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Biomedical subjects

S Shintani

Publications and source records attributed to S Shintani.

At least 73 records · Page 4Linked to original sources

Adsorption effects of activated charcoal on metaldehyde toxicity in rats.

Metaldehyde has been widely used as a main ingredient of solid fuel for making fire and slug baits in Japan. It is also marketed as a color flame tablet for party goods (ENGELFIRE). Consequently, children have been poisoned by eating such tablets which they mistook for candy. As a result, poison information center calls are increasing. According to POISINDEX, the treatment for metaldehyde poisoning consists in prevention of adsorption by activated charcoal, seizure control and airway protection. However, the optimum dose of charcoal is not established. We studied the quantitative adsorption capacity of activated charcoal for acute oral toxicity of metaldehyde in rats. In vivo toxicity and absorption tests for metaldehyde in Wister rats were done. The detoxifying effect of activated charcoal on metaldehyde toxicity and inhibition of metaldehyde absorption were investigated. Ratios used of po activated charcoal given 30 min after dosing to 400 mg metaldehyde/kg po were 5:1, 2:1, 1:1, 0.5:1. Serum metaldehyde was determined by gas chromatography in the control group (no charcoal) and the various experimental groups. Metaldehyde mortality was completely prevented at the ratio of 5:1. Gastrointestinal absorption of metaldehyde was reduced significantly by 45.3% in comparison to the control rats. There was no acetaldehyde detected in the serum of the metaldehyde-dosed rats. Metaldehyde poisoning may be prevented by early po administration of activated charcoal in a ratio of > 5:1 compared to metaldehyde. The theory that acetaldehyde is the primary toxic agent in metaldehyde poisoning should be re-evaluated.

Acetaldehyde↗

Silent lacunar infarction on magnetic resonance imaging (MRI): risk factors.

We investigated the risk factors for silent lacunar infarction and etat criblé detected by magnetic resonance imaging (MRI). Previous reports have evaluated white matter hyperintensities (WMHs) and periventricular hyperintensities (PVHs) on T2-weighted images, but have not distinguished between lacunar infarcts, état criblé, and leukoaraiosis of Binswanger's type. MRI scans were performed in 270 subjects without neurological deficits over the age of 40 years. They were classified into four subtype groups based on MR findings: normal group (n =60), état criblé group (n=69), silent lacunar infarct/PVH(-) group (n=61), and silent lacunar infarct/PVH(+) group (n=80). We examined the following biochemical variables and other potential risk factors by ordinary logistic regression analysis to identify independent and significant risk factors for silent lacunar infarction: serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein(a), HbA1c, age, sex, systolic blood pressure, diastolic blood pressure, duration of hypertension, family history, smoking habits, alcohol intake, obesity (body mass index), and atrial fibrillation. Subjects in the silent lacunar infarct/PVH(-) (P<0.01) and PVH(+) (P<0.001) groups were significantly older than normal subjects. The systolic blood pressure was also significantly higher in the silent lacunar infarct/PVH(-) (P<0.04) and PVH(+) (P<0.01) groups compared with the normal group. The duration of hypertension was significantly longer in the silent lacunar infarct/PVH(+) group (P<0.02). There were no significant differences in other risk factors between the normal group and the other groups. Ordinary logistic regression analysis showed that age (chi-square 51.8, P<0.0001) and systolic blood pressure (chi-square 5.7, P<0.02) were significant and independent risk factors for silent lacunar infarction. Aging and hypertension were shown to be independent risk factors for silent lacunar infarction.

Adult↗

GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice.

Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. To address this issue, 3-wk-old NOD mice received two injections of purified rat brain GAD; one mouse rapidly developed diabetes 3 wk later. Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. They are also cytotoxic against NOD-derived hybridoma cells (expressing I-Ag7) that were transfected with rat GAD65, but not nontransfected hybridoma cells. Adoptive transfer of 5A cells into NOD/SCID mice produced insulitis in all mice. Diabetes occurred in 83% of the mice. We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM.

Adoptive Transfer↗

Sleep apnoea in well-controlled myasthenia gravis and the effect of thymectomy.

We conducted overnight polysomnographic sleep studies of 16 patients (5 men and 11 women) with clinically well-controlled myasthenia gravis (MG). The subtypes of MG were IIA (3 patients), IIB (11 patients), IV (1 patient) and V (1 patient). Twelve patients were found on polysomnography to have obstructive and/or central types of the sleep apnoeas (SA). Their mean age was 42.4, SD 16.4 years, and the mean duration of MG was 7.4, SD 6.96 years. SA was not detected in 4 patients whose mean age was 30.8, SD 10.71 years and who had manifested MG for a mean duration of only 0.9, SD 0.65 years. Thus, patients with a longer duration of MG tended to have more SA. In 9 of the 12 SA patients, polysomnographic studies were repeated following thymectomy. SA had resolved in 6 patients, but persisted in 3. These findings suggest that SA is a possible clinical manifestiation of MG and that nocturnal dysfunction of both peripheral and central colinergic systems may be involved.

