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A prospective study was performed to determine the accuracy of magnetic resonance imaging (MRI) compared with operative findings in the evaluation of patients associated with rotator cuff tears. Fifty-four of 60 shoulders (58 patients) examined by MRI were confirmed as full-thickness tears and 6 as partial-thickness tears at the time of surgery. The oblique coronal, oblique sagittal, and axial planes of T2-weighted images with the 0.5 tesla MRI system were obtained preoperatively and compared with operative findings. MRI correctly identified 46 of 54 full-thickness rotator cuff tears and 5 of 6 partial-thickness tears. A comparison of MRI and operative findings in full-thickness cuff tears showed a sensitivity of 85%, a specificity of 83%, and a positive prospective value (PPV) of 99%. A comparison of partial-thickness tears showed a sensitivity of 83%, a specificity of 85%, and PPV of 39%. Linear regression analysis showed an excellent correlation between the MRI assessment and measurement at the time of surgery (r = 0.90, P < 0.01). MRI was useful in evaluating large and medium-sized rotator cuff tears, but less useful in distinguishing small full-thickness tears from partial-thickness tears.

With the development of new treatments, there is an increasing need for early diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing positive diagnosis early in the course of the disease are highly desirable. Cerebrospinal fluid levels of protein tau were shown to be significantly increased in patients with Alzheimer's disease. Although sensitivity is high, poor specificity limits the diagnostic value of this marker. The same is true for the 42 amino acid isoform of beta-amyloid protein that is significantly decreased in cerebrospinal fluid of Alzheimer's disease patients. However, combining both markers could improve specificity at least allowing differentiation between Alzheimer's disease, normal ageing and depressive pseudodementia. Other biological markers such as cerebrospinal fluid levels of neurotransmitters, cytokines or superoxide dismutase were shown to have even less diagnostic value. The apolipoprotein epsilon 4 allele is a risk factor for Alzheimer's disease but not a diagnostic marker as many individuals who inherit epsilon 4 do not develop the disease. Till now, a single diagnostic marker allowing

discrimination between Alzheimer's disease and other dementias does not exist. Combined cerebrospinal fluid levels of beta-amyloid protein and tau protein might be used as a marker that helps discriminating Alzheimer's disease from normal ageing and depression.

CD14 is a pattern recognition receptor on myeloid cells and plays a pivotal role in an innate immune system that is responsible for Gram-negative and Gram-positive bacteria infection. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, can induce production of a large quantity of proinflammatory cytokines into the circulation mediated by CD14-mediated macrophages and monocytes. These cytokines eventually cause septic shock. Several in vitro and in vivo studies have shown that suppression of a CD14 function by a CD14 antibody led to an inhibition of the production of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-8. In the present study, we found that CD14 antisense oligonucleotide (ODN) can prevent lethal LPS shock in D-galactosamine-sensitized mice. This ODN inhibited CD14 expression in a mouse macrophage cell line, RAW264.7, and suppressed production of TNF-alpha in LPS-stimulated RAW264.7 cells. Furthermore, we designed a consensus antisense ODN that could hybridize human and mouse CD14 RNA, and we evaluated its efficacy. The consensus antisense ODN rescued mice primed with Mycobacterium bovis bacillus Calmette-Guerin (BCG) from the LPS-induced lethal shock. In this model, the CD14 antisense ODN down-regulated LPS-elicited CD14 expression in the liver, resulting in a decrease in LPS-induced TNF-alpha production. These findings suggest that the CD14 antisense ODN is distributed in the liver and efficiently suppresses LPS-induced TNF-alpha production by reducing CD14 expression on Kupffer cells. This CD14 antisense ODN may be useful for the development of a therapeutic agent against sepsis and septic shock.

We performed an immunohistochemical analysis of 2 major DNA mismatch repair proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected specimens, as well as 30 samples from non-cancerous livers. In well-differentiated HCCs, the immunoreactivity for these antigens was well preserved, and the staining intensity was stronger compared to the surrounding liver tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the expression of both of these antigens was reduced. Moreover, in 41 tumors of differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively, contained a less-differentiated area with a reduced number of immunoreactive cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue were well immunostained for both hMLH1 and hMSH2. We confirmed in this series that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that it might play a role in tumor progression.

