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Biomedical subjects

Y Abe

Publications and source records attributed to Y Abe.

At least 145 records · Page 8Linked to original sources

[The role of ischemic preconditioning in off-pump CABG: is it really necessary to accomplish scrupulous ischemic preconditioning?].

In an attempt to avoid the deleterious effect of cardiopulmonary bypass, off-pump coronary artery bypass grafting has been rediscovered and spread. We often accomplish the ischemic preconditioning (IP) in off-pump CABG. IP is the phenomenon in which sublethal episode of myocardial ischemia result in increased tolerance to a later, potentially lethal, episode of ischemia. To evaluate the cardioprotective effect of IP and an ATP-sensitive potassium channel (KATP) opener, oxidative radical scavenger, 43 clinical cases were examined. The myocardial tissue oxygen saturation was measured by near-infra red spectroscopy during IP. Twelve cases were subjected to accomplish simple IP (5 min x twice), and 29 cases received pharmacological IP (administrated allopurinol preoperatively and nicorandil intraoperatively; 3 min x once). The result showed that the tissue oxygen of pharmacological IP group is superior to that of simple IP group. The concomitant use of IP and KATP opener, oxidative radical scavenger both ameliorated cardiac dysfunction during the ischemia in anastomotic occlusion of the coronary artery, and improved the postischemic functional recovery. These results suggest that we would be able to decrease both duration and the number of times of IP by using KATP opener and oxidative radical scavenger.

Allopurinol↗

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Angiogenesis Inhibitors↗

[Pulmonary hypertension associated with refractory hyperthyroidism: a case report].

A 25-year-old woman was admitted to our hospital with goiter. The diagnosis was Grave's disease. Diagnostic transthoracic echocardiography revealed a hyperdynamic stage of the heart with right ventricular dilation. Doppler echocardiography showed mild to moderate tricuspid regurgitation and elevated systolic right ventricular pressure. Right heart catheterization revealed high cardiac output (9.49 l/min) and pulmonary hypertension (57 mmHg) with increased pulmonary vascular resistance and total pulmonary resistance. No intracardiac shunts were detected. Since neither thiomazole nor propylthiouracil was effective and both caused side effects, she underwent subtotal thyroidectomy. After the surgery, pulmonary hypertension improved and cardiac output normalized, but without normalization of pulmonary vascular resistance and total pulmonary resistance. Reversible pulmonary hypertension may occur in patients with hyperthyroidism. Increased pulmonary blood flow and sustained high pulmonary artery resistance were suspected as the causes of pulmonary hypertension. In addition, pulmonary endothelial dysfunction as a result of sustained increased pulmonary blood flow could be another cause of pulmonary hypertension.

Adult↗

[Two-step tuberculin testing and BCG vaccination in the personnel of a medical and pharmaceutical university].

In an attempt to cope with recent nosocomial spread of tuberculosis, the tuberculin test with a 0.05 microgram of 0.1 ml intradermal dose of purified protein derivative was performed by a two-step procedure on the personnel of a medical and pharmaceutical university, followed by BCG vaccination for non-reactors in the second test. The second test was repeated after two weeks in all but those with erythema of 10 mm or more in diameter associated with double erythema, vesicle formation, and/or necrosis on the initial testing. The first test was done in a total of 935 participants (73% of all personnel) with a median age of 37 (range, 21-67) years. The rate of participation, by occupation, in the hospital personnel ranged from 63% (183/289) for doctors to 98% (351/358) for nurses. The size of erythema showed a unimodal distribution with a peak in the range of 10-19 mm, with a median of 20 mm (range, 0-102). Reactions below 9 mm, which are interpreted as negative, were found in 16% of all participants, and those above 30 mm in 35%. Among participants aged 20-49 years, especially among nurses, reactions tended to be larger with increasing age. Among 539 participants undergoing repeated testing, reactions between the first and second tests correlated well, showing a median increase in size of 10 mm (range, -43-(+)70) on retesting. Reactions above 30 mm associated with an increase in size larger than 20 mm, among those initially below 29 mm in diameter, were observed in 28% of those retested. Adverse reactions such as vesicle formation with or without hemorrhage, or lymphangitis occurred in 2.5% of all participants on the initial testing and in 1.5% on the retesting, with the highest frequency seen in those aged 30-39 years. BCG was administered to 26 of the 49 participants with a negative reaction on the second test. All vaccinees with a median age of 30 (range, 21-46) years showed tuberculin conversion after two months without developing Koch's phenomenon soon after the vaccination. Incidentally, it is desirable that two-step tuberculin testing such as that in the present study should also be performed using the diameter of induration, particularly that measured transversely, since erythema is not used in any other country than Japan.

