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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 577 records · Page 32Linked to original sources
PubMed1997

Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus. Evidence for close concordance of cutaneous delayed hypersensitivity and endothelial E-selectin expression.

BACKGROUND: The relationship of adhesion molecules in the dermis to immunologically mediated cutaneous inflammation can be understood by focusing on a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus anemicus (NA) in generalized contact dermatitis. The expression and induction of endothelial and epithelial adhesion molecules with intradermally injected cytokines were investigated. OBSERVATIONS: Nevus anemicus without dermatitis lacked histopathological changes consistent with inflammatory cellular infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis. However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR and ICAM-1 expression. Interferon gamma, injected intradermally, induced endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding normal skin. While interferon gamma strongly induced E-selectin expression on endothelial cells in normal skin, it failed to induce endothelial E-selectin expression in the NA. CONCLUSIONS: This study suggests that vessels in the NA do not respond normally to proinflammatory cytokines, at least at the level of E-selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in the NA lesion in contact dermatitis is likely caused by the absence of infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting circulating T lymphocytes to the skin.

Antigens, CD↗
PubMed1997

Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson syndrome. Contribution of perforin-positive cell infiltration.

OBJECTIVE: To clarify the mechanism of epidermal cell death in erythema multiforme. DESIGN: Retrospective study. SETTING: Academic referral center. PARTICIPANTS: Nine patients with Stevens-Johnson syndrome (SJS), 9 patients with Hebra disease (EMH), and 5 healthy volunteers. INTERVENTIONS: Biopsy specimens were obtained from the border of the fresh lesions before treatment. Control specimens were obtained from normal skin. MAIN OUTCOME MEASURES: Histopathological epidermal apoptosis detected with nuclear DNA fragmentation and counts of dermal immunoreactive perforin-positive infiltrates were compared between SJS and EMH. RESULTS: Eight patients (89%) with SJS showed clear apoptosis with keratinocyte DNA fragmentation. All SJS samples had intensive perforin-positive dermal infiltrates. Only 3 patients (33%) with EMH showed apoptotic change, and it was to a far less extent with far less dermal perforin-positive infiltrates. Control specimens showed no apoptotic cells in the epidermis or expression of perforin in the dermis. CONCLUSIONS: Perforin mediates apoptosis in the pathogenesis of the epidermal cell changes in SJS but not in EMH. In addition to the differences in clinical severity and histopathological conditions, our findings indicate a pathogenic difference between SJS and EMH.

Antibodies, Monoclonal↗
PubMed1997

[Evaluation of ischemic heart disease using the index of relative 99mTc-tetrofosmin uptake increase at exercise].

We calculated an increase of myocardial 99mTc-tetrofosmin uptake during exercise from resting condition, which was thought to reflect coronary flow reserve, and assessed whether this method enhanced the detection of coronary artery disease (CAD). Exercise myocardial SPECT was performed using 99mTc-tetrofosmin with one-day method (exercise-rest) in 26 patients. Twenty-one patients were suspected to have ischemic heart disease and 5 were control patients. A polar map was used to evaluate the increase in counts after exercise. The parameter of % uptake increase was obtained by the ratio of exercise and resting myocardial counts. The uptake was corrected for administration dose and time decay between the exercise and rest studies. The sensitivity for detecting patients with significant coronary stenosis by visual evaluation and % uptake increase map was 60% and 90%, respectively. In 5 patients, % uptake increase map detected stenosed coronary artery lesions that could not be detected by visual analysis. We concluded that the % uptake increase map combined with conventional SPECT images enhanced the detectability of coronary artery disease and the evaluation of the degree of coronary flow reserve.

Adult↗
PubMed1997

[Clinical significance of the guidelines for appropriate management of transfusion therapy and aim of introduction of inspection and accreditation program].

For these ten years we have had several guidelines and manuals published by Ministry of Health and Welfares (MOHW) and other organizations. In 1989 MOHW put a guideline for appropriate management of blood transfusions into effect. Some medicolegal scholars have made an evaluation of this guideline in the descriptions to consider what blood transfusion therapy should be and how to make up the control system of blood services in hospitals, but the guideline would be a double-edged sword to medical staffs. In this paper some main topics in the guideline were presented, on the background how to decide the expressions of the contents. Why inspection and accreditation programs should be introduced in hospital blood transfusion services in near future, promoting proper use of blood products by audits, was discussed.

Accreditation↗
PubMed1997

Extraorbital giant cell angiofibromas.

