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Biomedical subjects

N Takeda

Publications and source records attributed to N Takeda.

At least 415 records · Page 23Linked to original sources

Adenine photodimerization in deoxyadenylate sequences: elucidation of the mechanism through structural studies of a major d(ApA) photoproduct.

The mechanism of the photodimerization of adjacent adenine bases on the same strand of DNA has been elucidated by determining the structure of one of the two major photoproducts that are formed by UV irradiation of the deoxydinucleoside monophosphate d(ApA). The photoproduct, denoted d(ApA)*, corresponds to a species of adenine photodimer first described by Pörschke (Pörschke, D. (1973) J.Am.Chem.Soc. 95, 8440-8446). From a detailed examination of its chemical and spectroscopic properties, including comparisons with the model compound N-cyano-N1-(1-methylimidazol-5-yl)formamidine, it is deduced that d(ApA)* contains a deoxyadenosine unit covalently linked through its C(8) position to C(4) of an imidazole N(1) deoxyribonucleoside moiety bearing an N-cyanoformamidino substituent at C(5). On treatment with acid, d(ApA)* is degraded with high specificity to 8-(5-amino-imidazol-4-yl)adenine whose identity has been confirmed by independent chemical synthesis. It is concluded that the primary event in adenine photodimerization entails photoaddition of the N(7)-C(8) double bond of the 5'-adenine across the C(6) and C(5) positions of the 3'-adenine. The azetidine species thus generated acts as a common precursor to both types of d(ApA) photoproduct which are formed from it by competing modes of azetidine ring fission.

Adenine↗

High-performance liquid chromatography of biogenic amines in the corpus cardiacum of the American cockroach, Periplaneta americana.

The simultaneous determination of biogenic amines in the corpus cardiacum of the American cockroach, Periplaneta americana, was carried out using high-performance liquid chromatography with a Neurochem neurochemical analyser. Vanillic acid, dopamine, octopamine and tyramine were detected. Tyrosine and tryptophan were also detected at high levels. Octopamine levels in the corpus cardiacum were increased on injection of an acetone solution. The biological function of the biogenic amines detected is discussed.

Animals↗

Detection of ribose-methylated nucleotides in enzymatic hydrolysates of RNA by thermospray liquid chromatography-mass spectrometry.

A procedure has been developed for the detection and characterization of ribose-methylated dinucleotides of the type NmpN' in enzymatic digests of RNA. Differences in reaction products from hydrolysis using RNase T2, which will not cleave NmpN', and hydrolysis by nuclease P1 are analyzed by thermospray liquid chromatography-mass spectrometry. The method is applicable to dinucleotides present in nanogram range quantities and is suited for the characterization of new or unexpected ribose-methylated nucleotides for which chromatographic mobilities are not known.

Chromatography, High Pressure Liquid↗

Effects of long-term medication for essential hypertension on cardiac hypertrophy and function.

The effects of long-term treatment of hypertensive patients with alacepril (angiotensin-converting enzyme inhibitor) on cardiac mass and function were investigated. A total of 12 patients was examined. Both systolic and diastolic blood pressure were significantly reduced by treatment with alacepril for 1 year. Left ventricular mass, as estimated by echocardiography, was significantly decreased by alacepril treatment, although electrocardiographic and chest x-ray findings were not significantly altered. Cardiac pump function, which was also assessed by echocardiography, was not changed. These results indicate that long-term treatment of hypertension with alacepril induces regression of cardiac hypertrophy without any change in cardiac contractile function.

Adult↗

The nucleotide sequence of 3C proteinase region of the coxsackievirus A24 variant: comparison of the isolates in Taiwan in 1985-1988.

