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Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 73 records · Page 4Linked to original sources

Benidipine, a long-acting Ca channel blocker, limits infarct size via bradykinin- and NO-dependent mechanisms in canine hearts.

Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that a long-acting Ca channel blocker, benidipine, increases cardiac NO levels in ischemic canine hearts, suggesting that benidipine may also protect against ischemia and reperfusion injury via bradykinin- and NO-dependent mechanisms. We examined this possibility. In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and was occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed by TTC staining at 6 hours of reperfusion. When benidipine doses of 50, 100, and 200 ng/kg/min were infused via the bypass tube between 10 min prior to the onset of ischemia and after 60 min of reperfusion, systemic blood pressure did not change significantly. Infarct size decreased with the administration of benidipine (50, 100, and 200 ng/kg/min) when compared to the untreated condition (24.8+/-2.5, 17.3+/-3.1, and 16.5+/-2.0 vs. 43.4+/-5.6%, respectively) associated with the increased release of NO and bradykinin in the coronary venous blood upon reperfusion. Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by benidipine. The limitation of infarct size and the increase in myeloperoxidase activity were completely blunted by either L-NAME or HOE140. There were no significant differences in collateral blood flow assessed by the microsphere method after 45 min of ischemia for any of the groups. Thus, we conclude that the Ca channel blocker, benidipine, limits infarct size via bradykinin- and NO-dependent mechanisms.

Adrenergic beta-Antagonists↗

Immunohistochemical expression and pathogenesis of BLM in the human brain and visceral organs.

Bloom syndrome (BS) involves the clinical features of telangiectatic erythema, immunodeficiency, and an increased risk for cancer. In order to clarify the pathogenetic significance of the responsible gene, BLM, which encodes a protein possessing homology to Escherichia coli RecQ helicase, the immunohistochemistry of BLM was examined in human brains and visceral organs from fetuses to adults and an adult with BS, using anti-BLM antibodies. Purkinje cells exhibited positive BLM immunoreactivity from 21 gestational weeks (GW), which transiently increased at approximately 40 GW. Neurons of the pontine tegmentum were immunolabeled from the early fetal period. In visceral organs, positive BLM immunoreactivity was observed in the Hassal corpuscles in the thymus from 24 GW, in beta-cells in the Langerhans islets of the pancreas from 36 GW, and in sperm cells and sperms of the testes from 11 years of age. But in a patient with BS, it was negative in the pancreas and testis tissues examined. The characteristic effect of BLM on specific cells in different periods suggests that the BLM gene product is closely related to neuronal development as well as immune, insulin secretory and sperm functions, which appear in different periods, and disorders of which are major symptoms of BS.

Adult↗

D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes.

Fetal abnormalities including chylous ascites, polyhydramnios, claw hands, and hammer toes were identified in an infant who had a missense mutation R106P and a 52bp deletion in the gene for a peroxisomal beta-oxidation enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase, D-bifunctional protein. The patient had psychomotor retardation and craniofacial dysmorphism and died at 7 months of age. The patient had atypical fetal manifestations of this enzyme deficiency.

17-Hydroxysteroid Dehydrogenases↗

Effects of JPEG and wavelet compression of spiral low-dose ct images on detection of small lung cancers.

PURPOSE: To compare the effect of compression of spiral low-dose CT images by the Joint Photographic Experts Group (JPEG) and wavelet algorithms on detection of small lung cancers. MATERIAL AND METHODS: Low-dose spiral CT images of 104 individuals (52 with peripheral lung cancers smaller than 20 mm and 52 control subjects) were used. The original images were compressed using JPEG or wavelet algorithms at a ratio of 10:1 or 20:1. Five radiologists interpreted these images and evaluated the image quality on a high-resolution CRT monitor. Observer performance was studied by receiver operating characteristic (ROC) analysis. RESULTS: There was no significant difference in the detection of cancers measuring 6 to 15 mm in uncompressed images and in those compressed by either of the algorithms, although the quality of images compressed at 20:1 with the wavelet algorithm was somewhat inferior. A lower diagnostic accuracy was noted using images compressed by the JPEG or wavelet algorithms at 20:1 in detecting lung cancers measuring 6 to 10 mm and cancers measuring from 6 to 15 mm with ground-glass opacity. CONCLUSION: Compression of low-dose CT images at a ratio of 10:1 using JPEG and wavelet algorithms does not compromise the detection rate of small lung cancers.

