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F Yoshida

Publications and source records attributed to F Yoshida.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mechanisms of non-drowsiness after oral administration of TMK688, a novel antiallergic drug.

The mechanisms of non-drowsiness after oral administration of TMK688 (1- [[5'-(3"-methoxy-4"-ethoxycarbonyloxyphenyl)-2',4'-pentadienoyl ] aminoethyl]-4-diphenylmethoxypiperidine, CAS 110501-66-1) were investigated using mice. TMK688 inhibited the histamine-induced vascular permeability at oral doses of 3.2-10 mg/kg with an ID50 value of 5.4 mg/kg. More than 100 times higher doses were needed to prolong the hexobarbital-induced sleeping. Pyrilamine, a typical antihistamine agent, showed little difference among these doses and antiallergic drugs having antihistamine activity, i.e., terfenadine, azelastine and ketotifen, had effects between TMK688 and pyrilamine. The inhibitory activity of orally administered TMK688 against ex vivo [3H]-pyrilamine binding to mouse cerebral histamine receptors appeared at the same doses as its potentiating activity against hexobarbital-induced sleeping. When given orally, TMK688 was hydrolyzed to TMK777 (CAS 101619-11-8), then conjugated with glucuronic acid to TMK777-glucuronide. No TMK688 was detected in the blood. The main metabolite TMK777-glucuronide could hardly penetrate the blood-brain barrier because of its polarity. Although the plasma concentrations of TMK777 were far lower than those of TMK777-glucuronide, TMK777 was penetrable into the brain and the cerebral concentrations of TMK777 increased in parallel with the plasma concentrations of the drug. Since intracerebroventricularly-injected TMK777 prolonged the sleeping time, and since the threshold concentration of TMK777 in the cerebral cortex to potentiate the hexobarbital-induced sleeping was consistent despite different administration routes, the drowsiness elicited by markedly high doses of TMK688 is though to be caused by intracerebral TMK777. In other words, TMK688 does not seem to cause drowsiness at effective doses because of the poor prenetrability of its main metabolites into the brain.

Administration, Oral↗
PubMed1997

Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice.

Microcystin-LR (MCLR) is a hepatotoxic peptide produced by Microcystis aeruginosa, an alga found worldwide in reservoirs for drinking supply; however, acute oral toxicity of purified MCLR remains unknown. Therefore, a single dose of MCLR (more than 95% purity) ranging from 8.0 to 20.0 mg/kg body weight was orally given to female 6-week old BALB/c mice, and lethality and pathological changes were observed. Median lethal dose (LD50) of the orally given MCLR estimated by the up and down method was 10.9 mg/kg, which was 167 times higher than the i.p. LD50 value (65.4 microgram/kg by moving average method). Orally administrated toxin caused primarily hepatocellular injuries with characteristics of hemorrhage and necrosis. In situ end-labeling as well as electron microscopic observation revealed an induction of apoptotic cell death to hepatocytes. These results indicate the lethality of MCLR was much lower in oral dosage than by i.p. administration, but toxic effects are similar. In addition, apoptosis is considered one of major components in MCLR-induced hepatotoxicity.

Administration, Oral↗
PubMed1997

Increased natural killer resistance to cyclosporine A by continuous doses of dexamethasone in rats.

There is a controversy on the effects of physiological levels of glucocorticoids on natural killer (NK) cytotoxity. Therefore, the effects of exogenously administered dexamethasone on NK cytotoxity in 8-week-old male, Fischer 344 rats were studied. We suppose that the reason for the controversy is insufficient sensitivity of the ordinal radioactive chromium-release assay for normal healthy subjects or animals. Therefore, we developed a new index, a resistance to artificial immunosuppressor, cyclosporine A (CsA) using rat NK activity as an indicator, and named this index, increased resistance to immunosuppressor (IRIS). After some basic, characterizing studies, authors confirmed the fact that continuous doses of dexamethasone (DEX) attenuated NK suppression of CsA. In protocol 4, 18 rats were randomly divided into three groups: the first (DEX + CsA) was injected for 5 days with 0.1 mg DEX/kg/day and a single dose of CsA on the final day, intraperitoneally; the second (SAL + CsA) was treated with an equal volume of saline and CsA; the third (DEX + SAL) was treated with DEX but not CsA. The IRIS in NK activity was increased significantly (P < 0.01) with 5 days injection of DEX. These results demonstrated that physiological, and continuous dosage of glucocorticoids stimulated IRIS in NK activity in rats, and this suggests that appropriate stimuli through the hypothalamic-adrenal axis might be acting, at least, as a defence against immune collapses or dysfunctions.

