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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 19 recordsLinked to original sources
PubMed1992

Different sensitivities of human esophageal cancer cells to multiple anti-cancer agents and related mechanisms.

Mechanisms responsible for drug resistance in human esophageal cancer cell lines were investigated. Three cell lines established from human esophageal carcinoma (TE-1, SH-1, and TH) showed different sensitivities to vindesine, vincristine, cisplatin (CDDP), etoposide (VP-16), and pepleomycin. Both SH-1 and TH cell lines were twofold to sevenfold more resistant to pepleomycin, vindesine, and vincristine than TE-1 was. SH-1 showed twofold more resistance to CDDP than either TE-1 or TH did, and TH and TE-1 showed a 3-fold or 1.5-fold more resistance, respectively, to VP-16 than SH-1 did. The accumulation of tritiated vincristine in SH-1 and TH was approximately 50% that in TE-1. Two multidrug resistance reversal agents, cepharanthine and a synthetic dihydropyridine analogue (NK-252; Nikken Chemicals, Saitama, Japan), potentiated the cytocidal actions of vindesine against SH-1, TH, and TE-1 cells, with no apparent expression of P-glycoprotein in the three cell lines. The glutathione S-transferase pi gene was expressed in all three cell lines. DNA topoisomerase II levels were lowest in TE-1, followed by SH-1 and TH, although the accumulation of tritiated VP-16 was less in both TH and SH-1 than in TE-1. Differential sensitivities to anti-cancer drugs appear to be mediated through pleiotropic mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography.

Iodine-123 metaiodobenzylguanidine (mIBG) is taken up by sympathetic nerve endings, allowing scintigraphic imaging of myocardial sympathetic innervation. We investigated the denervated but viable canine myocardium after acute myocardial infarction by serial mIBG and thallium-201 chloride (201TlCl) single photon emission tomography (SPET). In 12 dogs, acute myocardial infarction was produced by ligation of the left circumflex coronary artery. Images of mIBG and thallium SPET were obtained 6 h, 1, 4 and 6 weeks later. The defect size was calculated in percentage points from short axial views, and the 123I-mIBG/201TlCl ratio was determined. The uptake ratio was high at 1 week but gradually decreased. Three dogs were killed at each time point, and tissue samples were obtained from infarcted (both 201TlCl and 123I-mIBG defects), peri-infarcted (123I-mIBG defect and 201TlCl normal) and normal myocardium (both mIBG and 201TlCl normal). The changes in tissue content of noradrenaline in these lesions were measured. Noradrenaline tissue content gradually recovered in the peri-infarcted area. However, no recovery was noted in the infarcted area at 6 weeks. We conclude that sympathetic denervation and re-innervation occur following acute myocardial infarction, and the denervated but viable myocardium could be detected non-invasively by combined mIBG and thallium SPET.

3-Iodobenzylguanidine↗
PubMed1992

Constitutive homologous recombination between mitochondrial DNA and a linear mitochondrial plasmid in Physarum polycephalum.

In one particular myxamoebal strain (NG7; mF+) of Physarum polycephalum, a linear mitochondrial plasmid (mF plasmid) which promotes mitochondrial fusion has been identified. A mating between mF- strains, that do not carry the mF plasmid, resulted in uniparental inheritance of the mtDNA. In matings between mF+ and mF- strains a recombination occurred between the mtDNA and the mF plasmid, and recombinant mtDNA was generated with the end of the mF plasmid as its ends. The DNA sequences of the recombination site in the mtDNA and the mF plasmid, and of the recombinant mtDNA, revealed that the mF plasmid had a 473-bp sequence that was identical to, but slightly shorter than, a 477-bp sequence of the mtDNA. This so-called identical sequence was found at the junction between unique sequences of the mF plasmid and the mtDNA in the recombinant mtDNA. Thus, the recombination between the mtDNA and the mF plasmid was due to reciprocal crossing-over at the identical sequence.

Animals↗
PubMed1992

Augmentative effects of tumor necrosis factor-alpha (human, natural type) on polymorphonuclear leukocyte-derived superoxide generation induced by various stimulants.

