Beneficial effects of combined use of phosphoenolpyruvate and gadolinium chloride on preservation-reperfusion liver injury in rats.
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Animals↗
Biomedical subjects
K Takeda
Publications and source records attributed to K Takeda.
[A case of common bile duct cancer responding to MMC leucovorin, 5-FU, and UFT combination chemotherapy and radiation].
A case of unresectable common bile duct cancer involving the portal vein and with Virchow lymph node metastasis was treated with MMC, Leucovorin, 5-FU and UFT combination chemotherapy as well as radiation. The case was a 71-year-old female who was admitted to the hospital with vomiting and anorexia. Abdominal US study showed obstructive jaundice. The PTCD tube was pierced to dilate the intrahepatic bile duct. Bile juice cytology was class V. Abdominal CT showed paraaortic lymph node metastasis. Angiography revealed portal vein invasion, and the diagnosis was unresectable common bile duct cancer. We started anticancer therapy and radiation. The anticancer therapy selected was MMC, LEUCOVORIN, 5-FU and UFT combination chemotherapy. After 2 cycles of the treatment, Virchow lymph node completely disappeared and the symptoms diminished. These combination therapies were effective for common bile duct cancer.
Aged↗
Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A.
Waardenburg syndrome type 2 (WS2) is a dominantly inherited disorder characterized by a pigmentation anomaly and hearing impairment due to lack of melanocyte. Previous work has linked a subset of families with WS2 (WS2A) to the MITF gene that encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif and that is involved in melanocyte differentiation. Several splice-site and missense mutations have been reported in individuals affected with WS2A. In this report, we have identified two novel point mutations in the MITF gene in affected individuals from two different families with WS2A. The two mutations (C760--> T and C895--> T) create stop codons in exons 7 and 8, respectively. Corresponding mutant alleles predict the truncated proteins lacking HLH-Zip or Zip structure. To understand how these mutations cause WS2 in heterozygotes, we generated mutant MITF cDNAs and used them for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose the DNA-binding activity and fail to transactivate the promoter of tyrosinase, a melanocyte-specific enzyme. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two families with WS2A in the present study are caused by loss-of-function mutations in one of the two alleles of the MITF gene, resulting in haploinsufficiency of the MITF protein, the protein necessary for normal development of melanocytes.
Amino Acid Sequence↗
[Efficacy of left atrial only procedure for the treatment of chronic atrial fibrillation associated with mitral valve disease].
We supposed that chronic atrial fibrillation originated as a result of discontinuity of the refractory period of the dilated left atrium in the mitral valvular disease. We then performed left atrial only procedures to treat the chronic atrial fibrillation (AF) associated with mitral valve disease. These procedures were the left atrial isolation and the modified left sided maze procedure, consisting of isolation of all pulmonary veins and cryoablation to the posterior wall of the left atrium, in addition to excision of the left atrial appendage. Twenty-eight patients underwent these procedures over the past thirty months. Patient ages and the duration of AF ranged from 37 to 71 years and from 0.5 to 26 years, with an average of 8.3 years, respectively. Chronic AF disappeared in twenty-four patients (86%) at discharge. Three patients with severe tricuspid insufficiency had sustained AF and one patient had atrial flutter postoperatively. Three patients showed sick sinus syndrome postoperatively and two of these required a DDD pacemaker. Severe tricuspid regurgitation (p < 0.020) was the factor in recurrence of AF. Left atrial only procedures were effective in the treatment of chronic AF associated with mitral valvular disease.
Adult↗
Blood pressure at health screening as a predictor of coronary heart disease in Kyoto.
