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Biomedical subjects

T Hachiya

Publications and source records attributed to T Hachiya.

At least 55 records · Page 3Linked to original sources
PubMed2001

Beneficial effect of balloon-induced pulsatility on brain oxygenation in hypothermic cardiopulmonary bypass.

BACKGROUND: Sufficient O2 delivery to meet the demand is an important factor for protecting the brain during cardiopulmonary bypass (CPB). This study was designed to investigate the influences of temperature, pulsatility of blood flow (intra-aortic balloon pump-induced) and flow rate during CPB on the cerebral oxygenation. METHODS: Patients were divided into five groups. Normothermia (36 degrees C): pulsatile (n=8, 2.5 L/min/m2), nonpulsatile (n=12, 2.5 L), and nonpulsatile perfusion (n=12, 2.8 L); hypothermia (30 degrees C): pulsatile (n=9, 2.5 L) and nonpulsatile perfusion (n=11, 2.5 L). The oxygen saturation (SjVO2), lactate and CPK-BB levels in the jugular venous blood were measured. RESULTS: In all of the normothermic groups, the SjVO2 value decreased during the CPB (p<0.1-0.01). No remarkable change was observed in the hypothermic groups, with the exception during the rewarming period in the nonpulsatile group. A higher SjVO2 and a lower frequency of SjVO2 values <50% were observed in the hypothermic pulsatile group, as compared with those in the normothermic groups (p<0.05). The levels of CPK-BB were nearly the same, however the levels of lactate were higher in the normothermic pulsatile and nonpulsatile (2.5 L) groups (p<0.05). CONCLUSIONS: We concluded that the hypothermic CPB was advantageous over normothermic CPB in regard to the SjVO2 levels and lactate production. The beneficial effect of intra-aortic balloon pump assist was only obtained in the hypothermic CPB.

Aged↗
PubMed2001

[A case of primary leiomyosarcoma of the pulmonary artery].

A 74-year-old woman was admitted to our hospital because of right chest pain. The chest radiograph showed right hilar pulmonary artery dilatation. A mass exhibiting low intensity in T1-weighted images and high intensity in T2-weighted images was disclosed in the right pulmonary artery. Because of its clinical course and the MRI findings, the mass was thought to be tumorous tissue, and so pneumonectomy was performed. Leiomyosarcoma was diagnosed from the histological findings. Primary artery sarcoma is rare and the prognosis is considered to be extremely poor. The patient was successfully treated and had a good clinical outcome.

Aged↗
PubMed2000

Negative regulation of Fas-mediated apoptosis by FAP-1 in human cancer cells.

FAP-1 (Fas-associated phosphatase-1) was previously identified as a protein that associates with a negative regulatory domain (C-terminal 15 amino acids) of Fas using the yeast 2-hybrid system. Functional analysis indicated that FAP-1 expression correlates with resistance to Fas-induced apoptosis in human cancer cells. We first generated anti-FAP-1 polyclonal antibody and confirmed the interaction of FAP-1 and Fas in vivo. FAP-1 interacted with wild-type, but not mutant, Fas (tPLV) in 293T cells after transfecting FAP-1 and Fas or its mutant. To investigate the functional role of FAP-1 in Fas-mediated signal transduction, we established stable transfectants of FAP-1 in 3 human cancer cell lines. Apoptosis assays demonstrated that cancer cells over-expressing FAP-1 increased the resistance to Fas-induced apoptosis by the anti-Fas antibody CH-11 in contrast with the wild types or the vector-transfected cells. In addition, FAP-1 regulated the activity of both caspases 3 and 8. Our data indicate a functional role for FAP-1 as a negative regulator of Fas-mediated apoptosis in human cancer cells and suggest that an additional signal-transducing molecule may be required for complete suppression of Fas-mediated apoptosis.

Antibodies↗
PubMed2000

NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.

The low affinity neurotrophin receptor p75NTR can mediate cell survival as well as cell death of neural cells by NGF and other neurotrophins. To elucidate p75NTR-mediated signal transduction, we screened p75NTR-associated proteins by a yeast two-hybrid system. We identified one positive clone and named NADE (p75NTR-associated cell death executor). Mouse NADE has marked homology to the human HGR74 protein. NADE specifically binds to the cell-death domain of p75NTR. Co-expression of NADE and p75NTR induced caspase-2 and caspase-3 activities and the fragmentation of nuclear DNA in 293T cells. However, in the absence of p75NTR, NADE failed to induce apoptosis, suggesting that NADE expression is necessary but insufficient for p75NTR-mediated apoptosis. Furthermore, p75NTR/NADE-induced cell death was dependent on NGF but not BDNF, NT-3, or NT-4/5, and the recruitment of NADE to p75NTR (intracellular domain) was dose-dependent. We obtained similar results from PC12 cells, nnr5 cells, and oligodendrocytes. Taken together, NADE is the first signaling adaptor molecule identified in the involvement of p75NTR-mediated apoptosis induced by NGF, and it may play an important role in the pathogenesis of neurogenetic diseases.

