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Biomedical subjects

T Fujino

Publications and source records attributed to T Fujino.

At least 145 records · Page 8Linked to original sources

Cloning and DNA sequencing of the genes encoding Clostridium josui scaffolding protein CipA and cellulase CelD and identification of their gene products as major components of the cellulosome.

The Clostridium josui cipA and celD genes, encoding a scaffolding-like protein (CipA) and a putative cellulase (CelD), respectively, have been cloned and sequenced. CipA, with an estimated molecular weight of 120,227, consists of an N-terminal signal peptide, a cellulose-binding domain of family III, and six successive cohesin domains. The molecular architecture of C. josui CipA is similar to those of the scaffolding proteins reported so far, such as Clostridium thermocellum CipA, Clostridium cellulovorans CbpA, and Clostridium cellulolyticum CipC, but C. josui CipA is considerably smaller than the other scaffolding proteins. CelD consists of an N-terminal signal peptide, a family 48 catalytic domain of glycosyl hydrolase, and a dockerin domain. N-terminal amino acid sequence analysis of the C. josui cellulosomal proteins indicates that both CipA and CelD are major components of the cellulosome.

Amino Acid Sequence↗

Clinical suppression of bradycardia dependent premature ventricular contractions by the potassium channel opener nicorandil.

OBJECTIVE: To assess the clinical antiarrhythmic effect of nicorandil, a potassium channel opener; on premature ventricular contractions. DESIGN AND PATIENTS: The effect of oral nicorandil (15 to 60 mg daily for four weeks) on premature ventricular contractions was investigated in 20 patients (11 female, nine male, mean (SD) age 63 (17) years) who underwent 24 hour ambulatory ECG. Patients were classified into two groups based on the relation between the frequency of premature ventricular contractions and heart rate: (1) those with a positive correlation (n = 9); and (2) those with a bidirectional correlation (n = 11), characterised by an increased frequency of premature contractions at low heart rates and a decreased frequency at high heart rates. RESULTS: Nicorandil reduced the frequency of premature ventricular contractions by 75% in five patients in group 2, but was not effective in any patient in group 1. The heart rate at which the frequency of premature ventricular contractions peaked was significantly lower in the five responders in group 2 than in the six non-responders (63.2 (3.7) v 76.3 (12.4) beats/min, p < 0.05). CONCLUSIONS: Nicorandil may suppress premature ventricular contractions when they occur mainly at a low heart rate.

Adult↗

Circadian rhythm of the signal averaged electrocardiogram and its relation to heart rate variability in healthy subjects.

OBJECTIVE: To examine the circadian variation in the signal averaged electrocardiogram (saECG) and heart rate variability and investigate their relations in healthy subjects. METHODS: 24 hour ECGs were obtained with a three channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The following variables were determined hourly: heart rate, filtered QRS (f-QRS) duration, low and high frequency components of heart rate variability (LF and HF), and the LF/HF ratio. RESULTS: Heart rate, f-QRS duration, HF, and the LF/HF ratio showed significant circadian rhythms, as determined by the single cosinor method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS duration and HF increased at night. f-QRS duration was negatively correlated with heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and positively with HF (r = 0.93, p < 0.001). CONCLUSIONS: f-QRS duration has a significant circadian rhythm in healthy subjects and is closely related to the circadian rhythm of autonomic tone.

Adult↗

Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.

Blotting, Southern↗

Postrest shortening of the action potential duration in rabbits: in vitro and in vivo correlation.

Previous evidence has shown that the action potential duration of rabbit ventricular muscle cells shortens after a rest period (postrest shortening). However, there has not been much research on postrest shortening in the intact heart. We recorded transmembrane action potentials (TAPs) of isolated papillary muscle from rabbit ventricle with glass microelectrodes and monophasic action potentials (MAPs) of the rabbit left ventricular endocardium with contact electrodes. In the in vitro experiments, repetitive regular stimuli (S1) at a cycle length of 1 sec were followed by a single extrastimulus (S2) at coupling intervals (S1S2) ranging between 0.5 sec and 8 sec. The increase in the S1S2 interval resulted in a progressive shortening of the duration of TAP elicited by the S2, which was abolished by the simultaneous application of 1 mmol/L 4-aminopyridine and 2 micromol/L ryanodine. In the in vivo experiments, regular right ventricular pacing (S1) at a cycle length of 0.35 sec was followed by a single extrastimulus (S2) with coupling intervals (S1S2) ranging between 0.25 sec and 3 sec. The increase in the S1S2 interval also resulted in a progressive shortening of the duration of MAP elicited by the S2. This is the first report to demonstrate postrest shortening in the intact heart, which probably occurs because of a mechanism analogous to that observed in the isolated ventricular muscle.

