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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 397 records · Page 22Linked to original sources
PubMed1991

[Human heart recovery during weaning from a left ventricular assist system: time course and outcome prediction].

To investigate the time course of recovery of a failing heart using the left ventricular assist system (LVAS) and to predict the outcome of weaning from the LVAS, 14 patients with a failing heart were studied. Among them, 5 had recovered and survived for more than 2 weeks after weaning from the LVAS (recovered group), while 9 could not be weaned or died within 2 weeks after weaning (unrecovered group). All patients were gradually weaned from the LVAS with adequate support for systemic circulation for 3 days. In the recovered group, indices of systolic time intervals (STIs) showed improvement within a week. However, improvement of STIs was slow reaching a plateau around the 10th day in the unrecovered group. On weaning from the LVAS, aortic systolic pressure and ejection time were regulated by the patients' own hearts and were nearly the same between the 2 groups. However, left atrial pressure was significantly higher in the unrecovered group than in the recovered group. These hemodynamic features were first present on the 7th day. Therefore, hemodynamic data on the 7th assistant day can be a reliable factor in predicting the possibility of successful weaning from the LVAS and recovery in patients with a failing heart.

Adult↗
PubMed1991

Hepatic venous oxygen saturation monitoring in patients with assisted circulation for severe cardiac failure.

In order to assess the adequacy of hepatic perfusion, hepatic venous oxygen saturation (ShvO2) was monitored in five patients undergoing mechanical circulatory support. Two patients were with intra-aortic balloon pumping (IABP), one was with a left ventricular assist device (LVAD), and two were with biventricular assist devices (BVAD). The mean ShvO2 values during assistance in each patient ranged from 27 to 84%. One patient with IABP showed persistently low ShvO2 (less than 30%) in spite of higher mixed venous oxygen saturation (SvO2) and subsequently developed hepatic dysfunction and multiple organ failure. In another patient, ShvO2 was 22% on average during LVAD, but increased to greater than 50% after adding a right ventricular assist device (RVAD). Of 3 patients with persistently high ShvO2 (44-80%, on average), only one developed hepatic failure--probably from prior severe shock--and the other two did not develop hepatic failure. There was a significant negative correlation between ShvO2 and splanchnic excess lactate, the parameter of anaerobic metabolism in the splanchnic area. In contrast, there was no correlation between simultaneously measured ShvO2 and SvO2 values when analyzed in a range of SvO2 below 70%. ShvO2 monitoring may be useful for evaluation of hepatic perfusion status in the management of critical patients, requiring assisted circulation.

Heart Failure↗
PubMed1991

The cycle of the seminiferous epithelium and stages in spermatogenesis in dd-mice.

For the basis to study the testicular functions using dd-mice, the cycle of the seminiferous epithelium and stages in spermatogenesis, classification of late spermatogenesis, and postnatal development of spermatogenesis were examined by light and electron microscopy in the testes from these animals at day of birth and 1, 2, 3, 4, 5, and 8 weeks of age. For light microscopy, paraffin sections of the testes were stained with periodic-acid and Schiff reagent (PAS) and hematoxylin. In spermiogenesis, 16 steps of spermatids were distinguished according to shapes of the nuclei and acrosomes. Step 15 and 16 spermatids, which have similar nuclei and acrosomes, were easily distinguishable by positions of nuclei and appearance of basophilic granules in the cytoplasm; steps 15 and 16 were thus subdivided into 3 and 2, respectively. The granules were accumulations of ribosome-like particles. Step 13 spermatids were present with step 1 spermatids, step 14 with steps 2 and 3, step 15 with steps 4-6, and step 16 with steps 7 and 8. Thus, the cycle of the seminiferous epithelium was divided into 12 stages (stages I-XII) in the order of steps 1 to 12. Type A spermatogonia were present in all stages, and intermediate and type B spermatogonia appeared from stages II and VI, respectively. In primary spermatocytes, the resting phase appeared from stage VII, leptotene from stage VIII, zygotene from stage X, pachytene from stage III, diplotene in stage XI, and diakinesis and secondary spermatocytes in stage XII. The seminiferous tubules were lined by Sertoli cells and contained gonocytes at day of birth, type A spermatogonia appeared at 1 week of age, spermatogenesis proceeded until pachytene spermatocytes at 2 weeks, until step 1 spermatids at 3 weeks, and all stages of the seminiferous epithelium were completed at 5 weeks. The findings indicate that combination of germ cells in each stage of the seminiferous epithelium in dd-mice does not correspond to generally accepted one, step 15 and 16 spermatids are accurately classified by referring the position of nuclei and appearance of granules in the cytoplasm, and spermatogenesis in immature mice proceeds faster than in adults.

