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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 415 records · Page 23Linked to original sources
PubMed1998

Sparfloxacin-induced photosensitivity and the occurrence of a lichenoid tissue reaction after prolonged exposure.

BACKGROUND: A new antibacterial quinolone, sparfloxacin (SPFX), frequently causes photosensitive dermatitis and sometimes induces a treatment-resistant lichenoid tissue reaction (LTR). OBJECTIVE: We attempted to determine the factors that induce LTR in SPFX-induced photodermatitis. METHODS: Thirteen patients with SPFX photosensitive dermatitis were studied clinically and histopathologically. RESULTS: Six of the 13 patients had acute dermatitis with epidermal spongiosis and focal epidermal HLA-DR and intercellular adhesion molecule-1 (ICAM-1) expression with CD4+ cell infiltration. The other seven displayed LTR with basal cell liquefaction degeneration and diffuse epidermal HLA-DR and ICAM-1 expression associated with CD8+ cells. The seven patients with LTR were exposed to UV and SPFX for more than 2 weeks after the appearance of their initial eruption, whereas the six patients with acute dermatitis were treated within 2 weeks. The acute dermatitis lesions cleared significantly within 2 weeks, but the LTR lesions persisted for more than 6 weeks. CONCLUSION: Patients with quinolone-induced photosensitivity should be treated within 2 weeks of onset to prevent LTR.

Adult↗
PubMed1998

Signaling pathways via NK1 receptors and their desensitization in an AR42J cell line.

Substance P (SP) has been shown to induce phosphatidylinositol (PI) hydrolysis and Ca2+ mobilization in AR42J cells. In this study, we confirmed the expression of NK1 but not NK2 or NK3 receptors in this cell line, and further investigated signaling pathways via NK1 receptors and their desensitization. The activation of NK1 receptors by SP affected neither basal cyclic AMP level nor cyclic AMP accumulation induced by secretin and forskolin, although it stimulated PI hydrolysis. Furthermore, SP induced Ca2+ mobilization even in the absence of extracellular Ca2+, though maximal response was reduced. U73122, a phospholipase C (PLC) inhibitor, nearly abolished Ca2+ response to SP. In addition, SP-induced Ca2+ signaling and PI hydrolysis rapidly desensitized following short exposure to SP, which did not affect the Ca2+ amount in intracellular Ca2+ stores or Ca2+ responses to carbachol and gastrin releasing peptide-10. These findings suggested that NK1 receptors do not couple to adenylate cyclase, although they induce PI response, and that NK1 receptors induce both intracellular Ca2+ release and Ca2+ influx through PLC activation. Ca2+ signaling and PI hydrolysis through NK1 receptors desensitized rapidly after the stimulation, maybe dependent on the modification of NK1 receptors.

Animals↗
PubMed1998

Endogenous neutralizing anti-IL-1 alpha autoantibodies in inflammatory skin diseases: possible natural inhibitor for over expressed epidermal IL-1.

Interleukin 1alpha (IL-1alpha) is thought to play a central role in inflammatory reactions of the skin. Its excessive production and discharge by keratinocytes has been implicated in psoriasis, bullous diseases and other skin diseases. In addition to the type 2 IL-1 receptor and the IL-1 receptor antagonist, anti-IL-1 antibody in human serum has been proposed as a potential means to down regulate systemic responses attributable to IL-1. However, the relationship of these antibodies to disease and particularly to disease pathogenesis is still unclear. To understand this relationship, we characterized the anti-IL-1 autoantibody in sera from various skin diseases. IL-1alpha and IL-1beta radioimmunoassay, and immuno-blotting study showed the existence of IL-1alpha autoantibody but not autoantibodies to IL-1beta or pro-IL-1beta. High titer of anti-IL-1alpha autoantibodies were detected in the sera from inflammatory skin diseases with epidermal injury, including psoriasis, palmoplantar pustulosis, pustular psoriasis, pemphigus and lichen planus. In contrast, few samples from non-epidermodestructive bullous pemphigoid, atopic dermatitis and healthy normal controls had autoantibodies. The titer of anti-IL-1alpha autoantibodies showed some relation to the clinical course of psoriasis and pemphigus. Anti-IL-1 autoantibody neutralized rhIL-1alpha in D10.G4 assay and inhibited receptor binding of FITC-rhIL-1alpha. Taken together present data, the keratinocyte derived IL-1alpha could be a source of autoantigen that provokes production of endogenous anti-IL-1alpha autoantibody, which may regulate IL-1alpha mediated cutaneous inflammation.

Adult↗
PubMed1998

Increased cutaneous immunoreactive stem cell factor expression and serum stem cell factor level in systemic scleroderma.