We herein describe two unusual neoplasms showing histopathologic features consistent with those of giant cell angiofibroma, which was originally described as a neoplasm arising in the orbit in adults: one of them arose in the right submandibular region of a 48-year-old woman and the other in the right parascapular region of a 49-year-old woman. Macroscopically, although the latter was characterized by a lymphangioma-like cystic appearance, both tumors were well circumscribed and encapsulated. Microscopically, in both cases, pseudovascular spaces lined by a discontinuous row of multinucleated cells were seen against a background of spindle-shaped fibroblastic cell proliferation. In the second case, the tumor presented increased cellularity and plump and somewhat atypical nuclei of proliferating fibroblastic cells, compared with the tumor in the first case. Immunohistochemically, the mononuclear and multinucleated cells within these tumors were positive for vimentin and CD 34 but negative for any other antigens, including Factor VIII-related antigen, desmin, alpha smooth muscle actin, myoglobin, S-100 protein, LeuM1, lysozyme, alpha-1-antitrypsin, and cytokeratins (AE1/AE3 and CAM5.2). The features in these cases indicate that giant cell angiofibroma can arise in an extraorbital site in middle-aged patients and presents some histopathologic diversity.

Angiofibroma↗
PubMed1997

[Outcomes of noninvasive positive-pressure ventilation in patients with acute hypercapnia complicating chronic respiratory failure].

We used noninvasive positive-pressure ventilation to treat hypercapnea due to acute exacerbations of chronic respiratory failure (21 episodes in 19 patients; COPD, 4; pulmonary tuberculosis sequelae, 4; silicosis, 3; silicotuberculosis, 3; bronchiectasis, 3; others, 2). All patients had acute onsets of severe hypercapnea (PaCO2 > 45 Torr), acute decreases in pH (< 7.35), and tachypnea, paradoxical breathing or both. During the first 2 to 4 hours of bi-level positive airway pressure, PaCO2 decreased from 72 to 61 Torr (p < 0.0005), pH increased from 7.26 to 7.31 (p < 0.001), and respiratory rate decreased from 30 to 25 breaths/min (p < 0.005). In three cases leakage of air through the mouth prevented improvement in the patients' conditions, but in two of those a face mask was then used successfully. In 17 of the 21 episodes (81%) gas exchange improved and intubation was not necessary. In those 17, the mean duration of noninvasive positive-pressure ventilation was 6.3 days. We conclude that noninvasive positive-pressure ventilation can improve gas exchange in patients with acute hypercapnea complicating chronic respiratory failure.

Acute Disease↗
PubMed1997

L-DOPA cyclohexyl ester is a novel stable and potent competitive antagonist against L-DOPA, as compared to L-DOPA methyl ester.

We explore stable potent competitive antagonists against L-DOPA. In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE) (30-100 ng) microinjected in depressor sites of the nucleus tractus solitarii dose-dependently shifted the dose-response-curve for L-DOPA (18-300 ng) to the right, with DOPA CHE (100 ng)-induced slight reduction of the maximum response. DOPA methyl ester (DOPA ME) at 100 ng also produced competitive antagonism. Antagonistic activity of DOPA CHE (100 ng) was similar to that of DOPA ME (300 ng). DOPA CHE is suitable for the purpose of screening.

Animals↗
PubMed1997

[Thoracoscopic resection of mediastinal parathyroid adenoma with cyst and hyperparathyroidism--a case report].

A 51-year-old woman was admitted because of general fatigue assumed to be due to climacteric disturbance. Laboratory examinations suggested a diagnosis of hyperparathyroidism based on high serum levels of Ca, intact PTH, and high-sensitivity PTH. No abnormalities were found in the cervix. Chest X-ray films and CT scans showed a mass measuring 4 cm in the right postero-upper mediastinum. The tumor was positive on a parathyroid scintigram, and was diagnosed as a mediastinal parathyroid adenoma with hyperparathyroidism. Operative findings showed a tumor surrounded by the superior vena cava, vagus nerve, azygos vein, and brachiocephalic artery. Careful resection of the hypervascular tumor from surrounding tissues was performed using a thoracoscopic technique alone. The postoperative course was uneventful. Serum values of Ca, intact PTH, and high-sensitivity PTH decreased to within normal ranges. after surgery. Pathohistological study confirmed the diagnosis of parathyroid adenoma including a cyst caused by degeneration of the tumor.

