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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 1,153 records · Page 64Linked to original sources

Conductivity of dorsal column fibers during experimental spinal cord compression and after decompression at various stimulus frequencies.

The effects of spinal cord compression on conduction of dorsal column fibers at various stimulus frequencies were analyzed in pentobarbital anesthetized cats. The responses to L6 dorsal root stimulation at 1 to 500 Hz were recorded from the L2 cord dorsum. The L4 cord segment was compressed gradually until the compound action potential (CAP) at 1 Hz was flat. There was no significant change of CAP at any frequency during the first part of compression, but there was progressive conduction failure, which was more severe with increased stimulus frequency, at a later stage. After decompression, the CAPs at all frequencies recovered progressively for 1 hour but slowly thereafter. However, marked differences were observed in recovery rate at different stimulus frequencies. The recovery rate at 500 Hz was much slower than that at 1 Hz, whereas the recovery rate at 100 Hz exceeded those at 1 Hz. Serial analysis of a train of high frequency impulses revealed the following different response patterns with stimulus frequencies after decompression. At 333-500 Hz the amplitude of CAPs decreased progressively, whereas at 33-125 Hz it increased up to 110-134% of the first CAP and then reached an almost steady level. At 200-250 Hz the amplitude increased transiently and then decreased progressively. The latency increased with decreased amplitude, and decreased with increased amplitude. Conduction failure at a high stimulus frequency (500 Hz) was observed at the compression site. In contrast, augmentation of CAPs at moderately high stimulus frequency (100 Hz) was observed rostral to the compressing site. The conduction failure at high stimulus frequency indicates incomplete impairment of spike generation in axons injured by mechanical compression and that these axons can transmit impulses at a low stimulus frequency. High frequency stimulation may be useful for monitoring of the function of the CNS axons. The mechanism underlying the augmentation of CAPs at moderately high stimulus frequency is briefly discussed.

Animals↗

Simulating evolution by gene duplication.

By considering the recent finding that unequal crossing over and other molecular interactions are contributing to the evolution of multigene families, a model of the origin of repetitive genes was studied by Monte Carlo simulations. Starting from a single gene copy, how genetic systems evolve was examined under unequal crossing over, random drift and natural selection. Both beneficial and deteriorating mutations were incorporated, and the latter were assumed to occur ten times more frequently than the former. Positive natural selection favors those chromosomes with more beneficial mutations in redundant copies than others in the population, but accumulation of deteriorating mutations (pseudogenes) have no effect on fitness so long as there remains a functional gene. The results imply the following: Positive natural selection is needed in order to acquire gene families with new functions. Without it, too many pseudogenes accumulate before attaining a functional gene family. There is a large fluctuation in the outcome even if parameters are the same. When unequal crossing over occurs more frequently, the system evolves more rapidly. It was also shown, under realistic values of parameters, that the genetic load for acquiring a new gene is not as large as J.B.S. Haldane suggested, but not so small as in a model in which a system for selection started from already redundant genes.

Alleles↗

Evidence for two activated forms of pyruvate kinase from Bacillus stearothermophilus in the presence of ribose 5-phosphate.

Allosteric activation of pyruvate kinase from a thermophilic bacterium, Bacillus stearothermophilus, by ribose 5-phosphate (R5P) was kinetically examined. Two activated forms of this enzyme could be distinguished, depending on the R5P concentration. One form (Form I) was observed at about 10(-5) M R5P. It showed a slightly negative cooperativity for phosphoenolpyruvate (PEP). The other form (Form II) was observed at more than 10(-3) M R5P and showed Michaelis-Menten kinetics for PEP. The PEP and ADP concentrations that yield half-maximal velocity were essentially identical for the two forms (about 0.1 and about 0.5 mM, respectively), but Form I had a larger Vmax value than Form II. In the absence of R5P, the enzyme showed a homotropic positive cooperativity for PEP; the concentration required for the half-maximal velocity was about 2 mM and that of ADP was about 1.6 mM. The enzyme was more susceptible to protease digestion in the presence of R5P than in the absence of it. The concentration of R5P required for the enzyme to be susceptible to protease digestion was approximately identical with that required to generate Form I. With more than 10(-3) M R5P, the thermostability of the enzyme was greatly increased. The concentration of R5P required for the enzyme to be thermostable was in good agreement with that required to generate Form II. These results indicate that the two activated forms distinguished kinetically differ in their conformations, too. The saturating level of PEP did not cause such a change in the thermostability or the susceptibility to protease.

Adenosine Diphosphate↗

A thermostable Gm-methylase recognizes the tertiary structure of tRNA.