The structure of the human genome is almost completely elucidated and the life sciences will now aim for a general and integrated study of gene expressions and the functional elucidation of proteins. In such a study, various new techniques have been developed, and DNA microarray technology is the most representative one. As for the DNA microarray techniques, several thousands to tens of thousands of gene segments are immobilized on a glass slide at high density, and cDNA probes prepared from specific cells or tissues are hybridized on the slides from which gene expression profiles are obtained at one sweep in a short time. The present development of this technique and its possible application to medicine-related fields are described.</P>

This study evaluated the effects of azathioprine in combination with low-dose prednisolone in the management of patients with intractable autoimmune hepatitis. Thirteen patients with intractable autoimmune hepatitis who had an incomplete or arrested response to conventional prednisolone therapy, or who relapsed during prednisolone maintenance therapy were additionally administered 50 or 100 mg/day of azathioprine in combination with prednisolone. This regimen reliably induced complete remission in 12 of 13 patients, and these 12 remained in remission during the follow-up period with maintenance therapy of 50 mg/day of azathioprine in combination with 5 mg/day of prednisolone. The findings of the current study indicate that the azathioprine and low-dose prednisolone combined therapy may offer a satisfactory alternative therapy for patients with intractable autoimmune hepatitis who have an incomplete or arrested response to conventional prednisolone therapy, or who relapse during prednisolone maintenance therapy.

In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions.</P>

The mechanisms of arterial hypotension following intravenous anesthetic induction agents are multifactorial. The purpose of this study was to evaluate and compare the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic outflow and arterial baroreflex sensitivity using not only neuraxis-intact but also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen (FiO2 0.5). The left renal sympathetic nerve was isolated and placed on a bipolar electrode to record renal sympathetic nerve activity (RSNA). Thirty animals underwent a surgical preparation of total baroreceptor denervation. Bolus injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the induction dose of propofol 4 mg/kg significantly decreased RSNA to the same extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM) and mean arterial pressure (MAP) also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction) in the neuraxis-intact animals. RSNA was increased (34.5+/-6%) without reduction of MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68% and 54% of control, respectively). Propofol at 2 mg/kg (induction dose) and etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated animals. It was found from the barosensitivity study that patients can be hemodynamically unstable even though blood pressure has returned to normal after thiopental and propofol administration. Data suggest that etomidate can even stimulate the sympathetic nervous system and increase sympathetic outflow. It was also clearly found from the baro-denervated animal study that thiopental was stronger than propofol in directly suppressing sympathetic outflow at the induction dose.

Postnatal adaptations of cardiac hemodynamics in infants born vaginally or by caesarean section may be different. These cardiac functions were evaluated by Doppler echocardiography to assess adaptation differences. Cardiac output, heart rate, stroke volume, mean arterial pressure, total systemic vascular resistance, ejection fraction, and ductus arteriosus diameter were determined and compared at 1, 24 and 72 h of life in 22 infants born vaginally (group 1) and 23 born by caesarean section (group 2). One hour after delivery, heart rate, mean blood pressure, and total systemic resistance were found to be higher in group 1 infants (P < 0.01, P < 0.05, P < 0.05 respectively). Stroke-volume measurements were significantly higher in group 2 (P < 0.05). The ejection fraction and cardiac output values were similar in both groups. At 24 and 72 h, no significant differences were observed in measurements of infants born vaginally or by caesarean section. We did not find a parameter negatively affecting healthy newborns in either mode of delivery. However, under pathological conditions affecting the cardiovascular system at 1 h of life, including perinatal infections and hypoxemia, a lower stroke volume, higher heart rate, higher mean blood pressure, and higher peripheral resistance may cause additional work load to the cardiovascular system in infants born vaginally.

Mutations of the c-KIT gene have been reported not only in gastrointestinal stromal tumors and mast cell tumors, but also in testicular germ cell tumors (TGCTs). In the present study we employed polymerase chain reaction and DNA sequencing analysis to characterize the c-KIT gene in a 29-year-old Japanese patient with bilateral testicular seminomas. Direct sequence analyses revealed a single base substitution in exon 17 in one c-KIT allele, resulting in an amino acid substitution of D816H in this mutated allele. This mutation was found in the left, but not in the right, testicular seminoma. This is the first description of a c-KIT gene mutation in a Japanese patient with bilateral TGCT. The mutational analysis of the c-KIT gene seems to provide crucial information for managing TGCT patients not only in Europe but also in Japan.