Skin hyperpigmentation and itching are characteristic findings in systemic sclerosis (SSC) patients. Stem cell factor (SCF, c-kit ligand) is a multifunctional cytokine which can promote melanocyte and mast cell development. We investigated the SCF expression histopathologically in normal and SSC skin, and compared the expression with the serum SCF levels measured with a specific enzyme-linked immunosorbent assay. The epidermal and dermal immunoreactive SCF expression was markedly higher in the forearm skin of edematous phase SSC patients than in that of normal subjects. Tissue SCF expression declined from the sclerotic phase to the atrophic phase, where it was close to the normal level. In contrast, the elevated serum SCF level seen in the edematous phase samples was further increased in the sclerotic phase samples. The serum SCF level decreased in the atrophic phase, but it still remained at a level higher than that of the normal controls. Itching and increase of dermal mast cell number are characteristic of edematous phase SSC, and are in bears a parallel to the presently observed dermal SCF expression profile. Pigmentation is significant in sclerotic phase SSC and lasts to the atrophic phase, which may correspond to the serum SCF level observed here. These results indicate a contribution of the fibroblast membrane integral SCF in dermal mast cell development, and of the soluble serum SCF to melanocyte activation in SSC.

Adult↗
PubMed1998

Sonographic analysis of recurrent parotitis in children: a comparative study with sialographic findings.

OBJECTIVE: The sonographic features of recurrent parotitis in children were studied to clarify a relationship between sonographic and sialographic findings in this disease. STUDY DESIGN: Twenty-one glands (7 on follow-up) were examined by 7.5 MHz ultrasonography and sialography. Echo intensity level, distribution of the internal echoes, and size of hypoechoic areas were compared with the size of punctate shadows on the sialograms. Twenty other histopathologic specimens were analyzed to investigate the entity of hypoechoic areas. RESULTS: Sonography showed hypoechoic, heterogeneous internal echoes, the level of which increased as the punctate shadows enlarged. Hypoechoic areas, all of which were larger than the sialographic punctate shadows, were observed in 62% of the glands. Histopathologic analysis suggests that these hypoechoic areas represent dilated peripheral ducts with lymphocytic infiltration. Sonography was likely to detect changes over time more sensitively than sialography. CONCLUSIONS: Sonography should be performed as the test of first choice, both in the primary and follow-up stages, in cases of recurrent parotitis in children.

Adolescent↗
PubMed1998

Immunological determination of faecal haemoglobin concentrations in dogs.

Faecal haemoglobin (Hb) concentrations in apparently healthy experimental Beagle dogs and in dogs of various breeds kept in private households or at breeders were measured by reversed passive latex agglutination (RPLA) and enzyme-linked immunosorbent assay (ELISA) in an effort to define the physiological concentrations of faecal Hb in the dog. In 88% (53) of 60 experimental Beagle dogs (30 males and 30 females), the RPLA titres were 1:2 and 1:8 and the faecal Hb concentrations ranged from 40.0 to 431.5 (mean 184.1 +/- 92.6) micrograms/g faeces by ELISA. No significant difference was found in Hb levels or RPLA titres between males and females. Seven dogs (12%) had significantly greater RPLA titres and Hb concentrations by ELISA than the remaining dogs. In 84% (45) of the 53 dogs kept in private households or at breeders, the RPLA titres were < 1:1 to 1:8 and the faecal Hb concentrations ranged from 7.1 to 456.7 (mean 137.5 +/- 128.7) micrograms/g faeces in ELISA. Eight of these dogs (15.1% of 53 dogs) had significantly greater RPLA titres and Hb concentrations by ELISA than the remaining dogs. There were no significant differences between the Beagles and dogs kept in private households or at breeders. In conclusion, in 98 (86.7% of 113) dogs the physiological concentrations of RPLA titres were < 1:1 to 1:8 and the faecal Hb concentrations were 143.5-185.1 micrograms/g (95% confidence level). Approximately 13.3% of apparently healthy dogs had higher faecal Hb concentrations, suggesting the presence of subclinical haemorrhages. Four dogs suffering from colorectal cancer also had high faecal Hb concentrations.

Animals↗
PubMed1998

Physiological levels of C-reactive protein in normal canine sera.

This study was undertaken to investigate whether the level of C-reactive protein (CRP) in the serum of dogs undergoes physiological variation, using 10 normal Beagle dogs (5 males and 5 females), 1-2 years old, maintained in a healthy condition in a controlled environment. The CRP concentration in the sera collected seven times each day at intervals of approximately 3 h ranged from 0.8 to 16.4 micrograms/ml (mean 5.06 +/- 3.60) in one experiment and from 0.8 to 14.0 micrograms/ml (mean 4.50 +/- 2.80) in a second experiment. On examining the 24-h variations in the concentration of CRP in serum, neither consistent changes nor a definite pattern of circadian rhythm was detected. During 28 days observation, only very slight changes, which seemed attributable to analytical errors, were seen in any of the dogs, except one. The concentration of CRP in the serum during the 28 days ranged from 0.8 to 22.6 micrograms/ml (mean 3.65 +/- 1.40). The concentrations underwent no significant variations in individual dogs, but significant differences were found between the dogs (p < 0.01).

