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Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active Apex gene and a processed pseudogene were isolated from a rat genomic library. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1) gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization. The processed pseudogene (designated as rat Apexp1) has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, although several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LINE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp1 arose 23 million years ago and that the non-functionalization occurred 15 million years ago.

A simulation model to predict the survival probability of individual patients with hepatocellular carcinoma (HCC) after therapy was derived from the results of various therapies and follow-up studies of 450 HCC patients. Twenty-two prognostically important variables were analyzed by Cox's proportional hazards model. The 9 significant variables that were extracted were used to build the simulation. In this model, S(t), the expected estimated survival rate for individual patient at time t (month), is calculated by the following equation: S(t) = (exp (-0.03655t) (exp [0.9479 ([portal vein invasion]-0.222) + 0.3846 ([tumor number]-2.00) + 0.2578 ([tumor size]-3.231) + 0.0742 ([loge AFP]-5.647) + 0.8184 ([metastasis]-0.036) + 0.2810 ([Child's class]-1.689)-0.7088 ([transcatheter arterial embolization]-0.578)-0.9746 ([percutaneous ethanol injection]-0.153)-0.5377 ([hepatectomy]-0.109)]) The validity of the model was assessed using a split-sample technique. This paper does not discuss the superiority or inferiority of the therapies, because some selection bias for prognostic factors among the therapies can not be completely excluded. But this model is proposed as a practical model to predict the survival of patients with HCC.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).

The extent of homology between two protein fractions was compared by simple electrophoretic analysis. Nuclear proteins of several rodent cells of different origins were fractionated into acid-soluble and acid-insoluble fractions. The two protein fractions were subjected to polyacrylamide gel electrophoresis in separate gel systems, and protein bands with identical mobilities were sought either in all possible combinational pairs of cell types or in all cell types. The paired and overall homology indices calculated from these data and chi-square testing of the results indicated that acid-soluble nuclear nonhistone proteins are more homologous than acid-insoluble nuclear proteins. Several factors which might have affected the results were discussed.

A photo tube dew-point hygrometer is used for measuring humidity of respiratory gases, which are in varying conditions. It makes it possible to make an accurate, precise, continuous and automatic recording of the dew point of gas flows. The most notable features of this device are: (1) Simplicity of calculating absolute humidity, since the humidity is indicated with dew point. (2) Calibration is easy and reliable. (3) Performance is stable, and its operation and maintenance are simple. (4) Indication is correct and unaffected by temperature. (5) There is good response to any quick changes in humidity. (6) There is continuous and automatic recording of humidity, especially with simultaneous temperature measurements on the same paper. (7) Impurities such as the vapors of organic substances or volatile agents do not affect the performance. Simple wiping can eliminate the disturbance from mirror contamination. (8) The entire apparatus is on a cart and easily movable. This device provides a new method of studying the functional relationship between humidity and various respiratory states, and it is hoped it will contribute much to physiological and clinical investigations. The principle and structure of the "automatic D.P. hygrometer", the apparatus and method for practical hygrometry and obtained results are described and discussed.

Through the use of an automatic photo tube dew-point hygrometer, the author succeeded in measuring dew point of gas flows continuously in anesthetic circuits. Simultaneous thermometries were done on the nasal or oral mucosa, on the respiratory gas flows in the anesthetic mask or the endotracheal tube, and on the gas in the inhaling conduit. Experiments were performed on ten adults patients undergoing various types of surgery under general inhalation anesthesia. Anesthetic technics were varied intentionally during the measurements. Thus, both absolute and relative humidities of exhaled and inhaled gases, and respiratory water and heat losses were calculated under various anesthetic conditions, and physiological and clinical considerations were discussed. The conclusions obtained from this research are as follows: (1) When a non-rebreathing system is applied, moisture content of exhaled gas is minimal, and respiratory losses of both water and heat are maximum. With a semi-closed circle method, according to decreasing fresh gas flows, the humidity of the inspiratory and expiratory gases becomes higher, and both heat and water losses through respiration are lessened. When a closed circle method, with carbon dioxide absorption, is employed, temperature and humidity of gas in the inhaling conduit are highest, and the expired gas offers the maximum temperature and moisture contenL Both water and heat losses from anesthesia become minimal when administered in a closed system. (2) While the water and heat that a patient loses through respiration increase with increasing breathing capacity, they are still small parts of the total water and heat losses of the patient. Water and heat losses via anesthesia systems are not so predominant in maintaining water balance and heat regulation of patients during anesthesia and surgery.