DNA damage causes chromosomal instability leading to oncogenesis, apoptosis, and severe failure of cell functions. The DNA repair system includes base excision repair, nucleotide excision repair, mismatch repair, translesion replication, non-homologous end-joining, and recombinational repair. Homologous recombination performs the recombinational repair. The RAD51 gene is an ortholog of Esherichia coli recA, and the gene product Rad51 protein plays a central role in the homologous recombination. In mammals, 7 recA-like genes have been identified: RAD51, RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, XRCC3, and DMC1. These genes, with the exception of meiosis-specific DMC1, are essential for development in mammals. Disruption of the RAD51 gene leads to cell death, whereas RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, and XRCC3 genes (RAD51 paralogs) are not essential for viability of cells, but these gene-deficient cells exhibit a similar defective phenotype. Yeast two-hybrid analysis, co-immunoprecipitation, mutation analysis, and domain mapping of Rad51 and Rad51 paralogs have revealed protein-protein interactions among these gene products. Recent investigations have shown that Rad51 paralogs play a role not only in an early step, but also in a late step of homologous recombination. In addition, identification of alternative transcripts of some RAD51 paralogs may reflect the complexity of the homologous recombination system.

On February 13, 2002, a public health center in Hiroshima Prefecture, Japan, was notified that many individuals living at the Japan Maritime Self-Defence Force base had symptoms resembling those of food poisoning. Self-administered questionnaires requesting information regarding meal consumption and symptoms were distributed to all 281 members at the base. A case of the illness was defined as a member who had had watery or mucousy stool, or loose stool with abdominal cramps, more than twice a day after consuming dinner on February 12. Control of the illness was defined as a member with no symptoms. The dinner on February 12 was significantly associated with the illness (Mantel-Haenszel odds ratio: 3.59, 95% confidence interval: 1.06-12.20). A case-control study showed that, among the food supplied at dinner on February 12, the braised chop suey was significantly associated with the illness (odds ratio: 12.30, 95% confidence interval: 1.90-521.00). The braised chop suey had been stored in a chafing dish. An environmental investigation indicated that Clostridium perfringens (C. perfringens) in the chafing dish proliferated under an inappropriate heat-retention temperature, and the contaminated braised chop suey could have caused the food poisoning. This study demonstrated that the recommended heat-retention temperature (over 65 degrees C) should be confirmed thoroughly.

We used a regression tree method (RTM) to determine risks of depression in children/adolescents. The survey records of 4,143 children/adolescents in a study based in Mersin, Turkey served as data in this study, and multi-step, stratified, and cluster sampling were used. Effects of 24 variables (sex, smoking, parental problems, etc.) were evaluated on depression scores. The Child Beck Depression Inventory (CBDI) was used to determine the level of depression. Subjects were into 12 different groups based on magnitudes of mean depression scores. The interactions among 7 variables determined to be risk factors are shown on a schema. The STATISTICA (ver.6.0) package program was used for all computations. Although traditional statistical methods have often been used for analysis in this field, such approaches are associated with certain disadvantages such as missing values, ignorance of interaction effects, or restriction of the shape of the distribution. To avoid such disadvantages, we therefore suggest the use of the RTM in studies involving numerical-based outcome variables and for the investigation of a large number of variables and it may be more effective than traditional statistical methods in epidemiological studies which determine risk factors.

In this study, we investigated the effects of both 25 and 50 mg daily doses of rofecoxib on the endothelial functions of patients with coronary artery disease (CAD). For this purpose, 34 patients with documented severe CAD and who were under aspirin treatment (300 mg/day) were randomized to receive 4 weeks of treatment with a placebo (n = 10, group I), rofecoxib 25 mg/day (n = 12, group II), and rofecoxib 50 mg/day (n = 12, group III). Brachial artery vasodilator responses were measured in order to evaluate endothelial function. The percentage of change in endothelial-dependent vasodilation in groups I, II, and III were similar at the baseline level and showed no significant change after treatment (6.2+/-3.9% vs. 5.9+/-3.1% and 5.8+/-3.3% vs. 5.6+/-3.8% and 6.1+/-4.5% vs. 5.8+/-4.1%, respectively; P > 0.05). Compared with the baseline, endothelium-independent vasodilatation, as assessed by nitroglycerine (NTG), remained unchanged after the treatment period (11.2+/-6.9% vs. 10.3+/-7.1% and 11.2+/-6.3% vs. 9.9+/-5.1% and 9.5+/-4.9% and 8.8+/-4.6%, respectively; P> 0.05). Treatment with both doses also showed no significant effects on high-sensitivity C-reactive protein (hs-CRP) levels and resting arterial diameters (P > 0.05). In conclusion, 4 weeks of treatment with standard and high doses of rofecoxib showed no significant effects on either endothelial-dependent or independent vasodilator response or plasma hs-CRP levels in patients with severe CAD taking concomitant aspirin.

