Okayama University Medical School

This experiment was carried out to evaluate the possibility of degradation of d-lactate into formate and acetaldehyde. In order to induce hyperproduction of d-lactate in rats. Donryu male albino rats were fed diets containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB), 4'-methyl-4-dimethylaminoazobenzene (4'-MDAB) or 2-methyl-4-dimethylaminoazobenzene (2-MDAB) for 10 weeks. During the experiment, body mass, food and water intake and volume of urine were documented. Methylglyoxal, d-lactate and formate in the urine samples were determined. On the first day of the eleventh week, methylglyoxal, d-lactate, glutathione and enzymatic activities of demethylation and glyoxalase I and II in liver were measured. Methylglyoxal, d-lactate and clinical chemistry parameters of blood plasma were also measured. The levels of methylglyoxal and d-lactate in livers of rats fed 3'-MDAB were very high, while those of 2-MDAB fed-rats and the control group were the same. The fact that glyoxalase I activity and the level of glutathione, a cofactor of glyoxalase I, were high in the livers of the 3'-MDAB-fed rats can explain the elevated levels of methylglyoxal and d-lactate in the liver. The most striking results were the elevated formate levels in the urine of rats fed 3'- and 4'-MDAB in a precancerous state. The degradation of d-lactate, an end product of the methylglyoxal bypass, into acetaldehyde and formate was suggested as a possible way to explain the results.

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.

Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR), or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n＝8), which had thrombocytopenia within 72h after birth, and group B (n＝19), which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA)-pulsatility index (PI), middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.

A minimally invasive plate osteosynthesis technique using a locking compression plate (LCP) has been used widely in trauma cases. Its advantages are that the MIPO technique does not interfere with the fracture site and thus provides improved biological healing, and that the LCP has excellent angular stability. Its use in bone lengthening, however, has not been established. In such cases, it is desirable to shorten the external skeletal fixation period as much as possible. Here, the MIPO technique using an LCP was applied to femoral distraction osteogenesis in an attempt to shorten the external skeletal fixation period. For femoral lengthening, the MIPO technique was performed in 2 stages. Orthofix external fixators (Orthofix, England) were used to insert screws from the anterolateral side rather than from the lateral side of the femur for bone lengthening. When sufficient callus formation was detected postoperatively at the site of bone lengthening, and the absence of infection was ensured, limb draping was performed, including a whole external fixator, and then the MIPO technique was applied with an LCP. In 3 cases (5 limbs), the average duration of external skeletal fixation was 134days, the average external-fixation index was 24days/cm, and the average consolidation index was 22days/cm. The MIPO technique using an LCP made it possible to shorten the external skeletal fixation-wearing period in femoral lengthening.

We discuss the concept of social capital, which has received much attention recently. Social capital is important for the following 2 key reasons:(1) a highly democratic polity and a strong economic performance that attaches great importance to the public good can be achieved on the basis of high social capital;and (2) social capital can effect health status in the human population, and widening of income inequality harms human health through the erosion of social capital. In addition, there are 3 political implications of social capital for Japanese society:(1) social capital has implications for the political decision of whether Japanese society should adopt a “medium burden for medium welfare” or a “low burden for small welfare” model together with the concept of social overhead capital;(2) reciprocity, which is one of the primary components of social capital, is similar to the philosophy underlying the health care system of Japan;(3) Japanese society needs to change from a society that emphasizes the relationships between its members to a society that is open to outsiders and has sufficient opportunities.

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.

The aim of this study was to determine the optimal temperature of graft preservation after ex vivo gene transfer to rat lung isografts. Left lungs were harvested and infused with cationic lipid/LacZ-DNA complex via the pulmonary artery, and the grafts were stored for 4h. The grafts (n＝7) were allocated into groups IﾝIV according to the storage temperature:4℃, 10℃, 16℃, and 23℃, respectively. Forty-eight h after orthotopic transplantation, the arterial blood gas was analyzed and the peak airway pressure (PAP) and the level of LacZ protein production in the grafts were measured by reverse transcription polymerase chain reaction. After reperfusion, the grafts were stained with hematoxylin and eosin. The grafts in groups III and IV showed more deterioration as evidenced by decreased arterial oxygen tension, increased PAP, and predominant infiltration of inflammatory cells compared with groups I and II. The level of LacZ production was significantly lower in group I than in groups IIﾝIV. The optimal temperature of lung graft preservation after ex vivo gene transfer was determined to be 10℃, balancing considerations of lung injury and efficiency of transgene expression.

