Search PubMed⌕ Search

Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 361 records · Page 20Linked to original sources

Chiral discrimination in the transport of ketoprofen and ibuprofen esters through an aqueous phase mediated by various serum albumins.

Serum albumins that act as carriers discriminated between enantiomers of alkyl esters of ketoprofen and ibuprofen in transport in the O/W/O (oil/water/oil) system using a U-shaped cell. The transport rate and the preferred enantiomer of the esters were substantially affected by pH, temperature, and species of albumin. Among five serum albumins studied, bovine serum albumin (BSA) showed the largest rate constant and rat serum albumin (RSA) manifested the highest enantioselectivity. Regarding enantiomer selectivity in transport overall, it is anticipated that the ester uptake step plays an important role for BSA, whereas the ester release is the key step for RSA.

Animals↗

Partial wavelet encoding: a new approach for accelerating temporal resolution in contrast-enhanced MR imaging.

We propose a new approach using wavelet encoding to improve temporal resolution in contrast-enhanced magnetic resonance (MR) imaging. Exploiting the unique property of wavelets localized in space and frequency, we construct an efficient encoding scheme to capture signal changes due to contrast agent uptake, which in general is spatially localized with low- and mid-range frequency components. On the basis of space-frequency analysis, we describe mathematical formulations of our method and discuss its theoretical advantages over Fourier-based phase-encoding methods (the keyhole and reduced-encoding imaging by generalized-series reconstruction [RIGR] techniques). The results obtained in computer simulations and a phantom study demonstrate the feasibility and practical advantages of our approach.

Computer Simulation↗

Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Adolescent↗

Complications associated with enteral nutrition using catheter jejunostomy after esophagectomy.

The present study was conducted on 78 patients, encountered over a 7-year period, who had a catheter-feeding jejunostomy placed at the time of thoracoabdominal esophagectomy for esophageal cancer. A broad-based attachment of the jejunal wall to the peritoneum at the place of entry of the catheter was used. Enteral nutrition was begun an average of 10 days after the operation, the caloric content was increased gradually, and the mean duration was 69 days. There were three patients who suffered from local skin erosion at the site of catheter entry, and seven who developed diarrhea and/or a feeling of abdominal fullness, but none of the patients showed any signs of peritonitis or ileus. The morbidity rates related to enteral nutrients and placement of the catheter jejunostomy were 8.9% and 3.8%, respectively. These findings demonstrate that a broad-based attachment of the jejunal wall to the peritoneum at the place of entry of the catheter is useful for preventing leakage or twisting of the jejunum, and for reducing the incidence and severity of the complications of catheter jejunostomy feeding.

Catheterization↗

Experimental analysis of the human perception threshold of a DC electric field.

To study the biological effects of extremely low frequency (ELF) electric fields, a fundamental study is conducted of the human perception threshold of an electric field. The perception threshold is measured with human subjects, and the results are analysed. It is clear that field perception is based on the movement of hair and not on other sensations. Variance in the perception threshold and its causes are investigated. The perception threshold decreases by almost 30% as the relative humidity increases from 50 to 90%. The perception threshold is also dependent on the physical condition (length and density) of the hair and the psychological condition (degree of awareness) of the subject. The dependence on these is much smaller than that on relative humidity. The cause of the gender difference in the threshold is ascribed to the difference in the physical condition of the hair. Through this study, some factors to be taken into account for the safety standard are made clear.

Adult↗

Potential of iodine-123 metaiodobenzylguanidine single-photon emission tomography to detect abnormal functional status of the pulmonary neuroadrenergic system in irradiated lung.