Age Factors↗
PubMed1991

[Evaluation of early and late results of open heart surgery in 74 patients 70 years of age and older].

A retrospective analysis of 12-year experience with open heart surgery in 74 patients 70 years of age and older during 1979 and 1990 was performed. The subjects consisted of 51 patients with coronary artery disease, 11 with acquired valvular disease, 2 with congenital heart disease and 10 with combined heart disease. Operative mortality was 9% and late mortality, 16%. The incidence of low output syndrome and respiratory failure were significantly high postoperatively. Multivariate analysis demonstrated that determinants of operative prognosis were postinfarction ventricular septal perforation, aortic cross-clamp time, preoperative renal dysfunction and coronary-valvular combined disease. Actuarial survival rate at 5 years was 89% for an entire series, which was favorably compared with age-sex matched population.

Age Factors↗
PubMed1991

[The artificial heart: present status and future prospects].

Artificial heart (AH) and heart transplantation (HTx) are complementary means of cardiac assistance and replacement. Temporary use AH including ventricular assist systems (VASs) and total artificial hearts (TAHs) have been put into clinical use. VASs applied to 848 patients in the world and 187 in Japan with acute profound heart failure. The short-term survival rates are 23.3% and 27.3%, respectively. HTx has become an accepted therapeutic procedures. To date, 255 patients received VAS and 182 received TAH as a bridge to HTx, because the number of candidates exceeds the supply of donor hearts. Long-term implantable AH is the future alternatives for cardiac replacement. It is recognized that several key components will be necessary for development of an AH with high performance including biomaterial with antithrombogenecity and durability, an implantable actuator, a noninvasive monitoring system and sensors, a miniature auto-control system, and an energy converter. Another types of devices are on the horizon. These are a muscle-powered biomechanical AH, an AH powered by artificial muscle, and an integrated artificial heart-lung device. With remarkable progress in medicine and engineering, we can expect to see totally implantable permanent use cardiac assist and replacement devices as an alternative for HTx in the near future.

Heart, Artificial↗
PubMed1991

Potentiation of etoposide and vincristine by two synthetic 1,4-dihydropyridine derivatives in multidrug-resistant and atypical multidrug-resistant human cancer cells.

Newly synthesized 1,4-dihydropyridine derivatives had been screened to determine whether they could overcome vincristine (VCR)-resistance in VCR-resistant (P388/VCR) leukemia-bearing mice, and six compounds had strong reversing ability among the screened compounds. We further determined whether NK-250 and NK-252 among the six compounds could potentiate cytocidal activities of etoposide (VP16) as well as VCR against both multidrug-resistant (MDR) cell line (VJ-300) and atypical MDR cell line (KB/VM-4). Both VJ-300 and KB/VM-4 were derived from the same parental human cancer KB cell line: VJ-300 cells showed enhanced expression of a MDR-specific glycoprotein of molecular weight of 170,000 Da (gp170) while KB/VM-4 cells were selected as teniposide (VM26)-resistant cell line with no expression of gp170. NK-250 and NK-252 potentiated the cytotoxic action of VCR about 2- to 10-fold against KB and KB/VM-4 cells, and they almost completely reversed VCR-resistance in VJ-300 cells. By contrast, NK-250 and NK-252 potentiated the cytotoxic action of VP16 about 2-fold against KB cells while they reversed 5- to 10-fold VP16-resistance in both VJ-300 and KB/VM-4 cells. The reversal effect by NK-250 and NK-252 of VCR-resistance in VJ-300 cells appeared to be due to enhanced cellular accumulation of radioactive VCR through interaction to 170-kDa P-glycoprotein. The potentiation effects by these dihydropyridines of VCR and VP16 on KB or KB/VM-4 cells also appeared to be due to enhanced accumulation of radioactive VP16 or VCR, but the effects might be mediated through other mechanisms, plausibly enhanced cellular uptake of the drugs.