Steady-state serum concentrations of carbamazepine (CBZ) and valproic acid (VPA) were investigated in normal weight (body mass index; BMI 20 to 25), lean (smaller than 20 BMI) and moderately obese subjects (greater than 25 BMI) who received either 400 mg/day of CBZ or 800 mg/day of VPA. The CBZ serum concentration in lean subjects was significantly higher than that in normal weight subjects. However, no significant differences in VPA serum concentration were found between the three groups. The CBZ serum concentration decreased with increases in total body weight, and the VPA serum concentration decreased with increases in ideal body weight. However, both serum concentrations were not correlated with BMI. These results suggest that VPA doses should be calculated using ideal body weight and that degree of obesity may affect CBZ serum concentration rather than VPA serum concentration.

The frequency of recessive gene, heterozygotes and homozygotes in Japanese acatalasemia were estimated as 0.0038, 7.5 X 10-3 and 3.0 X 10-5 by DAHLBERG'S formula, and estimated as 0.00087, 1.73 xl 0-3 and 4.23 X 10-6 by KIMURA'S formula. The frequency of recessive gene was calcu. lated from the frequency of hypocatalasemia obtained by the screening method as 0.00083, and it was almost identical with that calculated 1:'>y KIMURA'S formula. The number of acatalasemia was estimated as about 423 by KIMURA'S formula.

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.

Instability of the knee after the medial collateral ligament (MCL) injury is usually assessed with the manual valgus stress test, even though, in recent years, it has become possible to apply magnetic resonance imaging (MRI) to the assessment of the damage of the ligament. The valgus instability of 24 patients (12 isolated injuries and 12 multiple ligament injuries) who suffered MCL injury between 1993 and 1998 was evaluated with the Hughston and Eilers classification, which involves radiographic assessment under manual valgus stress to the injured knees. We developed a novel system for classifying the degree of injury to the MCL by calculating the percentage of injured area based on MRI and investigated the relationship between this novel MRI classification and the magnitude of valgus instability by the Hughston and Eilers classification. There was a significant correlation between the 2 classifications (p=0.0006). On the other hand, the results using other MRI based classification systems, such as the Mink and Deutsch classificaiton and the Petermann classification, were not correlated with the findings by the Hughston and Eilers classification in these cases (p0.05). Since MRI is capable of assessing the injured ligament in clinical practice, this novel classification system would be useful for evaluating the stability of the knee and choosing an appropriate treatment following MCL injury.

In the present study, we examined the dynamic of school-health-based parasite control and the related socio-economic influences. This is an ecological study based on data from 46 prefectures in Japan. The exponential decay of Ascaris lumbricoides prevalence was calculated by iterative least-squares method. Pearsonʼs correlation and multiple linear regression model analysis were performed to assess the associations between the prevalence of Ascaris lumbricoides in Japanese school children and socio-economic variables such as the prefecture income per capita, the percentage of primary industry, the population density per 1 km2, the diffusion rate of population under water supply, and the percentage of upper secondary school enrollment. The results indicated that the parasite carrier rate was higher in younger students. The half-life of Ascaris lumbricoides prevalence was approximately 3 years with significant variation among prefectures. Multiple regression analyses showed that the decrease of infection in elementary and lower secondary school children had a significant positive association with primary industry and a significant negative association with prefecture income per capita. The school-health-based parasite intervention differs by prefecture and has changed over time according to the respective prefectural stage of economic development.

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.

Improvement in tissue perfusion following surgically induced ischemia in limbs of dogs was experimentally evaluated to clarify the improvement of hemodynamics following walking exercise in chronic, peripheral arterial occlusive diseases. With the use of a computer system in conjunction with medical mass spectrometry, the local tissue perfusion rate was calculated on the basis of the clearance curve of tissue partial pressure of CO2 following electrical stimulation of the ischemic leg to simulate exercise. Ischemia was created in the leg by ligation of the proximal and peripheral arteries. In one month, intermittent claudication improved in accordance with improvement in muscle tissue perfusion. Angiographic evidence of distal runoff became visible six months after surgery, indicating that tissue perfusion played an important role in peripheral hemodynamics. The local tissue perfusion rate improved from 9.51 +/- 2.62 ml/100 g/min to 12.41 +/- 2.42 in one month, to 14.59 +/- 3.19 in three months, to 15.11 +/- 3.24 in six months and to 17.19 +/- 2.63 in twelve months. The improvement of ischemic symptoms following long-term exercise is attributed to improvements in tissue perfusion or collateral circulation.