AIM: Most epidemiologic studies that have evaluated coronary risk factors have measured either mortality or morbidity of coronary artery disease (CAD) as endpoints. However, earlier detection and elimination of coronary risk factors are crucial. We therefore performed Master's double (i.e. 1.5 min x 2 = 3 min) two-step exercise electrocardiograph (ECG) test in apparently healthy asymptomatic subjects (men, n = 2274; women, n = 959) to elucidate the risk factors for early-stage CAD or silent myocardial ischemia. METHODS: We examined the possible association of blood pressure at health screening and other suspected risk factors with exercise ECG test performance. The ischemic ECG response was determined by (1) > or = 0.5 mm horizontal or sagging S-T segment depression, (2) > or = 2.0 mm J-shaped S-T segment depression, or (3) T inversion in post-exercise ECG. RESULTS: We found that 4.7% of men and 10.6% of women exhibited ischemic responses. Among males, the ischemic responders to the exercise ECG test had higher systolic and diastolic blood pressure. In addition, the male ischemic responders were older, had a higher obesity index, higher serum cholesterol, triglyceride, low-density lipoprotein (LDL)-cholesterol, protein, glucose, and uric acid levels, and a lower serum potassium level than normal responders. In contrast, the female ischemic responders to the exercise ECG test had higher systolic pressure, and higher serum cholesterol, LDL-cholesterol, and protein levels than normal responders. Mean blood pressure was correlated positively with most of the other coronary risk factors, and mild hypertensives and hypertensives had abnormal lipid, glucose, and uric acid levels in both sexes. A comparison of risk factors by age group revealed that only younger and middle-aged ischemic responders had higher blood pressure, serum cholesterol, and glucose levels than normal responders of both sexes, and that in older subjects all the differences between normal and ischemic responders became insignificant. CONCLUSIONS: Elevated blood pressure at health screening, together with abnormal lipid and glucose metabolism, might be risk factors predicting early-stage or silent CAD. The elimination of these risk factors in younger men and women seems to be important.
Adult↗
[Epidural catheterization dose not meet our expectation].
According to the roentgenographically confirmed intervertebral space at which an epidural catheter was placed, 241 patients who underwent abdominal or orthopedic hip surgery were allocated into 3 groups. Groups A, B, and C received epidural catheterization at Th7-10, Th10-L1, and L1-4, respectively. In each group, we examined the intervertebral space, which the anesthesiologist who had placed epidural catheter had determined, and the one which had been confirmed roentgenographically. We also investigated the catheter movement during the postoperative period. Catheters were barely placed at the same intervertebral space which had been confirmed roentgenographically. Considering the iliac crest as a landmark of L3-4 intervertebral space, the puncture point agreed with the roentgenographically confirmed intervertebral space with a percentage of 33 in group A. The extent of agreement increased up to 47 and 55 percent, in groups B and C, respectively. In contrast, when we counted down from the cervical prominent vertebra, a landmark of C7, the agreement was better in group A (55%) than in group C (33%). In the postoperative period, catheters came out more frequently in groups A and B than in group C, resulting from the early ambulation in abdominal surgery groups. There results suggest that, to place the epidural catheter more properly, (1) we should start to count from the landmark which is close to the puncture point and (2) we should keep it in mind that catheters come out accidently in patients who are encouraged to ambulate in the early postoperative period.
Aged↗
[Intraoperative ST-T depression during extreme hemodilution].
A 45 year old woman undergoing a removal of cerebral arterio-venous malformation, suffered an unexpected massive bleeding. With transfusion of plasma constituents, her hemoglobin concentration decreased to about 5 g.dl-1, but her hemodynamic parameters remained unchanged. Electrocardiogram showed a depressed ST segment, indicating myocardial ischemia, when hemoglobin concentration decreased to 2.2 g.dl-1. Accompanied with the ECG change, her blood pressure fell down from 110/70 mmHg to 70/40 mmHg and an elevation of CVP was observed. With rapid transfusion of concentrated red cell and whole blood, hemodynamic parameters as well as ECG change were restored to normal. With hemodilutional myocardial ischemia which is caused by acute massive bleeding, hemoglobin concentration of about 2 g.dl-1 would be critical.
Anesthesia, General↗
Free thyroxine concentrations in serum measured by equilibrium dialysis in chronic renal failure.