Adult↗

[Gadolinium-enhanced MR imaging, T2-weighted MR imaging, and transurethral ultrasonography].

PURPOSE: To assess the value and problems of dynamic gadolinium-enhanced MR imaging, T2-weighted MR imaging, and transurethral ultrasonography(TUUS) in staging of urinary bladder cancer. MATERIALS AND METHODS: Dynamic gadolinium-enhanced MR imaging and FSE T2-weighted MR imaging of 64 patients with urinary bladder cancer who subsequently had surgery were retrospectively reviewed and compared with TUUS findings. RESULTS: Specificity for muscular invasion was 90.5% with TUUS, significantly better than with dynamic MR imaging (64.9%) (p < 0.05). The rates of overestimation of superficial cancer(pT1) with dynamic MRI and T2-weighted MR imaging were 35.1%(13/37) and 24.3%(9/37), respectively. The staging accuracy of invasive cancer(pT2 or over) was 85.2% with dynamic MR imaging, which was better than the rate of 75.0% achieved with T2-weighted MR imaging. CONCLUSION: Although TUUS was a better modality for diagnosing superficial cancer(pT1), dynamic MR imaging was found to be better for diagnosing invasive(pT2 or over) cancer.

Adolescent↗

[Protein S deficiency in three patients with thrombosis].

Protein S (PS) deficiency, which is caused by various factors including congenital and acquired disorders, is a risk factor for thrombophilia. We described 3 patients with different backgrounds, who all exhibited PS deficiency. The first patient was a 47-year-old woman who suffered from frequent cerebral infarctions, deep-vein thrombosis (DVT) of her lower extremities, and pulmonary thromboembolism. Her son suffered from skin necrosis due to PS deficiency and both had the same mutant allele of the PS gene. The second patient was a 50-year-old woman who experienced a cold sensation in her fingers. Her relatives had a history of cerebrovascular disease. No mutation was detected in her PS gene. The third patient was a 27-year-old man with antiphospholipid antibody. He suffered from thrombocytopenia, skin necrosis, DVT of his lower extremities, and pulmonary thromboembolism. A mutation was identified in the steroid hormone-binding globulin-like (SHBG) domain of his PS gene. Neither his parents nor siblings had a history of thrombosis. The mutations found in the first and third patients were both missense mutations in the SHBG domain that have not been reported previously. The third patient had a mutation in the site that is involved in binding to C4b-binding protein, which modifies the immune response. These three cases provide key insights into the pathophysiology of PS deficiency.

Adult↗

Endoscopic thoracic sympathicotomy in Japan.

We sent our members questionnaire asking about their activities. From December 1992 to the end of 2000, endoscopic thoracic sympathicotomy (ETS) was utilized in 7,017 cases in 50 hospitals and institutes. Of which 6,776 (96.6%) were performed on hypersweating. There have been no deaths related to ETS either during the hospital stay or following discharge. Intraoperative bleeding was reported in 28 cases (0.3%) and an open chest procedure to stop bleeding was required in 6 cases (0.08%). Short term Horner's syndrome after the operation was found in a few cases, however, permanent symptoms were recognized in only 18 (0.28%). The most common postoperative complaint was compensatory sweating on the chest, back, or abdomen. Most of these patients countered this condition by using several methods of prevention or protection and continued on their daily life with little restriction. However, 83 cases (1.2%) experienced severe compensatory sweating and consulted their doctors repeatedly for more than one year. All operators who perform ETS recognized the excellent results for hand and facial sweating. Further, many doctors prefer this procedure as a first treatment for vascular disorders in upper extremities.

