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Biomedical subjects

K Nakai

Publications and source records attributed to K Nakai.

At least 181 records · Page 10Linked to original sources

Functional prediction of B. subtilis genes from their regulatory sequences.

In bacterial cells, gene expression is regulated by multiple sigma factors, each of which has its promoter specificity, according to their conditions. Thus, if we can discriminate which sigma factor binds to the upstream region of a given coding sequence, we can predict in what condition it will be expressed. In this paper, we show this approach is feasible for the analysis of Bacillus subtilis genome. Based on our collection of known promoter sequences, we prepared 8 predictors to characterize known sigma factors using the hidden Markov model and their prediction accuracies were estimated with a cross-validation test. Furthermore, we predicted the sigma-dependencies for each of 1415 candidate genes in the genome. Our prediction results are experimentally testable and seem useful for the post-sequencing project.

Bacillus subtilis↗

[Angiotensin I-converting enzyme gene polymorphism and renal disease].

ACE inhibitor is known to have a therapeutic efficacy in renal diseases by reducing proteinuria and maintaining renal function. However, the relationship between ACE gene polymorphism and renal disease has not been fully elucidated. In this study, a 287 base pair(bp) I/D polymorphism of the ACE gene was examined with polymerase chain reaction(PCR) in 100 healthy subjects, 34 patients with chronic glomerulonephritis(CGN), 29 with chronic renal failure(CRF) and 25 with diabetes mellitus(DM) with(13) and without(12) nephropathy. We also measured serum ACE activity of these patients. ACE genotype and derived allele frequencies in each disease group did not differ significantly from those in healthy subjects. In all disease groups, values of serum ACE activity were higher in genotype DD than in genotype II. These findings suggest no significant association between I/D polymorphism of the ACE gene and renal disease. Further studies are needed to clarify these findings, considering renal function and type of renal disease.

Adult↗

Clinical usefulness of the effective regurgitant orifice area determined by transesophageal echocardiography in patients with eccentric aortic regurgitation.

BACKGROUND AND AIMS OF THE STUDY: The aortic regurgitant jet is frequently eccentric, and Doppler color flow mapping techniques of the distal jet is influenced by this eccentricity. The aim of the present study was to determine whether the effective regurgitant orifice area (EROA), determined by the proximal isovelocity surface area (PISA) method using multiplane transesophageal echocardiography (m-TEE), could be used to evaluate the severity of aortic regurgitation (AR) in patients with an eccentric jet. METHODS: Forty-eight patients with eccentric AR were studied. Values of EROA determined by the PISA method were compared with results from cross-sectional area (CSA), vena contracta (VC) width, aortic angiography, and regurgitant fraction. RESULTS: Values of EROA correlated well with results from CSA (r = 0.73, p < 0.001), VC (r = 0.74, p < 0.001), angiographic grade (rs = 0.90 p < 0.001), and regurgitant fraction (r = 0.84, p < 0.001) in patients with eccentric aortic regurgitation. Values of EROA > 0.27 cm2 were always associated with a regurgitant fraction > 0.4, while EROA values < 0.27 cm2 were always associated with a regurgitant fraction < 0.4. CONCLUSIONS: We conclude that, in patients with an eccentric jet, measurement of EROA values by the PISA method using m-TEE is a reliable method of assessing the severity of AR.

Aorta, Thoracic↗

A 5'-(trifluoromethyl)anthracycline glycoside: synthesis of antitumor-active 7-O-(2,6-dideoxy-6,6,6-trifluoro-alpha-L-lyxo-hexopyranosyl) adriamycinone.

7-O-(2,6-Dideoxy-6,6,6-trifluoro-alpha-L-lyxo-hexopyranosyl)adriam ycinone (3), whose substituent at C-5' is a lipophilic trifluoromethyl group, has been prepared by coupling of 3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-alpha-L-lyxo-hexopyran osyl bromide (20) with 14-O-(tert-butyldimethylsilyl)adriamycinone under the Koenigs-Knorr conditions. The key step in this synthesis was the C-trifluoromethylation of 5-O-acetyl-2,3-di-O-benzyl-4-deoxy-aldehydo-L-erythro-pentose (10), derived from D-lyxose in 10 steps, with (trifluoromethyl)trimethylsilane in the presence of tetrabutylammonium fluoride, whereupon 1,1,1-trifluoro-L-arabino-hexitol (11) was obtained along with its 2-epimer. The synthetic product 3 showed remarkable antitumor activity in vivo in a low dose range compared to the analogs including doxorubicin. The fact may be ascribed to the presence of a trifluoromethyl group at C-5', suggesting the importance of the group in view of biological activity.