The serum concentration of free thyroxine (FT4) is often low in patients with chronic renal failure (CRF) with low serum concentrations of triiodothyronine (T3). We evaluated the serum FT4 concentration by using both an equilibrium dialysis RIA kit (D-FT4) and a labeled-antibody kit (M-FT4) in two different groups of CRF patients, undergoing chronic hemodialysis (HD, n = 145) or not (non-HD, n = 30), and in a group of normal healthy subjects (n = 58). Thyroid peroxidase antibodies and thyroglobulin antibodies were not detected in any patient. Serum FT4 concentrations (mean +/- SD, pmol/L) by the D- and M-FT4 assays were, respectively, 21.5 +/- 4.6 and 16.6 +/- 2.0 in the healthy subjects, 17.8 +/- 4.3 and 13.9 +/- 3.6 in the non-HD patients, and 16.9 +/- 4.9 and 10.7 +/- 1.9 in the HD patients. By the D-FT4 assay, results for both CRF groups were significantly different from those for the healthy group (P <0.01), as were the results for each pair of groups by the M-FT4 assay (P <0.01). FT4 values were reported as being within the healthy reference range by D-FT4 in 73 of 113 HD subjects who had low T3 and low M-FT4 values. Serum FT4 concentrations measured by both assay kits showed a significant inverse correlation with the serum concentration of creatinine (P <0.01), but the serum concentrations of sex-hormone-binding globulin did not differ significantly among the three groups. Our results indicate that the low FT4 concentration measured by D-FT4 in patients with CRF, particularly those on HD, probably reflects the actual, mild nonthyroidal illness of renal failure.
Adult↗
The effects of electrolyte, lactate, high-concentrated glucose, and dialysate on peritoneal mesothelial cells.
In order to investigate which component of dialysate is responsible for mesothelial cell damage, we studied the chronic cytotoxicity to mesothelial cells by using four types of solution. Four different types of solution (Ringer's solution, lactate, high-concentrate glucose, and 4.25% Dianeal) were prepared and injected into the abdominal cavity of five ddY-mice, 5 mL every day for one month. The monolayer of the mesothelial cells was carefully removed from the liver surface by the imprint technique. Then, the mesothelial cell damage was evaluated by using trypan blue staining and comparing the results. Trypan blue-stained cells in 100 mm2 were observed in 7.0% of the control, 15.4% of the Ringer's solution, 18.7% of the lactate, 23.2% of the high-concentrate glucose, and 22.4% of the 4.25% Dianeal group, respectively. The damaged cells were significantly (p < 0.05) greater in the 4.25% Dianeal group than in the control group, and those in the high-concentrate glucose group also appeared to be greater in number compared to the control group It is concluded from these results that damage to the mesothelial cells is induced by chronic exposure to high-glucose dialysate, and its pathogenesis is deeply related to high concentration of glucose.
Animals↗
Effects of the new calcium antagonist efonidipine hydrochloride on resting and exercise hemodynamics in patients with stable effort angina.
The action of efonidipine hydrochloride ((+/-)-2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1, 3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxy late hydrochloride ethanol, CAS 1110011-76-8, NZ-105) a new dihydropyridine calcium antagonist, on cardiac hemodynamics at rest and during exercise as well as plasma concentration and pharmacokinetic parameters were studied in 9 patients with angina pectoris. NZ-105 was administered 40 mg once daily for a week and cardiac hemodynamics parameters were measured at rest and during exercise using a bicycle ergometer before and after treatment. All patients showed anginal symptoms during exercise before treatment, while only 4 showed anginal symptoms during exercise after treatment. Improvement on electrocardiograms (ECG) (> 0.1 treatment mV) was detected in 4 out of 9, and NZ-105 was recognized to have an anti-anginal action. The mean plasma concentration of NZ-105 at the time was 14.5 ng/ml. At rest, reduction in blood pressure and decrease in total peripheral vascular resistance were observed, however, NZ-105 showed no effect on heart rate, cardiac index, pulmonary arterial pressure and central venous pressure. During maximum exercise, a decrease in total peripheral vascular resistance, reduction in pulmonary arterial pressure and central venous pressure, increasing tendency of left ventricular ejection fraction, and increase in cardiac index were observed. However, NZ-105 showed no effect on heart rate and blood pressure. Based on the results mentioned above, cardiac hemodynamics of NZ-105 during exercise, featured primarily, reduction of afterload and improvement of cardiac functional deterioration due to exercise. In conclusion, NZ-105 is useful in patients with ischemic cardiac diseases by improving hemodynamics and ECG findings during exercise in patients with effort angina.
Angina Pectoris↗
Comparison of basophil histamine release, eosinophil cationic protein and non-specific airway responsiveness between mite-sensitive asthmatic and non-asthmatic children and non-allergic controls.