A very rare case of echinococcus cysts of the heart and brain in a 27ﾝyear-old man who worked as a butcher, lived on a farm, and had a dog before disease onset. The initial manifestation of hydatid disease was anaphylactic shock, the etiology of which remained unknown on initial hospitalization. On rehospitalization, the diagnosis of cardiac hydatidosis was made and the patient underwent surgery. Two years later, reoperation was required for hydatid cyst of the brain and cardiac cyst recurrence. There was no other organ involvement from the disease onset, which is rarely reported. Based on this case, we suggest that echocardiography be performed as a standard method in the diagnosis of anaphylactic reaction of obscure etiology in the areas endemic for hydatidosis, even in the absence of symptoms indicative of cardiac involvement. This especially applies to individuals with occupational or epidemiological exposure to the infection.

Posthumous reproduction has been performed in Japan several times, without sufficient civic discussion on its appropriateness or legislative regulation. There have even been several lawsuits on posthumous acknowledgment (in which a baby born to a deceased father has the same birthright as a baby born to a living father), and some judgments have proposed the need to develop societal agreement on posthumous reproduction and suggested legislative settlement. With this background, this study aims to clarify the views of the Japanese people regarding posthumous reproduction. In December 2007, we distributed a questionnaire on posthumous reproduction in relation to beliefs about family and religion to 32 universities across the country, and received 3,719 replies. It was found that about 60ｵ of respondents agreed with posthumous reproduction. Statistical analysis was applied to the relationship between this overall position on posthumous reproduction and views on assisted reproduction technologies, family, religion, and so on. The degree of support for posthumous reproduction was strongly correlated with the degree of affirmation of assisted reproduction technologies and a liberal worldview with emphasis on self-determination. On the other hand, there was also a strong correlation with having a traditional view of family, such as family succession. The degree of support for posthumous reproduction was also highly correlated with the intimacy among family members, underlying which was a strong connection to the traditional religious belief in Japan that deceased family members watch the living ones. The view on posthumous reproduction is culturally complex and cannot be explained by a simple dichotomy between traditional conservatives and liberals.

The Malaysian people consist of several ethnic groups including the Malay, the Chinese, the Indian and the Orang Asli (aboriginal Malaysians). We collected blood samples from outpatients of 2 hospitals in the State of Selangor and identified 27 glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects among these ethnic groups. In the Malay, G6PD Viangchan (871G＞A, 1311C＞T, IVS11 nt93T＞C) and G6PD Mahidol (487G＞A) types, which are common in Cambodia and Myanmar, respectively, were detected. The Malay also had both subtypes of G6PD Mediterranean:the Mediterranean subtype (563C＞T, 1311C＞T, IVS11 nt93T＞C) and the Indo-Pakistan subtype (563C＞T, 1311C, IVS11 nt93T). In Malaysians of Chinese background, G6PD Kaiping (1388G＞A), G6PD Canton (1376G＞T) and G6PD Gaohe (95A＞G), which are common in China, were detected. Indian Malaysians possessed G6PD Mediterranean (Indo-Pakistan subtype) and G6PD Namoru (208T＞C), a few cases of which had been reported in Vanuatu and many in India. Our findings indicate that G6PD Namoru occurs in India and flows to Malaysia up to Vanuatu. We also discovered 5 G6PD-deficient cases with 2 nucleotide substitutions of 1311C＞T and IVS11 nt93T＞C, but without amino-acid substitution in the G6PD molecule. These results indicate that the Malaysian people have incorporated many ancestors in terms of G6PD variants.

The vascular effects of an aqueous extract prepared from the leaves of Eucommia ulmoides Oliv. (ELE), a medicinal herb commonly used in antihypertensive herbal prescriptions in China, were investigated in rat mesenteric resistance arteries. The mesenteric vascular bed was perfused with Krebs solution and the perfusion pressure was measured with a pressure transducer. In preparations with an intact endothelium and precontracted with 7μM methoxamine, perfusion of ELE (10^－7－10^－2mg/ml for 15min) caused a concentration-dependent vasodilatation, which was abolished by chemical removal of the endothelium. The ELE-induced vasodilatation was inhibited by neither indomethacin (INDO, a cyclooxygenase inhibitor) nor N^G-nitro-L-arginine-methyl ester (L-NAME, a nitric oxide inhibitor). The ELE-induced vasodilatation was significantly inhibited by tetraethylammonium (TEA, a K⁺ channel blocker) and 18α-glycyrrhetinic acid (18α-GA, a gap-junction inhibitor), and abolished by high K⁺ -containing Krebsʼ solution. Atropine (a muscarinic acetylcholine receptor antagonist) significantly inhibited the vasodilatation induced by ELE at high concentrations. These results suggest that the ELE-induced vasodilatation is endothelium-dependent but nitric oxide (NO)- and prostaglandin I₂ (PGI₂)-independent, and is mainly mediated by the endothelium-derived hyperpolarizing factor (EDHF) in the mesenteric resistance arteries. Furthermore, the ELE-induced EDHF-mediated response involves the activation of K⁺-channels and gap junctions.