4-Aminopyridine↗

Antimicrobial activity of a compound isolated from an oil-macerated garlic extract.

A compound showing antimicrobial activity was isolated from an oil-macerated garlic extract by silica gel column chromatography and preparative TLC. On basis of the results of NMR and MS analyses, it was identified as Z-4,5,9-trithiadeca-1,6-diene-9-oxide (Z-10-devinylajoene; Z-10-DA). Z-10-DA exhibited a broad spectrum of antimicrobial activity against such microorganisms as gram-positive and gram-negative bacteria and yeasts. The antimicrobial activity of Z-10-DA was comparable to that of Z-ajoene, but was superior to that of E-ajoene. Z-10-DA and Z-ajoene are different in respect of substitution of the allyl group by the methyl group flanking a sulfinyl group. This result suggests that substitution by the methyl group would also be effective for the inhibition of microbial growth.

Anti-Bacterial Agents↗

Signal-averaged electrocardiogram shows a heart rate dependent diurnal variation in healthy subjects.

It has not been determined if signal-averaged electrocardiograms (SAECGs) have a diurnal variation. We recorded 3-channel 24-hour ECGs in 30 healthy volunteers and calculated the following parameters for the first 500 sec of every hour over the 24-hour period: the mean heart rate, the filtered QRS duration (f-QRS), the root-mean-square voltage of the signals in the last 40 msec of the QRS (RMS40), and the duration of low-amplitude signals (< 40 microV) in the terminal portion of the QRS (LAS40). Heart rate and RMS40 increased in the daytime compared with the nighttime; f-QRS and LAS40 increased during the nighttime hours. The f-QRS and LAS40 were negatively correlated with heart rate in all and 22 (73%) of 30 subjects, respectively, and RMS40 was positively correlated with heart rate in 21 subjects (70%). In conclusion, SAECGs exhibit a clear diurnal variation in healthy subjects, which is closely related to changes in heart rate.

Adult↗

Isoproterenol-induced creatine kinase leakage in Langendorff-perfused rat heart associated with significant myocardial edema.

Since the mechanism of creatine kinase (CK) leakage induced by beta-adrenoceptor activation remains unclear, we studied the effects of incremental application (10(-9) to 10(-4) M) of isoproterenol (ISP) on the CK efflux from Langendorff-perfused isolated rat hearts under aerobic conditions. Tissue water content was estimated after the perfusion experiment. ISP-induced dose-dependent CK leakage was noted in a sigmoidal fashion, which showed low temperature-dependency (Q10 of 2.41), sensitivity to cepharantine (10(-6) M) and propranolol (10(-7) to 10(-6) M) without any signs of demand ischemia or oxidant stress. CK liberation was not replicated at all by maneuvers activating cAMP-dependent protein kinase (A-kinase). Myocardial edema noted in the control ISP application was ameliorated by exposure to 10(-6) M propranolol or cepharantine (i.e., significant fall in tissue water content; p < 0.05). Histological study revealed nonspecific myocardial fiber swelling and separation without any myocyte necrosis for all the perfusion groups. These results suggest that ISP-induced CK leakage in this model is not mediated by beta-adrenoceptor stimulation, subsequent A-kinase activation or related demand ischemia, but is attributed most to the direct effects of ISP augmenting sarcolemmal CK and water permeability.