Algorithms↗

Detection of occult metastatic lymph nodes in the neck with gray-scale and power Doppler US.

PURPOSE: To determine the most accurate criterion for predicting malignancy of small cervical lymph nodes with gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS). MATERIAL AND METHODS: Findings of 69 pathologically verified cervical nodes (38 benign, 31 malignant) in 57 patients without wide echogenic hilum on GSUS that measured less than 10 mm in minimal axial diameter were prospectively studied. Minimal and maximal axial diameters, ratios of minimal to maximal axial diameters, and presence or absence of calcification or necrosis of the nodes were assessed. On PDUS, vascularity in the node was classified into 4 pattern groups. A logistic model was used to evaluate the significant factors for predicting malignancy. RESULTS: The logistic model revealed that the minimal axial diameter and vascularity patterns were the only significant factors for malignancy. Using the minimal axial diameter, a node larger than 8 mm showed the highest accuracy (73%) with 45% sensitivity and 93% specificity. Of the vascularity patterns, spotted or peripheral pattern had the highest accuracy (80%) with 61% sensitivity and 93% specificity. A combined criterion of the minimal axial diameter larger than 8 mm and spotted or peripheral pattern increased the accuracy to 82% and sensitivity to 77% but specificity decreased to 86%. CONCLUSION: A combined criterion of minimal axial diameter and vascular patterns was most accurate for diagnosing occult metastatic lymph nodes in the neck.

Adult↗

MR imaging of the lingual thyroid. Comparison to other submucosal lesions.

PURPOSE: To study MR findings for clues to the diagnosis of lingual thyroid. MATERIAL AND METHODS: MR findings and clinical and scintigraphic data of 5 cases of lingual thyroid were reviewed and the MR findings were compared to those of 16 cases of other submucosal lesions in the base of the tongue. RESULTS: Four of the 5 patients with lingual thyroid were women and all had hypothyroidism. MR imaging depicted lingual thyroid in the midline in the base of the tongue (n=5) and additional ectopic thyroid glands in the floor of the mouth (n=2) or between the right and left sternohyoid muscles (n=1). Ectopic thyroid glands appeared isointense or hyperintense relative to muscle tissue on T1-weighted images and showed slight or fair contrast enhancement. All glands had low to intermediate T2 signal, which was also seen in 1 case of non-Hodgkin's lymphoma and 1 case of adenoid cystic carcinoma. All ectopic thyroid glands had well-defined margins, whereas malignant tumors tended to have ill-defined margins and to invade the surrounding structures. All but the 5 cases of lingual thyroid had an MR-demonstrable thyroid gland in the normal cervical position. CONCLUSION: A well-defined mass of low-intermediate T2 signal in the midline base of the tongue, neither with invasive tendency nor with a cervical thyroid gland in the normal site on MR imaging, may strongly indicate lingual thyroid.

Adolescent↗

Postoperative chemoendocrine therapy for women with node-positive stage II breast cancer with combined cyclophosphamide, tamoxifen, and 1-hexylcarbamoyl-5-fluorouracil.