Animals↗
PubMed1997

A case report of salivary duct carcinoma.

We present a 65-year-old man with an enlarged mass in the right parotid gland. A fine-needle aspiration cytology suspected Warthin's tumor. The ill-defined margin of the tumor in diagnostic imaging and unexpected clinical course of the occurrence of facial nerve paralysis suggested malignant neoplasm. The patient was treated with surgical resection of the primary site and neck following radiation therapy. Pathologic diagnosis was a salivary duct carcinoma. Difficulty in early diagnosis of this tumor may result in local extension, early metastasis to regional lymph nodes and distant sites, and death.

Adenocarcinoma↗
PubMed1996

Survey of microcystins in environmental water by a highly sensitive immunoassay based on monoclonal antibody.

By using a highly sensitive enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody, microcystin (MC) concentration was analyzed in environmental water samples (total, 134), collected in 1993-1995 from ponds, lakes, reservoirs, and rivers in Japan, Thailand, Germany, and Portugal. MCs detected in the water samples filtered over a glass filter were designated as free MCs, and those samples that were freeze-thawed twice before the filtration were designated as total MCs. MCs (> 50 pg/ml) were detected in 14 of 24 samples collected from the lakes that were used as recreation and water supply in Japan in different regions. In the MC-positive samples, the concentration of free MCs was only a few percentages of the total MCs, indicating that the most part of MCs found in the water samples was present in algal cells. An additional trial on 33 samples collected continuously from Lake Inbanuma, Japan, during June-September 1994-1995 revealed that the total MCs were in a range of 52-52,000 pg/ml. In Chiang Mai, Thailand, 6 of 10 samples were positive, with the mean and highest of 161 and 354 pg/ml, respectively. In the Frankfurt area. Germany, 4 of 10 and 7 of 8 samples collected in the same lakes for recreation in July 1993 and November-December 1994 showed the presence of MCs, with their mean and highest values of 257 and 407 pg/ml, respectively. Another survey of MCs in dense bloomed samples collected with plankton net revealed a contamination of MCs up to 36,000 pg/ml. In Portugal, 28 of 29 samples from 4 lakes, 20 rivers, and 5 reservoirs were positive for MCs, with the respective means of 13,664, 11,048, and 2,278 pg/ml. These data indicated that MCs contaminate environmental water in ponds, rivers, lakes, and reservoirs worldwide. The present ELISA is considered to be a reliable tool for the mass monitoring and risk assessment of MCs in water supplies.

Antibodies, Monoclonal↗
PubMed1996

Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties.

Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distribution coefficients, log D for ionizable compounds), and the permeability in individual analyses of compound classes such as beta-adrenoceptor blockers and steroids, the correlation was reduced when taken together. However, delta log P (i.e., log Poctanol-log Palkane) correlated inversely with the combined permeability data for beta-blockers and steroids and played a key role as a unifying variable. To a lesser extent, lipophilicity itself also contributes positively to corneal permeation. Even with the addition of miscellaneous compounds such as methanol and ibuprofen, the delta log P and lipophilicity terms were still significant. However, small molecules were likely to be underestimated, which is consistent with penetration via another pathway besides that governed by delta log P and lipophilicity.

Adrenergic beta-Antagonists↗
PubMed1995

Partial purification and some properties of a neutral proteinase in rat ovary.

The ovary of rat possessed a neutral proteinase which had an optimum pH at around 8.5 in the presence of 0.5 M NaCl. The proteinase was soluble only in media of high ionic strength such as 2 M NaCl. In order to prevent the reprecipitation in media of low ionic strength of the enzyme solubilized, it is necessary to add protamine sulfate to the solubilizing medium. When the solubilized enzyme was applied to a Sephadex column, the proteinase activity was eluted at the same position as bovine alpha-chymotrypsinogen. The results using some protease inhibitors showed that the proteinase was a chymotrypsin-like serine enzyme. When rats were treated with compound 48/80, the proteinase activity almost completely disappeared, suggesting that the enzyme is of mast cell origin.

Animals↗
PubMed1995

The role of a complement regulatory protein in rat mesangial glomerulonephritis.