To understand the relevance of allergy to the development of asthma in children, we examined basophil histamine release (HR) with Df antigen, blood eosinophil counts, serum eosinophil cationic protein (ECP) levels, and bronchial responsiveness to methacholine (PC20) in three groups of children, including 36 asthmatics with high RAST titre for Df (group 1), 36 non-asthmatics with similarly high RAST titre for Df (group 2) and 21 non-asthmatics with negative RAST titre for Df (group 3). The amount of Df antigen inducing 50% HR from basophils did not vary significantly between group 1 and 2 (P > 0.05), while none of the cells responded to higher concentrations of Df in group 3. The mean number of blood eosinophils and level of serum ECP were highest in group 1, and lowest in group 3, with group 2 being intermediate, and the differences were significant between all three groups (P < 0.01). The mean PC20 value was the lowest in group 1, intermediate in group 2, and the highest in group 3, and the differences were significant between all three groups (P < 0.01). While correlation studies showed that PC20 values of group 2 subjects significantly correlated with their eosinophil numbers (r = -0.48, P < 0.01) and ECP levels (r = -0.49, P < 0.01), such correlations were not found in group 1 subjects. These results suggest that the degree of the eosinophilic inflammation caused by the allergic reaction to mites is an important factor in determining the clinical expression of asthma in atopic subjects.
Adolescent↗
Estimation of ascending aortic pressure from radial arterial pressure using a generalised transfer function.
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Adult↗
[Evaluation of regional cerebral blood flow in hippocampus by 99mTc-ECD SPECT: comparison with 123I-IMP SPECT].
We evaluated regional cerebral blood flow in the hippocampus in 21 patients with neurological disorders by 99mTc-ethyl cysteinate dimer (ECD) SPECT and compared the findings with those by 123I-N-isopropyl-p-iodoamphetamine (IMP) SPECT. In all subjects, SPECT was taken using ECD (740 MBq) and IMP (167 MBq) using high performance SPECT (3-head SPECT, Toshiba GCA-9300A/HG) within 3 weeks interval. Regional uptake in the hippocampus was examined in the coronal sections and images parallel to the longitudinal axis of hippocampus. ECD and IMP showed similar hippocampal uptake in 9 cases, but ECD showed less uptake than IMP in 12 cases (57%). Regional counts in the hippocampus were related to the counts in the lateral temporal cortices and the mean count ratio was lower in ECD by 8.8% than that in IMP (0.73 +/- 0.11 vs. 0.80 +/- 0.11, p < 0.001). In 6 patients suspected to have hippocampal lesion (4 cases of memory disturbance and 2 cases of epilepsy), all cases showed decreased uptake of ECD in hippocampus, but only 3 cases showed decreased uptake of IMP. This is suggestive to be relevant to the difference in the retention mechanism of ECD and IMP, but further investigation should be performed.
Aged↗
Voltage-dependent currents and modulation of calcium channel expression in zona fasciculata cells from rat adrenal gland.
1. Whole-cell voltage-activated currents from single zona fasciculata (ZF) cells from rat adrenal glands were studied. T- and L-type Ca2+ currents and a slowly inactivating A-type K+ current were the three major currents observed. 2. In freshly isolated cells, the A-type K+ current and the T-type Ca2+ current were predominant. The A-type current was activated at -50 mV and inhibited by 4-amino-pyridine with a half-maximal block (IC50) at 130 microM while the T-type current was activated at -70 mV and blocked by Cd2+, Ni2+ and amiloride with IC50 values of 24.1, 132.4 and 518.9 microM, respectively. 3. Under current clamp, depolarizing current pulses produced a single Ca2+ action potential with Cs+ in the pipette internal solution. Upon replacement of Cs+ by K+, the half-amplitude width of the action potential was shortened and membrane potential oscillations were seen after the spike. 4. In freshly isolated cells and during the first 24 h after plating, the T-type current was observed in all cells, with L-type current being observed in < 2% of cells, even in the presence of (+)SDZ 202,791, a dihydropyridine Ca2+ channel agonist. With time in culture, the T-type current disappeared, and a high-voltage-activated L-type current became increasingly apparent. In cells tested after > 2 days in culture, (+)SDZ 202,791 potentiated L-type current by 407 +/- 12% and the antagonist (-)SDZ 202,791 blocked this increase. The L-type current was activated between -30 and -20 mV and was sensitive to nitrendipine and omega-conotoxin GVIA. 5. Pre-incubation of cultured ZF cells with adrenocorticotrophic hormone (ACTH) or vasoactive intestinal peptide (VIP) for 3 days resulted in a high, sustained level of expression of T-type current, with a mean amplitude of 34.2 +/- 5.5 pA pF-1 for ACTH-treated cells compared with 3.4 +/- 1.8 pA pF-1 for untreated cells. Cycloheximide strongly inhibited this effect. Neither treatment affected L-type current expression. 6. The expression of both Ca2+ current types was unaffected by pre-incubation with 8-bromo-cAMP or forskolin. The protein kinase A antagonist, H89, did not inhibit the ACTH-induced upregulation of T-type Ca2+ currents. 7. It is concluded that the main voltage-dependent currents involved in cell excitability and steroidogenesis in rat adrenal ZF cells are an A-type K+ current and a T-type Ca2+ current. The physiological role and control of expression of L-type Ca2+ channels in rat ZF cells remain less clear.
