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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 865 records · Page 48Linked to original sources

Lock method using sodium hydroxide solution to clear occluded central venous access devices.

Occlusion of central venous access devices (CVADs) is not an uncommon problem duringlong-term parenteral nutrition. A number of techniques have been developed to deal with obstructed CVADs. This study investigated the effectiveness of the sodium hydroxide (NaOH) lock method for gradual CVAD occlusion. When a progressively declining flow was noticed, 0.1 N NaOH solution was injected into the CVAD and locked. Nineteen CVAD occlusions in 11 home parenteral nutrition patients were treated Sixteen of 19 trials cleared the occlusions, whereas 3 of 19 failed. One of the failures was due to a mechanical occlusion and the other two were able to be restored by using ethanol. There were no significant complications. The benefits of this method are: (1) a shorter treatment time and a lower dose than NaOH infusion therapy, (2) it does not require hospital admission and (3) it does not result in bursting of the catheter.

Journal Article↗

Effective immunoglobulin therapy for brief tonic seizures in methylmalonic acidemia.

We report on a patient with methylmalonic acidemia (MMA). He experienced a metabolic acidosis attack at 3 weeks of age. He immediately received peritoneal dialysis and exchange transfusion, and recovered from the attack. His MMA phenotype was mut0. Dietary therapy (strict protein restriction) was found to be effective in preventing further attacks, and he had mild hypotonia and impaired psychomotor development. At 9 months of age, he developed brief tonic seizures, which showed polyspike bursts under EEG. His psychomotor development continued to deteriorate. However, intravenous administration of immunoglobulin (200 mg/kg/day for 5 consecutive days) had a dramatic effect; his seizures disappeared and his psychomotor development improved.

Amino Acid Metabolism, Inborn Errors↗

Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing.

OBJECTIVES: We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing. BACKGROUND: Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina. METHODS: Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bull's-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bull's-eye was defined as an area > 2 SD below normal. An abnormal regional washout rate was defined as < 0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bull's-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement. RESULTS: Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bull's-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis. CONCLUSIONS: Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.

3-Iodobenzylguanidine↗

Implant site influence on arterial prosthesis healing: a comparative study with a triple implantation model in the same dog.

PURPOSE: The purpose of this study was to develop a cost-effective canine graft healing model that gives information on various implant sites and controls for variable factors between graft locations and between animals and to compare the influence of implant site (retropleural, retroperitoneal, and subcutaneous areas) on arterial graft healing in the same subject under such controlled study conditions. METHODS: Five mongrel dogs were studied for 8 weeks, and one was studied for 3 years. Each received three porous Dacron grafts during the same surgery: a carotid-femoral bypass (C-FB) and interposition grafts in the descending thoracic aorta and abdominal aorta. To produce comparable shear stress calibers of the C-FB and abdominal aorta grafts were 2 mm less than those of the descending thoracic aorta, and a distal arterio-venous fistula was created to further increase the C-FB flow. For comparable blood aggregation status platelet aggregation was preevaluated and adjusted with antiplatelet agents. Graft flow surfaces were assessed for thrombus-free surface and endothelial-like cell coverage scores. Tissue samples were studied with hematoxylin-eosin, factor VIII/ von Willebrand factor, smooth muscle alpha-actin staining, and scanning electron microscopy and transmission electron microscopy. RESULTS: All grafts were patent. Shear stress for the three grafts and platelet aggregation among the study subjects were comparable. Healing of descending thoracic aorta and abdominal aorta grafts was similar, but C-FB healing was slow, incomplete, and uneven, with a high incidence of seroma. Eight-week and 3-year results were comparable. CONCLUSIONS: This model gives broad healing information about the areas where grafts are often implanted in humans. Eight weeks appears to be a sufficient period to reflect basic and general healing characteristics. Grafts heal better in the retropleural and retroperitoneal areas than in the subcutaneous tissues.

Animals↗

The relationship of hyperinsulinemic state to left ventricular hypertrophy, microalbuminuria, and physical fitness in borderline and mild hypertension.