Antineoplastic Agents↗
PubMed1990

[Analysis of mesenteric thickening on computed tomography].

Computed Tomography (CT) provides a noninvasive information in the evaluation of abnormalities of the gastrointestinal tract by direct imaging of the bowel wall and adjacent mesentery. Several prior studies have discussed the variable CT appearances of mesenteric abnormalities, such as lymphoma, metastasis, inflammatory disease and edema. Although mesenteric thickening was mentioned in these studies, no study has provided a detailed analysis of the CT appearance of the thickened mesentery. Two characteristic types of mesenteric thickening were identified in 47 patients. Type I is "Intra-mesenteric thickening", which was noted in 25 patients with vascular obstruction, inflammatory disease and edema. Type II is "Mesenteric surface thickening", which was noted in 22 patients with peritonitis carcinomatosa, peritoneal mesothelioma, tuberculous peritonitis and pseudomyxoma peritoneal. An understanding of these two types of mesenteric disease is important in the identification of mesenteric pathology.

Adult↗
PubMed1990

Tissue-specific enhancer of the human multidrug-resistance (MDR1) gene.

Identification of cis-regulatory sequences is a first step in analyzing the regulation of the human multidrug-resistant 1 (MDR1) gene which encodes the 170-kilodalton membrane P-glycoprotein in normal tissues and tumor cells. We have studied several overlapping genomic clones containing the 5'-flanking region of the gene. These clones span about 30 kilobases (kb) of contiguous DNA containing 10 kb of the gene and 20 kb of the 5'-flanking sequence. The nucleotide sequence of the first exon and the 2 kb preceding the exon were determined. DNA sequences containing the 5'-flanking regions were linked to the chloramphenicol acetyltransferase (CAT) gene. For transient CAT assay, we have employed six cell lines, including human cancer KB, vincristine-resistant VJ-300 derived from KB, mouse adrenal tumor Y-1, African green monkey kidney CV-1, mouse fibroblast NIH3T3, and human adrenal carcinoma SW-13 cells. Promoter activity was very weak regardless of the length of the promoter region in mouse adrenal tumor Y-1 and monkey kidney CV-1 cells, in which endogenous P-glycoprotein was expressed. Introduction of a 700-base genomic DNA fragment from a site located at 10 kb far upstream of the initiation site increased the transcription of the CAT gene in Y-1, CV-1, and SW-13 cells. However, no significant increase in the CAT activity could be observed in NIH3T3, KB, and VJ-300 cells. This fragment markedly augmented the expression of the CAT gene regardless of orientation or position, and it acted in a cell type-specific manner even with heterogenous promoters. Our present study suggests that the 700-base pair fragment may carry a tissue-specific transcriptional enhancer that is active in at least some adrenal and kidney-derived cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Reduction of drug accumulation and DNA topoisomerase II activity in acquired teniposide-resistant human cancer KB cell lines.