We investigated the effects of pentoxifylline (PTX) on endotoxin-induced diaphragmatic dysfunction in vitro. Seventy-two rats were divided into 3 groups: a group in which endotoxin (20 mg/kg) was injected intraperitoneally (endotoxin-group), a group in which PTX (100 mg/kg) was injected intraperitoneally 30 min before injection of endotoxin (endotoxin-PTX group), and a group in which only saline was given (sham group). Left hemidiaphragms were removed 4 h after injection of endotoxin. We evaluated the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. We measured serum TNF-alpha concentrations, diaphragm malondialdehyde (MDA) levels (an index of oxygen-derived free radical-mediated lipid peroxidation), and diaphragm cAMP concentrations. Diaphragmatic force generation capacity was signifi cantly reduced after injection of endotoxin. Serum TNF-alpha concentrations and diaphragmatic MDA levels were significantly elevated after injection of endotoxin. PTX administration significantly improved diaphragmatic contractility and prevented the elevation in TNF-alpha concentrations and MDA levels after injection of endotoxin. There were no significant changes in the diaphragm cAMP concentrations among the 3 groups. These results demonstrated that PTX administration prevented endotoxin-induced diaphragmatic dysfunction without changing diaphragm muscle cAMP concentrations. The protective effects of PTX against endotoxininduced diaphragmatic contractile deterioration might be caused by attenuating TNF-alpha-mediated oxygen-derived free radical production.

In modern emergency and critical care, physicians tend to choose the mode of mechanical ventilation based on spontaneous breathing for the purpose of promoting discharge of pulmonary secretion and preventing atelectasis in patients with acute respiratory insufficiency. However, we often observe "differences in recovery" among patients treated using the same PSV settings beyond "differences in individual characteristics." We evaluated the Pressure Support Ventilation (PSV) mode aiming to certify the difference among 7 representative mechanical ventilators using the Active Servo Lung 5000 (ASL5000) respiratory simulation system. The following parameters were measured: The time delay that resulted in the lowest inspiratory pressure from the point at which the ventilator recognized spontaneous breathing (TD), the lowest inspiratory airway pressure (cmH2O) generated prior to the initiation of PSV (DeltaPaw), the work of breathing while triggering required to achieve the lowest inspiratory negative pressure from the beginning of inspiratory support (WOBtrig), and the inspiratory work of breathing (WOBi). The mean TD of the Puritan-Bennett type 840 (PB840) was signifi cantly shorter than those of other ventilators (p0.01). The WOBtrig of the PB840 was significantly lower than those of others (p0.01). However, the WOBi values of the Servo-I and T-Bird were greater than the others, with the Evita series showing the smallest WOBi of the 7 ventilators tested. According to this simulation study using ASL 5000, we concluded that PB840 was the most rapid response ventilator, but the Evita series was the gentlest mechanical ventilator among 7 ventilators from the standpoint of the total work of breathing during the inspiration phase in the setting of PSV.

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.

Hepatic and pancreatic differentiation from ES cells is of great interest for the impact that this knowledge could have on the treatment of hepatic and diabetic patients. The liver and pancreas initially develop by budding from the embryonic endoderm. Thus, the development of the endoderm represents an important step and has an integral common role in initiating the early stages of pancreatic and liver development. We know that the development of hepatocytes and insulin-producing pancreatic beta-cells from ES cells represents the culmination of a complex developmental program. However, there has been recent progress in directing ES cells to endoderm and early-stage hepatic and pancreatic progenitor cells. We here discuss the role of the microenvironment, transcriptional factors and cytokines, which have been recognized as important molecules during the major steps of the development of the liver and pancreas. We also present the most recent advances and efforts taken to produce definitive endoderm-committed ES cells for the further differentiation of hepatocyte-like and insulinproducing cells. Recent progress in the search for new sources of hepatocytes and beta-cells has opened up several possibilities for the future of new perspectives for future of new prophylactic and therapeutic possibilities for liver diseases and diabetes.