Amino Acid Sequence↗
PubMed2000

Basal layer reactivity in hyperplastic and metaplastic lesions of the bronchi as studied by lectin histochemistry.

The relationship between squamous metaplasia and squamous cell carcinoma of the bronchi has been the subject of controversy. We investigated basal cell hyperplasia, stratification, squamous metaplasia, and squamous cell carcinoma by means of lectin histochemistry with peanut agglutinin (PNA), Ulex europeus agglutinin-I, soybean agglutinin, and Dolichos biflorus agglutinin for all normal basal cells that are reactive. A basal layer stained with PNA was observed in basal cell hyperplasia, stratification, and squamous metaplasia, but this layer was not exhibited by squamous cell carcinoma. In hyperplasia and metaplasia, PNA staining was biased toward the lowest (basal) layer, whereas staining for the other lectins was more uniformly distributed across the layers. A PNA-positive basal layer may be important for the morphologic reversibility of the bronchial mucosa in hyperplastic and metaplastic lesions, and destruction of this layer may be associated with a progression from metaplasia to squamous cell carcinoma.

Adenocarcinoma↗
PubMed2000

Prediction of organ-confined disease by prostate-specific antigen nadir after neoadjuvant therapy.

BACKGROUND: It is not clear whether or not serum prostate-specific antigen (PSA) levels after androgen deprivation prior to radical prostatectomy (neoadjuvant therapy) have any value in the prediction of the final pathologic stage. METHODS: We conducted a study on 49 patients who underwent retropubic radical prostatectomy following neoadjuvant therapy for clinical stage T1c, T2, and T3a prostate cancer. We evaluated progression-free survival based on the PSA failure rate and the predictive value of the PSA nadir after neoadjuvant therapy and other clinical factors to determine the most important predictor of organ confinement. RESULTS: Of the 49 patients, 30 had organ-confined disease. Of 31 patients without adjuvant therapy after surgery, the PSA failure-free rates at 2 years were 81.6 and 34.3% in the subset of organ-confined disease and non-organ-confined disease, respectively (P= 0.0031). Of the 18 patients with adjuvant androgen deprivation therapy after surgery, the PSA failure-free rate at 2 years was 100% and 59.7% in patients with organ-confined disease and non-organ-confined disease, respectively. Baseline PSA (P=0.037), PSA nadir (P<0.0001) and PSA density (P=0.003) significantly correlated with organ confinement. Multivariate logistic regression analysis revealed that the PSA nadir was the only independent predictor of organ confinement (P = 0.044). CONCLUSIONS: There was a trend that the patients with non organ-confined disease had a higher probability of PSA failure than did the patients with organ-confined disease. The PSA nadir after neoadjuvant therapy was the strongest predictor of organ confinement. The predictive value of the serum PSA nadir should be validated in well-designed larger population-based studies.

Aged↗
PubMed2000

Unilateral hilar lymphadenopathy of sarcoidosis or sarcoid reaction compressing the trunk of the right pulmonary artery.

A case of sarcoidosis or sarcoid reaction with a rare manifestation of unilateral lymphadenopathy compressing the trunk of the right pulmonary artery is presented. A 71-year-old woman was admitted for evaluation of a left hilar mass. Chest CT scans showed a mass invading the right pulmonary artery. A frozen section obtained following open lung biopsy showed lymph node tissue largely replaced by noncaseous granulomas indicating sarcoidosis or sarcoid reaction. Old uveitis was compatible with sarcoidosis, and no malignancy was evident. These findings suggested sarcoidosis, however, other evidence of sarcoidosis was not obtained.

Aged↗
PubMed2000

Influence of cardiopulmonary bypass temperature on circulatory pathophysiology and clinical outcomes.