Animals↗

1 alpha,25-dihydroxyvitamin D3-induced upregulation of calcineurin during leukemic HL-60 cell differentiation.

Cyclosporin A and FK506, at concentrations that inhibited phosphatase activity of calcineurin in HL-60 cellular lysates, augmented the proliferation of leukemic HL-60 cells. These immunosuppressants did not affect 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced monocytic differentiation of HL-60 cells, but did abrogate the 1,25(OH)2D3-induced inhibition of HL-60 cell growth. Treatment with 20 nmol/L 1,25(OH)2D3 led to a progressive increase in calcineurin phosphatase activity in subcellular fractions from HL-60 cell extracts, the increase in this activity appeared to parallel the phenotypic and functional changes of HL-60 cells during monocytic differentiation induced by 1,25(OH)2D3. Immunoblot analysis indicated that increase in calcineurin activity was concordant with the increased expressions of calcineurin catalytic subunit isozymes, calcineurin A alpha (CNA alpha), and calcineurin A beta(CNA beta), and a regulatory calcineurin B subunit (CNB) proteins, which were preceded by a coordinate increase in the levels of CNA alpha, CNA beta and CNB mRNAs. The expression of calmodulin remained unaltered throughout 1,25(OH)2D3-induced monocytic differentiation. These results suggest that calcineurin activation has a net negative effect on HL-60 cell proliferation, and that the increased expression of calcineurin may be involved in 1,25(OH)2D3-induced inhibition of HL-60 cell proliferation.

Calcineurin↗

Articulation after uvulopalatopharyngoplasty.

We performed perceptual and acoustic studies to demonstrate articulation after uvulopalatopharyngoplasty (UPPP) in Japanese patients at 28.6 days (mean) after surgery (range 21-50 days). The results of listening tests showed that there were no significant changes between pre- and postoperative articulation scores for any of 25 monosyllables tested, and there were no significant changes in the timbres of 5 Japanese vowels after UPPP. In the acoustic study of the first and second formant frequencies of the vowels, some formant frequencies had significant changes after UPPP. However, these changes in formants fell within the range of intraindividual variation. In the acoustic study of /ka/ with a palatal plosive /k/, there was no significant change in the voice onset time or F2 transition after UPPP.

Adult↗

Transcortical mixed aphasia with left frontoparietal lesions.

We present a case of transcortical mixed aphasia following a left frontoparietal infarct caused by vasospasm after subarachnoid haemorrhage. Although CT showed low-density areas in the left frontal lobe and basal ganglia, single photon emission CT revealed a wider area of low perfusion over the entire left hemisphere, except for the left perisylvian speech areas. Hence, transcortical mixed aphasia may be caused by the isolation of perisylvian speech areas due to disconnection from surrounding areas.

Aphasia↗

Perceived pitch of whispered vowels--relationship with formant frequencies: a preliminary study.

To clarify the role of formant frequency in the perception of pitch in whispering, we conducted a preliminary experiment to determine (1.) whether speakers change their pitch during whispering; (2.) whether listeners can perceive differences in pitch; and (3.) what the acoustical features are when speakers change their pitch. The listening test of whispered Japanese speech demonstrates that one can determine the perceived pitch of vowel /a/ as ordinary, high, or low. Acoustical analysis revealed that the perception of pitch corresponds to some formant frequencies. Further data with synthesized whispered voice are necessary to confirm the importance of the formant frequencies in detail for perceived pitch of whispered vowels.

Adult↗

Inhibition of endothelium-dependent relaxation by hemoglobin in rabbit aortic strips: comparison between acellular hemoglobin derivatives and cellular hemoglobins.

