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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 469 records · Page 26Linked to original sources

Immunopharmacological study of CCA (Lobenzarit disodium), an anti-arthritis agent--I. Abrogation of IL 1 secretion by LPS-stimulated human monocytes and induction of gamma-interferon production with CCA.

In vitro effects of CCA, an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction (AMLR), lymphocyte mitogenesis, IL 1 and IL 2 production, immunoglobulin production and gamma-interferon (IFN) production. CCA at 50 micrograms/ml, which was not toxic to cells, blocked AMLR, IL 1 production and immunoglobulin production (IgM and IgG) significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20 ng/ml and 20 micrograms/ml induced human gamma/IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulator.

Humans↗

Pancreatic carcinoma in childhood.

A case of pancreatic carcinoma in a 14-year-old Japanese boy is reported. He complained of general fatigue, anorexia, abdominal distension, and abdominal mass. At autopsy, a whitish tumor was found from the head to the body of the pancreas. Metastasis was found in the liver, lungs, gall bladder, and various lymph nodes such as stomach, hilus, and periaorta. The tumor was histologically determined to be moderately differentiated adenocarcinoma (cribriform type) of duct cell origin. However, the tumors showed PAS-positive diastase-resistant mucus in the cytoplasm. Histocytology showed the positivity for alpha 1-antitrypsin, secretory component (sc), and CEA, but no S-amylase was detected in the cytoplasm. Electron microscopy revealed zymogen-like granules in the cytoplasm suggesting acinar differentiation.

Adolescent↗

Time-dependent biphasic response of aromatase to dexamethasone in cultured human skin fibroblasts.

Human genital skin fibroblasts grown in cell culture possess aromatase activity and, therefore, provide a model to investigate the molecular mechanisms that control aromatase in extraglandular tissues. Following the observation by other investigators that glucocorticoids stimulated aromatase activity in cultured stromal-vascular cells from adipose tissue, we examined the influence of dexamethasone (DEX) on aromatase in cultured skin fibroblasts. Preincubation of skin fibroblasts with DEX stimulated aromatase expression in all cell strains. In time-course studies, aromatase activity showed a biphasic curve, with peak levels at 12 h and a return to baseline levels by 72 h. When DEX was removed after 12 h, aromatase activity could be completely restimulated by DEX only after a period of 60-72 h. The DEX stimulation appeared to involve glucocorticoid receptor function, since the concentration of DEX required for half-maximal stimulation of aromatase activity (4.2 nM) was similar to the dissociation constant (Kd, 4.3 nM) of the receptor (for DEX). Actinomycin D and cycloheximide (CHX) inhibited DEX stimulation of aromatase when they were present in the preincubation and assay media. When cells were preincubated with DEX and CHX and then washed free of CHX and DEX before the assay, superinduction of aromatase activity occurred. Our data concerning the time course and superinduction of aromatase activity by DEX are in contrast to the findings reported by others for adipose tissue stromal-vascular cells and suggest that the mechanisms for the control of aromatase in extraglandular tissue may vary significantly in different tissues.

Adult↗

Bradykinin-induced cyclic AMP accumulation in mouse fibrosarcoma independent of prostaglandin E2 formation.

The relationship between bradykinin (BK)-induced prostaglandin E2 (PGE2) and cyclic AMP syntheses in mouse fibrosarcoma cells (HSDM1C1) was investigated. Maximal BK-induced increases in cyclic AMP preceded increases in PGE2 production. PGE2 synthesis reached maximum at a much lower concentration of BK than cyclic AMP synthesis. Indomethacin completely inhibited BK-induced PGE2 production, but did not influence the cyclic AMP levels. Arachidonic acid in the medium induced PGE2 production in large quantities, but increased cyclic AMP accumulation only slightly. A high PGE2 concentration increased cyclic AMP levels only slightly. Theophylline increased basal and BK-mediated cyclic AMP levels, but did not affect PGE2 production at all. These results indicate that BK-evoked PGE2 and cyclic AMP syntheses in HSDM1C1 are not dependent upon each other.