The relationship of the hyperinsulinemic state to left ventricular hypertrophy, left ventricular geometric patterns, microalbuminuria, and physical fitness were studied in 52 middle-aged unmedicated men with borderline and mild hypertension. Left ventricular mass index and relative wall thickness were assessed by echocardiography. Physical fitness was determined by symptom-limited maximal treadmill stress testings. The urinary concentration of microalbumin and C-peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary C-peptide excretion rate was correlated with left ventricular mass index (r = 0.46), relative wall thickness (r = 0.41), treadmill time (r = -0.35), normalized treadmill time (r = -0.52), systolic blood pressure at peak exercise (r = 0.29), and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression analysis identified the left ventricular mass index, the 24-h urinary albumin excretion, and the normalized treadmill time as variables in the equation for the 24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in patients with borderline and mild hypertension.

Adult↗

Toxic effects of arsenic (As3+) and other metal ions on acute promyelocytic leukemia cells.

Since arsenic compounds reportedly induced complete remission in patients with acute promyelocytic leukemia (APL) in China, we studied the in vitro effect of metal ions including As3+, As5+, Cd2+, Ga3+, Ge4+, Hg2+, Se4+, and Zn2+ on myeloid cell lines. One-tenth microM As3+ caused growth suppression and morphological changes resembling differentiation in NB4 cells, but did not induce the maturation-markers, CD11b, CD14 and NBT-reductase. More than 1 microM As3+ caused the time- and dose-dependent apoptosis of NB4 cells. Other metal ions at the same concentrations induced neither morphological changes nor apoptosis in myeloid cell lines including NB4, whereas Cd2+, Ga3+, and Hg2+ induced moderate and non-specific growth suppression. All-trans retinoic acid (ATRA)-resistant NB4 cells were similarly sensitive to As3+. Among the clinical leukemia samples, As3+ was selectively toxic to APL cells regardless of ATRA-sensitivity. These findings suggest that APL cells are sensitive to As3+, and that As3+ acts on APL cells via a different pathway than ATRA.

Apoptosis↗

Report on a patient with paroxysmal cold hemoglobinuria.

Antibodies against the human blood group P antigen (anti-P alloantibodies) agglutinate phenotype P1 and P2 erythrocytes treated with papain at 4 degrees C but not phenotype PK and p erythrocytes. This condition is referred to as an autoimmune disease of paroxysmal cold hemoglobinuria (PCH), and the anti-P specificity is found in the cold hemagglutinins. Serum from a patient suspected to be suffering from PCH by the cold auto-agglutination properties was tested for anti-P specificity, using papain-treated O blood group erythrocytes. The serum-mediated hemagglutination and the serum and complement-mediated immunohemolysis were inhibited by globoside (P antigen GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide) and Forssman glycosphingolipid (GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide). Therefore, we concluded that she had PCH. She was completely cured 6 months later.

Female↗

Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.

To clarify the pathogenesis of ossification of the ligamentum flavum (OLF), we examined the expression and localization of bone morphogenetic proteins (BMPs) and their receptors (BMPRs) in the ligamentum flavum of the patients with OLF by immunohistochemical staining and compared them with staining patterns in control patients. The BMPRs appeared extensively in mature and immature chondrocytes around the calcified zone and in spindle-shaped cells and round cells in the remote part from ossified foci in examined tissue of OLF. The ligands for BMPRs, BMP-2/-4 and osteogenic protein-1 (OP-1)/BMP-7, colocalized in OLF patients. In the control cases, expression of BMPs and BMPRs was observed around the calcified zone at the insertion of the ligamentum flavum to the bone, and limited expression was found in the smaller range. Thus, the expression profile of BMPs and BMPRs in OLF patients was entirely different from the control patients, suggesting that BMPs may be involved in promoting endochondral ossification at ectopic ossification sites in OLF, and that ossification activity is continuous in these patients.

Activin Receptors↗

Case-control study of risk factors for hip fractures in the Japanese elderly by a Mediterranean Osteoporosis Study (MEDOS) questionnaire.