Operative treatment of fractures of the neck and trochanter of the femur does not always produce a satisfactory result. This is usually due to biomechanical problems with the available internal fixation methods. We studied the anatomy of the neck of the femur by roentgenograms and sectional specimens from 70 cadavers. In addition, various nail-plates were subjected to buckling tests and, by simultaneously attaching a strain-gauge, stress distribution was calculated. The results of these preliminary studies were then used to design a new nail-plate better than those available at present. Testing of this new nail-plate confirmed that it had a strength equal to that of the Holt nail-plate (the strongest of the available nail-plates).

We purified a 44-kDa nuclear protein from salt-extract of permeable mouse ascites sarcoma cells in an effort to isolate factors involved in the repair of acid-depurinated DNA. It was copurified with a major AP endonuclease (APEX nuclease) by sequential column chromatography then further purified by sodium dodecyl sulphate-poly-acrylamide gel electrophoresis as a possible DNA repair support factor. Its partial amino acid sequences were determined, and a cDNA clone for the protein was isolated from a mouse T-cell cDNA library using long degenerate oligonucleotide probes deduced from the amino acid sequence. The complete nucleotide sequence of the cDNA (1.7 kilobases) was determined. Northern hybridization using this cDNA detected two transcripts: 1.8kb being the major one and 2.6 kb being the minor one. The complete amino acid sequence for the protein predicted from the nucleotide sequence of the cDNA indicates that the 44-kDa protein consists of 394 amino acids with a calculated molecular weight of 43,698. In tests performed thus far, the recombinant 44-kDa protein expressed in Escherichia coli has not expressed any repair-support activity. It remains to be analyzed whether the protein attains this activity after appropriate posttranslational modifications. Most parts of the 44-kDa protein cDNA and the deduced amino acid sequence were found to be identical to those of the protein p38 -2G4, recently reported as a cell cycle-specifically modulated nuclear protein of 38kDa. The p38-2G4 may be a truncated form of the present 44-kDa protein.

To evaluate worker's exposure to mixed solvents, equations for the calculation of the biological hazard index, which is defined as biological levels tolerable for exposure to mixture, were developed. When biological levels of exposure indicators were not affected by coexposure, rules similar to those for airborne monitoring could be applied. Namely, when the components had additive effects, the biological hazard index was calculated from the concentration of urinary metabolites or parent solvents, by an equation which was essentially similar to the equation for the calculation of the hazard index. In the present study, the confidence limits of the biological hazard index and predictive limits for individual specimens were calculated. These equations could be used under the condition that the uptake, metabolism and elimination of solvents were practically unaffected by coexposure. When urinary metabolites or solvents of some components of a mixed solvent alone were determined and those of the remaining components were not determined, the concentration of urinary metabolites or solvents of remaining components were estimated from the airborne concentration of the other components.

This study assessed total and segmental distribution of fat mass (FM) in athletes with spinal cord injury (SCI) and examined the relationships between segmental distribution of fat mass and age, injury level, athletic history, and training load in order to provide useful information for improvements in their physical strength and training. Twenty-five male athletes with SCI participated in the study. The whole bone composition was measured by a dual-energy X-ray absorptiometry (DXA) method for the calculation of bone minerals, FM, and fat-free mass. The percent fat of the trunk, arms, and legs was also calculated. The percent fat in the legs was highest in comparison with that in the trunk and arms (p < 0.001), and the percent fat in the trunk was higher than that in the arms (p < 0.001). The body fat (p < 0.01), waist circumference (p < 0.01), and waist-to-hip ratio (p < 0.0001) were higher in the group aged 40 or older in comparison with that aged 39 or younger. Path analysis revealed that training load was a factor decreasing the percent fat on the arms and trunk (p < 0.01), and athletic history was a factor reducing the percent fat on the arms (p < 0.05). Our study suggests that exercise is effective in reducing the waist circumference, waist-to-hip ratio, and percent body fat of SCI individuals, and that such effects can help to enhance athletic performance and likely to protect against development of metabolic syndromes resulting from a sedentary lifestyle.