Adenoma↗
PubMed1997

Activated T cells induce up-regulation of Fas antigen in cultured endothelial cells.

Recent evidence has shown that apoptotic cells are present in human atherosclerotic lesions. However, the molecular mechanism of the induction of apoptosis in atherosclerotic lesions is not clear. Since T cells are present in almost all stages of atherosclerosis, we examined whether T cells can modulate the expression of Fas, a death signal, in endothelial cells (ECs), using a coculture system. Human umbilical vein ECs were cultured alone or cocultured with human peripheral T cells activated with phorbol myristate acetate and ionomycin. Flow cytometric (FACscan) analysis showed that Fas antigen was up-regulated in ECs when ECs were cocultured for 24 h with activated T cells. However, Fas antigen was not up-regulated in ECs cocultured with non-activated T cells. The up-regulation of Fas antigen induced by coculturing ECs with activated T cells was partially, but significantly, neutralized by antibody against interferon-gamma (IFN-gamma). Actually, incubation with IFN-gamma induced a dose-dependent increase in the level of Fas antigen in ECs cultured alone. These findings indicate that activated T cells induce up-regulation of Fas antigen in ECs. Thus, the Fas system induced by activated T cells could participate in the mechanism of EC injury in atherosclerotic lesions.

Apoptosis↗
PubMed1997

Relationship between mortality rate of stomach cancer and cerebrovascular disease and concentrations of magnesium and calcium in well water in Hyogo prefecture.

The concentration of Mg, Ca and total hardness of well and tap water were examined in 98 towns and cities in Hyogo prefecture. The annual mortality rates of stomach cancer and CVD in these areas during 1975-1979 were analyzed by the concentration of Mg and Ca in well water. The mortality rate of stomach cancer was correlated significantly positively to Mg2+/Ca2+ ratio of well water, and a similar tendency was shown in tap water. A covariance analysis indicated Mg2+ to be correlated significantly to the mortality rate of stomach cancer. Thus, it is suggested that the relatively high concentration of Mg2+ compared to Ca2+ in drinking water might be one of the causes of stomach cancer in Japanese. But the concentration of Ca2+ was correlated significantly negatively to the mortality rate of CVD.

Calcium↗
PubMed1997

Dissection of the DNA binding domain of yeast Zn-finger protein Rme1p, a repressor of meiotic activator IME1.

A series of deletion mutants of the yeast Zn-finger protein Rme1p (Repressor of Meiosis) fused with maltose binding protein (MBP) were constructed, purified, and characterized to examine the DNA binding domain. It was shown by gel retardation assay that the DNA binding domain of Rme1p was attributed to C-terminal amino acid residues 171 to 300. All three Zn-fingers are involved in the DNA binding domain, but they are not sufficient for DNA binding ability. Notably, the C-terminal region (residues 285-300) is essential for DNA binding. Provided that the region folds into alpha-helix, the basic amino acid residues may form a ridge on one side of the helix, whereas the hydrophobic residues may form it on the other side. Thus, the DNA binding domain of Rme1p would be dissected two regions. The roles of C-terminal region in DNA recognition will be discussed.

Amino Acid Sequence↗
PubMed1996

Chronic amitriptyline exposure reduces 5-HT3 receptor-mediated cyclic GMP formation in NG 108-15 cells.

In the present study, we investigated the effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on cyclic GMP formation stimulated by 5-hydroxytryptamine (5-HT) in the neuroblastoma x glioma hybrid cell line, NG 108-15, 5-HT (0.01-100 microM)-stimulated cyclic GMP formation was concentration-dependent and was sensitive to ICS 205-930, a 5-HT3 receptor antagonist. Exposure of NG 108-15 cells to 5 microM amitriptyline for 3 days significantly reduced 5-HT-stimulated cyclic GMP formation. Acute treatment with amitriptyline had no effect on 5-HT-stimulated cyclic GMP formation. The reduction by chronic amitriptyline exposure of 10 microM 5-HT-stimulated cyclic GMP formation was concentration-dependent over the concentration range examined (0.5 to 10 microM). The IC50 of amitriptyline was 1.9 microM. In contrast, amitriptyline exposure, even at a concentration of 8 microM, failed to modify cyclic GMP formation stimulated by bradykinin, sodium nitroprusside, or atrial natriuretic peptide. Increases in intracellular Ca2+ concentration ([Ca2+]i) evoked by 10 microM 5-HT were attenuated in amitriptyline-exposed cells, while 100 nM bradykinin-induced [Ca2+]i increases were not affected. In addition, chronic exposure to 5 microM amitriptyline caused a decrease in affinity (Kd) of [3H]zacopride specific binding to 5-HT3 recognition sites. The Bmax for the labelled ligand remained unchanged. These results suggest that chronic amitriptyline exposure reduces 5-HT-stimulated cyclic GMP formation and [Ca2+]i increases, and this may reflect the functional changes of 5-HT3 receptors.