A case-control study of hip fracture among the Japanese elderly was carried out in order to assess the risk factors for fractures. On the data obtained from 249 cases and 498 controls matched with ethnicity, sex, age, and residential area, significant risk factors on the lifestyle by multivariate analyses included drinking more than three cups of coffee daily, living in rural areas in the past, sleep disturbance, stroke with hemiplegia, and sleeping in a (Western-type) bed. In contrast, in addition to possession of a large body mass index, moderate alcohol intake and eating fish appeared to be associated with a reduced risk of hip fracture. In conclusion, some traditional Japanese lifestyle characteristics may prevent hip fractures among the Japanese elderly.

Aged↗

High seropositivity of anti-CagA antibody in Helicobacter pylori-infected patients irrelevant to peptic ulcers and normal mucosa in Japan.

CagA-positive H. pylori is reported to be associated with gastroduodenal disease in Western countries. To evaluate the relationship between CagA and disease, cloning of the entire cagA gene (3771 bp), insertion of a partial fragment (1272 bp) into an expression vector, purification of the recombinant protein, production of an antibody against the recombinant CagA protein through rabbits, and use of the recombinant CagA protein as an antigen, detection of the anti-CagA antibody by western blotting were all performed. Sera of 132 H. pylori-infected patients undergoing endoscopy were studied. Anti-CagA antibodies were detected in 90%, 87%, 90%, 94%, and 93% of patients with gastric ulcer (N = 34), duodenal ulcer (N = 27), chronic gastritis (N = 31), gastric cancer (N = 17), and normal mucosa (N = 15), respectively. High seropositivity of anti-CagA antibody even in individuals with normal mucosa indicated that CagA may not be a unique marker for disease by H. pylori infection in Japan.

Amino Acid Sequence↗

Genetic polymorphism of cat (Felis catus) plasma orosomucoid.

Genetic polymorphism of orosomucoid (ORM) was observed in 22 breeds of cats (Felis catus) using isoelectric focusing (pH 4.0-6.5) of desialylated plasmas followed by immunoblotting with rabbit antiserum to human ORM. From a total of 943 plasma samples examined, 15 phenotypes were identified and family studies demonstrated an inheritance of five codominant alleles, ORMA, ORMB, ORMC, ORMD, and ORME, at a single locus.

Alleles↗

Induction of tumour differentiation and apoptosis and LeY antigen expression in treatment with differentiation-inducing agent, vesnarinone, of a patient with salivary adenoid cystic carcinoma.

A patient with locally-advanced submandibular adenoid cystic carcinoma with poorly differentiated solid type, was treated with differentiation-inducing agent, vesnarinone, per os at a dose of 60 mg/day daily for 8 weeks. The vesnarinone administration caused marked regression of the tumour. In addition to conversion into the well-differentiated tubular type from the poorly differentiated solid type, the induction of apoptosis and LeY antigen was observed in the treated tumour. These findings indicate that vesnarinone might be a useful therapeutic agent for treatment of salivary cancer. Since we found the new expression of LeY antigen in the well-differentiated tubular lesion in the salivary adenoid cystic carcinoma treated with vesnarinone, we examined the LeY antigen expression in relation to tumour differentiation in five cases of salivary adenoid cystic carcinoma. Consequently, tissue sections from all of the adenoid cystic carcinoma examined showed no positive LeY staining, except for some areas in the tumour lesion with the tubular pattern including the histologically normal-appearing tissue adjacent to the tumour tissue. These findings suggest that there is the intimate relationship between the LeY antigen expression and tumour differentiation in human salivary adenoid cystic carcinoma.

Journal Article↗

Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: association of the therapeutic effect with differentiation and apoptosis in the cancer cells.

Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone. Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy. Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma. When we examined immunohistochemically the expression of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate (p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05). From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells. In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.

Journal Article↗

The treatment with differentiation- and apoptosis-inducing agent, vesnarinone, of a patient with oral squamous cell carcinoma.

A patient with histopathological recurrent oral cancer with well-differentiated squamous cell carcinoma, was treated with differentiation- and apoptosis-inducing agent, vesnarinone, per os at a dose of 180 mg/day for 56 days and then at a dose of 60 mg/day for 93 days. The vesnarinone administration caused complete remission of the tumour. It has been found by immunohistochemical staining and PCR-SSCP analysis that the recurrent tumour has wild type p53 gene and relative high level of LeY expression as well as DNA fragmentation in the cancer cells, as assessed by nick-end labelling. These findings suggest that the cure of oral squamous cell carcinoma observed in this case might be associated with induction of differentiation and apoptosis of cancer cells by vesnarinone.