We investigated the effects of tumor necrosis factor-alpha (human, natural type: n-TNF) on polymorphonuclear leukocyte (PMN)-derived superoxide generation by the new method of Cypridina luciferin analog-dependent chemiluminescence, which had high sensitivity and specificity to superoxide. Preincubation of PMNs with n-TNF for 3 min increased PMN-derived superoxide generation induced by phorbol myristate acetate, A23187, opsonized zymosan and N-formyl-methionyl-leucyl-phenylalanine in a concentration dependent manner (0.5-50 Japan reference units/ml of n-TNF). In addition, the enhanced PMN-derived superoxide generation by n-TNF showed a positive correlation to the preincubation time of PMNs with n-TNF (3-15 min). However, a direct incubation of PMNs with n-TNF for 1 h did not induce superoxide from PMNs without the above stimulants. The augmentative effects of n-TNF on PMN-derived superoxide generation should be useful in the PMN-mediated host defense mechanism, such as bactericidal and antitumor activity. The local concentration of n-TNF and the n-TNF-PMN contact time are considered very important in obtaining these effects more efficiently in addition to the presence of PMN-stimulants including complements, chemotactic peptides and phorbol esters.

Dose-Response Relationship, Drug↗
PubMed1992

DNA topoisomerase-targeting antitumor agents and drug resistance.

A review of the chemotherapeutic agents which have been developed by targeting DNA topoisomerase I and II is presented. Camptothecins as topoisomerase I-targeting agents and newly developed topoisomerase II-targeting agents with unique properties are expected to be promising anticancer agents in the near future. An important issue is how cellular sensitivity to these agents is controlled. One approach is to establish and characterize drug-resistant human cancer cell lines, which would provide powerful tools to understand their intracellular target sites and also the mechanisms for acquirement of drug resistance to topoisomerase inhibitors. Drug resistance to topoisomerase-targeting agents appears to be closely correlated with two events, namely decreased expression and point mutation of topoisomerase genes.

Antineoplastic Agents↗
PubMed1992

Treatment of acute profound heart failure by ventricular assist device.

Sixteen patients with acute profound heart failure (HF) have been treated with the left ventricular assist device (LVAD), nine of them were successfully weaned from LVAD, and three of them were discharged and survived longer. Decompression of the left ventricle (LV) at the beginning will prevent overextension of impaired myocardium and accelerate scar formation. Gradual increase of LV work will promote the compensation ability of the residual myocardium. We found that continuous LVAD assistance can give time for the impaired heart to recover while maintaining normal circulation. For patients with profound HF which is beyond the limit of intra-aortic balloon pumping's (IABP) capability, LVAD is a more powerful and effective means. Although the heart recovered, many patients later died of multiple organ failure (MOF) which was probably caused by prolonged ischemia before LVAD application. For completely successful recovery from profound HF, diagnosis and deciding to use LVAD should not be delayed. It should be applied before major organs including the heart itself suffer irreversible damage. We have established a systematic therapeutic concept of treating acute HF patients using assisted circulation including LVAD.

Acute Disease↗
PubMed1992

Developmental process of Cryptosporidium in the intestine and bursa of Fabricius of chickens.

The developmental process of a Cryptosporidium isolated in Japan in the chicken intestine was investigated by scanning (SEM) and transmission electron microscopies (TEM). The parasites were detected in the ileum, cecum, colon, cloaca and bursa of Fabricius (BF). The intensity of infection tended to peak later in the BF than ileum. Trophozoites and schizonts were detected in all the portions of intestine, and were dominant in the developmental stages. Although macrogamonts were the secondary dominant stage, they were absent in the ileum and cecum at 60 hr postinoculation (PI). A few microgamonts were detected in the ileum at 36 hr PI and in the BF on day 19 PI. Oocysts were observed in the ileum at 48 hr PI and in the BF on day 19 PI.

Animals↗
PubMed1992

[A case of systemic lupus erythematosus complicated with monoclonal CD5 + B cell proliferation suspected as chronic lymphocytic leukemia].

A case of systemic lupus erythematosus (SLE) complicated with monoclonal CD5 + B cell proliferation in peripheral blood and bone marrow is reported. A 59-year-old man suffering from left chest pain was admitted to the hospital because of thrombocytopenia (platelets 1.9 x 10(4)/mm3). The diagnosis of SLE was made from (1) pleuritis (2) autoimmune thrombocytopenia (3) positive anti-DNA antibodies, positive LE cell preparation (4) positive antinuclear antibodies. Prednisolone 60mg per day was started. From that time monoclonal CD5 + B cells began to increase in peripheral blood (maximum lymphocyte counts 11000/mm3, CD5 + B cells 77.6%) and bone marrow, and the complication of chronic lymphocytic leukemia (CLL) was suspected. It is said that patients of CLL often have various autoantibodies, and in about 15% of CLL patients complicate autoimmune hemolytic anemia, but those who develop collagen diseases are rare. And while lymphoid malignancies occur more often in the patients of SLE in comparison with normal subjects, the reports of the patients who complicate the proliferation of monoclonal CD5 + B cells like CLL are very few. But from many facts that indicate the relation between CD5 + B cell or its proliferation and the production of autoantibodies or autoimmune diseases, we consider this case worth to be reported.