The efficiency of methylation of tRNA by a thermostable tRNA(guanosine-2')-methyltransferase (Gm-methylase) was examined at various temperatures using several species of tRNA isolated from Escherichia coli, yeast and Bacillus subtilis, each possessing different thermal properties. The optimal temperature for the methylation reaction was ca. 20 degrees C lower than the melting temperature of the tRNA in each case. Arrhenius plots of the methylation reactions with various tRNAs gave straight lines below the optimal temperatures in all cases, with similar activation energies of between 10 and 14 kcal/mol. Above the optimal temperatures, the methyl acceptor activity decreased as the incubation temperature was raised to 80 degrees C, at which point the methylase was still active. A correlation was observed between the remaining methyl acceptor activity and the hyperchromicity of tRNA. These results suggest that Gm-methylase recognizes the tertiary structure of tRNA, and it is not the substrate tRNA but the enzyme which is activated by heat.

Base Sequence↗

Primary structures of two types of alpha-subunit of rat brain Na+,K+,-ATPase deduced from cDNA sequences.

A rat brain cDNA library was screened by using as a probe a fragment of cDNA encoding the alpha-subunit of human Na+,K+-ATPase. Two different cDNA clones were obtained and analyzed. One of them was concluded to be a cDNA encoding the alpha-subunit of the weakly ouabain-sensitive rat kidney-type Na+,K+-ATPase. The deduced amino acid sequence consists of 1,018 amino acids. The alpha-subunit of the rat kidney-type Na+,K+-ATPase shows 97% homology in amino acid sequence with the alpha-subunit of human, sheep, or pig enzyme and 87% with that of Torpedo. Based on a comparison of the amino acid sequence at the extracellular domain of the alpha-subunit between weakly ouabain-sensitive rat kidney-type enzyme and the ouabain-sensitive human, sheep, pig, or Torpedo enzyme, it was proposed that only two significant amino acid replacements are unique to the rat kidney-type alpha-subunit. Another cDNA clone obtained showed 72% homology in nucleotide sequence with the former cDNA coding the alpha-subunit of the rat kidney-type Na+,K+-ATPase and the deduced amino acid sequence exhibited 85% homology with that of the alpha-subunit of rat kidney-type Na+,K+-ATPase.

Amino Acid Sequence↗

Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome.

The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of 3H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (Mr 35,614, rlpA lipoprotein) and 175 amino acids (Mr 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lipoproteins may be important in duplication of the cells.

Amino Acid Sequence↗

Total biopterin levels of plasma in patients with depression.

The total biopterin levels of plasma in 12 patients with depression were measured. They were elevated significantly as compared with those in normal controls. The plasma biopterin levels in 6 of 12 patients were measured both in the depressive and in the remissive phases. In the depressive phase the total biopterin levels were increased, whereas in the remission phase they did not differ from those in normal controls. Antidepressants did not affect the plasma biopterin levels. We speculate that the elevation of the plasma biopterin levels in patients with depression was related to the depressive state itself.

Adult↗

Endocardial excitation and conduction during reperfusion arrhythmias.

In order to clarify the role of Purkinje fibers in the occurrence of reperfusion arrhythmias, endocardial mapping was performed on perfused canine hearts by attaching 42 close bipolar electrodes to the endocardial surface of the left ventricular septum. Reperfusion with oxygenated Krebs-Ringer solution following 30 min of coronary occulusion induced ventricular tachycardia (VT) in 14 out of 23 preparations. These VT degenerated into ventricular fibrillation (VF) within 1 min after the reperfusion in all but 3 cases. Endocardial mapping revealed that the excitations during VT were always initiated by the Purkinje activities and that myocardial excitations were expanded in a centrifugal manner through Purkinje-muscle junctional area. Furthermore, this excitation pattern was preserved, in the early phase of VT, even though the propagation pattern was distorted. VF was always induced by reperfusion following 30 min of ischemic condition, that is, coronary perfusion with a hyperkalemic (K = 10 mM), acidic (pH = 6.8) and hypoxic (PO2 = 20-40 mmHg) solution (4/4 cases). Elimination of hyperkalemia from the ischemic condition markedly prevented occurrence of VF (1/6 cases) during reperfusion but it did not affect occurrence of VT (4/6 cases); this implies that hyperkalemia causes the onset of VF but has less effect on the occurrence of VT. It has been separately confirmed by micro-electrode experiment, using the dissected papillary muscle of the canine right ventricle, that abnormal impulse formation during re-oxygenation was triggered in Purkinje fibers around Purkinje-muscle junction.

Animals↗

13 trisomy born to a mother treated with bromocriptine: incidental or not?