OBJECTIVE: To find out whether the addition of 1-hexylcarbamoyl-5-fluorouracil to a postoperative regimen of oral cyclophosphamide and tamoxifen improved the prognosis of carcinoma of the breast. DESIGN: Randomised controlled clinical trial. SETTING: 127 Institutions in Japan. SUBJECTS: 785 Patients with stage II carcinoma (palpable axillary nodes) who had total mastectomy and axillary clearance. INTERVENTIONS: The control group were given oral cyclophosphamide 50 mg/day and tamoxifen 20 mg/day for 2 years; the experimental group were given these drugs plus 1-hexylcarbamoyl-5-fluorouracil 300 mg/day for 2 years. RESULTS: There was no survival advantage (and more toxicity) in the experimental group, except in a subgroup with 1-3 axillary nodes involved. CONCLUSION: The advantage of triple chemotherapy in the subgroup must be substantiated by a new randomised trial confined to patients with 1-3 axillary nodes involved.

Administration, Oral↗

Prognostic significance of magnetic resonance findings in advanced papillary thyroid cancer.

We assessed the prognostic importance of magnetic resonance (MR) findings in locally advanced papillary thyroid cancer. MR findings, clinical data, and pathologic (and surgical) data for 66 patients, including 51 women and 15 men with a mean age of 57 years, who had primary surgery for papillary thyroid cancers were correlated with prognosis. Mean follow-up was 27.5 months (range, 5-117 months). Recurrence was seen in 18 patients (27%). In univariate analyses, age of 60 years or more (p = 0.0066), male gender (p = 0.0373), six MR findings (tumor size of > or = 4 cm ([p = 0.0002], ill-defined margins ([p < 0.0001], tumor extension of the trachea [p = 0.0337], carotoid artery [p = 0.0028]), esophagus [p < 0.0001], and lymph nodes [p = 0.0005]), and three pathologic findings (tumor extension of soft tissues [p = 0.0288], carotid artery [p = 0.0013], and esophagus [p < 0.0001]) had a significant adverse effect on disease-free survival. In multivariate analyses, tumor size (p = 0.0169) and nodal metastasis (p = 0.0393) determined on MR imaging and pathologic esophageal invasion (p = 0.0016) were the only significant independent variables. Esophageal invasion was accurately diagnosed with MR imaging (94% accuracy). MR findings may contain prognostic importance of locally advanced papillary thyroid cancer.

Adult↗

Breast biopsy for mammographically detected non-palpable lesions using a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit.

BACKGROUND: It is planned to start screening mammography throughout Japan in the near future. However, a minimally invasive biopsy procedure for mammographically detected non-palpable breast lesions is not available in almost all Japanese hospitals. It is crucial to develop a useful minimally invasive biopsy method which can be applied without difficulty. METHODS: Eighty-nine biopsies for 88 mammographically detected non-palpable breast lesions, consisting of 70 lesions with microcalcifications alone, eight masses without calcifications and 10 with both masses and microcalcifications, were performed using the combination of a vacuum-assisted biopsy device (Mammotome) and an upright-type stereotactic mammography unit. RESULTS: Microcalcifications were confirmed radiographically in the tissue obtained from 78 biopsies among 81 biopsies for the lesions with microcalcifications (96.3%). All the lesions without calcifications were considered to be biopsied successfully. Five patients complained of nausea or fainted during the localization or biopsy procedure and an additional patient suffered from hyperventilation syndrome. Five cases experienced mild subcutaneous bleeding in the breasts. CONCLUSIONS: The biopsy technique using the combination of a vacuum-assisted biopsy device and an upright-type stereotactic mammography unit is a cost-effective, safe and very useful method for mammographically detected non-palpable breast lesions. It is expected to be a standard method of biopsy for such lesions in many developed countries other than the USA. However, it is important to make the patients relaxed during the biopsy to prevent mental strain.

Adult↗

Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.

The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARgamma ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present time-course study was conducted to investigate possible modifying effects of a PPARgamma ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg / kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg / kg b.w.)-induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARgamma ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.

Animals↗

Head and neck lesions: characterization with diffusion-weighted echo-planar MR imaging.