Hemoglobin (Hb)-based artificial oxygen carriers are supposed to induce vasoconstriction through the inactivation of endothelium-derived relaxing factor (EDRF). We examined the vasoconstrictive activity of acellular Hb and cellular Hb solutions in rabbit aortic strips. Unmodified Hb, pyridoxalated Hb, bovine unmodified Hb, haptoglobin-Hb complex (Hp-Hb), and polyoxyethylene glycol-conjugated Hb (PEG-Hb) were used as acellular Hbs having different molecular masses. Cellular Hbs included liposome-encapsulated Hb and red blood cells (RBC). In the first experiment, Hb (10 ng/ml to 1 mg/ml) was cumulatively added to the tissues in which steady-state relaxation was evoked by acetylcholine (ACh) after precontraction induced by phenylephrine. Although all Hb solutions induced a dose-dependent reversal of ACh-induced relaxation, the most potent vasoconstrictive effect was noted with acellular Hbs, and their contractile activities were almost the same independent of molecular mass. On the other hand, liposome-Hb and RBC showed reduced potencies in this order. These results indicate the importance of cellularity as the major factor determining Hb-related EDRF inactivation. In another experiment, the tissues were exposed to Hb at 0.01, 0.1, or 1 mg/ml for 30 min and ACh-induced relaxation was recorded after the complete removal of Hb in an organ bath chamber. Exposure to unmodified Hb at > 0.1-mg/ml concentrations significantly reduced the ACh-induced relaxation, whereas the relaxation was not affected by PEG-Hb, Hp-Hb, liposome-Hb, or RBC. These results suggest that unmodified Hb might be persistently associated with tissues and thereby inhibit ACh-induced relaxation. From these findings, we propose two attributes of Hb-related inhibition of endothelium-dependent relaxation: Acellular Hbs inhibit EDRF more efficiently in the luminal space than cellular Hbs, and unmodified Hb can also inhibit it adluminally and/or adventitially.

Acetylcholine↗

[Onset of dyspnea on exertion in elderly and young patients with congestive heart failure].

We previously reported that dyspnea on exertion in patients with congestive heart failure was not associated with pulmonary function ar rest, but was associated with the appearance of the anaerobic threshold and with the respiratory compensation point during exercise. Here we described a study of the influence of aging on the onset of dyspnea on exertion in elderly and in young patients with congestive heart failure. A total of 53 patients were studied: 35 were less than 65-year-old (average age, 47-year-old; 19 men and 16 women) and 18 were more than 65-year-old (average age, 70-year-old; 13 men and 5 women). All patients underwent maximal graded exercise testing on a bicycle ergometer. The workload increased according to a ramp protocol, and perceived exertion was evaluated with the Borg scale. The anaerobic threshold, the respiratory compensation point, and the peak VO2 were recorded. Values of 13 (somewhat hard) and 17 (very hard) on the Borg scale were considered to mark the start of dyspnea on exertion and an increase in dyspnea on exertion respectively. In the young patients, dyspnea on exertion began at about the time that the anaerobic threshold was reached, and it increased at about the time that the respiratory compensation point was reached. In contrast, elderly patients dyspnea on exertion began 70 seconds after the anaerobic threshold was reached, and it increased 30 seconds after the respiratory compensation point was reached. The VO2 at the start of dyspnea on exertion and the VO2 at the anaerobic threshold correlated more closely in the young patients than in the old patients. The same was true of the VO2 at the time that dyspnea on exertion increased and the VO2 at the respiratory compensation point. These findings suggest that elderly patients with congestive heart failure are less sensitive to the stimuli that cause dyspnea than are young patients.

Adolescent↗

[Clinical studies on autologous blood transfusion].