Adult↗

A case of well-differentiated minute hepatocellular carcinoma with extrahepatic metastasis.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) metastasizing to distant sites in a 77-year-old man with hepatitis C virus (HCV)-related cirrhosis is presented. Ultrasonography (US) disclosed a 9 mm hypoechoic lesion in segment seven (S7) of the liver, although computed tomography (CT), magnetic resonance imaging (MRI) and angiography did not reveal any space-occupying lesion. Ultrasound-guided biopsy showed the histological features of well-differentiated HCC. A plain film of the abdomen and CT revealed osteolytic changes in the sacrum and the lumbar vertebra. Ultrasound-guided biopsy of the sacrum revealed well-to-moderately differentiated HCC metastasizing from the liver. Percutaneous ethanol injection therapy (PEIT) effected complete response and completely eliminated the abnormal findings on US. Three months after PEIT, metastasis to the thoracic vertebra was revealed by CT, despite negative alpha-fetoprotein-mRNA in serum. This is the first report describing a well-differentiated HCC with metastatic potential. Further studies may provide insights into metastasis of well-differentiated HCC.

Aged↗

Subclinical cerebral lesion accumulation on serial magnetic resonance imaging (MRI) in patients with hypertension: risk factors.

OBJECTIVES: We investigated the occurrence in hypertensive patients of new subclinical changes in the brain by serial magnetic resonance imaging (MRI). METHODS: MRI was performed serially in 98 hypertensive subjects without neurologic deficits at least once a year for 3 years. All received antihypertensive medicines Blood pressure, serum lipids, diabetes mellitus, body mass index (BMI), and other clinical factors were correlated with results. RESULTS: Seventy-nine patients had unchanged MRI findings, while 19 developed new lesions (silent lacunar infarct and etat criblé in 3, silent lacunar infarct in 9, and etat criblé in 7). Follow-up systolic blood pressures were significantly higher than individual baselines in the unchanged group, while the follow-up diastolic blood pressures in the new lesion group were significantly lower than in the unchanged group. BMI was significantly lower in the new lesion group. Follow-up HbA1c levels in both groups were significantly higher than at baseline. Diabetes mellitus was significantly more frequent in the new lesion group than in the unchanged group. No significant differences were apparent in serum lipids level, prescribed antihypertensive medications, and other potential risk factors. CONCLUSIONS: New subclinical MRI changes in hypertensive subjects occurred relatively frequently (19 of 98 subjects, or 19.4%). An excessive fall in diastolic blood pressure, diabetes mellitus, and low BMI emerged as candidate risk factors for these changes.

Aged↗

Clinical-radiologic correlations in pure sensory stroke.

Clinical-radiologic correlations in 27 patients with pure sensory strokes (PSS) were retrospectively studied. Dysesthesias from pontine lesions were more severe than those from thalamic lesions. Pontine PSS but not thalamic PSS selectively affected vibration and position sense, leaving pinprick and temperature perceptions intact. Thalamic lesions but not pontine tended to spare the trunk.

Adult↗

Dual effects of anti-inflammatory 2-arylpropionic acid derivatives on a major isoform of human liver 3alpha-hydroxysteroid dehydrogenase.

Nonsteroidal anti-inflammatory drugs have been shown to be potent inhibitors of mammalian 3alpha-hydroxysteroid dehydrogenase. Here, we report that the drugs of the 2-arylpropionic acid class act as both activators and inhibitors for a predominant isoform of the human liver enzyme which is involved in the metabolism of steroid hormones, bile acids, drug ketones and xenobiotic aromatic hydrocarbons. Flurbiprofen, fenoprofen, ibuprofen, naproxen, ketoprofen and suprofen stimulated the activity of the human enzyme (1.5-2.4-fold) at low concentrations of less than 20-100 microM, whereas at higher concentrations they inhibited the activity. Comparison of the effects of the structurally related compounds with the drugs revealed that the essential structure required as the activator molecule is 2-phenylpropionic acid with a hydrophobic substituent on the aromatic ring. In addition, an R-enantiomer of ibuprofen showed higher activation (3-fold) than its S-enantiomer. Kinetic analysis with respect to NADP+ concentration indicated that R- and S-ibuprofens are nonessential activators showing binding constants of 23 and 34 microM, respectively. Neither enantiomers activated, but rather inhibited the enzyme, with Met replacing Arg-276 which has been shown to interact with the 2'-phosphate of NADP+. The inhibitions of the mutant enzyme by R- and S-ibuprofens were competitive with respect to the substrate, giving Ki values of 95 and 18 microM, respectively. The results suggest that the human liver 3alpha-hydroxysteroid dehydrogenase isoform possesses the two distinct sites, activator and inhibitor sites, to which anti-inflammatory 2-arylpropionates stereoselectively bind.