PURPOSE: To evaluate whether apparent diffusion coefficients (ADCs) calculated from diffusion-weighted echo-planar magnetic resonance (MR) images can be used to characterize head and neck lesions. MATERIALS AND METHODS: Diffusion-weighted echo-planar MR imaging was performed with a 1.5-T MR unit in 97 head and neck lesions in 97 patients. Images were obtained with a diffusion-weighted factor, factor b, of 0, 500, and 1,000 sec/mm(2), and an ADC map was constructed. The ADCs of lesions, cerebrospinal fluid, and spinal cord were calculated. RESULTS: Acceptable images for ADC measurement were obtained in 81 (84%) patients. The mean ADC of malignant lymphomas, (0.66 +/- 0.17[SD]) x 10(-3) mm(2)/sec (n = 13), was significantly smaller (P <.001) than that of carcinomas. The mean ADC of carcinomas, (1.13 +/- 0.43) x 10(-3) mm(2)/sec (n = 36), was significantly smaller (P =.002) than that of benign solid tumors. The mean ADC of benign solid tumors, (1.56 +/- 0.51) x 10(-3) mm(2)/sec (n = 22), was significantly smaller (P =.035) than that of benign cystic lesions, (2.05 +/- 0.62) x 10(-3) mm(2)/sec (n = 10). No significant differences were seen in the mean ADC of cerebrospinal fluid and of spinal cord among four groups of lesions. When an ADC smaller than 1.22 x 10(-3) mm(2)/sec was used for predicting malignancy, the highest accuracy of 86%, with 84% sensitivity and 91% specificity, was obtained. CONCLUSION: Measurement of ADCs may be used to characterize head and neck lesions.

Adolescent↗

Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.

We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Adenosine Triphosphate↗

Generation of periventricular leukomalacia by repeated umbilical cord occlusion in near-term fetal sheep and its possible pathogenetical mechanisms.

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. However, pathogenetic mechanisms of PVL have not been fully understood. Although it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an association of umbilical cord occlusion with 'periventricular' white matter lesions. The purpose of this study is to determine whether umbilical cord occlusions could produce periventricular white matter lesions in fetal sheep and to examine how changes in fetal cardiovascular and metabolic variables are related to the induction of brain damage. Fourteen near-term fetal sheep underwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-min intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fetuses. According to the pattern of brain damage, we classified the fetal sheep into three groups: 5 fetuses with dominant lesions in the periventricular white matter (group I), 4 fetuses with brain lesions in the cerebral cortex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while group II showed systemic hypotension during cord occlusion. No significant differences in changes in pH, PaCO2, PaO2 and heart rate were found between the three groups. It is speculated that PVL might be produced by an association of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion.

Animals↗

Prevalence of emphysema in individuals who underwent screening CT for lung cancer in Nagano prefecture of Japan.

BACKGROUND: Screening for lung cancer with low-dose spiral computed tomography (CT) was carried out in Nagano prefecture in Japan. OBJECTIVE: To study the prevalence of emphysema in 7,847 individuals based on the Nagano spiral CT screening and to correlate the prevalence and severity of emphysema with various factors. METHODS: Spiral CT images with scan parameters of 120 kV, 50 mA, 10-mm collimation and a pitch of 2 obtained at full inspiration were retrospectively evaluated in 7,847 individuals. Emphysema was defined as the presence of low-attenuation areas in the lung parenchyma. Extent of emphysema was graded on a four-level scale and correlated with gender, age and smoking habits. RESULTS: There were 4,288 males and 3,559 females. Mean age of the subjects was 61 years; 45.8% of the participants were smokers. Overall prevalence of emphysema was 2.9%; the prevalence was significantly higher in males (5.0%) than in females (0.5%); it was also significantly higher in smokers, and increased with age. Emphysema was positively correlated with age, but there was no correlation with smoking indices. Emphysema was mostly mild and localized in the upper lung. The logistic model revealed that gender, age and smoking indices were significant factors for developing emphysema. CONCLUSIONS: Overall prevalence of emphysema was 2.9%. The prevalence was higher in males and in older people. Smoking was also related to a higher prevalence of emphysema but not to its severity.

