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Biomedical subjects

M Kadota

Publications and source records attributed to M Kadota.

At least 19 recordsLinked to original sources

Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome.

Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed to result in apparent neuropathological abnormalities and to contribute to the phenotypic characteristics of mental retardation and premature development of Alzheimer disease. In order to identify the aberrant and specific genes involved in the early differentiation of DS neurons, we have utilized an in vitro neuronal differentiation system of mouse ES cells containing a single human chromosome 21 (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal differentiation were subjected to two-dimensional polyacrylamide gel electrophoresis protein separation followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to identify the proteins differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a novel set of specific gene products altered in early differentiating DS neuronal cells, which differs from that identified in adult or fetal brain with DS. The aberrant protein expression in early differentiating neurons, due to the hChr21 gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth, proliferation and differentiation, producing developmental abnormalities in neural patterning, which eventually leads to formation of a suboptimal functioning neuronal network in DS.

Animals↗

A new mouse model for Down syndrome.

Trisomy 21 (Ts21) is the most common live-born human aneuploidy and results in a constellation of features known as Down syndrome (DS). Ts21 is a frequent cause of congenital heart defects and the leading genetic cause of mental retardation. Although overexpression of a gene(s) or gene cluster on human chromosome 21 (Chr 21) or the genome imbalance by Ts21 has been suggested to play a key role in bringing about the diverse DS phenotypes, little is known about the molecular mechanisms underlying the various phenotypes associated with DS. Four approaches have been used to model DS to investigate the gene dosage effects of an extra copy of Chr 21 on various phenotypes; 1) Transgenic mice overexpressing a single gene from Chr 21, 2) YAC/BAC/PAC transgenic mice containing a single gene or genes on Chr 21, 3) Mice with intact/partial trisomy 16, a region with homology to human Chr 21 and 4) Human Chr 21 transchromosomal (Tc) mice. Here we review our new model system for the study of DS using the Tc technology, including the biological effects of an additional Chr 21 in vivo and in vitro.

Animals↗

[Surgical treatment for giant ascending aorta-arch aneurysm coexisted with DeBakey type II dissection on elderly women: report of a case].

A 78-year-old woman was admitted to our hospital after computed tomography (CT) had revealed in her the presence of a giant ascending aorta-arch aneurysm. This aneurysm was about 8 cm in diameter and associated with DeBakey type II dissection. Aortography showed the same condition as the CT view with the entry on the ascending aorta. The ascending aortaarch was replaced with a Hemashield 24 mm, by using deep-hypothermic selective cerebral perfusion and the open distal method. There were no complications during her peripostoperative state and no evidence of leakage and remnant dissection on CT and aortography. This is a rare case in which thoracic aortic aneurysm coexisted with dissection. In this case of severe atherosclerosis, deep-hypothermic selective cerebral perfusion and the open distal method provided effective treatment.

Aged↗

[Assessment of extracellular fluid in cardiac surgery using cardiopulmonary bypass].

Extracellular fluid (ECF) was assessed before and after the cardiac surgery using cardiopulmonary bypass (CPB), by means of a bioimpedance spectrum analyzer to see volumes of the fluid based on changes of the impedance to various frequencies. Difference between the levels before and after the operation was divided by body weight to study about a % BW. Simultaneously its relation to the lung compliance [tidal volume/(peak inspiratory pressure-end expiratory pressure)] was studied. Mean age of the 18 patients was 59.1 +/- 19 years old. ECF was assessed before to 24 hours after the operation continuously and once more after 48 hours. Mean CPB time was 165 +/- 52 minutes, and aortic cross clamp time was 121 +/- 4 minutes. A remarkable increase of ECF was noted immediately after the operation, which further increased gradually till arriving at the peak 4 hours after the operation (4.52 +/- 1.8% BW). Then it gradually decreased to 0.641 +/- 2.7% BW 48 hours later. Lung compliance measured at the same time showed the lowest level 6 hours after the operation. It was known that the bioimpedance spectrum analysis is a simple and non-invasive method, which enables to monitor the vital stable before and after the operation.

Adult↗

[A case of emergency coronary artery bypass graft for the patient using chronic hemodialysis, where in blood volume was measurable in the perioperative period].

An emergency coronary artery bypass graft (CABG) was given to a 66 year-old patient due to acute myocardial infarction (AMI). Circulating blood volume (BV) was measured to study in the perioperative period. Three coronary artery bypasses were made under cardiopulmonary bypass, being managed by ultrafiltration when the pump-oxygenator was in action and by peritoneal dialysis in the early postoperative period. Preoperative BV reduced immediately after the operation. It showed an increasing trend 4 hours after the operation, but after that BV reduced from that before the operation while water balance was kept positive. Cardiac output after the operation was higher than before. It suggested that in this patient using hemodialysis BV levels turned to be lower compared with that before the operation, as excessive water leaked out of the blood vessel, although water balance was kept positive due to improved cardiac functions after the operation.