Alcohol Oxidoreductases↗

Helicobacter pylori infection affects gastric ulcer healing in Japanese monkeys.

Although peptic ulcer frequently recurs in the presence of Helicobacter pylori infection, the effects of H. pylori on ulcer healing have yet to be studied in detail. Using an animal model, we examined the effects of H. pylori infection on the healing of peptic ulcer in Japanese macaques. Forty-four Japanese macaques, aged 5 years, were randomly divided into two groups, an H. pylori-infected group and a control group, with 22 animals in each. A total of 10(9) colony forming units per ml of an H. pylori strain clinically isolated from patients positive for the cagA gene, the vacA gene, and vacuolizing toxin production, was inoculated into the stomachs of the monkeys to induce H. pylori-associated gastritis. The monkeys were examined by endoscopy, and then 0.1 ml of 10% ammonia solution was injected into the angulus to produce an active ulcer. Endoscopic observations was performed every week for 8 weeks. Acid-reducing drugs and other cytoprotective agents were not administered during the 8-week observation period. No difference in the healing of the ulcers was seen between the two groups from the first to the third week. However, a significant delay in healing was noted in the H. pylori-infected group from the fourth week on wards (P < 0.05). At the sixth week, the proportion of ulcers in the S2 stage (presence of a complete scar) was 0% in the H. pylori-infected group and 38% in the control group, again indicating that healing was significantly delayed in the H. pylori-infected group (P = 0.0187). By the eighth week, the proportion of ulcers in S2 stage had increased to 18% in the H. pylori-infected group and 67% in the control group (P = 0.0719). In Japanese macaques with persistent H. pylori infection in the stomach, the speed of repair of the ulcer surface was reduced, leading to delayed ulcer healing, compared with the controls.

Animals↗

Extracellular matrices expression in invasion area of adenoid cystic carcinoma of salivary glands.

Adenoid cystic carcinoma (ACC) is a salivary malignant tumor with poor long-term prognosis, that is known to have predilection for invasion of the adjacent stroma and neural tissues. This carcinoma has shown a high incidence of recurrence and distal metastasis. Invasive carcinomas have been associated with the distributions of extracellular matrices (ECM). Cell proliferation as a marker of tumor growth has been related to poor prognosis in oral carcinomas. Immunohistochemical analysis of 15 cases of ACC was done using antibodies to laminin, type IV collagen, fibronectin, tenascin and anti-proliferating nuclear antigen (PCNA). Laminin and type IV collagen were totally or partially absent in the ACC invasive areas. Tenascin was expressed in the stroma and cytoplasm and was associated with tumor cell proliferation. It can be concluded that basement membrane represents a barrier that is lost during cell invasion and tenascin may be involved in the detachment of cancer cells, increasing the invasive potential of ACC.

Adult↗

Exacerbated autoimmune hepatitis successfully treated with leukocytapheresis and bilirubin adsorption therapy.

A 58-year-old man with subacute fulminant onset of autoimmune hepatitis (AIH) was treated by leukocytapheresis (LCAP) and bilirubin adsorption therapy (BAT), rather than by administration of high-dose corticosteroids as he had mild glucose intolerance, and a definitive diagnosis of AIH was not obtained on admission; further, there was a risk of viral infection. After initiation of the therapies, serum transaminases and bilirubin, immunoglobulins, anti-nuclear antibodies, and rheumatoid factor decreased rapidly, as did the initially high levels of activated cells and several pro-inflammatory cytokines. Liver inflammation observed on liver biopsy settled during the course of the therapies, with no adverse side effects. A pause in the therapies was associated with deterioration; however, restoration of apheresis was followed by normalization. Remission was sustained throughout the period monitored, except for a recurrence 14 months after discharge, which was successfully resolved by two additional LCAP sessions. These results suggest that LCAP influences the causal mechanism(s) of exacerbation of AIH.

Adsorption↗

Intraoral ultrasonography is useful to evaluate tumor thickness in tongue carcinoma.

