration and mannitol diuresis on day 1. From day 2 through day 6, peplomycin (PEP) 5 mg/day was administered by 5-hr i.v. or i.a. infusion, or 24-hr continuous hypodermic injection. Of 85 who were evaluable, there were 22 complete responses or CR (26%) and 36 partial responses or PR (42%), with an overall response rate of 68%. Concerning of the route of administration, i.a. infusion obtained the higher CR and overall response rates than i.v. infusion. Effectiveness was clearly greater in previously untreated cases than in cases that had received some previous therapeutic modality. Looking at response in relation to the number of the courses, at least 2 courses of CP therapy are required. Side effects were recognized in 68 out of 87 evaluable cases (78%). Nausea and vomiting were the most common (62%). Renal toxicity was observed in 24% and was mostly transient. From the above results, it is considered that the CP therapy is effective, not only for the palliative treatment of advanced and recurrent cancer of the head and neck, but also as neo-adjuvant chemotherapy of stage III and IV cases.

Adult↗

Pirenzepine inhibits pancreatic exocrine secretion in the rat.

Pirenzepine is a newly developed anticholinergic drug that reduces gastric acid secretion and is therefore used in Europe and Japan to treat patients with peptic ulcer. The inhibitory effect of pirenzepine on pancreatic exocrine function and its reversibility were studied in the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine caused a concentration-dependent rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase. Addition of 10 microM pirenzepine at the beginning as well as after 10 or 20 min of stimulation with 1 microM carbamylcholine rapidly abolished pancreatic secretions in both the isolated acini and isolated perfused pancreas. The inhibitory effect of pirenzepine was fully reversible in the isolated acini, whereas pirenzepine caused a small residual inhibition on pancreatic exocrine secretion in the isolated perfused pancreas. These results suggest the existence of pirenzepine-sensitive receptors in the pancreatic vagal pathway at a site remote from the acinar cell. The present data indicate that pirenzepine may have an influence on pancreatic exocrine function by inhibiting not only acinar cell cholinergic receptor but also endogenous cholinergic activity of the pancreas when a large dose is given.

Amylases↗

Enhancement of anti-inflammatory effects of biphenylylacetic acid by its incorporation into lipid microspheres.

Using lipid microspheres (LM), average diameter 0.2 micron, and containing methyl and ethyl esters of biphenylylacetic acid (BPAA) in the carrageenan paw oedema tests in rats, it was found that their anti-inflammatory activities were enhanced 3 to 8 times over that of free BPAA. By electron microscopy, LM were seen to be taken up into the endothelial cells of the blood vessels and macrophages at the inflamed sites. In a study using dogs, after an intravenous injection of BPAA-methyl ester incorporated into LM (lipo-BPAA-Me), lipo-BPAA-Me rapidly disappeared from the blood and the BPAA serum level was gradually elevated. These results, together with previous findings, suggest that part of lipo-BPAA-Me was immediately transferred to the inflamed site and taken up by prostaglandin (PG)-producing cells as macrophages. It is considered that the anti-inflammatory effects of BPAA are enhanced by incorporating it into LM.

Animals↗

Inhibition of microtubule assembly by poly(L-glutamic acid) and the site of its action.

Poly(L-glutamic acid) (PGA) suppresses the polymerization of porcine brain microtubule proteins and induces the depolymerization in vitro in a concentration-dependent manner. The extent of inhibition increases with increasing molecular weight of the PGA tested. A 50% inhibition of the protein polymerization was observed at a PGA (molecular weight = 60,000) to microtubule protein ratio of 0.04 (w/w), and complete inhibition was obtained at a ratio of 0.07. Such an inhibition on the polymerization by PGA is greatly decreased when Mg2+ is present at a higher concentration. The addition of PGA raises the critical concentration of microtubule proteins necessary for assembly. During incubation with PGA, microtubule proteins retain the ability to assemble, i.e., substoichiometric amounts of taxol considerably relieve the inhibition of assembly by PGA. PGA interacts with microtubule-associated proteins (MAPs) preferentially, because the amount of MAPs binding to PGA-Sepharose 4B is much larger than that of tubulin. Tau proteins were observed only in adsorbed fractions, while MAP-2 was present in both unbound and adsorbed fractions.

Animals↗

Action of cholecystokinin analogues on exocrine and endocrine rat pancreas.