To study the present status of blood transfusion in head and neck surgery, we investigated recent cases of intraoperative transfusion in our department. In addition, we present our autologous blood transfusion cases, presently involved in an ongoing clinical trial for patients with head and neck cancer in our department which began in 1989. 1. Investigation of intraoperative blood transfusion cases There were 37 cases of intraoperative blood transfusion among 677 cases who underwent surgery under general anesthesia during the period from May, 1991 to December, 1993. We divided these 37 cases into three groups according to the amount of intraoperative blood loss: less than 600ml (10 cases), more than 600ml and less than 1200ml (11 cases), and more than 1200ml (16 cases). Average amounts of intraoperative blood transfusion in each group were 195ml, 475ml and 780ml, respectively. As we noted that most of these 37 cases received a blood transfusion of less than 800ml, the majority needing intraoperative blood transfusion during head and neck surgery are potential candidates for autologous blood transfusion. Therefore, we have promoted autologous blood transfusion for intraoperative blood transfusion in head and neck surgery. Thus, the patients undergoing intraoperative autologous blood transfusion increased to seven annually as of 1994. 2. Clinical studies on autologous blood transfusion Among 677 cases of head and neck surgery conducted during a six year period (1989-1994), we experienced ten cases of autologous blood transfusion. For the prevention of anemia due to repeated blood withdrawal, we administered an iron preparation. Patients who preoperatively showed a low value of Hb (less than 11g/ dl) received intravenous drip infusion of erythropoietin. Since some patients selected for autologous blood transfusion, who also received neo-adjuvant chemotherapy and preoperative radiotherapy, exhibited a generally chronic anemia status, an iron preparation and erythropoietin should be preoperatively administered in combination.

Adolescent↗

[A case of amnesic syndrome caused by hematoma in the left anterior medial thalamus].

We reported a case of amnestic syndrome caused by a hematoma in the left thalamus. The case was that of a 68-year-old, right-handed man who suddenly showed amnestic syndrome. He had neither motor paresis nor sensory disturbance. Clinical examination showed he had disorientation, anterograde amnesia and mild retrograde amnesia. Immediate recall and remote memory were intact, but recent memory was severely impaired. CT scan revealed a high density area in the anterior medial part of the left thalamus. We concluded that amnesia in this patient was caused by fasciculus mamillothalamicus damage because of a hematoma during thalamic hemorrhage.

Aged↗

[Change in argatroban concentration within the vessel wall after local administration using hydrogel-coated balloon catheter].

Acute coronary occlusion after percutaneous transluminal coronary angioplasty is one of the major problems in coronary intervention. This study evaluated the hydrogel-coated balloon delivery of argatroban to the arterial wall and argatroban persistence after angioplasty in 17 rabbits. A hydrogel-coated balloon was immersed three times in argatroban/saline solution (1 mg/ml) and inflated at 6 atm pressure for 1 min in the common carotid artery. The transfer of argatroban to the vascular wall was measured by high-performance liquid chromatography. The concentrations of argatroban at 0, 5, and 15 min after deflation were 14.8, 4.2, and 3.9 nmole/g.wet weight. The hydrogel-coated balloon catheter can deliver argatroban to the local arterial wall during balloon inflation.

Angioplasty, Balloon, Coronary↗

Donor leukocyte transfusions and discontinuation of immunosuppressants to achieve an initial remission after allogeneic bone marrow transplantation in a patient with primary refractory acute leukemia.

We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.

Adult↗

[A case of new stenosis in the distal portion following transaortic patch angioplasty for the left main coronary stenosis].

A 75-year-old man who had unstable angina underwent transaortic vein patch angioplasty for isolated 60% stenosis of the left main coronary artery. About four months after the operation, he developed effort angina and angiographycally new stenosis was detected in the distal portion of patch dilatation. So he underwent emergency aorto coronary bypass grafting. Transaortic patch angioplasty is attractive technique because of restoration of the original antegrade coronary flow, but this direct surgical approach may induce the stimulation of intima, and may injure the intima. It is important to bear this technique in the mind for selected patients with left main coronary lesions.

Aged↗

A probabilistic classification system for predicting the cellular localization sites of proteins.

We have defined a simple model of classification which combines human provided expert knowledge with probabilistic reasoning. We have developed software to implement this model and have applied it to the problem of classifying proteins into their various cellular localization sites based on their amino acid sequences. Since our system requires no hand tuning to learn training data, we can now evaluate the prediction accuracy of protein localization sites by a more objective cross-validation method than earlier studies using production rule type expert systems. 336 E. coli proteins were classified into 8 classes with an accuracy of 81% while 1484 yeast proteins were classified into 10 classes with an accuracy of 55%. Additionally we report empirical results using three different strategies for handling continuously valued variables in our probabilistic reasoning system.

Cells↗