The host cells are protected from the indiscriminate attack of homologous complement by the membrane-associated complement regulatory proteins. A mouse monoclonal antibody (mAb) 512 (immunoglobulin G1 subclass) has recently been described that recognizes and inhibits the function of a rat complement regulatory protein, a rat homologue of mouse Crry/p65. The aim of this work is to assess the role of a complement regulatory protein (512Ag) recognized by mAb 512 in the complement-dependent glomerular injury induced by mAb OX7 against rat Thy-1.1. For the induction of mesangial injury, the left kidney of a rat was perfused with a combination of OX7 and 512 and the perfusate was discarded from the renal vein (Group I). After the renal artery and vein were restored, the left kidney was connected to the systemic circulation. Rats were euthanized 3 h, 2 days, and 14 days later. Rats perfused either with OX7 (Group II) or with 512 (Group III) or with vehicle only (Group IV) were used as controls. At 3 h, rats of Group I showed more prominent cellular infiltration and mesangial lysis and more C3 deposition in the glomeruli than rats of Group II. Rats of Groups III and IV showed no significant changes. At Day 2, there was still significant mesangial lysis and leukocyte infiltration in Group I rats, whereas rats in other groups showed an almost normal appearance. Glomerular injury in Group I rats returned to normal by Day 14.

Animals↗
PubMed1995

In vivo effects of hyperglycemia on the outcome of acute mesangial injury in rats.

To assess the effects of high blood glucose concentration on glomerular changes after the acute mesangial cell injury in the rat, the monoclonal anti-Thy1.1 antibody OX-7 was injected into streptozoticin-induced diabetic rats or normal rats. The increase in proliferating cell nuclear antigen-positive cells in glomeruli at day 4 and glomerular hypercellularity at day 18 was less prominent in diabetic rats than in normal rats. The expansion of mesangial matrix area assessed by fibronectin immunostaining was more prominent, and segmental glomerulosclerosis was observed at day 60 in the diabetic rats. These data suggest that the insulin-deficient group may reflect impaired "wound-healing," leading to the prolonged ECM accumulation under the hyperglycemic condition in vivo.

Acute Disease↗
PubMed1994

Role of CD59 in experimental glomerulonephritis in rats.

CD59 is a molecule which is present on the host cell membranes and inhibits formation of membrane attack complex. A monoclonal antibody, 6D1, recognizes a rat analogue of human CD59. 6D1 inhibits function of rat CD59 and can enhance complement-mediated hemolysis in vitro. To assess the role of CD59 in complement-mediated glomerular injury, 6D1 was tested in a model of experimental glomerulonephritis induced by a lectin and its antibodies. The left kidney of a rat was perfused either with 200 micrograms of Lens culinaris hemagglutinin (LCH) plus 1 mg of 6D1 (IgG1 fraction) (Group I and III) or with LCH only (Group II) through a cannula placed in the left renal artery. All the perfusate was discarded from a cannula in the renal vein. The holes in the artery and vein were repaired by microsurgery and the blood circulation was re-established. Rats were injected either with 0.125 ml of rabbit anti-LCH serum (Group I and II), or with normal rabbit serum (Group III) via tail vein one minute after the recirculation. Fifteen minutes after injection, significant C9 deposition in the glomeruli was observed only in Group I, whereas C3 deposition in Group I and II were comparable. At Day 4, total glomerular cells, proliferating cells, glomerular expression of intercellular adhesion molecule-1 and fibrin deposition in Group I were all significantly increased when compared with Group II. At Day 7, number of total glomerular cells and leukocytes in the glomeruli of Group I were significantly higher than in Group II. The glomeruli in Group III appeared normal throughout experiments. These data indicate that the functional inhibition of a rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo.

Animals↗
PubMed1994

Renal lesions of the FGS strain of mice: a spontaneous animal model of progressive glomerulosclerosis.

The strain of FGS/Nga mouse is reported to develop proteinuria and progressive glomerulosclerosis. We studied the renal pathology of that strain periodically for 1 year. Focal and segmental glomerulosclerosis was observed 3 months after birth and the lesion progressed to the glomerular obsolescence in a year. Electron microscopic study revealed electron dense deposits (DD) in the mesangium and the splitting of glomerular basement membrane. Studies using immunofluorescence and immunoelectron microscopy revealed that these DD were contained IgA, IgM, C3 and the retroviral envelope antigen (gp70). Clinically, proteinuria began at the age of 3 months and the renal function was decreased on time course. No other organs were involved. We studied the renal lesions of FGS mice by the histological and immunohistochemical methods and concluded that this mouse strain provides the tool for studying the mechanisms of the progression of glomerulosclerosis.

Animals↗
PubMed1994

[Minority versus majority: intergroup discrimination in the minimal group paradigm].