Humans↗

Microtensile bond strength of eleven contemporary adhesives to dentin.

PURPOSE: To evaluate the microtensile bond strength (microTBS) of eleven contemporary adhesives to dentin, including three one-step self-etch systems, four two-step self-etch systems, three two-step total-etch systems, and one three-step total-etch system. MATERIALS AND METHODS: Resin composite (Z100) was bonded to flat, mid-coronal dentin from 33 extracted human third molars using the adhesives strictly according to the respective manufacturer's instructions. After storage overnight in 37 degrees C water, the bonded specimens were sectioned into 3 to 6 slabs of approximately 1 mm thickness and 2.5 mm width. They were then trimmed into an hourglass shape resulting in an interface area of approximately 1 mm2, and subsequently subjected to microTBS testing with a crosshead speed of 1 mm/min. RESULTS: The microTBS varied from 30.0 MPa for the one-step self-etch adhesive Prompt L-Pop 2 (ESPE) to 63.1 MPa for the three-step total-etch adhesive OptiBond FL (Kerr), the latter being the only one that significantly differed from all other microTBS values. Although not significantly different, one-step self-etch adhesives tended to have lower microTBS than two-step self-etch and two-step total-etch adhesives. Specimen failures during sample preparation occurred with Prompt L-Pop 2 (4 pretesting failures out of 17 specimens) and NRC/Prime & Bond NT (7 pretesting failures out of 14 specimens). CONCLUSION: Adhesives with simplified application procedures, either following a total-etch or self-etch approach, produced lower bond strengths to dentin than a conventional three-step total-etch adhesive. Some concern exists regarding the consistency in bonding effectiveness to dentin of some self-etch adhesives.

Acid Etching, Dental↗

Wound healing acceleration of a novel transforming growth factor-beta inducer, SEK-1005.

The studies were carried out to elucidate the effect of a novel cyclic peptide, SEK-1005 (C(45)H(70)N(8)O(13)), on wound healing. SEK-1005 (4-10 microg/wound) applied topically significantly accelerated the healing of a full-thickness wound on the dorsal skin of a rat. In a healing-impaired mouse, the peptide (2-10 microg/wound) had more potent activity, exerting an effect comparable to that of basic fibroblast growth factor (FGF). However, SEK-1005 (0.1-100 ng/ml) scarcely promoted the proliferation of cultured fibroblasts (NIH3T3 cells) while basic FGF (0.2-5 ng/ml) showed marked mitogenic activity. SEK-1005 (2-10 microg/wound) significantly increased the topical production of transforming growth factor (TGF)-beta1, a cytokine that is known to accelerate wound healing. This activity was closely correlated with the wound-repairing effect. From the above, SEK-1005 can be considered as a new type of wound healing agent with potent TGF-beta1-inducing activity.

3T3 Cells↗

Neuronal apoptosis by apolipoprotein E4 through low-density lipoprotein receptor-related protein and heterotrimeric GTPases.