Aged↗

Effects of lysozyme and bovine serum albumin on membrane characteristics of dipalmitoylphosphatidylglycerol liposomes.

The effects of adsorption of two kinds of proteins on the membrane characteristics of liposomes were examined at pH 7.4 in terms of adsorption amounts of proteins on liposomes, penetrations of proteins into liposomal bilayer membranes, phase transition temperature, microviscosity and permeability of liposomal bilayer membranes, using positively charged lysozyme (LSZ) and negatively charged bovine serum albumin (BSA) as proteins and negatively charged L-alpha-dipalmitoylphosphatidylglycerol (DPPG) liposomes. The saturated adsorption amount of LSZ was 720 g per mol of liposomal DPPG, while that of BSA was 44 g per mol of liposomal DPPG. The penetration of LSZ into DPPG lipid membranes was greater than that of BSA. The microviscosity in the hydrophobic region of liposomal bilayer membranes increased due to adsorption (penetration) of LSZ or BSA, while the permeability of liposomal bilayer membranes increased. The gel-liquid crystalline phase transition temperature of liposomal bilayer membranes was not affected by adsorption of LSZ or BSA, while the DSC peak area (heat of phase transition) decreased with increasing adsorption amount of LSZ or BSA. It is suggested that boundary DPPG makes no contribution to the phase transition and that boundary DPPG and bulk DPPG are in the phase-separated state, thereby increasing the permeability of liposomal bilayer membranes through adsorption of LSZ or BSA. A possible schematic model for the adsorption of LSZ or BSA on DPPG liposomes was proposed.

Journal Article↗

Construction of 700 human/mouse A9 monochromosomal hybrids and analysis of imprinted genes on human chromosome 6.

As an in vitro assay system for the identification of human imprinted genes, a library of human/mouse A9 monochromosomal hybrids containing a single, intact bsr-tagged human chromosome of known parental origin, derived from normal human fibroblasts, has been previously generated by microcell-mediated chromosome transfer (MMCT). To supplement this assay system, we constructed additional 700 A9 monochromosomal hybrids, using a pSTneo or pPGKneo selection marker. To validate the A9 hybrids, we screened them with chromosome-specific polymorphic markers, and identified the hybrids containing either human chromosome 6, 7, 14, 18, or 21 of known parental origin. Matching paternal and maternal chromosome pairs of A9 hybrids were identified for chromosomes 6, 7, 14, and 18. The paternal-specific expression of ZAC (zinc finger protein, which regulates apoptosis and cell cycle arrest) and HYMAI (hydatidiform mole-associated and imprinted transcript), and the maternal-specific methylation of a CpG island within an imprinted domain on human chromosome 6q24, were maintained in A9 hybrids. For an example, we profiled the expression of expressed sequence tags (ESTs) and the methylation of CpG islands in the 300-kb imprinted domain around 6q24, which may be associated with cancers and transient neonatal diabetes mellitus (TNDM). Thus, the 700 A9 hybrids should be useful for various aspects of imprinting studies.

Animals↗

Adrenal masses: quantification of fat content with double-echo chemical shift in-phase and opposed-phase FLASH MR images for differentiation of adrenal adenomas.

PURPOSE: To quantify fat content in adrenal lesions with double-echo chemical shift magnetic resonance (MR) imaging in a phantom study and to differentiate adrenal adenomas from other adrenal masses by assessing fat content in a clinical study. MATERIALS AND METHODS: The study consisted of two parts: a phantom study and a clinical study. To explore the effect of the T1 value on in- and opposed-phase MR images of fat-containing tissues, phantom models with various proportions of fat and gadopentetate dimeglumine concentrations were implemented. Signal intensity (SI) indexes ([SI in-phase - SI opposed-phase]/SI in-phase) were calculated with double-echo fast low-angle shot (FLASH) MR imaging. In the clinical study, 23 patients with 28 adrenal masses (16 adrenal adenomas, nine adrenal metastases, and three pheochromocytomas) underwent double-echo FLASH MR imaging, and SI indexes were calculated. RESULTS: SI index reached a maximum of 0.87 at 53% fat fraction for gadopentetate dimeglumine concentration at 0.5 mmol/L as the simulated T1 of the adrenal mass. The SI indexes of the adrenal adenomas, adrenal metastases, and pheochromocytomas, respectively, were 0.36, -0.15, and -0.07, and estimated fat fraction from the phantom study was 26.5%, 0%, and 0%. All adrenal adenomas contained fat on double-echo FLASH images. There was no overlap in SI index between adenomas and other tumors. CONCLUSION: Preliminary experience indicates that quantitative measurement of the fat fraction of adrenal masses is possible with the double-echo chemical shift FLASH technique and allows for differentiating adrenal adenomas from other adrenal masses.

