Biomedical subjects
Publications and source records attributed to T Takeda.
A complex translocation t(7;11)(7qter----7p15::11q13----11qter;11pter ----11p15::11q13----11p15::7p15----7pter) was detected in the leukemic cells from a 67-year-old woman with Ph chromosome negative chronic myelocytic leukemia. This translocation has not been previously reported in Ph-negative CML.
We have analyzed the function of the only ras homolog in S. pombe detectable by Southern blotting, ras1, which is homologous to mammalian ras genes and has been cloned. We have disrupted the ras1 gene and have replaced it with ras1Val17, which corresponds to a transforming variant of mammalian ras. Loss of ras1 activity by disruption results in the complete inability to mate. The cell body of a ras1- strain is extensively deformed, and a ras1-/ras1- diploid sporulates very poorly. Unlike RAS1 and RAS2 of S. cerevisiae, ras1 of S. pombe appears to have no effect on adenylate cyclase activity. This suggests that the target enzymes presumably modulated by ras proteins in signal transduction are not the same for all organisms.
To investigate the involvement of thyroid hormone on the release of atrial natriuretic polypeptide (ANP), we have measured immunoreactive ANP in the atria and plasma of experimental hyperthyroid and hypothyroid rats. Plasma ANP was higher (p less than 0.05) in hyperthyroid rats and was lower (p less than 0.05) in hypothyroid rats than in euthyroid rats. ANP content and concentration in the atria were lower (p less than 0.01) in hyperthyroid rats than in hypothyroid rats. An inverse correlation was found between the plasma ANP and ANP concentration in the atria (n = 15, r = 0.60, p less than 0.01). The results indicate an increased systemic release of ANP from the atria in hyperthyroidism and a decreased systemic release in hypothyroidism.
Human T-cell leukemia virus type I has a unique sequence, pX, between the env gene and the 3'LTR (long terminal repeat). This sequence codes for p40x, which was proposed to trans-activate transcription from the LTR. Recently, we identified novel pX proteins coded by frame III, which mostly overlaps frame IV (x-lor, coding for p40x), in a region also overlapped by frame II. To determine which product is responsible for the trans-acting function, we constructed an active provirus clone, pMTPX, that contained a genomic fragment of the env, pX and 3'LTR, and introduced site-directed mutations into the active site. The effects of various deletions and point mutations that distinguished each of the overlapping open reading frames (ORFs), II, III and IV, on trans-activation of pLTR-CAT were treated by co-transfection assays. The results showed that only mutations which affected p40x expression resulted in loss of activity for transcriptional activation. These findings clearly indicate that p40x coded by frame IV is responsible for the transcriptional activation of the LTR. This conclusion was confirmed by studies on expression of cDNA of pX mRNA.
In an attempt to find a reliable method to assess fever in patients with systemic lupus erythematosus (SLE), a multifactorial analysis was applied to the routine laboratory examinations, including white blood cell count (WBC) and serum globulin fraction concentrations. During 74 febrile episodes, 49 SLE patients showed increased disease activity and the remaining 25 febrile episodes were due to intercurrent infection. The two different groups of fever episodes were clearly separated by a principal component analysis using five variables from the routine laboratory tests, including WBC, serum alpha-1, alpha-2, beta, and gamma globulins. Discriminant analysis showed that 95% of 74 febrile episodes could be correctly classified as to the cause of fever when a combination of WBC and alpha-2 globulin level was used as variables. A simple discriminant formula which we calculated was considered to be of practical use for the differentiation of the two clinical entities.