We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or those who smoke, on embryonal development. Pronuclear (PN) embryos were obtained by flushing the fallopian tubes of rats after superovulation and mating. The cleavage rate and blastocyst yield were evaluated at 24, 72, 96, and 120 h of culture. Glyoxal, an AGE-forming aldehyde, suppressed embryonal development at every stage from PN to blastocyst in a concentration-dependent manner. The cleavage rate of the embryo was also signifi cantly decreased by treatment with glyoxal at concentrations of 1 mM or higher. The blastocyst yield was significantly decreased by treatment with glyoxal at concentrations of 0.5 mM or higher. N-acetyl-L-cysteine (L-NAC) at 1 mM significantly suppressed the glyoxal-induced embryonal toxicity. BSA-AGEs at 5 microg/ml or higher concentration signifi cantly reduced the cleavage rate and blastocyst yield compared to those for BSA-treated embryos. L-NAC at 1 mM significantly suppressed BSAAGE-induced embryonal toxicity. Because AGEs are embryo-toxic, AGE contamination may influence the pregnancy rate of in vitro fertilization and embryo transfer. AGEs, which are increased in women under pathological conditions, may also be involved in their infertility.

The purpose of the present study was to assess the association between job strain and smoking cessation among Japanese male employees. In 1997, a baseline questionnaire was given to 2,625 (2,113 males and 512 females) employees of an electronics firm in Gifu Prefecture, Japan. The self-administered questionnaire was a set of questions on smoking habits and consisted of items on socio-demographic variables and smoking habits, including the Japanese version of the Job Content Questionnaire (JCQ). The JCQ consists of scales of job control, job demand, supervisory support, coworker support, job insecurity, physical demands, and isometric load. A total of 733 male smokers were then followed for 2 years, with 446 completing a follow-up questionnaire in 1999 (follow-up rate, 61%). Logistic regression analyses were performed to examine associations between job strain and smoking cessation. Among the 446 participants, 38 had quit smoking. After adjusting for age ((odds ratio: OR) = 0.38, 95% (contidence interval: CI) = 0.15-0.94), men with a high level of physical demands at baseline showed a lower smoking cessation rate at follow-up than did those with a low level. However, when adjustments were made for age and other socio-demographic variables, the odds ratio of smoking cessation showed marginal significance (OR = 0.45, 95% CI = 0.16-1.29). There was no significant association between other job strain variables and smoking cessation at the 2-year follow-up. No significant association was found between job strain and change in the number of smoked cigarettes per day. The present study did not support the hypothesis that higher levels of job stressors are associated with a lower rate of smoking cessation among men.

A rare complication of percutaneous endoscopic gastrostomy (PEG) is gastrocolocutaneous fistula which usually occurs after replacement of the PEG tube. As tube feeding is directly delivered to the transverse colon, patients typically present with a sudden onset of transient diarrhea within minutes after PEG tube feeding. A radiographic study using water-soluble contrast material via the PEG tube shows the tip of the tube in the transverse colon. We present here a patient who had this complication after PEG insertion. A PEG tube for enteral feeding was placed in a 27-year-old man with cerebral plasty and a severe scoliosis. After replacement of the PEG tube, he developed diarrhea after each PEG tube feeding. The diagnosis of gastrocolocutaneous fistula was made after injection of gastrografin from the PEG tube. Another gastrostomy tube was placed surgically and the fistula was then also excised. In conclusion, gastrocolocutaneous fistula must be considered as a complication of PEG tube placement when patients with a PEG tube develop a sudden onset of transient diarrhea immediately after PEG tube feeding.

To decrease the incidence of pneumoconiosis, we examined dust protective mask performance and its relation to pulmonary function as well as the effects of worker education on the proper wearing of masks. One hundred and seventy-eight workers from 15 factories subject to dust exposure participated in this study. All participants were interviewed to obtain relevant personal information and underwent both a mask leakage and a pulmonary function test. The mask leakage was expressed as a percentage, with under 10% leakage indicating that the dust protective mask worked efficiently. In addition, 23 workers from 2 factories were educated on how to wear masks properly. The average mask leakage was 24.3%, and 58% of workers wore ineffective masks. Though pulmonary function was almost normal, the percent vital capacity (%VC) tended to be lower depending on the mask leakage. Mask education, which was very easy and took only a short time, dramatically decreased average mask leakage from 32.1% to 10.5% (p0.001). Educating workers to wear masks properly might prevent the worsening of pulmonary function in response to dust exposure. Appropriate mask fitness by education could be useful in preventing the development of pneumoconiosis.

Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1beta expression was also signifi cantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1beta. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1beta expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes.