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Biomedical subjects

H Tsuruta

Publications and source records attributed to H Tsuruta.

At least 91 records · Page 5Linked to original sources

An accelerative enumeration algorithm for the bottle combination problem and the menu planning problem.

In the clinical practice, there are a number of instances in which the request tailored to each patient must be satisfied with a combination of ready-made medical supplies. For example, in intravenous infusion and feeding, an appropriate combination of commercially available bottles must be chosen such that fluid, electrolyte, and nutritional requirements can be satisfied for the individual patient. Menu planning also has the same feature. However, the problem of the optimal combination of medical supplies is difficult to solve exactly and quickly even with the aid of the computer, because of the combinatorial nature of this problem. We formulate the combinatorial problem of medical supplies as a nonlinear all-integer programming problem and present a fast exact algorithm to solve the problem. The proposed algorithm is proved to find an optimal combination in an acceptable calculation time for medical problems of the usual size.

Algorithms↗

In vivo differences between Asian, black and white in the stratum corneum barrier function.

The stratum corneum barrier function of Blacks, Caucasians and Asians were compared in vivo. A noninvasive technic, laser doppler velocimetry (LDV), was used to evaluate the cutaneous penetration of nicotinates by the determination of the lag time before vasodilatation induced by the application of those local vasodilator drugs. The study was performed on untreated skin and after removal of the stratum corneum by 12 strips. The influence of molecular weight and solubility of different nicotinates (methyl, ethyl, hexyl and vitamin E) were also studied on Japanese skin. Vasodilatation lag times assessed by LDV, with methyl nicotinate (MN), showed that skin permeability was more important in Asians (P < 0.01) and in Caucasians (P < 0.05) than in Blacks. Moreover Asian skin was significantly more sensitive to stripping (P < 0.05) than Black skin. A significant shorter lag time was obtained with small and hydrophilic nicotinates (methyl and ethyl) (P < 0.01) compared to a lipophilic one (hexyl). The alteration of the stratum corneum barrier function by stripping showed a more important modification with MN (P < 0.05) than with hexyl nicotinate. Consequently, this noninvasive method can evaluate the modifications of the stratum corneum barrier function and racial origin has to be taken into account in the determination of skin absorption.

Adult↗

Electroencephalographic and autonomic responses to trichloroethylene inhalation in freely moving rats.

Effects of trichloroethylene (TRI) on the central nervous system (CNS) and autonomic functions were examined by means of continuous polygraphic measurements of electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG) in electrode-implanted and freely moving rats, while they were exposed via inhalation to TRI vapor of 300, 1000 or 3000 ppm for 8 h/day or 6000 ppm for 4 h/day on 3 consecutive days. The exposures to 3000 and 6000 ppm produced abnormal EEG activity and incapacitation of postural maintenance during the exposure period, while the post-exposure period was characterized by decreased waking (W) time, lowered heart rate (HR) and increased numbers of bradyarrhythmic episodes after recovery from anesthesia. The exposure to 1000 ppm decreased W time without the appearance of anesthesia. The exposure to 300 ppm did not produce any observable effects except the lowered HR, which occurred during the post-exposure period. The relationships between internal doses of TRI and its metabolites and these TRI-induced pathophysiological responses were determined by blood and brain analyses of TRI, trichloroethanol and trichloroacetic acid in the TRI-exposed rats. Recordings of respiratory chest wall movement revealed that the number of TRI-induced bradyarrythmias accompanying apnea during paradoxical sleep (PS) increased significantly after cessation of exposure to 6000 ppm TRI. This suggests that TRI-induced hypoxemia due to apnea during PS triggers bradyarrhythmogenesis through increased cardiac vagal efferent tone.

Administration, Inhalation↗

Evidence of an associative intermediate on the myoglobin refolding pathway.

Time-resolved small-angle x-ray scattering using the stopped-flow method has been applied successfully to investigate the refolding of myoglobin. This is the only method to date that yields direct information on protein physical dimensions during the folding process. It has the potential to detect and probe important processes, such as protein compaction and association, on a millisecond time scale. Initial experiments were performed with horse myoglobin denatured in high concentrations of urea. The denatured protein was diluted rapidly into a buffer containing no urea or low concentrations of urea. The time-course of the forward-scattered intensity shows a decrease in amplitude which is clearly not engendered by the compaction of the protein, but does correspond well to a dimer dissociation process. Initial and final radii of gyration correspond well to a dimer and a monomer, respectively. Kratky plots of the initial and final states also support the transient dimerization model. The apparent dissociation rate constant was obtainable directly from the data. An association rate constant and an equilibrium constant could be estimated. The dimerizing intermediate is speculated to be a globular non-native state with an exposed hydrophobic surface.

Animals↗

Establishment of a highly sensitive and specific exon-trapping system.

We have established a highly sensitive and specific exon-trapping system (SETS) with a specific plasmid vector in which an exon in a given DNA segment is identified by its ability to remain as a mature mRNA after splicing. The SETS provides us with the isolation of possible exons rapidly and easily from DNA fragments in chromosomal regions of more than 300 kilobase pairs. Genomic DNA fragments were partially digested and subsequently cloned into plasmid pMHC2, an exon-trapping vector we have constructed. These constructs were transfected into COS-7 cells, and consequent RNA transcripts were spliced in the cells. The resulting mature mRNA was harvested and amplified by using reverse transcription-PCR. Possible exons can be recognized by the sizes of PCR products and cloned into a plasmid vector. The SETS provides a direct means of cloning exons from genomic DNA of more than 300 kilobase pairs within a short period of time. Using this system, we have screened 300-kilobase-pair genomic DNA segments derived from human chromosome 11q13. Human chromosome 11q13 may contain genes responsible for human cancers, because DNA amplification is observed in several malignant tumors. We have successfully identified exon 2 of the HST1 gene and additional transcribed sequences.

Base Sequence↗

[Analysis of urinary tract infections in hospitalized elderly patients, with particular reference to the use of diapers].

We investigated the clinical and laboratory data of 215 hospitalized patients (mean age were 76.9 +/- 12.1) to analyze both the characteristics of senile UTI and the influence of the way of urination. UTI was present in 121 of 1897 patients (6.4%), 95 of whom (78.5%) were female. Comparison of the parameters between non-infected and infected patients were as follows: body temperature was 36.57 +/- 0.64 degrees C vs. 37.49 +/- 0.77 degree C; WBC, 5410 +/- 2040/microliters vs. 7260 +/- 3230/microliters; CRP, 1.2 +/- 2.4 mg/dl vs. 3.5 +/- 3.4 mg/dl; mean class of urinary RBC, 0-1/hpf vs. 3-5/hpf; and mean class of urinary WBC, 5-10/hpf vs. 30-50/hpf. All parameters were significantly elevated (p < 0.001) in the patients with UTI. The rate of detection of causative bacteria was 88.7%; with 14.8% Escherichia coli, 12.8% Providencia species, 9.6% Enterococci, and 8.7% Pseudomonas aeruginosa. Patients with UTI were divided into three groups according to their method of urination: normal urination, use of diapers and catheterization. Body temperature (> or = 37.5 degrees C) was 2.8%, 10.1% and 34.9%; WBC (> or = 9.000), 2.7%, 6.1%, and 14.3%; CRP, 16.9%, 36.1% and 51.1%; urine RBC (> or = 6-10/hpf), 8.4%, 7.1% and 36.1%; urine WBC (> or = 15-30/hpf), 20.4%, 44.4% and 76.9%, respectively. There was a significant difference (p < 0.05-0.001) between all parameters except for urine RBC between the normal-urination patients and diaper using patients. This investigation suggested that the use of diapers was a risk factor for UTI in elderly patients.

Adult↗

Biological significance of gene amplification in carcinogenesis.

K-SAM gene was originally isolated as an amplified gene in a stomach cancer cell line by in-gel DNA renaturation method. K-SAM encodes a membrane receptor with tyrosine kinase and is often amplified in poorly differentiated type of stomach cancer, while c-ERBB-2 is often amplified in well differentiated type of stomach cancer. There are several forms of K-SAM mRNAs which are generated by alternative splicing, and two types of K-SAM protein without transmembrane region. The ligand of K-SAM is considered to be growth factor(s) belonging to fibroblast growth factor (FGF) or heparin binding growth factor (HBFG) family. We have also frequently found amplification of HST-1 or HSTF1 gene in esophageal cancer. HST-1 gene, originally found as a transforming gene, is located on human chromosome 11q13, and it locates 35 kbp apart from its related gene, INT-2. Neither of the genes was expressed even in cancer cells with the co-amplification. By cosmid walking, we have identified at least two genes, designated tentatively as EXP1 and EXP2, on the same amplicon as HST-1 and INT-2, and the mRNAs for EXP1 and EXP2 genes were increased in amounts proportional to the degree of amplification.

Esophageal Neoplasms↗

[Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period].

Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram-negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study.

Adult↗

Structural kinetics of the allosteric transition of aspartate transcarbamylase produced by physiological substrates.

We have studied the kinetics of the quaternary structure change associated with the allosteric transition of aspartate transcarbamylase (ATCase) (E. coli), inducing this change by exposure to the natural substrates (carbamyl phosphate and L-aspartate). The presence of 30% ethylene glycol slowed the quaternary structure change sufficiently for it to be followed by stopped-flow X-ray scattering at -5 degrees C. After adding substrates to the enzyme, the change occurred, with a half-life of a few seconds, yielding a mixture of the two standard quaternary structures (or, conceivably, a state intermediate between them). This mixture persisted until the enzyme reduced the substrate concentration below a threshold value.

Allosteric Regulation↗

Dissociation of Limulus polyphemus (horseshoe crab) hemocyanin. I. Solution X-ray scattering study in equilibrium.

A solution X-ray scattering study has been performed on Limulus polyphemus (horseshoe crab) hemocyanin and its dissociated fragments at various pH values in the presence and absence of Ca2+. The scattering patterns of native hemocyanin (48-mer), the half molecule (24-mer), quarter molecule (12-mer) and monomer fraction were measured. The radii of gyration for the four molecular species were calculated from the Guinier plots to be 110.7, 91.3, 77.3, and 36.5 A, respectively. Models which yield good fits to the experimental data are presented. The models were constructed using eight, four and two spheres with a radius of 58 A, assuming the sphere to be the submultiple composed of six subunits. The radii of gyration were calculated on the basis of the model and the values found to be 106, 94 and 73 A, respectively, in good agreement with the experimental results.

Journal Article↗

A fluorescence temperature-jump study on Ca2(+)-induced conformational changes in calmodulin.

Calmodulin has been shown to alter its conformation so as to interact with a number of target proteins upon Ca2+ binding. A Ca2(+)-binding study of calmodulin was performed by monitoring the fluorescence of intrinsic tyrosine residues and the probe 1-anilinonaphthalene-8-sulfonate (ANS). ANS fluorescence was shown to reflect Ca2+ binding to both high- and low-affinity sites. On the one hand, tyrosine fluorescence was sensitive only to the high-affinity Ca2+ binding. Temperature-jump investigation of the ternary complex of Ca2(+)-calmodulin-ANS in combination with monitoring of ANS fluorescence demonstrated the kinetic characteristics of the conformational change. The relaxation process was attributed to Ca2(+)-induced conformational change and the rate constants of this process were evaluated. On the basis of the rate constants of the conformational change, a rapid response of calmodulin in Ca2+ signaling is suggested.

Calcium↗

[Retrograde continuous cold blood cardioplegia for aortic valve surgery].

From September 1983 to February 1987, 45 consecutive aortic valve operations were performed using the retrograde continuous cold blood cardioplegia (RCCBC) via the coronary sinus. Except one patient died of stuck valve after aortic and mitral valve replacements, 44 patients were subjected for this study and all survived patients were symptomatically improved. They were divided into two groups according to the aortic cross clamps time (ACCT). Group 1; 23 patients, ACCT within 120 minutes, and Group 2; 21 patients, ACCT exceeding 120 minutes. After the operation blood was taken periodically to check creatine phosphokinase (CPK) and its iso-enzyme creatine-kinase (CK-MB) and GOT etc. Then their levels were compared between the two groups. Although there seemed to be a tendency that the highest levels of these enzymes increase according to the ACCT, there was no significant difference in CK-MB level between the two groups. Judging from the operative results and the postoperative study of enzymatic level, RCCBC is safe and useful for aortic valve surgery, especially when long ACCT is necessary for correcting complicated lesions or when the coronary orifice is not suitable for coronary perfusion in aortic dissection.

Aortic Valve↗

Kinetic study on the dimer-tetramer interconversion of phosphorylase b by a stopped-flow X-ray scattering method.

The dimer-tetramer interconversion of phosphorylase b induced by the binding of AMP and Mg2+ was monitored using a stopped-flow X-ray scattering method. The rate constants of this second-order reaction have been determined by a nonlinear least-squares method. Burst phases in both radii of gyration and zero-angle intensities were detected at the initial step of the reaction. This suggests that rapid association might take place, followed by a slow association process of which the kinetics were measured in the present study. The radius of gyration of tetrameric phosphorylase b was determined and found to be in excellent agreement with that of phosphorylase a, but different from that of phosphorylase b reported elsewhere (G. Puchwein, O. Kratky, C. F. Golker and E. Helmreich, Biochemistry 9 (1970) 4691). The reason for this inconsistency is discussed.