Acute hemorrhagic conjunctivitis caused by coxsackievirus A24 variant (CA24v) first appeared in Taiwan in October 1985, followed by two other sequential epidemics in 1986 and 1988. In order to know the evolutionary relationship of the CA24v strains isolated in Taiwan, we first determined the nucleotide sequence of the 3C proteinase (3Cpro) region of the prototype strain (EH24/70), isolated in Singapore in 1970, by molecular cloning. The nucleotide sequence of the 3Cpro region thus sequenced showed striking homology with polioviruses and coxsackievirus A21. Viral RNA of eight isolates obtained from the three epidemics was reverse transcribed, amplified by the polymerase chain reaction, and cloned into M13 phage for the production of ssDNA for nucleotide sequencing by the dideoxy chain termination method. When the number of nucleotide difference was taken as a genetic distance between isolates, all isolates showed a very similar distance from the EH24/70, the earliest isolate of CA24v, indicating that they evolved at a constant evolutionary rate. Phylogenetic analysis by the unweighted pairwise grouping method of arithmetic average (UPGMA) indicated that the six isolates collected in 1985 and 1986 were closely related, while two 1988 isolates were more distant from them. The branching time between these two groups was estimated to be May 1984, 18 months before the first recognition of the CA24v epidemic in Taiwan. This is the first report of the nucleotide sequence of CA24v genome RNA and of an evolutionary analysis of the virus using the nucleotide sequence.

3C Viral Proteases↗

Anti-bovine thyrotropin autoantibodies in patients with Hashimoto's thyroiditis, subacute thyroiditis, and systemic lupus erythematosus.

We report four cases found to have anti-bovine thyrotropin (bTSH) antibodies, two with Hashimoto's thyroiditis and the other two, each with subacute thyroiditis and systemic lupus erythematosus (SLE). The unusually high negative titers of anti-TSH receptor antibodies (Case no. 1, -43.1%; Case no. 2, -34.9%; Case no. 3, -55.2%; Case no. 4, -59.9%) led to the incidental finding of the presence of anti-bovine (bTSH) antibodies in each patient. Case no. 1 was diagnosed to have Hashimoto's thyroiditis and was treated with L-thyroxine (L-T4). With the treatment, serum free T4 (FT4)normalized with a decline in the serum TSH concentration. The other patient diagnosed to have Hashimoto's thyroiditis (Case no. 2) remained euthyroid even without supplemental thyroid hormone therapy and the serum concentrations of FT4 and TSH stayed within the normal range. The third is a case of subacute thyroiditis (Case no. 3) with a typical clinical course of the disease. She had the anti-bTSH antibodies on her first outpatient visit. Serial examination of her sera disclosed the antibody titers to be on the same range over the 28 months after the onset of the symptoms. The fourth is a patient with SLE who had been treated with steroid (alternative day therapy of 40 mg/day prednisolone). Titers of the anti-bTSH antibodies spontaneously declined to the negative level 5 months later. None of the four cases had antibodies against human TSH alpha-subunit of bovine LH and alpha-subunit of bovine FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sequence analysis of the 3'-end of feline calicivirus genome.

The nucleotide sequence of the 3'-end of the Japanese F4 strain of feline calicivirus (FCV) RNA was determined from a cloned cDNA of 3.5 kbp. We found three open reading frames (ORFs). The largest ORF encoded a 668-amino acid protein of 73,588 Da, which was presumably the capsid precursor protein of FCV and had significant amino acid sequence homology with the VP3 of picornaviruses. A small ORF at the extreme 3'-end was compared with that of the F9 strain of FCV, a vaccine strain originally from the U.S. Highly conserved amino acid sequences were shown, suggesting that this ORF might be functional and encode a putative 106-amino acid protein of 12,153 Da. The other ORF in the 5'-flanking region of the cDNA had consensus amino acid sequences conserved among the RNA-dependent RNA polymerases.

Amino Acid Sequence↗

Comparative effects of diet or glibenclamide on insulin secretion and action in non-obese NIDDM.

We compared the effects of dietary treatment (D) and diet plus glibenclamide (DPG), for 3 weeks, on glycemia, insulin secretion and action in 2 groups of non-obese patients with NIDDM matched for fasting plasma glucose level. Fasting glycemia decreased in both groups with greater reductions after DPG (n = 7, 10.0 +/- 0.6 to 6.3 + 0.3 mmol/l, M +/- SEM, P less than 0.02) than after D (n = 7, 10.1 +/- 0.8 to 8.7 +/- 0.7 mmol/l, M +/- SEM, P less than 0.02). The magnitude of day-time elevation of plasma glucose over the fasting level, however, was reduced only after DPG. DPG but not D improved the plasma insulin response to glucose ingestion and in vivo insulin action measured by insulin tolerance test with unaltered erythrocyte 125I-insulin binding. This might indicate potentiation of insulin action at post-receptor binding steps. Improvements in in vivo insulin action and in insulin secretion after DPG closely correlated with decrease in fasting glycemia and reduction in the day-time elevation of plasma glucose levels, respectively. In conclusion, diet improved glycemic control in non-obese patients with NIDDM mainly by reducing fasting glycemia, although the mechanism remains unknown. Glibenclamide added to the diet further decreased fasting glycemia by improving in vivo insulin action and reduced the magnitude of day-time elevation of plasma glucose by enhancing endogenous insulin secretion.