It was recently reported that gene therapy using hepatocyte growth factor (HGF) has the potential to preserve cardiac function after myocardial ischemia. We speculated that this HGF gene therapy could also prevent ventricular arrhythmia. To investigate this possibility, we examined the antiarrhythmic effect of HGF gene therapy in rat acute and old myocardial infarction models. Myocardial ischemia was induced by ligation of the left descending coronary artery. Hemagglutinating virus of Japan (HVJ)-coated liposome containing HGF genes were injected directly into the myocardium fourteen days before programmed pacing. Ventricular fibrillation (VF)was induced by programmed pacing. The VF duration was reduced and the VF threshold increased after HGF gene therapy ( p< 0.01). Histological analyses revealed that the number of vessels in the ischemic border zone was greatly increased after HGF gene injection. These findings revealed that HGF gene therapy has an anti-arrhythmic effect after myocardial ischemia.

We investigated the usefulness of helical computed tomography(CT)in the morphological diagnosis of pulmonary vein stenosis, particularly that in infants and small children. In total, 20 helical CT examinations were performed in 10 post-operative cases of Total Anomalous Pulmonary Venous Drainage(TAPVD), 3 cases of single right ventricle, and 1 case of single left ventricle. In all cases, distinct morphological imaging was possible. Pulmonary vein stenosis could be categorized into three types: (1)stenosis from the anastomosis of the common pulmonary vein (CPV)-the left atrium (LA) to the peripheral pulmonary vein; (2) stenosis only at the anastomosis of CPV-LA; and (3) stenosis due to compression by nearby organs. Coronal views by multiplanar reconstruction (MPR) provided morphological information along the up-down direction of the body axis. Morphological diagnosis of pulmonary vein stenosis is important in deciding prognosis and therapeutic regimens, and helical CT was considered useful for such diagnosis in our 14 young patients.

Hepatic outflow obstruction created by balloon occlusion of the hepatic vein induces characteristic angiographic findings in the occluded area: prolonged enhancement on hepatogram followed by reversed portal opacification on the hepatic arteriogram and perfusion defect on the arterial portogram. The following induced hepatic hemodynamic changes are suggested: hepatic arterial flow increases, and the portal vein acts as a draining vein with slow reversed flow. These unique hemodynamic changes enhance the effect of hepatic interventional therapies. In transcatheter arterial infusion, increasing hepatic arterial flow and absence of portal inflow can bring about a high concentration of drugs, the presence of which is greatly protracted due to outflow blockage. In transcatheter arterial chemoembolization, reversed portal flow can allow portal embolization in addition to arterial embolization. In microwave coagulation therapy and radiofrequency ablation therapy, decreasing portal flow can cause larger areas of coagulation. Further, the technique of hepatic venous occlusion has potential therapeutic applications.

We have improved on conventional methods for HLA-DRB1 genotyping and devised a new method that is simple, cost-effective, and adequately applicable to routine forensic practice. This method consists of group-specific polymerase chain reaction (PCR) of the exon 2 region of the HLA-DRB1 gene and simultaneous detection of single nucleotide polymorphisms (SNPs) at multiple sites using multiplex primer extension reactions. With this method, we successfully detected HLA-DRB1 genotypes from the following materials: the peripheral blood of 142 donors, 6 aged saliva stains of known DRB1 genotype stored for 5-10 years at room temperature, 10 aged bloodstains of unknown DRB1 genotype stored for 29 years at room temperature, and minimal bloodstains and saliva stains from 3 donors of known DRB1 genotypes. Furthermore, we were able to type DRB1 alleles of the minor component in mixed samples at a proportion of 1/1,000 or 1/10,000. In a criminal case, DRB1 alleles detected from mixed bloodstains on a sword found at the scene enabled us to explain the case. This method is expected to be useful for forensic medicine.

In this study, we evaluated the effects of trapidil on crush injury by monitoring nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels and by transmission electron microscopy in the rat sciatic nerve. The sciatic nerve was compressed for 20 sec by using a jewelers forceps. Trapidil treatment groups were administrated a single dose of trapidil (8 mg/kg) intraperitoneally just after the injury. The crush and crush + trapidil treatment groups were evaluated on the 2nd, 7th, 15th, 30th and 45th days of the post-crush period. On the 7th and 15th days, damage in thin and thick myelinated axons, endoneural edema and mitochondrial swelling were less severe in the trapidil group histopathologically. These findings supported the idea that trapidil prevented cell damage and edema at the injury site. Day/group interaction with regard to serum nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels did not show significant changes.