Amitriptyline↗
PubMed1996

A trial to kill tumor cells through Fas (CD95)-mediated apoptosis in vivo.

We tried to induce tumor cell death in vivo through Fas (CD95)-mediated apoptosis. Murine hepatoma MH 134 (Fas-) was transfected with murine Fas antigen cDNA. Fas+ F6b but not Fas- N1d cells underwent apoptosis after treatment with anti-Fas antibody in vitro. The possibility of eradicating tumor cells in vivo with anti-Fas antibody was investigated using double-mutant gld/gld lpr/lpr mice which lack both Fas ligand (FasL) and Fas to avoid cytotoxic activity of the antibody to the liver and interference from endogenous FasL. A single administration of anti-Fas antibody efficiently suppressed the growth of F6b tumors but not that of N1d tumors in these mice. Thus, the therapy with Fas-FasL system may be a promising approach for cancer treatment, and this model is useful for study on in vivo apoptosis-mediated antitumor activity.

Animals↗
PubMed1996

Long CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes.

The rare folate-sensitive, fragile sites on chromsomes X, 11, and 16 contain blocks of CCG triplet repeats and large expansions of the CCG block at the FRAXA site produce the fragile X syndrome (FraX). The fragile, poorly staining nature of these sites suggested an altered chromatin structure. Here, repeating CCG DNAs from FraX patients were tested for their ability to assemble into nucleosomes, the basic subunits of chromatin, using in vitro nucleosome reconstitution, electron microscopy and competitive assembly gel retardation assays. CCG blocks of >50 repeats displayed strong nucleosome exclusion, providing a possible explanation for the nature of these sites.

Base Sequence↗
PubMed1996

Decreased inositol 1,4,5-trisphosphate-specific binding in platelets from alcoholic subjects.

We measured the degree of inositol 1,4,5-triphosphate (IP3)-specific binding in platelets from alcoholic and nonalcoholic subjects. IP3-specific binding in alcoholic subjects was 45% less than that in nonalcoholic subjects. There was no significant difference in the number of IP3 receptors as detected immunologically in the platelet membrane fractions from alcoholic and nonalcoholic subjects. These results indicate that the decrease in IP3-specific binding in alcoholic subjects may have been due to a decreased affinity, but not number of IP3 binding sites. In contrast to the decrease in IP3 receptor binding, there were no significant changes in phospholipase-C activity or immunoreactivity of phospholipase C-beta 1 in platelet membranes from alcoholic subjects. The decreased IP3-specific binding in platelets may allow for the development of biological markers for alcoholism.

Adult↗
PubMed1996

Augmentation of antitumor immunity with bacterial superantigen, staphylococcal enterotoxin B-bound tumor cells.

We have examined the effectiveness of a bacterial superantigen, staphylococcal enterotoxin B (SEB)-coupled tumor cells, to induce antitumor activity. SEB was chemically conjugated to tumor cells using a heterobifunctional cross-linking agent acting through NH2 and SH groups. V beta 8+ T cells were activated and increased in number after the culture with SEB-bound Meth A cells. The cultured T cells exhibited an antitumor activity in the Winn assay. Interleukin 2 (IL-2) receptor alpha + (IL-2R+) V beta 8+ T cells but not IL-2R+ V beta 6+ T cells increased in number in mice injected with SEB-bound Meth A cells. However, the percentages of V beta 8+ and V beta 6+ T cells did not change by this immunization. The antitumor effector cells were V beta 7- 8- CD4+ T cells. In vivo immunization with SEB-bound cells induced a strong antitumor activity, i.e., tumor-free mice/total mice = 14 of 15 (93%) for Meth A and 7 of 15 (47%) for hepatoma MH134. The induced antitumor activity was both dose dependent and tumor specific. Treatment with SEB-bound cells prolonged the survival days of Meth A-bearing mice by 62%. These results suggest that SEB-bound tumor cells may be a powerful method for induction of in vivo antitumor activity.

Animals↗