Antigens, CD↗
PubMed1992

[High incidence of left ventricular thrombosis and systemic embolism in patients with left ventricular assist system].

The purpose of this study was to determine the incidence of left ventricular (LV) thrombosis and systemic embolism in 14 patients with LV assist systems. Echocardiography was used to detect LV wall motion abnormalities, intracavitary smoke-like echoes and thrombosis, and the effect of anticoagulant therapy was serially examined. During full assist of the circulation, the aortic valve did not open in any patient. Smoke-like echoes were observed in 9 patients (64%) and thrombi in 8 (57%). The thrombus developed within the first 3 assist days. Systemic anticoagulant therapy decreased the thrombus size in only 3 patients, but there was a possibility of intracranial or mediastinal bleeding in other 3 patients. Systemic embolism was noted in 7 of 11 autopsy patients (64%). The characteristic finding was that there were multiple embolized organs, such as the brain, kidneys, spleen and liver, in all patients. Development of a thrombus is a serious complication in all patients with LV assist systems. However, the problem does not lie in the assist system but in the left ventricle of the patient's own heart. It is also noteworthy that systemic anticoagulation is not effective for an LV thrombus. A new method of assisting the failing heart, or a new anticoagulant delivery technique for the LV cavity to prevent LV thrombus development is needed.

Adult↗
PubMed1992

Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat.

Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.

Animals↗
PubMed1992

[Comparison of long-term patency rates of transluminal angioplasty and bypass grafting].

We have applied transluminal angioplasty (TAP) and bypass grafting (BG) to the lower-limb ischemia for ten years since 1982. We have treated 176 cases (194 limbs) by TAP and 250 cases (323 limbs) by BG. The TAP treated group was divided into two groups. The first was classified as a stenotic artery group (TAPs) and the other was as an obstructive artery group (TAPs). BG was also divided into two groups, the first belonged to a ringed graft (RPTFE) while the other was a bypass with a saphenous vein (BG sv). The registered patent rates for TAP and TAPs are 61.2%, 75.1% recorded after 5 years and 51.4%, 57.0% after 7 years, respectively. The patent registry rates for BG and RPTFE are evaluated as being 64.2%, 82%, after 5 years and 48.2%, 82% after 7 years, respectively. The results showed that the patent registry rate for BG is significantly better than that of the TAP but the results indicate similarities between TAPs and RPTFE. As a conclusion, we recommend the use of TAP for the stenotic lesion of the artery and RPTFE for obstructive lesion of arteries.

Adolescent↗
PubMed1992

Long-term circulatory maintenance with a left-sided single artificial heart.

The purpose of this study is to examine the feasibility of long-term circulatory maintenance with only a left-sided single artificial heart that is inserted between the left atrium and the aorta to assist a nonfunctioning heart. The basic hemodynamics were determined in short-term experiments in goats (n = 4), and feasibility studies of long-term circulatory maintenance with a single artificial heart during cardiac arrest were performed in long-term experiments (n = 12). When pulmonary vascular resistance was less than 15,000 dynes .sec.cm-5.kg, which was twice the normal value, the circulation was well maintained with the single artificial heart alone, so long as the right atrial pressure was kept at 14 to 16 mm Hg. Under such conditions the flow yielded by the single artificial heart fluctuated between 80 and 140 ml/kg/min depending on the animal's demand, while the mean arterial pressure was kept above 80 mm Hg. The goats behaved normally, although retention of pleural effusion was a serious problem in maintaining normal circulation over a long-term. Maintaining the plasma total protein level above 6.0 gm/dl delayed the onset of retention or even prevented pooling of pleural effusion. The longest survival period to date has been 38 days. We conclude that when the pulmonary vascular resistance is less than twice the normal value and the total protein level is above 6.0 gm/dl, a left-sided single artificial heart alone can maintain normal circulation and provide time for patients with a nonfunctioning heart to undergo a further treatment, such as heart transplantation.

Animals↗
PubMed1991

Increased phosphorylation of DNA topoisomerase II in etoposide-resistant mutants of human cancer KB cells.