Animals↗
PubMed1998

Myocardioprotective effects of felodipine in an antihypertensive dosage: an experimental study in pigs.

The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of ischemia followed by reperfusion. Comparing the cardioprotective effects of felodipine and an agent of another class allowed the influence of blood pressure reduction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes before the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) serving as controls received a mixture of polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion levels, respectively. Infarct size as a percentage of the area at risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the vehicle groups, respectively. Felodipine, given in a dose resulting in plasma levels corresponding to the therapeutic range in patients on antihypertensive treatment, reduced infarct size following myocardial ischemia/reperfusion. Afterload reduction induced by nitroprusside did not influence infarct size. Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism of afterload reduction in clinically relevant antihypertensive dosages.

Animals↗
PubMed1998

Combined effect of navelbine with medroxyprogesterone acetate against human breast carcinoma MCF-7 cells in vitro.

Navelbine (NVB, vinorelbine ditartrate, KW-2307), a new vinca alkaloid analogue, has been shown to be clinically effective against advanced breast cancer. In this report, the combined effect of NVB with medroxyprogesterone acetate (MPA), a synthetic progesterone derivative, was examined in vitro against human breast carcinoma MCF-7 cells. The combined effect was demonstrated to be synergistic using the isobologram and median-effect plot analyses. To elucidate the mechanism of action, we further examined effects of both drugs on cell cycle distribution of the cells in combination and/or alone. NVB at 2 nM induced apparent G1-phase accumulation as well as the induction of cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1) protein and the dephosphorylated form of retinoblastoma protein (pRb). In contrast, MPA at 0.1 microM also induced G1-phase accumulation as well as the reduced expression of cyclin D1 protein. In addition, the combination of both drugs induced augmented G1-phase accumulation, which occurred along with p21(WAF1/CIP1) protein induction, cyclin D1 protein reduction and pRb dephosphorylation. These results demonstrate that the synergistic combined effect of NVB with MPA was mediated through enhancement of G1-phase accumulation that resulted from the different action point(s) of each drug. Furthermore, the synergistic combined effect of NVB with MPA was also observed in other human breast carcinoma cell lines, such as T-47D and ZR-75-1. These results suggest that combination therapy of NVB with MPA in breast cancer might be effective in clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Computed tomographic features of calcifying odontogenic cysts.

OBJECTIVES: To describe the CT appearances of 4 cases of the calcifying odontogenic cyst (COC) with particular reference to the effect of varying the window settings. METHODS: Conventional radiographs and CT scans of 4 calcifying odontogenic cysts were analyzed with respect to the presence of an impacted tooth, root resorption and calcification. In addition, increased attenuation by desquamated keratin was examined by varying the window settings on CT. RESULTS: All lesions were located in the maxilla and on conventional radiographs, had unilocular radiolucency with a well-defined margin. Calcifications and inclusion of an impacted tooth were seen in all cases. Root resorption was observed in two cases, but was not prominent. On CT, calcification was detected at the periphery of the lesion and/or around the impacted tooth in all cases. Varying the window setting revealed an increased attenuation area due to desquamated keratin. CONCLUSIONS: Varying the window setting on CT is useful as a means of identifying both desquamated keratin and peripheral calcification in COC.

Adolescent↗
PubMed1998

The novel non-peptide selective endothelin A receptor antagonist LU 135,252 protects against myocardial ischaemic and reperfusion injury in the pig.

The aim of the study was to investigate the efficacy of the novel non-peptide selective endothelin A (ETA) receptor antagonist LU 135,252 to limit the extent of myocardial ischaemic and reperfusion injury. Administration of LU 135,252 (1 and 5 mg kg-1 i.v.) to anaesthetised pigs reduced mean arterial pressure (MAP) from 91 +/- 4 to 79 +/- 3 mmHg (P < 0.05) and 96 +/- 3-82 +/- 3 mmHg (P < 0.01), respectively. Heart rate, coronary blood flow and coronary vascular resistance were not affected by LU 135,252. The infarct size induced by 45-min ligation of the left anterior descending coronary artery (LAD) followed by 4-h reperfusion in pigs was 81 +/- 5% of the area at risk in control animals given vehicle (n = 8). In pigs receiving 1 mg kg-1 (n = 6) or 5 mg kg-1 (n = 8) of LU 135,252 i.v. 20 min before ischaemia the infarct size was reduced to 64 +/- 3% (P < 0.05) and 35 +/- 4% (P < 0.001), respectively, of the area at risk. During the reperfusion period there was a non-significant trend towards a higher coronary blood flow and a lower coronary vascular resistance in the groups given LU 135,252 compared to controls. Myocardial overflow of ET-like immunoreactivity was increased during the reperfusion period but it was not affected by administration of LU 135,252. It is concluded that administration of the selective ETA receptor antagonist LU 135,252 effectively protects the myocardium from ischaemia/reperfusion injury, indicating that the ETA receptor subtype is involved in the development of ischaemia/reperfusion injury.