The potential of iodine-123 metaiodobenzylguanidine (MIBG) to detect functional abnormalities of the pulmonary neuroadrenergic system (PNS) in irradiated lung areas (ILAS) was preliminarily explored using single-photon emission tomography (SPET). The subjects included five healthy subjects and a total of 31 patients with peripheral-type lung cancer treated by radiation; 15 patients (group A) had received a dose of less than 36 Gy (mean +/- SD: 28.2 +/-6.2 Gy), and 16 patients (group B) had received a higher dose (mean +/- SD: 51.2 +/- 3.5 Gy) at the time of examination. MIBG SPET scans acquired 15 min and 3 h after injection were used to measure the MIBG uptake ratio (count ratio of the ILA to the contralateral non-ILA) and the clearance rate [percentage of (early counts - delayed counts)/early counts] from the ILAs without noticeable abnormal opacities on chest computed tomography scan. Lung perfusion changes were also assessed by technetium-99m macroaggregated albumin SPET. By contrast to the homogeneous MIBG uptake in the lungs of the healthy subjects, MIBG uptake was folcally decreased in correspondence with the ILAs in all patients, including 11 patients (73.3%) of group A with relatively preserved lung perfusion. The reduction MIBG uptake was significant (P<0.0001), and the MIBG clearance rate from the ILAs was also significantly faster than the clearance rates from the normal lungs and contralateral non-ILAs (both P<0.01). Group B patients showed significantly lower MIBG uptake and faster clearance from the ILAs than group A patients (P<0. 001 and P<0.05, respectively), although there was no significant difference in the clearance from the non-ILAs. Overall, MIBG uptake/clearance from the ILAs correlated significantly with the radiation dose in the 31 patients (r = -0.656; P<0.0001 and r = 0. 387; P<0.05, respectively). Perfusion changes were inversely correlated with the clearance from the ILAs (r = -0.432, P<0.05), but did not correlate with MIBG uptake. These preliminary results suggest that MIBG may have the potential to be a marker of abnormal functional status of the PNS produced by irradiation and may facilitate investigation of irradiation lung injury independently of morphological or lung perfusion changes.

3-Iodobenzylguanidine↗

A case of juvenile myelomonocytic leukemia with ocular infiltration.

We present a case of juvenile myelomonocytic leukemia (JMML) with ocular infiltration. A 1-month-old boy presented with myeloid precursors in peripheral blood and a white blood cell count >10x10(9)/l. His peripheral blood monocyte count was >1x10(9)/l, bone marrow blasts were <20%, and no Ph chromosome was identified. The boy also presented with hepatosplenomegaly, pallor, fever, and skin rash. We diagnosed this case as JMML, although hemoglobin F was within the normal range and no spontaneous colony growth was observed from peripheral blood mononuclear cells. Neither Epstein-Barr (EB) virus nor cytomegalovirus was detected by PCR in bone marrow aspirate or peripheral blood. The patient had several lesions into which JMML cells might have infiltrated, including skin, liver, spleen, oral cavity, right lung, sigmoid colon, and both eyes. To our knowledge, this is the first reported case of JMML with ocular involvement. Since infiltration of JMML cells into both eyes causes blindness, further consideration of the timing of bone marrow transplantation (BMT) in JMML is necessary.

Biopsy↗

Revascularization and new bone formation in heat-treated bone grafts.

Human imnmunodeficiency virus (HIV) infection is one of the possible serious complications associated with bone allografts. In order to prevent infection, grafted bone is sterilized by various treatments. Heat treatment has attracted attention as a simple and practical method. We carried out a histological study of the influence of heat treatment on autogenic bone grafts. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Three types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min, at 80 degrees C for 10 min, and at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the rabbits' ilium. One, 2, 4 and 8 weeks after grafting, we performed microangiography and prepared two types of samples: transparent and haematoxylin-eosin (H&E) stained. Then, using an image analyzer, we quantitatively measured revascularization and new bone formation in the grafted bone. The grafts heat-treated at 60 degrees C showed early and good revascularization and new bone formation, from 1 to 8 weeks. The grafts heat-treated at 80 degrees C showed relatively good revascularization and new bone formation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory revascularization and bone formation, less than 40% of control 8 weeks after grafting. Therefore, heat treatment at 60-80 degrees C does not seriously affect revascularization and new bone formation.

Animals↗

Development of full-length Trk B-immunoreactive structures in the hippocampal formation of the macaque monkey.

Distribution and morphological changes of cells containing the signal transducing neurotrophin receptor, full-length Trk B (fl-Trk B), were investigated in the hippocampal formation of the macaque monkey between embryonic day 140 and the adult stage. Western blot analysis showed that one main protein band, which migrated at 141 kDa, was detected in both the embryonic and adult hippocampal formation. In the pyramidal cells in CA1 and CA3 subfields, the subiculum, and the entorhinal cortex, fl-Trk B-immunoreactive dendrites were observable in the embryonic stage. In contrast, in the granule cells of the dentate gyrus, few dendrites were immunoreactive during embryonic and early developmental stages. This difference may be due to the later growth of the granule cells of the dentate gyrus. The existence of fl-Trk B immunoreactivity in the cell body and dendrites in the embryonic hippocampal neurons, suggests that BDNF and/or NT4/5 act on the hippocampal cells by autocrine/paracrine mechanisms. In the entorhinal cortex, fl-Trk B immunoreactivity became localized in the stellate cells in layer II and the pyramidal cells in layers III, V and VI in adulthood. This indicates that BDNF and/or NT4/5 are important for the maintenance of the projection neurons in the entorhinal cortex at the adult stage. The strongest fl-Trk B immunoreactivity in the hippocampal neurons occurred at postnatal month 4, corresponding to the period of greatest synapse production in the monkey hippocampus, suggesting that BDNF and/or NT4/5 with fl-Trk B may play a role in synapse formation in the monkey hippocampus.

Animals↗

Ret/PTC3 is the most frequent form of gene rearrangement in papillary thyroid carcinomas in Japan.

Rearrangements of the RET and TRK proto-oncogenes, which generate fusion oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations. To determine the spectrum of gene rearrangements in Japanese patients, we systematically examined 40 papillary thyroid carcinomas for all possible types of gene fusion events involving RET or TRK genes. RET rearrangements were found in ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3 in six, and a novel RET rearrangement in the remaining patient. In this last patient, the 5' novel sequence was fused in-frame to the RET amino acid sequence; thus, the fusion gene may encode a protein with a RET kinase domain at the carboxy terminus. The RET gene was fused to 5' donor sequences at the beginning of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found in this panel of carcinomas. Our results indicated that constitutive activation of the RET by gene rearrangement is a frequent mechanism of papillary thyroid carcinogenesis in Japanese adults.

Adult↗

Can beta-blocker therapy be withdrawn from patients with dilated cardiomyopathy?

BACKGROUND: It has yet to be determined whether withdrawing beta-blocker therapy from patients with dilated cardiomyopathy (DCM) is safe. METHODS: The influence of tapering and then stopping metoprolol was clarified in 13 patients with DCM who had been receiving this agent for >/=30 months. RESULTS: Seven of the 13 patients deteriorated, including 4 who died suddenly or of congestive heart failure during the 4-month period after metoprolol cessation. CONCLUSION: In patients with DCM in whom beta-blocker therapy is effective, withdrawal of these agents may lead to death. We conclude that beta-blockers should not be stopped in this patient group.

Adrenergic beta-Antagonists↗

Interleukin-10 (IL-10) augments allograft arterial disease: paradoxical effects of IL-10 in vivo.

Interleukin-10 (IL-10) is an anti-inflammatory helper T cell type 2 (Th2) cytokine that modulates Th1-type cytokine production. Graft arterial disease (GAD) is a vascular obliterative process mediated via the Th1 cytokine interferon-gamma (IFN-gamma); allografts in IFN-gamma-deficient animals do not develop GAD. We investigated the effect of IL-10 and anti-IL-10 on GAD in murine heart transplants and whether anti-IL-10 reestablishes GAD in IFN-gamma-deficient hosts. Major histocompatibility complex class II-mismatched hearts were transplanted for 8 weeks into wild-type or IFN-gamma-deficient mice. In one set of experiments, wild-type hosts received daily administration of phosphate-buffered saline (PBS) or increasing IL-10; in a subsequent set of experiments, wild-type hosts received weekly PBS, rat IgG, or anti-IL-10 monoclonal antibody; IFN-gamma-deficient recipients received weekly PBS or anti-IL-10 monoclonal antibody. Explanted allografts were assessed for parenchymal rejection and GAD, cytokine profiles, and adhesion/costimulatory-molecule expression. Exogenous IL-10 resulted in increased Th2-like cytokine production; nevertheless, it exacerbated parenchymal rejection and GAD and increased CD8(+) infiltration. Anti-IL-10 did not significantly affect the extent of rejection or GAD, cytokine profiles, or immunohistology of the allografts in wild-type hosts. Adhesion molecule (CD54 and CD106) expression was not diminished by IL-10 treatment, and costimulatory-molecule (CD80 and CD86) expression was augmented by administration of exogenous IL-10. Allografts in IFN-gamma-deficient recipients showed mild rejection and no GAD, regardless of anti-IL-10 treatment. IL-10 in vivo thus has markedly different effects than predicted from in vitro experience. Although allografts develop Th2-like cytokine profiles treatment with IL-10 causes exacerbated rejection and GAD.