Blood Glucose↗

Mass spectrometric identification of a phorbol diester 12-O-hexadecanoylphorbol-13-acetate, an Epstein-Barr virus-activating substance, in the soil collected from under Sapium sebiferum.

Soil-extracts collected from the ground from under several Euphorbiaceae plants have been known to possess Epstein-Barr virus (EBV)-activating substances which are thought to be one of the environmental co-factors causing nasopharyngeal carcinoma (NPC) in southern part of China and Burkitt's lymphoma (BL) in tropical Africa. Then, a model experiment aimed at chemical characterization of such active substances was carried out using a soil-extract around Sapium sebiferum, a Japanese representative Euphorbiaceae plant. Chromatographic separation guided by the EBV early antigen (EA) inducing activity gave a highly active fraction. Application of this fraction to desorption chemical ionization mass spectrometry identified a major active substance to be 12-O-hexadecanoylphorbol-13-acetate (HPA), which originally occurs in this plant. The method in this model experiment is suggested to be applicable to other samples from the endemic areas of NPC and BL.

Herpesvirus 4, Human↗

Effects of long term treatment with an alpha 1 adrenoceptor blocker on cardiac hypertrophy, contractility, and myosin isoenzymes in spontaneously hypertensive rats.

STUDY OBJECTIVE: The aim was to investigate the effects of long-term treatment with an alpha 1 blocker, bunazosin hydrochloride, on blood pressure, heart weight, myocardial contractility, and ventricular myosin isoenzyme pattern in spontaneously hypertensive rats (SHR). DESIGN: Bunazosin hydrochloride was given orally in a dose of 10 mg.kg-1.d-1 for 8-9 weeks. Isometric tension development was measured in isolated left ventricular papillary muscles. The left ventricular myosin isoenzyme pattern was determined by pyrophosphate gel electrophoresis. SUBJECTS: 14 male SHR (seven treated and seven untreated rats) aged 23 to 24 weeks were studied. MEASUREMENTS AND MAIN RESULTS: The blood pressure of the bunazosin treated rats was approximately 14% lower than that of the untreated rats at the end of the treatment period. The ventricular weight of treated SHR was significantly lower (around 8%) than that of untreated rats, but there were no significant differences between the two groups in the mechanical data obtained from isolated left ventricular papillary muscles. The myosin isoenzyme pattern of the left ventricle was significantly shifted toward VM-1 in the bunazosin treated SHR, the VM-1 concentration in the treated group being 38% greater than in the untreated group. CONCLUSIONS: These results indicate that long term treatment with bunazosin hydrochloride reduces blood pressure and leads to the regression of cardiac hypertrophy in SHR. Myocardial energetics (as represented by the myosin isoenzyme pattern) were affected, but there was no influence on myocardial tension development.

Adrenergic alpha-Antagonists↗

Extracorporeal spread and its prognostic impact in stages I and II (FIGO) endometrial carcinoma.