We have isolated stable teniposide (VM26)-resistant cell lines from human cancer KB cells by stepwise exposure to increasing doses of the drug. At each step, we have purified VM26-resistant cell lines. KB/VM-a, KB/VM-b, KB/VM-1, KB/VM-2, KB/VM-3, and KB/VM-4 showed 3-, 6-, 12-, 16-, 74-, and 95-fold higher resistance to VM26 than did KB. We have further characterized KB/VM-2 and KB/VM-4 which showed about 15- and 100-fold higher resistance to VM26 or etoposide (VP16) than did KB. Both VM26-resistant cell lines showed 4- to 11-fold higher relative resistance to daunomycin and Adriamycin than did KB. Steady-state levels of the cellular accumulation of radioactive VP16 in KB/VM-2 and KB/VM-4 cells were about 40% of that of KB cells, whereas similar levels of radioactive daunomycin accumulation were observed in KB/VM-2 and KB/VM-4 cells as KB cells. Topoisomerase II activity of nuclear extracts of both KB/VM-2 and KB/VM-4 assayed by decatenation of kinetoplast DNA was consistently two-thirds or less the activity of KB cells. A similar reduction was seen in both immunoblot assays with specific anti-topoisomerase II antibody and Northern blot analysis with specific human DNA topoisomerase II complementary DNA. DNA topoisomerase I activity, however, was similar between the mutants and their parent. Furthermore, cell growth of KB/VM-2 and KB/VM-4 was more thermolabile than that of KB, while KB/VM-b already showed temperature-sensitive growth. KB/VM-1 did show reduced accumulation of VP16 as in KB/VM-2 or KB/VM-4, but it had a normal level of topoisomerase II content as in KB cells. These data suggest that the reduced expression of DNA topoisomerase II, possibly combined with decreased permeability to the drugs, can account for the acquired VM26 resistance of KB/VM-2 and KB/VM-4 cells and also that the temperature-sensitive phenotype might not be obligatorily coupled with the reduced expression of topoisomerase II or the decreased permeability.

DNA Topoisomerases, Type I↗
PubMed1990

Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas.

Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.

Cell Differentiation↗
PubMed1990

Cytotoxic component(s) of Klebsiella oxytoca on HEp-2 cells.

A cytotoxic component(s) was detected in culture filtrates of Klebsiella oxytoca isolated from patients with antibiotic-associated hemorrhagic colitis. Eleven of 12 isolates exhibited cytotoxicity on HEp-2 cells. The cytotoxic activity of K. oxytoca strain MH43-1 was stable for the treatment of 60 C for 30 min, but inactivated by the treatment of 100 C for 15 min. This cytotoxicity was not destroyed by the treatment with trypsin or pronase, and the component was filtrable through a membrane filter which cut off molecular weight 5,000.

Cells, Cultured↗
PubMed1990

Reversal by two dihydropyridine compounds of resistance to multiple anticancer agents in mouse P388 leukemia in vivo and in vitro.

We investigated whether two representative 1,4-dihydropyridine derivatives, NK-250 and NK-252, could potentiate the antitumor activity of multiple anticancer agents including vincristine (VCR), vinblastine, vindesine and actinomycin D in drug-resistant tumor cells and their parental drug-sensitive tumor cells. NK-250 and NK-252 at 5-10 microM almost completely reversed VCR resistance in cultured VCR-resistant P388/VCR cells derived from the mouse drug-sensitive P388/S leukemia cell line and also potentiated the cytocidal activity of VCR in drug-sensitive P388/S cells. NK-250 and NK-252 at 1-10 microM inhibited the photoaffinity labeling by [3H]azidopine of the cell-surface 170,000-molecular-weight P-glycoprotein. In chemotherapeutic experiments with leukemia-bearing mice, NK-250 or NK-252 was orally administered in combination with different drugs of the MDR phenotype administered intraperitoneally. The antitumor activity of the various combinations was found to be augmented in mice bearing P388/S- and P388/VCR-leukemia. Among the combinations examined, the combination of NK-250 and VCR was the most effective. These two 1,4-dihydropyridines, NK-250 and NK-252, are unique compounds because they were effective not only in circumventing the drug resistance, but also in potentiating the action of antitumor drugs against drug-sensitive tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

A pediatric ventricular assist device: its development and experimental evaluation of hemodynamic effects on postoperative heart failure of congenital heart diseases.