This study was designed to investigate the effects of cardiopulmonary bypass (CPB) perfusion temperature. Forty-four patients who had undergone elective coronary bypass surgery were randomly divided into 2 groups (22 patients each) according to their perfusion temperature (N group=36 degrees C; L group=30 degrees C). The concentrations of endogenous catecholamines, complements, elastase, serotonin, arachidonic acid metabolites and endothelin underwent various changes throughout the CPB but did not exhibit any statistical differences in either group. None of the substances measured correlated with systemic vascular resistance at any time. The temperature of the perfusion appears to be a major determinant of vascular tone. The postoperative PO2 was better, and postoperative pulmonary vascular resistance lower in the N group (p<0.05), most likely because of a much larger water balance during hypothermic CPB (p<0.01). The postoperative blood loss was statistically less in the N group (p<0.05). Although apparent brain damage, evidenced by the leakage of creatine kinase-BB, was not seen, the jugular bulb venous hemoglobin saturation levels (<50% in 27% of the N group, p<0.05) and higher lactate levels suggested that normothermic perfusion was relatively disadvantageous. It is concluded that normothermic CPB was relatively safe and advantageous with regard to hemostasis and pulmonary function.

Aged↗
PubMed2000

Aortic valve replacement with concomitant annular enlargement for small aortic annulus of less than 19 mm.

Three female patients with aortic stenosis associated with a severely small annulus underwent aortic valve replacement. In intraoperative measurements, a 19-mm obtulator could not pass through the aortic annulus in each case. We therefore concluded that it would be difficult to implant an appropriate-sized prosthesis in a routine fashion, so we performed an annular enlargement in a modified Nicks procedure. By using a wide teardrop-shaped patch for enlargement and slightly tilting insertion of a prosthesis, a 21 mm bileaflet mechanical prosthesis could be inserted into the enlarged annulus. Despite being a simpler method than other enlarging procedures, a two- or three-sizes larger prosthesis than the native annulus can be inserted with relative ease. Thus, the use of a 19 mm mechanical prosthesis may be avoidable in most adult cases.

Aged↗
PubMed2000

[Combined use of ante- and retrograde cardioplegia: limited efficacy in elective coronary artery bypass].

One Hundred and twenty-four patients undergoing elective coronary bypass surgery were retrospectively selected and divided into two groups according to their difference of cardioplegic methods, either antegrade (AC) only (n = 65) or combination of ante- and retrograde (AC + RC) cardioplegic delivery (n = 64). Myocardial blood flow in the right (RV) and left ventricles (LV) was measured during the cardioplegia by a laser Doppler. Peak CPK-MB levels were compared postoperatively between the two groups and more in detail according to extent of coronary obstructive disease. 1) The antegrade administration of cardioplegic solution provided preferential flow to the RV compared to the LV, whereas the retrograde administration resulted in the opposite result (AC; LV 6.9 +/- 4.7, RV: 8.6 +/- 5.3, p < 0.05, RC; LV: 9.0 +/- 4.9, RV: 5.9 +/- 4.6 ml/min/100 g, p < 0.05). This result suggested that the combination of both administrations was meaningful to obtain uniform distribution of cardioplegic solution. 2) The peak CPK-MB, compared in the entire two groups, was slightly low in the combination use (AC; 48 +/- 16, AC + RC; 43 +/- 15 IU/l, p = 0.08), but the clinical meaning did not exist. However, in the severe cases, which involved two of following criteria (left main disease, severe occlusion of left or right coronary), the max CPK-MB level was statistically decreased by the combined use of ante- and retrograde cardioplegia (AC; 50 +/- 16, AC + RC; 40 +/- 12 IU/l, p < 0.05). We concluded that the merit of combined use was limited to the cases with severely extended coronary obstructive disease.

Aged↗
PubMed1999

Functional interaction of Fas-associated phosphatase-1 (FAP-1) with p75(NTR) and their effect on NF-kappaB activation.

The common neurotrophin receptor p75(NTR), a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role in several cellular signaling cascades, including that leading to apoptosis. FAP-1 (Fas-associated phosphatase-1), which binds to the cytoplasmic tail of Fas, was originally identified as a negative regulator of Fas-mediated apoptosis. Here we have shown by co-immunoprecipitation that FAP-1 also binds to the p75(NTR) cytoplasmic domain in vivo through the interaction between the third PDZ domain of FAP-1 and C-terminal Ser-Pro-Val residues of p75(NTR). Furthermore, cells expressing a FAP-1/green fluorescent protein showed intracellular co-localization of FAP-1 and p75(NTR) at the plasma membrane. To elucidate the functional role of this physical interaction, we examined TRAF6 (TNF receptor-associated factor 6)-mediated NF-kappaB activation and tamoxifen-induced apoptosis in 293T cells expressing p75(NTR). The results revealed that TRAF6-mediated NF-kappaB activation was suppressed by p75(NTR) and that the p75(NTR)-mediated NF-kappaB suppression was reduced by FAP-1 expression. Interestingly, a mutant of the p75(NTR) intracellular domain with a single substitution of a Met for Val in its C-terminus, which cannot interact with FAP-1, displayed enhanced pro-apoptotic activity in 293T transfected cells. Thus, similar to Fas, FAP-1 may be involved in suppressing p75(NTR)-mediated pro-apoptotic signaling through its interaction with three C-terminal amino acids (tSPV). Thus, FAP-1 may regulate p75(NTR)-mediated signal transduction by physiological interaction through its third PDZ domain.