In the present study we have examined the abilities of cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH (deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7) to stimulate exocrine pancreatic secretion from both isolated pancreatic acini and isolated perfused pancreas. We have also compared this action with their ability to cause insulin release. The modification of either the N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the magnitude of the stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same. The minimal effective concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release from the isolated rat pancreas in the presence of 8.3 mM glucose was the same as that for pancreatic exocrine secretion. In contrast, the concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to produce insulin release were 5-10 times higher than those required to cause stimulation of pancreatic enzyme and juice secretion. It is concluded therefore that the N-terminal 4-amino acid residues or the C-terminal 2-amino acid residues of CCK-8 are not essential for biological activity but do contribute to its potency. In addition, the C-terminal 2-amino acid residues and an amide group in the C-terminal phenylalanine residue of CCK-8 appear to be important determinants of the insulin-releasing activity of the CCK peptides.

Amylases↗

Effect of Bt2cGMP on action of cholecystokinin in isolated perfused rat pancreas.

We have examined the effects of Bt2cGMP on cholecystokinin stimulation of pancreatic exocrine secretion in the isolated perfused rat pancreas. Bt2cGMP produced a concentration-dependent inhibition of the stimulatory effects of cholecystokinin octapeptide (CCK-8, 100 pM) on both pancreatic juice flow and enzyme secretion. Adding 1 mM Bt2cGMP rapidly and completely abolished CCK-8-stimulated pancreatic juice and enzyme secretion. Adding 500 microM Bt2cGMP for 10 min at the termination of 1 nM of CCK-8 infusion caused an immediate and persistent inhibition of the residual response. In contrast, treatment with C-terminal CCK antiserum I had no influence on the residual response. To account for the ability of Bt2cGMP to function as a competitive antagonist of the action of CCK and the ability of the nucleotide to inhibit the residual stimulation caused by CCK, we feel that Bt2cGMP hindered the binding of CCK not only by reducing the association rate constant for hormone binding but also accelerating the dissociation rate.

Amylases↗

Evaluation of anticancer drugs by lymphocyte electrophoresis.

The spleen cells in tumor-bearing and normal mice treated with Krestin (PSK), mitomycin C (MMC) or adriamycin (ADM) were analyzed by cell electrophoresis and flow microcytometry. In normal mice, the splenocyte electrophoretic mobility histogram was observed as a bimodal pattern, and low and high mobility cells (LMC and HMC) corresponded with B and T cells, respectively. In sarcoma-180-bearing mice, an intermediate mobility peak (IMC) appeared between the low and high peaks. Although every anticancer drug depressed the IMC when the tumor was cured, MMC reduced the absolute number of splenic Ig+ and Thy-1+ cells, and ADM injured Ig+ cells in normal as well as in tumor-bearing mice. PSK, however, depressed splenomegaly by tumor-burden in spite of a slight increase in splenocytes of normal mice. In a previous paper, it was reported that the thymocyte mobility histogram was restored to a normal pattern by treatment with PSK in tumor-bearers, while it was made more abnormal by treatment with MMC because of injury to cortical thymocytes. From these results, it may be considered that an anticancer drug which restored the splenocyte mobility histogram to a normal pattern without damages to thymocytes is preferable for cancer therapy.

Animals↗

Aromatization of norethindrone to ethynylestradiol in human adult liver.

Homogenates of human adult liver are capable of aromatizing norethindrone (17 alpha-ethynyl-19-nortestosterone) to ethynylestradiol (17 alpha-ethynylestradiol). The evidence of ethynylestradiol formation was obtained using a Bio-Rad AG1-X2 column, thin layer chromatographies and co-crystallization. Neither acid nor base was used in any step in product identification.

Adult↗

Cardiovascular effects of nipradilol, a beta-adrenoceptor blocker with vasodilating properties.

In anesthetized dogs, an intravenous injection of nipradilol produced a long lasting fall in mean arterial blood pressure which was accompanied by transient decreases in peripheral vascular resistance and sustained decreases in heart rate, cardiac output and left ventricular (LV) dP/dt. LV end-diastolic pressure (LVEDP) was not changed while LV diameters and central venous pressure were slightly increased. Under propranolol pretreatment conditions, nipradilol no longer affected the heart rate, but the drug still induced a transient reduction in peripheral vascular resistance, and sustained decreases in arterial blood pressure and cardiac output. Furthermore, indicators of LV preload (LVEDP, LV end-diastolic diameter and central venous pressure) were significantly reduced, suggesting a direct dilating action of nipradilol on capacitance vessels. In intact conscious dogs, nipradilol caused a sustained reduction in LVEDP, while propranolol increased LVEDP. After administration of nipradilol, coronary blood flow in anesthetized dogs decreased in association with diminished myocardial oxygen consumption, and large coronary vessel resistance also decreased. Nipradilol competitively antagonized the isoproterenol-induced positive chronotropic response (DR10: 0.04 mg/Kg, i.v.) and the phenylephrine-induced vasopressor response (DR10: 3.95 mg/Kg, i.v.). In conclusion, nipradilol, in contrast to propranolol, possesses the properties to decrease arterial blood pressure, LV preload and large coronary vessel resistance through its dilating action on arterial and venous vessels. It is proposed that nipradilol may be beneficial for the treatment of hypertension and coronary heart disease.