The epsilon4 genotype of apolipoprotein E (apoE4) is the most established predisposing factor in Alzheimer's disease (AD); however, it remains unclear how apoE4 contributes to the pathophysiology. Here, we report that the apoE4 protein (ApoE4) evokes apoptosis in neuronal cells through the low-density lipoprotein receptor-related protein (LRP) and heterotrimeric GTPases. We examined neuron/neuroblastoma hybrid F11 cells and found that these cells were killed by 30 microg/ml ApoE4, but not by 30 microg/ml ApoE3. ApoE4-induced death occurred with typical features for apoptosis in time- and dose-dependent manners, and was observed in SH-SY5Y neuroblastomas, but not in glioblastomas or non-neuronal Chinese hamster ovary cells. Activated, but not native, alpha2-macroglobulin suppressed this ApoE4 toxicity. Suppression by the antisense oligonucleotide to LRP and inhibition by low nanomolar concentrations of LRP-associated protein RAP provided evidence for the involvement of LRP. The involvement of heterotrimeric GTPases was demonstrated by the findings that (1) ApoE4-induced death was suppressed by pertussis toxin (PTX), but not by heat-inactivated PTX; and (2) transfection with PTX-resistant mutant cDNAs of Galpha(i) restored the toxicity of ApoE4 restricted by PTX. We thus conclude that one of the neurotoxic mechanisms triggered by ApoE4 is to activate a cell type-specific apoptogenic program involving LRP and the G(i) class of GTPases and that the apoE4 gene may play a direct role in the pathogenesis of AD and other forms of dementia.

Animals↗

Functional analysis of five endothelin-B receptor mutations found in human Hirschsprung disease patients.

Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified. Five mutated EDNRB (A183G, W276C, R319W, M374I and P383L) cDNAs were transiently expressed in several cell lines to examine the effects of these mutations. Ligand-receptor binding experiments demonstrated that all mutants examined here accept endothelins with a high affinity. Especially, the affinity of endothelins to P383L was increased. However, the number of binding sites of A183G, W276C and P383L was markedly decreased. The subcellular localization of these mutant receptors was the same as that of wild-type EDNRB, whereas the amount of protein of each mutant receptor was decreased. All mutant receptors were impaired in intracellular Ca(2+) mobilization. These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals.

Animals↗

Agmatine suppresses nitric oxide production in microglia.

We investigated the effect of agmatine, an arginine metabolite synthesized in the brain, in cultured microglia obtained from neonatal rat cerebral cortex. Agmatine (1-300 microM) did not affect viability of cultured microglia. Activation of microglia by lipopolysaccharide (LPS, 1 microg/ml) caused the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) assessed as the accumulation of nitrite in the culture supernatants. Agmatine had no effect on the expression of iNOS, but significantly suppressed the LPS-induced NO production in a concentration-dependent manner. Agmatine was also effective in suppressing the production of NO induced by a combination of interferon-gamma (500 U/ml) and amyloid beta protein (10 microM). In co-cultures of rat cortical neurons and microglia, LPS caused significant loss of neuron viability. The LPS neurotoxicity was not observed in the absence of microglia, and was completely blocked by the NOS inhibitor diphenyleneiodoium chloride. The neuronal death induced by microglia-derived NO was significantly attenuated by the presence of agmatine. These results suggest that agmatine works to protect neurons by inhibiting the production of NO in microglia.

Agmatine↗

Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells.

A novel protein kinase, TOPK (T-LAK cell-originated protein kinase), was isolated from a lymphokine-activated killer T (T-LAK) cell subtraction cDNA fragment library. The open reading frame of the TOPK gene encodes a protein of 322 amino acids, possessing a protein kinase domain profile. The cap site analysis of the 5'-end of TOPK mRNA revealed two forms, a major full-length form and a minor spliced form at the 5'-site, both encoding the same protein. A BLAST homology search and phylogenetic analysis indicated that TOPK is related to dual specific mitogen-activated protein kinase kinase (MAPKK). The transfection of the TOPK gene to COS-7 cells up-regulated a phosphorylation of p38 MAPK but not ERK1/2 or SAPK/JNK. Gel precipitation study indicated that TOPK protein can be associated with p38 in vitro. Tissue distribution of TOPK mRNA expression was specific for the testis, T-LAK cells, activated lymphoid cells, and lymphoid tumors. On the other hand, deactivated T-LAK cells did not show TOPK mRNA expression. These data suggest that TOPK is a newly identified member of a novel MEK3/6-related MAPKK that may be enrolled in the activation of lymphoid cells and support testicular functions.