The present study was conducted to investigate the intergroup behaviour from the perspective of social identity theory. It was predicted that (a) when group membership was based on trivial categorization (e.g., by drawing lots), minority group members would be more conscious of their social identity, and favour their own group more in reward distribution than majority group members; (b) when based on value-loaded categorization (e.g., by social attitudes), both minority group and majority group members would favour their own group; (c) both minority group and majority group members would perceive converted members, who move away from their initial attitudes, as a threat to their social identity, and discriminate them. Results from three experiments under the minimal group paradigm, with undergraduate students, supported these predictions. Findings were discussed in terms of salience of social identity in categorization of minority versus majority, and the impact of anonymity in the minimal group paradigm. They were also discussed to compare the theory with belief congruence theory, which argues that attraction due to similarity of belief is the cause of ingroup favoritism.

Adult↗
PubMed1994

[Bacterial cerebritis developed from purulent meningitis--serial CT and MRI study of a case].

A 54-year-old woman was admitted to our hospital because of purulent meningitis caused by Streptococcus pneumoniae during a long-term administration of prednisolone for the treatment of bronchial asthma. After admission, both antibiotics and steroids were given, which resulted in her good general and neurological condition, and the normal protein and glucose content in her cerebrospinal fluid three weeks later. However, post-contrast computerized tomography (CT) at this time showed various size of multiple irregular high-densities devoid of capsular component in the white matter of the bilateral cerebral hemisphere. MRI examination revealed that the lesions were of low intensity on the T1-weighted sequence whereas high on T2-weighted sequence. Gd-DTPA enhanced the T1-weighted images on these lesions. These findings may indicate that the lesions were at the pre-encapsulation stage of cerebritis, because the lesions were gradually reduced and disappeared after the subsequent antibiotic therapy. It is emphasized that patients with purulent meningitis under steroid therapy require careful observation for the risk of bacterial cerebritis.

Encephalitis↗
PubMed1994

[Study of cardiac function in first stage examination of RA-700. RA-700 Clinical Study Group].

There are many studies in the literature on the subject of anti-neoplastic drugs for acute and chronic cardiac toxic function. It is important to check previously the cardiac toxicity of the new anti-neoplastic drugs. Now we have had a chance to study the first stage examination of RA-700, isolated from Rubia akane or Rubia cordifolia. Then we tried to study several kinds of parameters, for instance ECG, ultrasonic cardiograms and arterio-grams on cardiac toxicities of RA-700. We injected the first group of neoplastic patients only once with RA-700, while in the second group, we injected them with RA-700 for 5 consecutive days (see our previous report.) In the present study, we made some conclusions about the administration of RA-700. 1) Changes in cardiac function were noted in both groups. 2) Changes in blood pressure, sigma QRS, ejection fraction, and fractional shortening of the second group tended to be more extreme than those of the first group. Care for continuity is a concern with long-term and high doses of RA-700. 3) Because of the small sample, we could find no relationship between the changes in cardiac function and the injection doses of RA-700. 4) Therefore, the cardiac function must be checked by giving anti-neoplastic drugs to neoplastic patients.

Adult↗
PubMed1993

Acute renal failure and degenerative tubular lesions associated with in situ formation of adenovirus immune complexes in a patient with allogeneic bone marrow transplantation.

We describe the development of acute renal failure and degenerative tubular lesions associated with local immune deposits in a patient with allogeneic bone marrow transplantation. A 21-year-old man with an acute myelocytic leukemia received a bone marrow graft from a cousin mismatched for a single HLA-DR locus antigen. Hemorrhagic cystitis due to adenovirus type 11 infection occurred 26 days after transplantation, and 17 days later the patients developed acute renal failure. A study of renal tissue obtained by needle biopsy showed degenerative and necrotic lesions, especially in the distal part of the nephron. By electron microscopy adenovirus type 11 particles were found in the nuclei of tubular cells and in cellular debris in tubular lumina. By immunofluorescence technique, granular immune deposits containing adenovirus type 11 related antigen(s), immunoglobulins, C3, and membrane attack complex (MAC) C5b-9 of the complement system were detected along the tubular basement membranes but not in glomeruli. The patient's IgG did not bind to normal human kidneys. These findings suggest that adenovirus type 11 directly induced acute tubular damage, and that the tubular immune deposits were formed "in situ" by viral antigens and circulating viral antibody.

Acute Kidney Injury↗
PubMed1993

Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits. Possible mechanisms.

We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques.

Animals↗