Abnormal granular structures, which stained positively with periodic acid-Schiff (PAS-positive granular structures; PGS), were observed in the brain of senescence accelerated mouse (SAM). They were small, round to ovoid, homogeneous structures measuring up to 5 microns in diameter and usually grouped in clusters. PGS were localized in the hippocampus, piriform cortices, olfactory tubercle, nucleus of the trapezoid body, and cerebellar cortices. Quantitative analysis revealed that PGS remarkably increased in the hippocampus of SAM-P/8, a substrain of SAM, with advancing age, although a few PGS also appeared in the aged control mice, SAM-R/1 and DDD. Their histochemical nature, morphological features and distribution pattern were different from those of corpora amylacea and other similar bodies. A close anatomical relationship between PGS and glial fibrillary acidic protein-positive astrocytes was inferred from immunohistochemical studies. PGS is considered to be one of the morphological manifestations of senescence in mice brains, and are found to occur more numerously in the brains of learning or memory deficit mice, SAM-P/8.
In 21 patients with typical exercise-induced anginal pain but normal coronary arteriograms (group N) and in 14 patients with angiographically proved coronary stenosis (group C), symptom-limited ergometer exercise ECG and radionuclide angiocardiography were performed twice on two different days. Exercise-induced ST changes showed larger variations between the two exercise tests in group N than in group C ([delta ST1-delta ST2]: 0.07 +/- 0.06 mV in group N, 0.03 +/- 0.03 mV in group C, p less than 0.05). Rate pressure product and left ventricular ejection fraction at exercise also showed larger variations between the two tests in group N than in group C (p less than 0.001, p less than 0.05, respectively). However, substantial overlaps existed in some cases in the two groups. In conclusion, some of the patients with exercise-induced anginal pain but normal coronary arteriograms may have a variable threshold of exertional chest pain probably caused by variation in coronary vascular tone, and the other patients may have a fixed threshold of chest pain caused by other mechanisms.
Age-related changes in learning ability were studied in senescence-accelerated mice (SAM) reared under specific pathogen-free (SPF) conditions. SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) showed an age-associated increase in spontaneous motor activity (SMA) compared with SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain) in a novel environment when the activity was measured in the light period, although there was no significant difference in the dark period. In observations of the circadian rhythm of SMA, SAM-P/8 showed a significant increase in diurnal SMA. In SAM-P/8 mice, the acquisition of passive avoidance response was slightly but significantly impaired even at 2 months of age, compared with SAM-R/1 control; the impairment became obvious with aging. In a one-way active avoidance task, SAM-P/8 did not show any impairment in the acquisition of avoidance response at 2 and 4 months of age. However, significant impairment was observed in SAM-P/8 at 12 months of age. The impairments of avoidance tasks were not due to a decrease in shock sensitivity, as indicated by no significant change in the flinch-jump threshold. In a water-filled multiple T-maze task, there was no difference in the number of errors between the two groups. With regard to the performance time to reach the goal, however, SAM-P/8 showed a mild prolongation at 2 months of age, and the prolongation became marked with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)
The cytoplasmic free calcium concentration ([Ca2+]i) in the platelets of spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), deoxycorticosterone-salt hypertensive rats (DOC) and normotensive Sprague-Dawley rats (SD) was measured with the fluorescent dye, quin-2-tetra-acetoxymethyl ester. No significant difference in platelet [Ca2+]i was found between SHR and WKY or between DOC and SD rats. No correlations were found between systolic blood pressure and [Ca2+]i. These results suggest that the elevation of platelet [Ca2+]i does not necessarily accompany hypertension in rats.
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The antihypertensive effect and possible adverse effects of bisoprolol were assessed in 96 Japanese patients with mild to moderate hypertension. After a 2- to 4-week placebo period, bisoprolol was administered to 68 outpatients at a daily dose of 5 mg to 20 mg for 6 to 8 weeks, and to 28 inpatients with the same dose range up to a maximum of 4 weeks. For outpatients, blood pressure and heart rate were recorded every 2 weeks, while for inpatients, in addition to daily measurements, the effect of bisoprolol on diurnal variation of blood pressure was also studied. Bisoprolol lowered blood pressure and heart rate significantly in both groups of patients. The most common adverse effect was bradycardia. It is expected that bisoprolol will be a very effective and useful antihypertensive drug.