Action Potentials↗
Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice.
Eight muteins of recombinant human tumor necrosis factor-alpha (rhTNF; 1SSSRTP...29RR...155L), in which 29Arg was replaced by another amino acid, were prepared and their anti-tumor effects in BALB/c mice bearing Meth A fibrosarcoma were evaluated. The therapeutic indices, which mark the extent of the therapeutically effective dose, of V29 (29Arg-->Val) and D29 (-->Asp) were 3.5 and 3.2, respectively, whereas that of rhTNF was 1.4. Clearly, the therapeutically effective range of these muteins was extended along with a decrease in lethal toxicity. V29 did not produce hypotension in the rat system, but D29 did. In addition, V29 showed potent anti-tumor activity (Tumor Volume Inhibition Rate = 81% on day 15 after implantation) in 3 consecutive injection schedules despite the decreases in toxicity compared with rhTNF. The relative receptor binding constant was determined using HEp-2 cells (expressing mainly 55-kDa-TNF receptor; p55R) and HL60 cells (expressing mainly 75-kDa-TNF receptor; p75R), and revealed that the reduced toxicity of V29 in mice was due to the reduced binding to p55R (34% of rhTNF). On the other hand, the ratio of the constants HEp-2/HL60 of V29 was 11 in comparison with the value of 1.0 for rhTNF, suggesting that this mutein binds preferentially to p55R. The biological activities in human cell lines (HEp-2 and HL60 cells) correlated well with the binding activities to each receptor in vitro. Therefore, the much lower toxicity and the potent anti-tumor activity of this mutein suggest that V29 merits further investigation in pre-clinical and clinical trials.
Amino Acid Sequence↗
Superconductivity of ZrRuSi prepared at high pressure.
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Journal Article↗
Dynamics of a photoinduced phase transition in polydiacetylene crystals.
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Journal Article↗
Young borderline hypertensives are hyperreactive to mental arithmetic stress: spectral analysis of R-R intervals.
To investigate whether sympathetic tone and its reactivity to stress are increased in borderline hypertension, we compared pressor and autonomic nervous responses to mental arithmetic stress in male borderline hypertensives (BH) and normotensive volunteers (NT). Three age groups, 30, 40 and 50-year-old groups, which included 30 to 39, 40 to 49 and 50 to 59-year-old subjects, were studied. Fractional LF (%LF), fractional HF (%HF) and L/H, obtained from the power spectrum of R-R intervals, were used as indices of autonomic nervous function. Baseline autonomic nervous indices did not differ between NT and BH of any age group. Blood pressure rose higher during mental arithmetic stress in 50 than in 30-year-old NT but not in comparable age groups of BH. Pressor responses were augmented in BH compared to NT only in the 30-year-old group. However, the differences were not significant when pressor responses were expressed as percent increases in blood pressure. Both %L and L/H increased during arithmetic stress. The increase in %L did not differ between NT and BH but that in L/H (% delta L/H) was larger in 50 than in 30-year-old NT. % delta L/H was larger in BH than in NT only in the 30-year-old group. These findings suggest that both pressor and autonomic nervous responses to metal arithmetic stress were altered by aging and augmented in BH compared to NT in the 30-year-old group.
Adult↗