Amino Acid Sequence↗

Phenytoin inhibits both the first ovulation and uterine development in gonadotropin-primed immature rats.

This study was planned to determine the effects and possible mechanism of action of phenytoin on development of the reproductive tract and first ovulation in immature rats. Rats were injected s.c. with 5 IU of equine chorionic gonadotrophin (equine CG) on day 26 to induce ovarian and uterine development. Treatment with phenytoin (140 mg/kg) at 1200 h on day 28, which induces serum levels approximately twice those reached with the clinical dose as anticorvulsant drug for humans, was effective for inhibiting the first ovulation and normal secretion of serum follicle - stimulating hormone and luteinizing hormone (LH) on day 29 as well as the preovulatory gonadotrophin surge on day 28. The block of ovulation was overcome by administration of human chorionic gonadotrophin or LH-releasing hormone on day 28. Simultaneous treatment with equine CG and phenytoin at 0800 h on day 26 did not affect either ovarian weight or ovarian hormones secretion, whereas phenytoin clearly inhibited the normal increase in uterine weight on day 27. Furthermore, phenytoin suppressed uterine growth after 17beta-oestradiol injection. These results indicate that phenytoin inhibits the first ovulation by inhibiting the gonadotrophin surge and further, that the drug impairs the stimulatory effects of oestrogen on uterine proliferation in the gonadotropin-induced ovulation model.

Animals↗

Dietary troglitazone decreases oxidative stress in early stage type II diabetic rats.

Oxidative stress is involved in the initiation and development of atherosclerosis in diabetes. We tested the hypothesis that oxidative stress is already increased in early stage type II diabetes, and that troglitazone may prevent the increase. Three groups of 20 week old rats were studied: untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II diabetes, OLETF rats treated with troglitazone, and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma lipid hydroperoxides (LOOH) concentration, as an indication of lipid peroxidation, and superoxide dismutase (SOD) activity in the thoracic aorta were measured. Plasma LOOH concentration was significantly higher in non-treated OLETF rats compared to LETO rats and treatment with troglitazone completely prevented this increase. SOD activity was significantly decreased in non-treated OLETF rats compared to LETO rats and troglitazone attenuated the diminution of it. These observations demonstrate oxidative stress is already increased in the early stage of type II diabetes and we confirmed troglitazone has the effect of an antioxidant in vivo.

Animals↗

Subtype-specific trafficking of endothelin receptors.

We investigated the subcellular localization of two endothelin receptors (ET(A)R and ET(B)R). To visualize these receptors directly, the C terminus of each receptor was fused to the N terminus of enhanced green fluorescent protein (designated as ETR-EGFP). When transiently expressed in various mammalian cell lines, ET(A)R-EGFP was predominantly localized on the plasma membrane. By contrast, ET(B)R-EGFP was, independent of ligand stimulation, predominantly localized on the intracellular vesicular structures containing Lamp-1. Immunoblot analyses revealed that at steady state ET(B)R-EGFP was highly degraded, and its degradation was inhibited by bafilomycin A(1). Antibody uptake experiments suggested that the ET(B)R-EGFP molecules were internalized from the plasma membrane. It is therefore likely that ET(B)R is first transported to the plasma membrane and then internalized, irrespective of ligand stimulation, to lysosomes where it undergoes proteolytic degradation. Exchanging the C-terminal cytoplasmic tails of the two ETRs revealed that the cytoplasmic tail is responsible for both the intracellular localization and the degradation of the receptors. Deletion of the extreme C-terminal 35 amino acids from both receptors allowed the receptor proteins to localize predominantly in the intracellular vesicles and to degrade. These observations indicate that the cytoplasmic tail of ET(A)R determines its plasma membrane localization. Stimulation with endothelin-1 increased the amount of intact ETR-EGFP fusion proteins without increasing their de novo synthesis, suggesting that binding of endothelin-1 stabilizes the ETRs.

Amino Acid Sequence↗