We have isolated two etoposide (VP16)-resistant cell lines, KB/VP-1 and KB/VP-2, from human cancer KB cells after stepwise exposure to increasing doses of VP16. KB/VP-1 and KB/VP-2 showed 30- and 50-fold higher resistance to VP16 and also 20- and 30-fold higher resistance to teniposide than the parent cell line. Furthermore, both resistant cell lines showed more than 2-fold cross-resistance to Adriamycin and daunomycin than KB cells. The levels of accumulation and outward transport of radioactive VP16 were similar in KB/VP-1, KB/VP-2, and KB. The activity of nuclear extracts of DNA topoisomerase II for both KB/VP-1 and KB/VP-2 assayed by decatenation of kinetoplast DNA was consistently similar to that of KB. However, in both immunoblot assay with specific anti-topoisomerase II antibody and Northern blot analysis with specific human DNA topoisomerase II complementary DNA, cellular levels of topoisomerase II in both resistant cell lines were less than one-tenth the level in KB. The cellular levels of DNA topoisomerase I, however, were similar between the mutants and their parent. A quantitative precipitation assay of covalent DNA-topoisomerase II complexes showed greatly reduced VP16-induced cleavages of 3'-32P-DNA by nuclear extracts of KB/VP-1 or KB/VP-2 cells in comparison with KB cells. The relative specific phosphorylation of DNA topoisomerase II was about 14- to 18-fold higher in the mutants than in the parental cells. Phosphoamino acid analysis of DNA topoisomerase II showed that serine was the phosphorylated amino acid in all three cell lines, KB, KB/VP-1, and KB/VP-2. These data suggest that reduced expression of DNA-topoisomerase II might account for the acquired VP16 resistance and reduced VP16-induced cleavages of DNA-topoisomerase II complexes in both VP16-resistant variants.

Carcinoma, Squamous Cell↗
PubMed1991

Delayed changes of vascular permeability in the cat's spinal cord following continuous electrical stimulation.

Liquefactive necrosis coexistent with alteration of vascular permeability was studied following electrical stimulation of the spinal cord. Evans blue albumen complex (EBA) (2.5%) was perfused one hour before electrical stimulation for 30 min with 10 mA current of 0.3 msec duration at a frequency of 20 Hz. Perfusion with saline and formalin was carried out at 0, 1, 3, 6 and 12 h after stimulation had been completed. Results were independent of the time lapse after completion of the stimulation. Liquefactive necrosis, swelling and moniliform degeneration and myelinoclasia of the myelin sheath were noted only in the external layer of the white matter. EBA leakage occurred, but there was no further expansion with time.

Animals↗
PubMed1991

Platelet aggregation induced by platelet-activating factor is suppressed by cystine protease inhibitor.

The effect of NCO-700, a cystine protease inhibitor, on platelet-activating factor-induced platelet aggregation was determined. A newly synthesized cystine protease inhibitor (calcium-activated neutral protease and cathepsin B inhibitor), NCO-700 (bis[ethyl (2R, 3R)-3-[(S)-methyl-1-[4-(2,3,4- trimethoxyphenylmethyl) piperazine-1-ylcarbonyl]butylcarbonyl]oxiran-2-carboxy late]sulfate), inhibited platelet-activating factor-induced platelet aggregation. The inhibition was dependent on the preincubation time with NCO-700 and on the concentration of the inhibitor. The release of serotonin was also inhibited almost completely by the 20-min preincubation with 10(-4) M NCO-700. Leupeptin also inhibited platelet-activating factor-induced platelet aggregation. But calcium-activated neutral protease inhibitor did not inhibit it. These observations suggest that NCO-700-sensitive protease(s) such as cystine protease may contribute to platelet aggregation induced by platelet-activating factor.

Animals↗
PubMed1991

Origins and conducting tracts of evoked spinal cord potentials in cats.

The origins and the conducting tracts of the evoked spinal cord potential elicited by sciatic nerve stimulation (spinal somatosensory evoked potential: spinal SEP) were studied in cats. The potentials were recorded at various levels of the intact spinal cord and partially resected spinal cord and analyzed with special reference to four negative potentials (N1, N2, N3, and N4 waves). The conduction velocities of N1, N2, N3, and N4 waves were 101.8, 52.7, 88.7, and 42.7 m/s, respectively. N1 and N3 waves are considered to originate from Group I fibers and to be conducted by second-order neurons ascending the ipsilateral-dorsolateral funiculus (dorsal spinocerebellar tract) after synaptic delays. N3 wave may have a longer synaptic delay than N1 wave. N2 and N4 waves are considered to originate from nerve fibers other than Group I and to be conducted primarily in the posterior funiculus. N1 and N3 waves have synaptic delays at the L3 level, but N2 and N4 appear to be conducted without synaptic delay. Therefore, N2 and N4 waves precede N1 and N3 at the upper lumbar and thoracolumbar junction levels, respectively. After that, N1 and N3 waves are conducted with greater velocity than N2 and N4 waves. Because of different conduction velocities, N1 overtook N2 and N3 overtook N4 at the midthoracic region. N2 and N1 waves had the shortest latency in the upper lumbar to thoracolumbar junction levels and the upper thoracic region, respectively.

Action Potentials↗