Animals↗

Neuroprotective effects of a dihydropyridine derivative, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarbox ylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (CV-159), on rat ischemic brain injury.

CV-159, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic++ + acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester, is a dihydropyridine derivative that blocks the L-type Ca2+ channel and inhibits the calmodulin (CaM)-dependent pathway. In this study, we examined the effects of CV-159 on rat ischemic brain injury. CV-159 (5 and 10 mg/kg, p.o.) gave significant protection against delayed neuronal death in the hippocampal CA1 region after 15-min transient forebrain ischemia. In contrast, the Ca2+ antagonists nicardipine (1 and 10 mg/kg, p.o.) and nifedipine (1 mg/kg, i.p.) and the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7, 500 ng, i.c.v.) had no effect on this hippocampal neuronal death. CV-159 also diminished the size of the brain infarct after permanent middle cerebral artery (MCA) occlusion, although physiological variables, including regional cerebral blood flow, were not affected. The increase in the water content of the infarcted cortex induced by MCA occlusion was significantly reduced by CV-159. On the other hand, neither nicardipine nor nifedipine affected the brain infarct size, volume or increased water content induced by MCA occlusion, as previously reported (A. Sauter and M. Rudin, Am. J. Hypertens. 4 121S-127S, 1991). These findings indicate that Ca2+ antagonists, such as nicardipine and nifedipine, and W-7 have no effect on rat ischemic brain injury. The results suggest that CV-159 protects against ischemic brain injury. This might be mediated by both blocking the L-type Ca2+ channel and inhibiting CaM-dependent function via Ca2+/CaM binding at a different binding site from that of W-7 to CaM (H. Umekawa, K. Yamakawa, K. Nunoki, N. Taira, T. Tanaka, and H. Hidaka, Biochem. Pharmacol. 37 3377-3381, 1988).

Animals↗

Effect of AA-2414, a thromboxane A2 receptor antagonist, on airway inflammation in subjects with asthma.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways. The chemokines are potent chemoattractants for eosinophils and other types of cells associated with allergic inflammation. AA-2414, a new thromboxane A2 receptor antagonist, reduces bronchial hyperresponsiveness in asthmatic subjects, but its mechanism of action is unclear. OBJECTIVE: We tested the hypothesis that the beneficial effects of AA-2414 in asthma result from reduction in the number of inflammatory cells infiltrating the airway associated with inhibition of chemokine release. METHODS: We studied bronchial biopsy specimens from 31 asthmatic subjects before and after oral treatment with AA-2414 (80 mg/day) or matched placebo for 4 months in a double-blind manner. Biopsy specimens were examined by immunohistochemistry. Each subject recorded symptom score and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. RESULTS: After treatment, significant improvements in symptom score (P <.05), PEF (P <.01), diurnal variation of PEF (P <.01), and bronchial responsiveness (P <.01) were observed in the AA-2414 group compared with the placebo group. These improvements were accompanied by a significant decrease in the number of submucosal EG2(+) eosinophils (P <.05). There was also a reduction in the number of cells expressing RANTES (P <.05) and macrophage inflammatory protein (MIP)-1alpha (P <.05) in the epithelium and of cells expressing monocyte chemotactic protein-3 (P <.01), RANTES (P <.05), MIP-1alpha (P <.01), and eotaxin (P <.01) in the submucosa in the AA-2414 treatment group. A significant correlation was found between the number of EG2(+) eosinophils and numbers of monocyte chemotactic protein-3(+) (rs = 0.52, P <.005), MIP-1alpha+ (rs = 0.34, P <.05), and eotaxin+ cells (r s = 0.47, P <.01) in the submucosa. There was a significant negative correlation between the increase in bronchial responsiveness and the change in number of submucosal EG2(+) cells (rs = -0.65, P <.001). CONCLUSIONS: These findings suggest that AA-2414 treatment of patients with asthma may inhibit activated eosinophil infiltration in part by modulating the expression of chemokines in bronchial tissues.