Animals↗

Skin absorption of organic solvent vapors in nude mice in vivo.

Nude mice each attached to a respirator to avoid pulmonary uptake were exposed in a glass exposure chamber to 200, 1000 or 3000 ppm of benzene, toluene or tetrachloroethylene (perclene) for 2, 4 or 6 h. The animals were killed at the end of the study and the amount of each solvent retained in the whole body was determined by gas chromatography. Skin absorption rates were calculated from the amount retained in the whole body using the single compartment model (elimination rate constant) obtained in a previous experiment. There was a linear relationship between the amount of skin absorption and exposure time, and also a linear relationship between the skin adsorption rate and concentration of exposed vapors. Skin absorption of solvent vapors occurs by passive diffusion as defined by Fick's law. The skin absorption coefficient (cm/h) of each solvent vapor was calculated by dividing the skin absorption rate by exposure concentration; the values were 1.24 for toluene, 1.00 for perclene and 0.619 for benzene. The coefficient may be useful for evaluating the amount of skin absorption (ng) was calculated by multiplying the skin absorption coefficient (cm/h), concentration of solvent vapor (ng/cm3), exposure time (h) and exposed skin area (cm2).

Animals↗

[A case of concomitant surgery of advanced valvular disease and lung cancer under cardiopulmonary bypass].

We successfully performed a concomitant operation in a patient with severe valvular heart disease with a giant left atrium and a pulmonary cancer. The operation was done via a median sternotomy under cardiopulmonary bypass. The patient was a 62-year-old man with congestive heart failure, NYHA class III. The CT ratio was 76%, and the volume of the left atrium estimated by a CT scan was above 900 ml. An abnormal shadow was recognized in the left upper lung field. Mitral valve replacement with St. Jude Medical valve (31 mm), and tricuspid annuloplasty with a Bex Reducer were performed. After an autonomous cardiac rhythm and a decrease in the size of the left atrium were confirmed, we went on to remove the upper lobe of the left lung under cardiopulmonary bypass. Twelve months postoperatively, the patient was doing well. For a complex case such as the present one, we recommend lobectomy via a median sternotomy using cardiopulmonary bypass as the technique of choice. This method assures good hemodynamic control and provides improved visibility of the pulmonary hilus.

Cardiopulmonary Bypass↗

Changes in sleep and wakefulness following single and repeated exposures to toluene vapor in rats.

Male rats with indwelling electrodes for electroencephalographic (EEG), electromyographic (EMG) and electrooculographic (EOG) recordings were exposed via inhalation to 900 ppm and 2700 ppm toluene vapor continuously for a 8-h period or repeatedly for 3 weeks at a rate of 8 h/day and 5 days/week. Rats exposed to a clean air-stream under the same exposure schedules served as controls. Polygraphic recordings were made on 3 consecutive days after cessation of the single 8-h and repeated 3-week exposures to 900 ppm and 2700 ppm toluene vapor or clean airstream. Amounts of time spent in wakefulness (W), slow-wave sleep (SWS) and paradoxical sleep (PS) were quantified by visual inspection of the polygraphic records. Single exposure to toluene produced a prolonged PS latency and a long-lasting increase in SWS at the expense of depressed W, whereas repeated exposures prolonged both SWS and PS latencies, abolished the initial increase of SWS and increased the light-phase level of W on Days 1 and 2. The prolonged PS latency and the decreased light-phase PS on Day 2 induced by single exposure to toluene still persisted after repeated exposures. There were no statistically significant differences in attenuation of brain and blood toluene levels between single and repeated exposures to toluene vapor of 900 ppm and 2700 ppm.

Animals↗

Potentiometric studies of selective reactions of bioactive substances on the surface-modified tantalum electrodes.

The method of highly selective potentiometric detection of bioactive substances developed by us has been much improved by using tantalum metal as a electrode material, by employment of a new method of modification (using gamma-aminopropyltriethoxysilane and cyanogen bromide), and by the pretreatment with inert protein before the measurement. As the consequence, the response in the electrode potential shift has been increased and the reproducibility of the data reached almost 100%.

Adsorption↗