Animals↗

Intrinsic gamma aminobutyric acid receptors modulate the release of catecholamine from canine adrenal gland in situ.

Immunohistochemical analysis documented the presence of gamma-aminobutyric acid (GABA)-containing fibers and GABA-containing chromaffin cells in canine adrenal glands. A dense network of fibers was visualized at the boundary between medullary and cortical cells, and, in the medullary tissue, GABA-containing fibers surrounded chromaffin cells. Some of these fibers enter the adrenal medulla together with splanchnic cholinergic nerves. The functional role of the GABAergic system in the regulation of catecholamine release from adrenal chromaffin cells was studied in canine adrenal glands in situ, using an autoperfusion system for the adrenal gland that was designed to eliminate indirect central effects of drugs or their metabolites on catecholamine release. The present study documents that GABA modulates the spontaneous release of catecholamines and the release elicited by electrical stimulation of the splanchnic nerve. GABAA receptor agonists such as THIP or muscimol increased the catecholamine content in adrenal effluent blood, whereas bicuculline (0.05 mmol/2 ml min-1), a GABAA receptor antagonist, reduced it. Baclofen (0.094 mmol/2 ml min-1), a GABAB receptor agonist, failed to alter the catecholamine content in adrenal effluent blood. The increased release of catecholamines elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3[2H]-one (THIP; 0.143 mmol/2 ml min-1) was prevented by bicuculline (0.05 mmol/2 ml min-1) but not by hexamethonium (2.48 mmol/2 ml min-1) or naloxone (0.122 mmol/2 ml min-1). Furthermore, denervation of the adrenal glands failed to prevent the THIP-elicited release of catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

[Significance of amikacin administered orally prior to operation for prevention of postoperative infections in colonic cancer surgery].

Since December of 1983, clinical trial was undertaken on the prophylactic use of amikacin sulfate (AMK) and metronidazole (MET) in colonic cancer surgery. Daily dose of AMK 1,600 mg and MET 1,000 mg was administered orally in 4 divided doses to 17 patients with colonic cancer for 3 days prior to operation. As a result, wound infection was recognized in only one of 17 cases treated (5.9%). An examination was also performed on bacterial flora in the feces. After the administration of AMK and MET, E. coli and Klebsiella were remarkably decreased, however, E. faecalis and Candida remained unchanged. P. aeruginosa and Bacteroides detected in a few cases were also reduced. These bacteria were restored to the pretreatment level in 1 or 2 weeks after operation.

Administration, Oral↗

[Clinical evaluation of astromicin administered by intravenous drip infusion. Report II. Bacterial infections in the field of surgery].

A clinical evaluation of astromicin (ASTM) administered by intravenous drip infusion against infections in the surgical field was made, and the results were summarized as follows. Excellent effect was observed in 19 out of a total of 44 cases, good effect in 19, fair in 1 and poor in 5. The efficacy rate calculated from the 38 cases of "excellent" and "good" was 86%. In stratification by disease, the efficacy rate was 91% in localized peritonitis (31/34 cases) and 63% in diffuse peritonitis (5/8 cases); the overall efficacy rate in peritonitis was 86%. The efficacy rate in 2 cases infected by Gram-positive bacteria was 50%, and that in 16 cases by Gram-negative bacteria was 94%. The disappearance rate of Gram-negative bacteria was 93%, and this drug was especially effective against E. coli. There were no subjective or objective side effects and no abnormal laboratory test values that were related to the administration of ASTM.

Adult↗

[A randomized controlled study of (2'' R)-4'-O-tetrahydropyranyladriamycin and adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer].