Adenoma↗

[Blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation?].

To investigate that blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation, a retrospective study was made with 20 adult patients who underwent coronary artery bypass grafting. The subjects were divided into two groups; transfusion group (group T) including 9 patients who received blood transfusion during cardiopulmonary bypass and the control group (group C) including 11 patients who did not undergo perioperative transfusion. Respiratory index as an indicator of respiratory functions was determined before and immediately after cardiopulmonary bypass, at the end of surgery and 4 hours thereafter. Cardiac index and arterial pressure were determined as the indicator of cardiac function. Moreover, interleukin 6 and 8 (IL-6 and IL-8), inflammatory cytokines were measured and compared between the two groups. The mean amount of blood transfusion was 2.1 units per individual of group T. The minimum value of hematocrit during cardiopulmonary bypass was significantly lower in group T (15.8 +/- 1.8%) than group C (19.1 +/- 1.4%), but the difference became not significant after cardiopulmonary bypass. There were no significant differences either in aortic pressure or cardiac index between two groups. The respiratory index at the end of surgery was higher in group T but the difference was not significant. Meanwhile IL-8 level at the end of cardiopulmonary bypass was significantly higher in group T (67.9 +/- 36 pg/ml) than group C (35.1 +/- 21 pg/ml). However, there was no difference in IL-6 level between the two. These results suggested that inflammation might be aggravated by an increase of IL-8 induced by blood transfusion.

Aged↗

Suppressive effects of novel ferulic acid derivatives on cellular responses induced by phorbol ester, and by combined lipopolysaccharide and interferon-gamma.

A total of 23 ferulic acid (FA) derivatives were synthesized, and investigated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) activation and superoxide (O(2)(-)) generation. Most of the derivatives showed significant EBV activation suppression or cytotoxicity at a concentration of 100 microM, with FA15 as the most potent suppressor. In both assays, FA6-FA17, bearing straight- or branched-alkyl side chains, exhibited marked suppression of O(2)(-) generation, with both FA16 and FA17 being highly active, while FA itself was virtually inactive. The activity differences seen between FA16/FA17 and FA are attributable, at least in part, to their cellular incorporating efficiencies. Further, both FA15 and FA21 attenuated the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins, while FA did not. Our results suggest that these novel FA derivatives are effective chemopreventive agents.

Animals↗

Detection of microsatellite alterations in nipple discharge accompanied by breast cancer.

Nipple discharge in breast cancer cases was examined loss of heterozygosity (LOH). DNA samples were extracted from both supernatant and cell pellet components of the discharge, and examined for LOH at microsatellite markers, D11S1818, D11S2000, D16S402, D16S504, D16S518, D17S520, and D17S786. At least one LOH was found in either the supernatant or cell pellet in seven out of 10 patients (70%). Five of seven samples, which were cytologically negative, were LOH positive, and only one case, which was cytologically positive, showed no LOH on the markers examined. All three samples, which were judged 'negative' by CEA measurement (<400 ng/ml), were LOH positive. This method could be a useful novel diagnostic modality for nonpalpable breast cancer with nipple discharge.

Adult↗

[A simultaneous operation on coronary artery disease and abdominal aortic aneurysm during extracorporeal circulation in patient with impaired left ventricular function].

A 74-year-old man had an previous antero-septal and inferior myocardial infarction and an abdominal aortic aneurysm (AAA) 48 mm in diameter. Coronary angiography showed obstruction of the left anterior descending artery and of the right coronary artery, and 95% stenosis of the circumflex artery. The value of an ejection fraction of the left ventricle was 33%, measured by left venticulography. CABG and replacement of the aneurysm were performed simultaneously, because of the necessity of an intra-aortic balloon pumping (IABP) due to the impaired left ventricular function. First, CABG was performed under cardiac arrest. After declamping the ascending aorta, subsequently, replacement of AAA was performed while extracorporeal circulation (ECC) assisted heart beating. Weaning from ECC was smooth, and the operation was successful without using IABP. The patient was discharged 32 days after the operation. Consequently, cardiopulmonary bypass during AAA operation could decrease heart loads when hemodynamic states change in aortic clamping or after declamping. A simultaneous operation of CABG and AAA using ECC is safe and effective for impaired left ventricular function.

Aged↗

Clinical significance of micrometastases in axillary lymph nodes assessed by reverse transcription-polymerase chain reaction in breast cancer patients.