Carrier Proteins↗
PubMed1999

WAF1 genotype and endometrial cancer susceptibility.

The WAF1 protein, which is a downstream mediator of p53, functions as a universal inhibitor of cyclin-dependent kinases. The functional link between p53 and WAF1 suggests the possibility that alteration in WAF1 function constitutes an alternative mechanism to p53 inactivation. However, there are few reports describing somatic mutations of the WAF1 gene in various human malignancies. A polymorphism in the WAF1 gene, a C-to-A transversion at codon 31 resulting in the change of a serine (Ser) to an arginine (Arg), is well known. We found this substitution in 42 of 54 endometrial carcinoma patients. Allele frequency was 0.44/0.56 for the codon 31 polymorphism (Ser/Arg), the difference of allele frequency between patients and normal controls being significant (0.59/0.41 in normal controls). In addition, individuals carrying the codon 31 Arg allele had a tendency to develop histologically high-grade (odds ratio, 6. 11) and clinically advanced tumors. We investigated the association of the Arg allele with the known risk factors of endometrial carcinomas. Statistical analyses of 42 cases and 32 controls carrying the codon 31 Arg allele identified hypertension (odds ratio, 4.33) and family history of cancer (odds ratio, 2.81) as positive risk factors. This implies that these two parameters may be associated with a tendency to develop endometrial carcinomas in individuals carrying the codon 31 Arg allele of the WAF1 gene.

Alleles↗
PubMed1999

Expression patterns of type II pneumocyte apical surface glycoconjugates in lung adenocarcinoma cells.

Monoclonal antibodies and lectins were used to examine the expression patterns of apical membrane oligosaccharide sequences specific to type II pneumocytes in atypical adenomatous hyperplasia (AAH) and lung cancer. Atypical cells of AAH and papillary adenocarcinoma cells expressed abundant sialyl Thomsen-Friedenreich (TF) antigen: this was not observed in acinar adenocarcinoma, bronchioloalveolar carcinoma with mucin production or squamous cell carcinoma. Sialyl Tn antigens was also detected on a few cells in AAH and papillary adenocarcinomas. Asialo TF and Tn antigen were not observed on the surface of carcinoma cells of any type. Alpha(alpha)2,3-linked sialic acids predominated in type II pneumocyte, AAH and papillary adenocarcinoma, whereas ciliated columnar cells expressed alpha2,6-linked sialic acids. Lewisx and sialyl Lewisx antigens capped the TF antigen in both O- and N-linked side chains on the surface of AAH and papillary adenocarcinoma cells, but were not expressed by type II pneumocytes. The findings demonstrate that papillary adenocarcinoma cells resemble type II pneumocytes in that they express abundant sialyl TF surface antigen, but they also express TF-related antigens not found in type II pneumocytes. Apical surface glycoconjugates of AAH have structural characteristics shared by both type II pneumocytes and papillary adenocarcinoma cells.

Adenocarcinoma↗
PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗
PubMed1999

Immunoelectron microscopy of peroxisomes employing the antibody for the SKL sequence PTS1 C-terminus common to peroxisomal enzymes.

Immunohistochemistry employing a new hapten antibody that detects the SKL sequence and its variants of the PTS1 C-terminus of peroxisomal enzymes was attempted to visualize peroxisomes across species. Rabbits were immunized with the SKL sequence coupled with KLH, between which an arm molecule was interposed. IgG fractions of antisera were affinity-purified against the hapten and employed for immunochemical analyses and immunoelectron microscopy. The specificity of the antibody was examined by immunoblot analyses for various purified enzymes of rat liver peroxisomes and by dot-blot analyses inhibited by SKL peptide and its variants. Various animal and plant tissues were subjected to immunoelectron microscopy with the protein A-gold technique. The antibody reacted with various enzymes in the peroxisome with the SKL motif. The affinity of the antibody for tripeptides, which varied depending on their structures, was higher for SKL than for its variants. Hepatic and renal peroxisomes of vertebrates, peroxisomes in the fat body of an insect, and the cotyledon of a plant were visualized by immunoelectron microscopy. Immunohistochemistry employing this SKL antibody may provide specific staining that can detect peroxisomes across different species.

Animals↗