A case of 13 trisomy born to a mother treated with bromocriptine is described. She, 27 years old, was treated with bromocriptine (5 mg/day) as a galactorrhea amenorrhea syndrome with hyperprolactinemia (basal 34-122 ng/ml). After the treatment for about a month, disappearance of galactorrhea and occurrence of menstruation were observed. She became pregnant on the second ovulation. On the 34th week she got a male 13 trisomy (47, XY, +13) baby with premature delivery. The baby died 11 hr after his birth. After the first delivery, bromocriptine was readministered. Following the induced abortion on the second pregnancy, she borned a healthy baby on the third pregnancy in spite of taking bromocriptine. This case of 13 trisomy might be incidental. However, the effect of bromocriptine on chromosome should be further evaluated in detail.

Adult↗

The effects of twice daily captopril and once daily enalapril on ambulatory intraarterial blood pressure in essential hypertension.

Intraarterial ambulatory pressure (AP) was recorded before and during therapy with captopril or enalapril in two groups with hypertension. Seven patients were admitted during the study. The monitoring of AP and heart rate (HR) was performed during placebo therapy and following a minimum period of 7 days of 25 mg twice daily captopril or 2.5 to 10 mg once daily enalapril. The AP and HR following percutaneous insertion of a cannula into the brachial artery were sampled then data were analyzed as reported previously. After the cannula was inserted, examinations of tilt-up, handgrip and ergometer were performed. Both drugs produced a significant reduction of ambulatory AP throughout 24 hours with preservation of the overall shape of the circadian curve. The results also demonstrated that both drugs had not affected normal daily activities. Thus, twice daily captopril and once daily enalapril can be used as the first-line therapy of hypertension.

Adult↗

Evaluation of fetal development and well-being with ultrasonic Doppler fetal actocardiogram.

A new ultrasonic technique for objective, continuous and simple recordings method of fetal movements on CTG chart has been introduced. Fetal activity and heart-rate will be correlated. This allows a differentiation of fetal active and resting states. The duration of the first one was 24 to 150 minutes, that of the last one 10 to 36 minutes. Fetal actogram is useful in the prediction of imminent fetal distress.

Embryonic and Fetal Development↗

A case report of pulmonary adenocarcinoma responding to (glycolato-0,0') diammineplatinum (II), a new platinum complex.

The first patient to respond to [(glycolato-0,0') diammineplatinum (II)] (254-S) in a clinical phase I study is reported. The patient was a 52-year-old man complaining of nausea and weight loss. A chest X-ray demonstrated a diffuse infiltrating shadow in the right lung. A transbronchoscopic brushing of the right upper lobe and a biopsy specimen from the right supraclavicular lymph node revealed adenocarcinoma of the lung. He was diagnosed as having primary lung cancer with distant lymph node metastasis. 254-S was administered by intravenous drip infusion to a dose of 100 mg/m2. Two weeks after the second 254-S treatment, a chest X-ray demonstrated a more than 50% reduction in the pulmonary shadow and met the WHO criteria for a partial response. Thrombocytopenia, leukocytopenia and moderate nausea were observed as adverse effects of 254-S but renal toxicity was not found. Pharmacokinetics of free platinum in this patient demonstrated biphasic decay with a peak plasma concentration of 8.09 micrograms/ml. A disease-oriented phase II study of 254-S against non-small cell lung cancer should be performed to establish the efficacy of this new platinum complex.

Adenocarcinoma↗

[Effect of valve replacement on left ventricular function in chronic aortic regurgitation].

To ascertain the optimal time for surgery in chronic aortic regurgitation (AR), 66 patients with and without surgical correction were reviewed from the standpoint of left ventricular (LV) function based on their serial echocardiographic studies. Aggravation of the clinical status was usually associated with enlarged LV dimension, decreased %fractional shortening (%FS), and increased LV end-systolic meridional stress (sigma m). Fourteen patients developed congestive heart failure during follow-up periods of up to five years, and most of their echocardiographic findings showed %FS less than 27%, and LV end-systolic dimension (LVD) greater than 50 mm. Thirty-two patients underwent surgery. Preoperatively, sigma m and %FS were closely correlated, including cases whose %FS was decreased. This linear regression equation became steeper with dobutamine administration; however, in patients, whose mean preoperative LVD value exceeded 50 mm, the %FS remained depressed (delta FS less than 6%) and sigma m did not significantly decrease during dobutamine administration. Marked or moderate resolution of LV dilatation and hypertrophy was observed in all patients postoperatively. Compared to patients with preoperative %FS greater than or equal to 27%, much more time was required for recovery of patients with %FS less than 27%, though their %FS and their exercise capacity improved within two years of surgery. Immediate postoperative recovery was observed in cases with excellent preoperative response to dobutamine (delta FS greater than or equal to 6%). However, in patients with severely depressed preoperative %FS less than 20%, postoperative improvement was not so marked and the surgical results were unsatisfactory. From these results, we concluded that the optimal time for surgery for AR is when %FS = 27% and LVDs = 50 mm.

Adult↗