Adolescent↗

Detection of translocation 8;21 on interphase cells from acute myelocytic leukemia by fluorescence in situ hybridization and its clinical application.

To detect a translocation (8;21)(q22;q22) in interphase cells by fluorescence in situ hybridization (FISH), we investigated three probe combinations: single-color hybridization with two cosmid probes (cY8 and cY3), single-color hybridization with four cosmid probes (cY8, cY3, cY107, and cYR4), and dual-color hybridization with two cosmid probes (cY107 and cYR4) from the AML1 gene flanking or overlapping the breakpoint region. Over 95% of nuclei gave sufficient signals in all three probe combinations, and the detection rates were not statistically different among them. Among 18 patients examined at diagnosis, 12 with t(8;21) were also monitored for the number of residual leukemic cells after chemotherapy or bone marrow transplantation (BMT). There were some discrepancies between morphology and genetic (especially FISH) results at partial, or even complete remission. As leukemic cells with t(8;21) can maturate, morphological assessment alone is insufficient to evaluate the residual leukemic cells. Interphase FISH provided more precise information about the clinical status of patients with an 8;21 translocation after treatment.

Adult↗

Effects of abdominal belts on intra-abdominal pressure, intra-muscular pressure in the erector spinae muscles and myoelectrical activities of trunk muscles.

OBJECTIVE: To evaluate the effects of abdominal belts on lifting performance, muscle activation, intra-abdominal pressure and intra-muscular pressure of the erector spinae muscles. DESIGN: Simultaneous measurement of intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles was performed during the Valsalva maneuver and some isometric lift exertions. BACKGROUND: While several hypotheses have been suggested regarding the biomechanics of belts and performance has been found to increase when lifting with belts, very little is known about the modulating effects on trunk stiffness. At present, there is no reason to believe that spine tolerance to loads increases with belts. METHODS: An abdominal belt designed for weightlifting was used. Intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and myoelectric activities of trunk muscles (erector spinae, rectus abdominis and external oblique) were measured simultaneously during the Valsalva maneuver as well as three types of isometric lifting exertions (arm, leg and torso lift). A paired t-test was used to analyze for statistical differences between the two conditions (without-belt and with-belt) in intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and in the integrated EMG of the trunk muscles. RESULTS: Intra-muscular pressure of the erector spinae muscles increased significantly by wearing the abdominal belt during Valsalva maneuvers and during maximum isometric lifting exertions, while maximum isometric lifting capacity and peak intra-abdominal pressure were not affected. Integrated EMG of rectus abdominis increased significantly by wearing the abdominal belt during Valsalva maneuvers (after full inspiration) and during isometric leg lifting. CONCLUSIONS: Wearing abdominal belts raises intra-muscular pressure of the erector spinae muscles and appears to stiffen the trunk. Assuming that increased intra-muscular pressure of the erector spinae muscles stabilizes the lumbar spine, wearing abdominal belts may contribute to the stabilization during lifting exertions.

Abdominal Muscles↗

Bronchial arterial infusion with cisplatin followed by irradiation successfully treats recurrent stage IVb thymic large cell carcinoma.

A 48-year-old female was treated with three courses of chemotherapy combined with bronchial arterial infusion (BAI) with cisplatin and intravenous drip infusion with bleomycin and vinblastine for a recurrent thymic large cell carcinoma seen 1 year after the initial operation. The patient had subsequently undergone irradiation. No sign of recurrence has been noted with a follow-up period of 6 years after the initial operation. This is the first reported case of survival from recurrence of thymic large cell carcinoma. BAI combined with irradiation should be considered as one of the treatments of choice in a recurrence like we present herein.

Antineoplastic Agents↗