Animals↗
PubMed1998

Contribution of endothelin to the coronary vasoconstriction in the isolated rat heart induced by nitric oxide synthase inhibition.

The possible involvement of endothelin-1 (ET-1) and angiotensin II in the coronary vasoconstriction induced by nitric oxide synthase (NOS) inhibition was investigated in isolated Langendorff-perfused rat hearts. Fifteen minutes of perfusion with the NOS inhibitor NG-nitro-L-arginine (L-NNA, 0.1 mM) reduced coronary flow by 31%. Pre-treatment with the non-selective ETA/ETB receptor antagonist bosentan (1 and 10 microM) attenuated this reduction in coronary flow to 16% (P < 0.05) and 8% (P < 0.01), respectively. The selective ETA receptor antagonist BQ-123 (1 microM) induced a similar inhibitory action, whereas the selective ETB receptor antagonist BQ-788 and the angiotensin II type 1 receptor antagonist candesartan did not affect the vasoconstrictor response to L-NNA. In addition, bosentan administered after 15 min of L-NNA perfusion reversed the L-NNA-induced reduction in coronary flow in a dose-dependent manner. The high concentration of bosentan (10 microM) increased the basal coronary flow by 17%, while the lower concentration of bosentan, BQ-123, BQ-788 and candesartan did not affect basal coronary flow. Bosentan (10 microM) increased the level of ET-like immunoreactivity (-LI) in the coronary effluent twofold. L-NNA did not affect ET-LI level. These results indicate that ET-1 contributes to the coronary vasoconstrictor effect of L-NNA in the isolated rat heart, and that this action of ET-1 is mediated through ETA receptor activation. Angiotensin II does not seem to contribute to L-NNA-induced vasoconstriction under the present condition.

Animals↗
PubMed1998

Allopurinol hypersensitivity syndrome: hypersensitivity to oxypurinol but not allopurinol.

Allopurinol is a xanthine oxidase inhibitor widely used to control plasma uric acid levels. Episodes of hypersensitivity to the drug are not rare. A severe form of this with a generalized exanthem, fever and liver involvement has been termed the allopurinol hypersensitivity syndrome (AHS). Patch testing and lymphocyte stimulation testing (LST) are not helpful in confirming this sensitivity. Allopurinol works as a substrate of xanthine oxidase, and is rapidly oxidized into oxypurinol in vivo. Therefore, the biological half-life of oxypurinol is markedly longer than that of allopurinol. In addition, conspicuous pre-existing renal impairment has been noted in many AHS patients. Thus, it is possible that AHS is a manifestation of hypersensitivity to oxy-, not allopurinol. Here, we now report three cases of AHS in which there were significant lymphoproliferative reactions to oxypurinol but not allopurinol.

Adult↗
PubMed1998

Chlormadinone acetate pellet implantation plus short-term oral administration in dogs with benign prostatic hypertrophy.

Eight beagles with benign prostatic hypertrophy (BPH) were treated by subcutaneous implantation of pellets containing 10 mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen, plus daily oral administration of CMA at 2 mg/kg per day for 7 days as a therapy for BPH. Prostatic and testicular size were measured and prostatic and testicular biopsies were performed by laparotomy before and after CMA treatment. Plasma levels of luteininzing hormone (LH), testosterone and oestradiol were also measured. The clinical signs of BPH, for example haematuria and dysuria, resolved within 1 week of treatment. Mean prostatic volume decreased to 56% of the pretreatment value. At 40 weeks after treatment, prostatic volume had decreased by 36%. Histological examination of the prostate 1 week after treatment revealed reduction in diameter of the alveoli and in height of the glandular epithelium. Degeneration and atrophy of the glands were marked 4-12 weeks after treatment. In the testis, the diameter of seminiferous tubules and the number of germ cells in the seminiferous tubules had decreased markedly at 12 and 24 weeks after treatment. Although plasma LH concentrations did not undergo any marked fluctuations after CMA treatment, levels of testosterone and oestradiol were lower than before treatment. The results indicate that implantation of 10 mg/kg CMA, plus 7-day oral administration of 2 mg/kg CMA, bring about resolution of the clinical signs and marked reduction in prostatic volume within 1 week of treatment.

Administration, Oral↗