A comparative study of two combination chemotherapy regimens including (2'' R)-4'-O-Tetrahydropyranyladriamycin (THP) or Adriamycin (ADR) was performed to evaluate its efficacy and safety in advanced and recurrent breast cancer. In this study 64 patients were evaluated, and the response rate was 35.1% (13 of 37 patients) in group A (combination chemotherapy of THP, 5-Fluorouracil and cyclophosphamide), and 29.6% (8 of 27 patients) in group B (ADR, 5-Fluorouracil and cyclophosphamide). There was no statistically significant difference between the response rates of the two groups. As for safety, that of group A was significantly superior to group B for alopecia while that of group A tended to be lower than group B for anorexia. From the above results, THP in combination with cyclophosphamide and 5-Fluorouracil is comparable to ADR in efficacy and can be regarded as having better safety than ADR for the treatment of breast cancer.

Anorexia↗

[The establishment of the assay-system of blood adrenal steroids in the method of gaschromatograph/mass spectrometry (GC/MS)].

In this study, we established a method for the quantitative measurement of native adrenal steroids with GC-MS equipped with capillary column (cross-linked methyl silicone 25 m X 0.2 mm I.D., 0.11 m thin film). 1 ml of serum sample containing 5 alpha-cholestane as internal standard (IS) was elicited by organic solvent using extrelunt column. These samples were derived by n-butylboronic acid, o-methylhydroxylamine and trimethyl-silylating agents, then were finally applied to GC-MS. The intensities of molecular ions were used for the measurement of the serum concentration of steroids. The molecular ion peaks of steroids were obtained at m/z460 (17 alpha-hydroxyprogesterone; 17OHP), m/z548 (corticosterone; B), m/z470 (11-deoxycortisol; S), m/z417 (pregnenolone; PL), m/z372 (progesterone; PT), m/z558 (cortisol; F), m/z389 (dehydroepiandrosterone; DHEA), m/z371 (estrone; E1), m/z416 (estradiol; E2), m/z504 (estriol; E3), m/z389 (testosterone; T), m/z344 (androstenedione; A) and m/z372 (IS). The curve of calibration for each steroid showed good linearity. The sensitivities of the GC/MS method were less than 5pg/one shot of each sample. The coefficients of variations of accuracies and precisions in this GC/MS method were less than 15% of each steroid. The samples from normal subjects after metyrapone and ACTH loading tests, and the patients of congenital adrenal hyperplasia showed a good correlationship between the data of GC/MS and the data of RIA after sephadex LH-20 column-chromatography. These results implied the usefulness of our system in clinical application. Moreover, this assay takes only 3 hrs. Thus it saves much time in comparison with the time-consuming radioimmunoassay system.

Adrenal Cortex Hormones↗

Diazepam-binding inhibitor: a neuropeptide located in selected neuronal populations of rat brain.

An endogenous polypeptide of rat brain has been identified that is capable of displacing 1,4-benzodiazepines and the esters of the 3-carboxylic acid derivatives of beta-carbolines from their specific synaptic binding sites. This polypeptide was termed diazepam-binding inhibitor (DBI). Previous studies have shown that DBI injected intraventricularly in rodents elicits "proconflict" responses and antagonizes the "anticonflict" action of benzodiazepines. An antiserum to this peptide, directed toward an immunodeterminant near its amino terminus, makes it possible to detect, measure, and study the neuronal location of this peptide in rat brain. In the rat cerebral cortex, DBI immunoreactivity is located in neurons that are not GABAergic (GABA, gamma-aminobutyric acid); in the cerebellum and hippocampus, however, it might be present also in GABAergic neurons.

Animals↗

Effects of caerulein-related peptides on cholecystokinin receptor bindings in brain and pancreas.