Adrenergic beta-Agonists↗

An Assessment of Amniotic Fluid Index Among Japanese (A Longitudinal Study)

>Objective: To obtain a longitudinal gestational reference range for the amniotic fluid index (AFI) among Japanese women and to compare the study with those of previous reports.Methods: A total of 739 measurements of the AFI of 96 Japanese women with normal pregnancies were analyzed. The criteria were singleton pregnancies between 20 and 40 weeks, without fetal anomalies, diabetes mellitus, hypertension, and other maternal complications. Logarithmic transformation was used to obtain the predicted mean AFI values with 95% confidence intervals at each gestational week.Results: The AFI rose from 20 weeks reaching its peak at 30 weeks. After the peak, it declined toward 40 weeks. Comparison of this study with previously published reports revealed differences in the mean AFI values.Conclusions: We obtained the gestational age-specific value of AFI in normal pregnancy for Japanese women.

Journal Article↗

[Attributable factors to the emergence of multidrug-resistant Mycobacterium tuberculosis based on the observation of consecutive drug resistance test results].

Thirty six cases with multidrug-resistant tuberculosis were retrospectively studied to define the causes attributable to the emergence of multidrug-resistant M. tuberculosis. All these tuberculosis cases were microbiologically confirmed and resistant to at least isoniazid and rifampicin. Data analysis using matched-pair sampling methods (1:3) demonstrated that the followings are the significant risk factors for the emergence of multidrug-resistant tuberculosis; incompliance to treatment (Odds ratio 21.0: 95% CI 4.10-107.63), alcohol abuse (Odds ratio 15.0: 95% CI 2.34-96.1) and the history of previous treatment (Odds ratio 5.0: 95% CI 2.04-12.21), while diabetes mellitus is not statistically significant. The incompliance to treatment which is primarily thought to be patient's responsibility results in non-optimal administration of antituberculous agents, leading to the multidrug-resistant tuberculosis. Other factors that may have contributed to the emergence of resistance included the unnecessary change of regimen before completion of chemotherapy. This is patient-unrelated situation where responsibility lies in the medical side. A clinical case presented here is an example. In this case RFP was replaced with ethambutol 3-months after the initiation of regimen including SM, INH and RFP because of abnormal elevation of GOT and GPT without any supporting evidence that RFP was causative. The readministration of RFP after 1-year cessation did not induce liver dysfunction, while the drug resistance was observed not only to RFP but also to INH. This case suggests unnecessary interruption of RFP could lead to the emergence of resistance to INH as well as RFP. One known mechanism of drug resistance is random mutation and the selection by drugs administered during the course of chemotherapy. The cases with advanced cavitary lesions would have a higher probability of the occurrence of mutation. The more the number of mutant bacilli, the higher the probability of emergence of multidrug resistance. Those cases in which longer period of time is needed for the negative conversion of M. tuberculosis should be treated with potent chemotherapy regimens under the intense supervision. Since both INH and RFP are the most potent among currently available antituberculous agents. It is crucial to preserve the potency of these essential agents before novel antituberculous are developed.

Antitubercular Agents↗

Increased plasma epinephrine but not reduced heart rate variability leads to ventricular arrhythmias in patients with acute myocardial infarction.

Ventricular arrhythmia observed in the acute stage of myocardial infarction is profoundly related to the autonomic balance. To investigate prediction of ventricular arrhythmia, heart rate variability and plasma catecholamine concentration were simultaneously measured for a week in 17 consecutive patients with first anterior or anteroseptal Q wave infarction treated without specific coronary intervention. The cross-sectional plot of coefficient of variance (= standard deviation of N-N interval/mean N-N interval x 100; %) as a function of plasma epinephrine on the day of admission remained lower than the standard average. Ventricular premature contractions increased in proportion to the plasma epinephrine concentration. In the first week of hospitalization, plasma epinephrine concentration and frequency of premature contraction decreased exponentially, whereas the coefficient of variance showed a modest decline. Ventricular tachycardia refractory to xylocaine with rate accelerating with persistence was observed only in patients with the peak epinephrine concentration > 375 pg/ml. Plasma epinephrine concentration rather than coefficient of variance during sleep after the first acute episode is more closely related to the following triggered ventricular arrhythmia.

Aged↗

[Surgical treatment of an aortic arch aneurysm: reports of 2 cases with lesion of the arch vessels].