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A toxin which causes rapid fluid accumulation in a suckling mouse assay and which was produced by Vibrio cholerae non-O1 was investigated. The toxin was purified from the culture supernatant of V. cholerae non-O1 (strain A-5) by ammonium sulfate fractionation, hydroxyapatite treatment, ethanol extraction, column chromatographies on SP-Sephadex C-50 and DEAE-Sephadex A-25, and high-pressure liquid chromatography on a Lichrosorb RP-8 column. About 1.4 X 10(5)-fold purification was achieved, with a recovery of about 12%. Although the crude preparation was heat labile, the purified toxin was heat stable. The minimum effective dose of purified toxin was about 5 ng in the suckling mouse assay. The amino acid composition of the purified toxin was determined to be Asp(3), Glu(1), Ala(1), half-Cys(6), Ile(2), Leu(1), Phe(1), and Pro(1). These data show the production of a new type of heat-stable enterotoxin (NAG-ST) by V. cholerae non-O1.
The water content in erythrocytes of subjects with borderline or established essential hypertension was measured by using gas-liquid chromatography and was found to be lower than that in normotensive controls (p less than 0.01). The water content in erythrocytes of normal controls (n = 14), borderline hypertensive subjects (n = 18), and established essential hypertensive subjects (n = 23) was (mean +/- SE) 71.0 +/- 0.2%, 69.9 +/- 0.2%, and 69.3 +/- 0.1% (vol/vol), respectively. A definite negative correlation was found between water content of erythrocytes and mean arterial pressure in normotensive and hypertensive subjects (n = 60, r = -0.59, p less than 0.001). Although there was no statistically significant between-group difference in the sodium content, the potassium content of erythrocytes from subjects with essential hypertension was significantly lower than that of normotensive controls (0.205 +/- 0.003 vs 0.222 +/- 0.004 mumol/mg dry red blood cells; p less than 0.01). There was no between-group correlation of sodium and water content in erythrocytes, but the potassium content correlated with the water content (n = 46, r = 0.49, p less than 0.001).
Since a dynamic exercise stress test cannot always be performed adequately in elderly patients, an alternative method is needed for evaluation of coronary reserve. We studied two-dimensional echocardiographic (2-DE) and electrocardiographic (ECG) responses to infusion of isoproterenol (ISP) at a rate of 0.02 micrograms/Kg/min in 40 elderly patients with chest pain. The results were compared with exercise ECG (EX-ECG) tests and exercise radionuclide angiocardiography (EX-RNA) in 13 of these patients. No serious complications were encountered in the ISP test. The diagnostic sensitivity for coronary artery disease (CAD) was 71% for ISP-2-DE, 71% for ISP-ECG, 86% for EX-ECG and 71% for EX-RNA. The specificity for CAD was 83% for ISP-2-DE, 33% for ISP-ECG, 50% for EX-ECG and 100% for EX-RNA. In conclusion, the ISP-2-DE test is a safe, easily available and useful method for the assessment of coronary artery disease in elderly patients.
A NH4Cl-HCO3(-)-mediated, acetazolamide modulated hemolysis test was carried out in seven patients with hereditary spherocytosis (HS), and the amount of enzyme antigen as well as activities of carbonic anhydrase (CA) were determined. Except for a decrease in CA-B activity (p less than 0.05), the amount of enzyme antigen, total and specific activities of both isozymes of CA and dependent activity of CA-C were within the normal range. Fifty percent and 95% hemolysis times were significantly shorter than the normal range, and they remained abnormal even in the presence of acetazolamide. This hemolysis test, especially H50 valuse, was therefore shown to have diagnostic value in HS.
In order to develop a mass screening method for the early detection of neuroblastoma, we measured urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) by a high performance liquid chromatography (HPLC) equipped with an electrochemical detector. Urinary samples were collected on a piece of filter paper and then pre-treated by a simple method. Measurement of VMA and HVA was performed within a short period of time, and by about 80 samples per a day could be analyzed by automatic system. The method described herein proved to be reliable, and we thus recommend it as a useful method for measurement of both VMA and HVA, leading to more accurate detection of neuroblastoma in mass screening test.
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