A number of caerulein (CLN)-related peptides were synthesized and compared in terms of their affinities for cholecystokinin (CCK) receptors. We have found that these peptides can be classified into three types according to their relative affinities for the brain and pancreatic receptors. The first group (type A) of peptides includes CLN and analogs retaining the Tyr(SO3H)4 residue and the COOH-terminal amide group. Type A peptides were as potent as CLN in inhibiting [125I]BH-CCK-8 binding and showed almost the same affinities for pancreatic and brain receptors. When the Tyr(SO3H)4 residue was either deleted or desulfated (type B), the affinities of the peptides decreased remarkably for the pancreatic receptors but much less for the brain receptors. The type C peptides were deamidated, oxidized, or shortened in the COOH-terminal region and exhibited greatly decreased affinities for both brain and pancreatic receptors but a much greater decrease for the brain receptor. These results indicate that, although the Tyr(SO3H)4 residue and the COOH-terminal structure are both essential for CLN to bind to the CCK receptors, the former is of critical importance for the binding to the pancreas and the latter is rather important for the binding to the brain.

Animals↗

Studies of cefotaxime serum concentrations during surgery under general anaesthesia and its passage to the wound fluid after surgery for breast cancer.

We are reporting on a comparison of serum concentrations of cefotaxime during and after surgery and on its passage to the wound fluid after surgery. Five patients undergoing mastectomy and dissection of the axillary lymph nodes for breast cancer were studied. Serum concentrations were compared after 2 g of cefotaxime dissolved in 20 ml of saline had been administered by i.v. bolus injection intraoperatively during general anaesthesia and six to eight days postoperatively in a conscious state. After intraoperative administration under general anaesthesia, cefotaxime serum concentrations were 157.3 mg/l at 15 min, 87.5 mg/l at 30 min, 43.08 mg/l at 1 h, 15.54 mg/l at 2 h and 9.56 mg/l at 3 h. In a conscious state, cefotaxime serum concentrations were 122.0 mg/l at 15 min, 84.35 mg/l at 30 min, 47.63 mg/l at 1 h, 18.2 mg/l at 2 h and 9.63 mg/l at 3 h, comparable to the time course under general anaesthesia. The half-life of cefotaxime was 0.86 h under general anaesthesia and 0.92 h in a conscious state. Urinary recovery of cefotaxime (0 to 3 h) under anaesthesia and in a conscious state was 53.8% and 56.3%, respectively (as reported previously for a nonsurgical state). Samples of wound fluid were taken at the completion of surgery from the drain inserted subcutaneously into the wound or by means of a tracheal aspirator kit attached to a portable aspirator. Cefotaxime concentrations were determined postoperatively on days six to eight, when the wound fluid became no longer serous.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Regulatory mechanism of cell pH in the renal proximal tubule of bullfrog nephron.

To examine the cellular mechanism of urinary acidification in detail, micropuncture studies were performed on the in situ bullfrog proximal tubule with nigericin-based pH microelectrodes. Pencil-type double-barreled antimony microelectrodes were also used for monitoring pHs of the tubular fluids. Luminal perfusion of 10(-3) M cyanide caused a biphasic change in cell pH (pHi): i.e., early acidification by 0.04 pH unit in 2 min and later alkalinization by 0.04. A profound depolarization of 30-35 mV was observed in the peritubular membrane potential (EM Peri), although the tubular fluid pH (pHTF) was elevated by 0.11 unit. Luminal substitution of 100 mM Na+ by Li+ acidified the cell by 0.06 pH unit with a depolarization of EM Peri by 8 mV and an alkalinization of pHTF by 0.10 unit. It is a fact that cellular acidification and luminal alkalinization are in good agreement with the depression of luminal H+ secretory mechanism. Perfusion of 10(-4) M SITS from the peritubular side caused a rise in pHi by 0.04 without appreciable changes in EM Peri in the short period application. Peritubular perfusion of 10(-4) M ouabain lowered the pHi by 0.07 with a resulting depolarization of EM Peri by 15.4 mV, meanwhile, the pHTF, while initially lowered by 0.07 unit, was elevated 4 min later by 0.12. Inhibitions of the peritubular ion transport mechanism caused some pH changes in the same direction, both in the cell interior and the tubular fluid. Further, from the ouabain experiment, it is inferred that some linkages, mediated by Na+ and H+(or HCO3-), would exist between the peritubular and luminal membranes.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