A 48-year old woman underwent surgery for an aortic arch aneurysm with stenosis or dilatation of three arch vessels caused by aortitis syndrome. Total arch replacement and reconstruction of three arch vessels were performed with hypothermic selective cerebral perfusion (SCP). To avoid atheroembolism and malperfusion to the brain, the rt. common carotid artery was perfused via the rt. subclavian artery through the dacron vascular graft and the lt. subclavian artery was cannulated and perfused distally to stenosis. A 65-year-old man who had an atherosclerotic aortic arch aneurysm with severe stenosis of the brachiocephalic artery underwent operation. In the operation, extracorporeal circulation was instituted with the arterial return through the lt. subclavian artery. Same as case 1, total arch replacement and reconstruction of three arch vessels were performed under hypthermic SCP. In this case, the left common carotid artery was transected and cannulated directly into the vessel, instead of cannulation through the aortic lumen because of atheromatous plaques in the orifice of the left common carotid artery. The patients recovered uneventfully and doing well now.

Aged↗

A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis.

We report herein the cDNA cloning of a novel rat acyl-CoA synthetase (ACS) that preferentially uses arachidonate and eicosapentaenoate. This newly identified ACS (designated ACS4) contains 670 amino acids and is 68% identical to rat ACS3, a previously characterized ACS that is highly expressed in brain. ACS4 was overproduced in Escherichia coli and the resulting enzyme was purified to homogeneity. The purified enzyme utilizes arachidonate and eicosapentaenoate most preferentially among C8-C22 saturated fatty acids and C14-C22 unsaturated fatty acids. Kinetic analyses revealed that the enzyme has a high affinity for arachidonate and eicosapentaenoate and low affinity for palmitate. ACS4 transcripts are detectable in a wide range of tissues, with the highest level in adrenal gland. Immunoreactivity to ACS4 was detected in the zona fasciculata and reticularis of adrenal gland, in the corpus luteum and stromal luteinized cells in ovary, and in the Leydig cells of testis.

Adrenal Glands↗

Extended lifespan and immortalization of human fibroblasts induced by X-ray irradiation.

The induction of immortalization of human fibroblasts by carcinogens is a very rare process. Hybrids between immortal cells and normal fibroblasts senesce, indicating that immortal cells must lose one or more senescence genes for immortalization. To examine the possible involvement of multiple gene alterations in extended lifespan or immortalization of normal human fibroblasts, normal human fibroblasts (WHE-7 cells) and skin fibroblasts (MDAH 087 cells) derived from a Li-Fraumeni syndrome patient with a mutated p53 allele were periodically irradiated with x rays. All six unirradiated control MDAH 087 cell cultures ceased growing by 37 population doublings (PD) and senesced. In contrast, one of six MDAH 087 cultures irradiated one to three times with x rays (2 or 4 Gy at 2 Gy/min) grew continuously for over 450 PD, indicating that the cells were immortal. All 12 WHE-7 cell cultures that were irradiated under the same conditions and all 20 unirradiated control WHE-7 cultures did not become immortal. Single-stranded DNA conformation analysis and DNA sequencing revealed that no additional mutations were induced by x-ray irradiation in exons 2-10 of the p53 gene of the immortal cells (LCS-4X2 cells) and that loss of the wild-type p53 gene was necessary but not sufficient for immortalization. Karyotypic analysis and chromosome painting analysis demonstrated that a high percentage (more than 98%) of LCS-4X2 cells had lost chromosome 6. Irradiation of WHE-7 cells nine times with x rays (2 Gy at 2 Gy/min) extended the cells' lifespans but did not immortalize them. These cells (X9 cells) exhibited a nonrandom karyotypic alteration, monosomy 6, that was confirmed by loss of heterozygosity for a polymorphic dinucleotide repeat sequence on chromosome 6. DNA analysis showed that X9 cells had no mutations in exons 2-10 of the p53 gene. DNA fingerprint analysis with a multi-locus probe detected DNA rearrangements in LCS-4X2 cells and X9 cells, indicating that both cells could have mutations at a gene or genes other than the p53 gene. The results are consistent with our previous findings that cells with a mutation in one gene involved in cellular senescence (i.e., the p53 gene in Li-Fraumeni fibroblasts) are prone to immortalization. Furthermore, we conclude that immortalization of normal human fibroblasts is a multistep process involving loss or inactivation of multiple genes, such as p53 and a gene on chromosome 6. Loss of a gene on chromosome 6 without p53 alterations extends cellular lifespan without immortalizing the cells.

Adult↗