Journal Article↗

Functional expression and germline transmission of a human chromosome fragment in chimaeric mice.

Human chromosomes or chromosome fragments derived from normal fibroblasts were introduced into mouse embryonic stem (ES) cells via microcell-mediated chromosome transfer (MMCT) and viable chimaeric mice were produced from them. Transferred chromosomes were stably retained, and human genes, including immunoglobulin (Ig) kappa, heavy, lambda genes, were expressed in proper tissue-specific manner in adult chimaeric tissues. In the case of a human chromosome (hChr.) 2-derived fragment, it was found to be transmitted to the offspring through the germline. Our study demonstrates that MMCT allows for introduction of very large amounts of foreign genetic material into mice. This novel procedure will facilitate the functional analyses of human genomes in vivo.

Animals↗

Mutant AF-2 domain of PML-RARalpha in retinoic acid-resistant NB4 cells: differentiation induced by RA is triggered directly through PML-RARalpha and its down-regulation in acute promyelocytic leukemia.

To study the molecular mechanism of the differentiation induced by retinoic acid (RA) in acute promyelocytic leukemia (APL), we established a new RA-resistant NB4 subline, NB4/RA. The NB4/RA cells were neither differentiated by a single or a combination of RA isoforms, nor by the addition of clotrimazole (P450-inhibitor) or interferon gamma. However, the combination of RA and 8-(4-chlorophenylthio) adenosine cyclic 3',5'-monophosphate (a cAMP analog, 8-CPT-cAMP) induced differentiation. Immunostaining of NB4/RA cells using anti-PML antibody showed a microgranular pattern which was not restored even by the combination of RA and 8-CPT-cAMP, whereas the microgranular pattern in NB4 cells was rapidly restored to the normal speckled pattern by RA. Western blot analysis revealed that RA alone or the combination with 8-CPT-cAMP did not down-regulate PML-RARalpha in NB4/RA cells, which was in contrast to NB4 cells. The PML-RARalpha fusion gene and transcript in NB4/RA cells were conserved as well as the RARalpha gene and transcripts. Sequence analysis of the PML-RARalpha transcript in NB4/RA cells indicated a Pro (CCG) to Leu (CTG) mutation at codon 900 (type L) in AF-2 domain, while the RARalpha transcript had a normal sequence. These data suggest that differentiation of APL by RA is triggered directly through PML-RARalpha, and is associated with its degradation. Furthermore, there might be another mechanism of differentiation which does not require the down-regulation of PML-RARalpha and the restoration of the PML-staining pattern.

Amino Acid Sequence↗

Ultrastructure of quick-frozen and freeze-substituted chick osteoclasts.

For comparison with chemically fixed osteoclasts, we prepared chick osteoclasts by quick freezing followed by freeze-substitution. In spite of technical difficulties this demonstrated that osteoclasts can be satisfactorily frozen in situ by the metal contact method. Ultrastructural differences were revealed between conventional fixation and quick freezing. Compared with conventional fixation, the quick freezing method appeared to improve preservation: (1) a discrete trilaminar plasma membrane and other intracellular membranes showed a smooth profile without undulation or rupture; (2) cytoskeletal components appeared to be clearer, straighter, and more numerous; (3) the interior of the ruffled finger contained interconnected lattice structures whereas highly organised microfilaments were seen in the clear zone; (4) well developed tubulovesicular structures (TVSs) that branched or anastomosed with each other were revealed in the cytoplasm; (5) the contents of intracellular membrane systems including the nuclear envelope, endoplasmic reticulum, and Golgi complex were stained to a various extent; (6) vesicles and vacuoles were much smaller, round and well-defined with electron-dense contents; (7) crystalline structures were seen at the extracellular channels of the ruffled border, in the lumen of TVSs, and in vesicles; (8) in some instances mitochondrial granules were visible; (9) within the resorptive lacuna, osteoclasts adhered to the degraded bone matrix without any intervening empty space.

Animals↗