Adult↗

Differential subcellular actions of ACE inhibitors and AT(1) receptor antagonists on cardiac remodeling induced by chronic inhibition of NO synthesis in rats.

Chronic inhibition of NO synthesis induces cardiac hypertrophy independent of systemic blood pressure (SBP) by increasing protein synthesis in vivo. We examined whether ACE inhibitors (ACEIs) enalapril and temocapril and angiotensin II type-I receptor antagonists (angiotensin receptor blockers [ARBs]) losartan and CS-866 can block cardiac hypertrophy and whether changes in activation of 70-kDa S6 kinase (p70S6K) or extracellular signal-regulated protein kinase (ERK) are involved. The following 13 groups were studied: untreated Wistar-Kyoto rats and rats treated with NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), D-NAME (the inactive isomer of L-NAME), L-NAME plus hydralazine, L-NAME plus enalapril (3 mg. kg(-1). d(-1)) or temocapril (1 or 10 mg. kg(-1). d(-1)), L-NAME plus losartan (10 mg. kg(-1). d(-1)) or CS-866 (1 or 10 mg. kg(-1). d(-1)), L-NAME plus temocapril-CS866 in combination (1 or 10 mg. kg(-1). d(-1)), and L-NAME plus rapamycin (0.5 mg. kg(-1). d(-1)). After 8 weeks of each experiment, ratios of coronary wall to lumen (wall/lumen) and left ventricular weight to body weight (LVW/BW) were quantified. L-NAME increased SBP, wall/lumen, and LVW/BW compared with that of control. ACEIs, ARBs, and hydralazine equally canceled the increase in SBP induced by L-NAME. However, ACEIs and ARBs equally (but not hydralazine) attenuated increase in wall/lumen and LVW/BW induced by L-NAME. The L-NAME group showed both p70S6K and ERK activation in myocardium (2.2-fold and 1.8-fold versus control, respectively). ACEIs inactivated p70S6K and ARBs inactivated ERK in myocardium, but hydralazine did not change activation of either kinase. Thus, ACEIs and ARBs modulate different intracellular signaling pathways, inhibiting p70S6K or ERK, respectively, to elicit equal reduction of cardiac hypertrophy induced by chronic inhibition of NO synthesis in vivo.

Angiotensin Receptor Antagonists↗

Right sylvian fissure subarachnoid hemorrhage has electrocardiographic consequences.

BACKGROUND AND PURPOSE: Abnormal ECG changes are frequently observed in patients with subarachnoid hemorrhage (SAH). Recently, evidence has been obtained that right insular cortex mediates sympathetic cardiovascular effects. We therefore assessed the laterality and location of SAH dominance in inducing cardiovascular changes as measured by ECG, blood pressure, and heart rate. METHODS: After exclusion of 11 SAH patients who died within 1 month after onset, we studied 118 consecutive patients. Data were obtained from records of blood pressure and pulse on admission. Abnormal ECG changes were determined from ECGs on admission and almost 1 month later. From brain CT scans performed immediately after admission, the amount of SAH in each of the 8 cisterns and fissures was measured semiquantitatively. RESULTS: Twenty-six patients had abnormal changes on admission ECG, while 92 patients did not. Systolic blood pressure, diastolic blood pressure, and the amounts of blood in the left ambient cistern, left suprasellar cistern, quadrigeminal cistern, right ambient cistern, right suprasellar cistern, right sylvian fissure, and the set of all cisterns were significantly greater in the group with ECG change than in the group without ECG change. Multivariate logistic regression analysis with stepwise method indicated that systolic blood pressure >160 mm Hg (P=0.0006) and the amounts of SAH in the quadrigeminal cistern (P=0.022) and right sylvian fissure (P=0.0019) were independently associated with abnormal ECG change. CONCLUSIONS: Cardiac consequences are possible in patients with massive right sylvian fissure SAH or when systolic blood pressure is >160 mm Hg.

Autonomic Nervous System Diseases↗