We evaluated the clinical significance of micrometastases in axillary lymph nodes (AxLNs) of breast cancer patients for prediction of prognosis. Archived formalin-fixed paraffin-embedded AxLN specimens from 129 node-negative breast cancer patients diagnosed by routine H&E staining between 1986 and 1990 were subjected to carcinoembryonic antigen-specific reverse transcription-PCR analysis. Micrometastases were detected in 40 of 129 (31.0%) node-negative breast cancer patients. After a median follow-up period of 105.6 months, log-rank test analysis indicated that 10-year disease-free and overall survival rates by Kaplan-Meier methods were significantly better in patients without micrometastases than in patients with micrometastases [disease-free survival, 87.6% versus 66.1% (P = 0.0008); overall survival, 93.7% versus 67.8% (P = 0.0024)]. The presence of micrometastases in AxLNs was revealed by multivariate analyses to be an independent and significant predictor of clinical outcome. The hazard ratio was 3.992 (95% confidence interval, 1.293-12.323; P = 0.0161) for relapse and 4.293 (95% confidence interval, 1.043-17.675; P = 0.0436) for cancer-related death. The molecular staging of AxLNs using reverse transcription-PCR is useful for prediction of clinical outcome in early-stage breast cancer patients and can provide a powerful and sensitive complement to routine histopathological analysis.

Adult↗

Comparative genomic hybridization defines frequent loss on 16p in human anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is one of the malignant tumors with the poor prognosis that is thought to arise from well-differentiated thyroid cancer (DTC). To investigate the molecular mechanism of ATC, we studied genomic alterations of eight ATC cell lines and three DTC cell lines by means of the comparative genomic hybridization (CGH) method. Loss of 16p was observed in five of eight ATC cell lines (62. 5%), but none of the three DTC cell lines showed loss of this chromosome arm. It is notable that loss of 18q [7/8 of ATC (87.5%), 2/3 of DTC (67%)] and gain of 20q [5/8 of ATC (62.5%), 3/3 of DTC (100%)] were frequently seen in both histologic types. Our results suggest that there is a gene in 16p that is closely associated with transformation from well-differentiated thyroid cancer to anaplastic cancer.

Carcinoma↗

[A case report: effective trans-arterial neoadjuvant chemotherapy with docetaxel for a local advanced breast cancer patient].

Recently, there have been some reports about the effectiveness of docetaxel for breast cancer patients who had polychemotherapy previously in vein. We report here a case of a 47-year-old woman, who had been diagnosed as local advanced breast cancer. She was given trans-arterial chemotherapy with docetaxel after four series of CEF (cyclophosphamide, epirubicin, fluorouracil) therapy resulted in PD (progressive disease). Local disease was successfully controlled, and she could undergo standard radical mastectomy.

Antineoplastic Agents, Phytogenic↗

Transaxillary endoscopic partial mastectomy for comparatively early-stage breast cancer. An early experience.

For optimal cosmetic results in breast cancer surgery, we developed an alternative operation using endoscopy to remove tumors through a small single incision remote from the breast itself. The tumor is endoscopically resected with electrocautery and low constant suction through a short incision in the axilla, 5 cm long, after which axillary dissection is performed through the same wound in the usual manner, under visualization by the naked eye. Primary reconstruction of the breast is performed with the remaining mammary gland and a subcutaneous fat flap on the serratus muscle. Seven patients underwent this surgery. The postoperative shape of the breasts was judged to be cosmetically satisfactory, and the surgical wounds were not visible from the front in all cases. This operation has the same therapeutic oncological effect as a standard lumpectomy and, in addition, offers a greater cosmetic advantage in cases of early breast cancer.

Adult↗

Evaluation of the disinfectant effect of a quick drying rubbing type povidone-iodine alcoholic solution by the glove juice method.

The antiseptic effect of povidone-iodine alcoholic solution (HAD Hand Wash), a newly developed quick drying rubbing type disinfectant, was evaluated in 40 subjects. Samples of hand bacteria were collected by the glove juice method. The bacteria were incubated, and a cell count was performed. Disinfection was carried out by rubbing 3 ml of HAD Hand Wash carefully on to the skin of the subjects' hands. The efficacy of the solution was evaluated by computing the bacterial reduction rates as compared to the pre-disinfection bacterial count after disinfecting once and three times. The bacterial cell count was significantly reduced from the pre-disinfection count for one hour after disinfecting once and for two hours after disinfecting three times. In addition, the bacterial reduction rate after disinfecting three times remained superior to that after disinfecting once over a period of two hours. We concluded that disinfecting once with HAD Hand Wash is sufficient for routine hygienic hand washing, while disinfecting three times is desirable when, as with surgical hand washing, the strictest antisepsis is required. HAD Hand Wash produced no adverse side effects.

Antisepsis↗