To evaluate the effectiveness of a pediatric ventricular assist device (VAD), hemodynamic effects of the VAD were investigated experimentally in two types of postoperative profound heart failure models of congenital heart disease. In the model I Fontan or modified Fontan operation model, right ventricular pump function was excluded surgically and a shunt between the right atrium and the pulmonary artery was constructed in four dogs. With a VAD between the left atrium and the aorta, pressure gradient across the lung and the cardiac output increased. Right ventricular failure was induced surgically and high pulmonary vascular resistance was made by injection of glass beads in five dogs in model II. Cardiac output increased and the right atrial pressure decreased when a VAD between the right atrium and the pulmonary arterial trunk was activated. In conclusion, the VAD will become a promising modality to manage pediatric profound heart failure cases.

Animals↗
PubMed1990

Effects of cardiac assist on the bulk and regional mechanics of the ischemic left ventricle in dogs.

Pneumatically driven left ventricular assist devices (LVADs) were implanted between the left atria and the descending thoracic aortas of dogs and were counter-pulsated synchronously with the electrocardiogram at 1:1 and 2:1 duty ratios. Seven pairs of miniature sonomicrometers were implanted into the left ventricle (LV) to measure the LV muscular length and diameter. Ischemia was induced by the ligation of the left anterior descending coronary artery (LAD). Bulk and regional mechanical work were calculated from these dimensions and the left ventricular pressure. LVAD reduced the bulk work in the ischemic and normal hearts not only in the 1:1, but also in the 2:1, pumping modes. The left ventricular bulk work measured under the pump-off condition decreased progressively until around 2 h after the LAD ligation, and thereafter, it became constant. The regional myocardial work in the normal area of the ischemic heart was significantly decreased by the LVAD pumping (by 55%), whereas that in the ischemic area remained at near zero level regardless of pumping or nonpumping. The results obtained indicated that LVAD is useful not only to rest the severely damaged natural heart, but also to maintain the viability of ischemic myocardium.

Animals↗
PubMed1990

Continuous in-line monitoring of oxygen delivery to control artificial heart output.

In order to evaluate the pump output control based on the oxygen delivery to peripheral tissues, arterial and mixed venous hemoglobin content ([Hb]) and oxygen saturation (SO2) were continuously monitored in three biventricular bypass animals (3-, 6-, and 40-day experiments) with fibrillating ventricles. The specially developed oxygen sensors were mounted in the outflow ports of the artificial hearts to measure [Hb] and SO2. One animal was exercised on the treadmill at 2.0 mile/h for 15 min with pump flows fixed to deliver oxygen of (a) above 13 cc/min/kg, (b) 10, and (c) 9. In (a), the mixed venous saturation (SvO2) dropped to approximately 25% with no increase in the blood lactate level. In (b) and (c), the SvO2 decreased to approximately 10-15% with increase in blood lactate levels from 4 to 10-30 mg/dl. Also, the recovery of the SvO2 in these groups following the termination of the exercise was slower in comparison to (a). The lower limit of the SvO2 level that would create oxygen debt situation in the peripheral tissues was approximately 25-30% for the exercise of 2.0 mile/h. The SvO2 reflects changes in respiratory status, pump output, hemoglobin level, and metabolism, and is thus a useful indicator to diagnose quickly the circulatory status as well as possibly to control the artificial heart output.

Animals↗
PubMed1990

Trehalose levels and survival ratio of freeze-tolerant versus freeze-sensitive yeasts.

Five freeze-tolerant yeast strains suitable for frozen dough were compared with ordinary commercial bakers' yeast. Kluyveromyces thermotolerans FRI 501 cells showed high survival ability after freezing when their resting cells were fermented for 0 to 180 min in modified liquid medium, and they grew to log and stationary phases. Among the freeze-tolerant strains of Saccharomyces cerevisiae, FRI 413 and FRI 869 showed higher surviving and trehalose-accumulating abilities than other S. cerevisiae strains, but were affected by a prolonged prefermentation period and by growth phases. The freeze tolerance of the yeasts was, to some extent, associated with the basal amount of intracellular trehalose after rapid degradation at the onset of the prefermentation period. In the freeze-sensitive yeasts, the degree of hydrolysis of trehalose may thus be affected by the kind of saccharide, unlike in freeze-tolerant yeasts.

Disaccharides↗