BACKGROUND: A number of studies have reported that tumor thickness (the depth of invasion) is a valuable prognostic factor in oral cancers, especially as a predictor of cervical lymph node metastasis. Accurate preoperative assessment of the tumor thickness of tongue cancer would provide useful information for targeting those patients for whom elective treatment of the neck is appropriate when the primary tumor is resected. No studies have been done measuring the tumor thickness of tongue cancer preoperatively. The present study was undertaken in order to evaluate the clinical usefulness of intraoral ultrasonography as a tool to delineate tumor extent and measure the thickness of tongue carcinomas. MATERIALS AND METHODS: Twenty-four patients with tongue carcinoma were preoperatively evaluated with intraoral ultrasonography. The tumor thickness measured by ultrasonography was compared with the measurements by histological sections. RESULTS: High-quality ultrasonic images were obtained, and the tumor thicknesses were measurable within 1 mm. There was a significant correlation (P <0.001) between measurements by ultrasonography and histological sections. CONCLUSION: Our results demonstrated that intraoral ultrasonography is an excellent method to delineate tumor extent and measure tumor thickness in tongue carcinomas.

Adult↗

Fine needle aspiration of salivary gland tumors.

The usefulness of fine needle aspiration (FNA) as a preoperative diagnostic procedure was studied in 43 patients with salivary gland tumors. Nine of the tumors were malignant and 34 benign. The diagnostic sensitivity of FNA was 88.9% (8/9), the specificity 94.1% (32/34) and the accuracy 93.0% (40/43). These results indicate that FNA is a highly sensitive and specific screening procedure.

Adenocarcinoma↗

Immunohistochemical study on the nm23 gene produce (NDP kinase) in oral squamous cell carcinoma.

The nm23 gene is a potential metastasis suppressor gene originally identified using a murine melanoma cell line. Immunohistochemical investigation on the role of nm23 gene product (nucleoside diphosphate kinase: NDPK) in squamous cell carcinomas of the oral cavity was performed and compared to clinical and histopathological factors. The stainability of NDPK did not correlate to tumour extent, differentiation and mode of invasion. However, the NDPK positive group tended to have a lower frequency of lymph node metastasis, and a better prognosis than the NDPK negative group. Consequently, nm23/NDPK is suggested to be a metastasis suppressor factor that may be useful for predicting tumour metastasis and prognosis in oral squamous cell carcinoma.

Biomarkers, Tumor↗

Does the presence of serum autoantibodies influence the responsiveness to interferon-alpha 2a treatment in chronic hepatitis C?

The serum autoantibodies, antinuclear antibody, anti-DNA antibody, anti-smooth muscle antibody, antithyroglobulin antibody, antimicrosomal antibody, antimitochondrial antibody, rheumatoid factor and antibody to deoxyribonucleoprotein were measured at the baseline and on completion of interferon-alpha 2a (IFN-alpha 2a) treatment in chronic hepatitis C (CHC) patients who did not present with any autoimmune disease prior to treatment. Of the 57 patients examined, 27 spontaneously manifested at least one autoantibody. Only the prevalence of rheumatoid factor (26%) was significantly higher in the CHC patients than in the control subjects. There were no differences in the prevalence of the 8 autoantibodies examined between hepatitis C virus (HCV) genotypes 1b and 2a/2b. Twenty-six patients responded to IFN-alpha 2a. Subclinical hypothyroidism developed in two patients with elevated antithyroid antibody titres during treatment. No relationship was observed between changes in the status of autoantibodies and either response to IFN-alpha 2a or HCV genotype. Irrespective of the HCV genotype, autoantibodies might be present in CHC patients before and during the IFN-alpha 2a treatment. The presence of such antibodies does not represent a contraindication to the use of IFN-alpha 2a in CHC patients not complicated by autoimmune diseases. Careful observations are necessary for CHC patients positive for antithyroid antibodies during the IFN-alpha 2a treatment. Preexisting or newly developed autoantibodies do not necessarily predict a poor response to IFN-alpha 2a.

Adult↗

Sudden "stroke-like' onset of homonymous hemianopsia due to bacterial brain abscess.

A previously healthy 40-year-old man experienced the sudden 'stroke-like' onset of homonymous hemianopsia due to a bacterial brain abscess. Clinical features and initial computed tomography (CT) suggested a stroke. Subsequent CT and magnetic resonance (MR) demonstrated a cerebral abscess, proven at surgery. It is extremely rare that a healthy individual without various risk factors, such as congenital heart disease, immunologic deficiency, diabetes mellitus, or pregnancy, presents with the above symptoms. The exact mechanism of this sudden 'stroke-like' onset in a patient with a bacterial brain abscess is unknown. One possibility is that paroxysmal septic emboli led to abscess formation within or near areas of embolic infarction. Another possibility is that a primary cerebral infarction was associated with secondary bacteremia. Surgical drainage revealed a bacterial (Streptococcus) abscess, but no identifiable source of infection.

Adult↗