Adrenergic beta-Antagonists↗

Effect of high carbohydrate diet on serum gamma-glutamyl transpeptidase fraction pattern in Japanese young men.

Changes in the activity of serum gamma-glutamyl transpeptidase (gamma-GTP) and the percentage of the gamma-GTP fraction in healthy young men given a high carbohydrate diet (480-636 g/day, 80% of the total energy) for 21 days were examined. Serum total gamma-GTP activity showed no significant change in four healthy young volunteers who received high carbohydrate diet for 21 days. However, the percentage of the gamma-GTP (1) fraction increased significantly (P less than 0.01) from the basal level of 55.6 +/- 4.0% to 67.6 +/- 0.9% on day 10, and then decreased to 58.4 +/- 1.4% on day 21. When the experimental diet was replaced by usual diet, the percentage of the gamma-GTP (1) fraction returned to the same level as before the experiment. It is concluded from the results that the nutrient intake affects the percentage of gamma-GTP (1), but not the total serum gamma-GTP activity.

Adult↗

[Clinical significance of the measurement of serum neuron-specific enolase levels in patients with lung cancer].

Subjects were comprised of 100 healthy adults, 85 patients with primary lung cancer, 20 with benign lung disease and 4 with metastatic lung cancer. Serum neuron-specific enolase (NSE) levels were estimated by means of an NSE RIA kit produced by Eiken Radiopharmaceutical Co., Ltd. The normal range of serum NSE level was between 4.5 and 10.30 (mean: 6.81) ng/ml in the 100 healthy adults. The serum NSE level in patients with small cell carcinoma was significantly higher than the mean in patients with other histological types. Positive rates of serum NSE levels were 80% in patients with small cell carcinoma, 54% in patients with adenocarcinoma, 52% in patients with squamous cell carcinoma and 1% in healthy adults, respectively. According to the progress of staging in lung cancer patients, serum NSE levels became increased. Serum NSE level seems to be specific marker in patients with small cell lung cancer and to be useful for diagnosis and the monitoring of cancer treatment.

Adenocarcinoma↗

Effect of high carbohydrate diet on serum lactate dehydrogenase isozyme pattern in Japanese young men.

Changes in the activity of serum lactate dehydrogenase (LDH) and the serum LDH isozyme pattern in healthy young men given a high carbohydrate diet (480-636 g/day, 80% of the total energy) for 21 days were examined. Serum total LDH activity showed no significant change in four healthy young volunteers who received high carbohydrate diet for 21 days. However, the percentage of LDH-4 increased significantly (P less than 0.01) from 8.5 +/- 2.4 to 10.9 +/- 1.9% after 21 days, as did also the percentage of LDH-5 (P less than 0.01) from 5.1 +/- 1.9 to 10.7 +/- 2.9%. The percentage of M-type LDH activity increased 30% during the experiment (P less than 0.05). It is concluded from the results that the high carbohydrate intake affects the percentage of LDH-4 and LDH-5, but not the total serum LDH activity.

Adult↗

[Non-Hodgkin's lymphoma: correlation of cell surface marker phenotype with clinical features and prognosis].

The correlation of surface marker phenotype with prognosis was analysed in 64 patients with non-Hodgkin's lymphoma who had been treated in Shikoku Cancer Center Hospital. B-cell lymphomas (21 cases) had significantly better prognosis than T-cell lymphomas (21 cases). The complete remission (CR) rate was 52%, and the 50% survival time was 13 months for T-cell lymphomas. All T-cell lymphoma patients died within 31 months. In B-cell lymphomas, on the other hand, the CR rate was 100%, 50% survival time was 30 months, and there were no cases of relapse in patients who had been in continuous CR for more than 2 years. About 40% of B-cell lymphomas appeared to have the potential for cure.

Adolescent↗