Prognostic risk factors were statistically analyzed from the histopathologic data obtained from 90 Japanese women with stages I and II endometrial carcinoma treated surgically, including systemic retroperitoneal lymph node dissection, between June 1979 and June 1989. In stage Ia endometrial carcinoma, pelvic and paraaortic nodes metastasis were seen in 13.8(4/29)% and 0.0(0/19)% of patients, respectively. In stage Ib, the incidence of pelvic and paraaortic node metastasis was 25.6(11/43)% and 9.7(3/31)%, respectively. In stage II, the incidence was 38.9(7/18)% and 13.3(2/15)%, respectively. Prognosis of patients even with deep myometrial invasion (greater than or equal to 2/3) or G3 tumor was fairly good (5-year survival rate: 87.5% and 85.7%, respectively) if the disease was histologically confined to the uterine corpus. Once the tumor spread outside the corpus uteri, the survival rate of patients was strongly affected by the grade of the tumor, moderate to marked lymph-vascular space invasion of tumor cells, or tumor invading middle or outer third of myometrium (P less than 0.05 for each factor). In summary, endometrial cancer frequently metastasize to pelvic and paraaortic lymph nodes even in the early stages, and lymph node metastasis and other extracorporeal spread of disease have a serious impact on patient survival. Prognosis of patients with extracorporeal spread of disease seems to be determined by the high grade of tumor and lymph-vascular space invasion. These results suggest that surgical exploration including paraaortic lymph node dissection to accurately evaluate the extent of the disease is essential to estimate the patient's prognostic risk and to individualize the treatment schedule.

Female↗

Triazole antifungals. IV. Synthesis and antifungal activities of 3-acylamino-2-aryl-2-butanol derivatives.

New triazole compounds were designed and synthesized as potential inhibitors of the fungal cytochrome P-450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (2R,3R)-3-acylamino-2-aryl-2-butanol derivatives III exhibited remarkably high efficacy after oral or parenteral administration. The structure-activity relationships of these amidoalcohols were evaluated.

Antifungal Agents↗

Thrombin-induced breakdown of phosphoinositides in platelets from patients with NIDDM.

We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM (non-insulin-dependent diabetes mellitus) patients and fifteen healthy subjects (control). The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [32P] orthophosphate for 80 min, the incorporation of 32P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP2 radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy.

Adult↗

Effects of otolith stimulation in eccentric rotation on the vestibulo-ocular reflex in squirrel monkeys.

When a subject is rotated around an axis located behind his head (eccentric rotation, ECR), he experiences a combination of angular acceleration and two kinds of linear accelerations, tangential and centrifugal. The effects of stimulation of the otolith organs by linear acceleration in ECR on gain of the vestibulo-ocular reflex (VOR) were examined in squirrel monkeys. The VOR gain in ECR with the animal's head facing away from the rotation axis was significantly higher than that in centric rotation (CR) at 1.0 Hz, but not at 0.5 Hz. However, the VOR gain did not increase in eccentric-lateral rotation when the animal faced tangentially, even at 1.0 Hz. After bilateral ablation of the otolith organs (sacculectomy and utricular neurectomy), the VOR gain in ECR did not increase, even at 1.0 Hz. These findings demonstrate that tangential acceleration along the interaural axis in ECR stimulates the utricular maculae, resulting in enhancement of the VOR gain. The results also suggest that ECR is a useful clinical test for the function of the otolith organs.

Animals↗

Centric and eccentric VOR tests in patients with Menière's disease and vestibular Menière's disease.

Pendular rotation in the eccentric position produces the same angular stimulation as that in conventional pendular rotation and, in addition, involves linear centrifugal and tangential acceleration forces which act on the otolith organs. In the eccentric position, normal subjects showed an increase in gain at 0.64 Hz, when compared with the gain with the head in the centered position. Therefore, we concluded that it is possible to diagnose otolith dysfunction by this comparison. In this study, we applied centric and eccentric pendular rotation tests to patients with Menière's disease and vestibular Menière's disease and investigated their otolith function. Patients with Menière's disease or vestibular Menière's disease within 1 month after the first attack or the most recent attack showed no gain enhancement with eccentric rotation. However, others showed gain enhancement with eccentric rotation. Therefore, we concluded that there seems to be no difference in the otolith function, especially in utricular function between Meniere's disease and vestibular Menière's disease.

Adult↗

Accumulation of quinolinic acid in uremic serum and its removal by hemodialysis.

Quinolinic acid was first identified in uremic serum by use of gas chromatography/mass spectrometry. Quantification by selected ion monitoring revealed that the serum concentration of quinolinic acid was markedly increased in chronic hemodialysis patients, and that the acid could be removed by conventional hemodialysis. The serum concentration of quinolinic acid was weakly but significantly correlated with the serum uric acid concentration. Accumulation of quinolinic acid in uremic blood may be involved in the pathogenesis of anemia, suppressed immune system, and uremic encephalopathy.

Adult↗