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Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age 5 years, nephrotic syndrome was the most frequent diagnosis at age

【要旨】2012年度から2014年度入学生の学生の入試成績，メンタルヘルス調査，Grade Point Average（GPA），国家資格取得相互の関係を統計学的に分析した。入学年度，性別，保護者居住地により，入試成績，GPA，国家資格取得に差があった。学生を取り巻く環境が，学修姿勢に影響していると考えた。退学・除籍した学生はGPAが有意に低かった。GPAの低い学生には学修意欲を高める刺激が必要であろう。在学中の国家試験受験で資格を得たかに強く関連する要因は，入試成績，GPA，性別であった。GPAは様々な試験に対する強さを示す指標といえるかもしれない。しかし，本学の使命は学生に国家資格を取得させることだけではない。資格取得に強く関連するGPAのみで学生を評価することには慎重であるべきである。学年間のGPAの相関とトレンドは学科により異なるが，他大学の調査ほど顕著ではなかった。, We analyzed statistically the relationships among admission examination score, mental health checkup, Grade Point Average (GPA) and acquisition of national certification in undergraduate students admitted to the classes of 2012 to 2014. The admission examination score, GPA, and acquisition of national certification showed statistical difference among admission year, sex and hometown environments (which might influence students’ willingness to study). The GPAs of dropout or retired students were low. For such students, more effective stimuli to promote motivation for study is necessary. Acquisition of the national certification was significantly related to admission examination score, GPA and sex. The GPA might be a strong indicator of skill at taking exams. The academic mission of the university, however, is not only to have students acquire national certification. There is the need for greater caution about assessing students only by their GPA, which is strongly related to national certification. Though there are some differences between academic departments, the relationships between the GPA by cohort year, and GPA trends, were less notable than in previous studies at other universities.

Introduction: Mutations in genes encoding nucleoporins (NUPs; components of nuclear pore complexes [NPCs]), such as NUP93, have been reported to cause steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS), which often progresses to end-stage renal disease (ESRD) in childhood. The expression of NUP93 in renal or extrarenal tissues, and the mechanism by which NUP93 mutations cause this renal phenotype, remain unclear. Methods: The expression of NUP93 in normal control kidney and in a patient with FSGS carrying NUP93 mutations was examined by immunofluorescence analysis. The expression of NUP93 in blood cells was analyzed by Western blot analysis. Results: Immunofluorescence analysis detected NUP93 expression in nuclei of all glomerular and tubulointerstitial cells in human kidneys. Whole-exome sequencing identified a compound heterozygous NUP93 mutation comprising a novel missense mutation p.Arg525Trp, and a previously reported mutation, p.Tyr629Cys, in a patient with FSGS that developed ESRD at the age of 6 years. In the patient’s kidney, the intensity of NUP93 immunofluorescence was significantly decreased in the nuclei of both glomerular and extraglomerular cells. The expression of CD2-associated protein (CD2AP) and nephrin in the patient’s podocytes was relatively intact. The amount of NUP93 protein was not significantly altered in the peripheral blood mononuclear cells of the patient. Conclusion: NUP93 is expressed in the nuclei of all the cell types of the human kidney. Altered NUP93 expression in glomerular cells as well as extraglomerular cells by NUP93 mutations may underlie the pathogenic mechanism of SRNS or FSGS. Keywords: focal segmental glomerulosclerosis, nuclear pore complex, nucleoporin, NUP93, steroid-resistant nephrotic syndrome

Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR).This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age 15 years) and 6,532 AYA (age 15-30 years) patients.Although chronic nephritic syndrome was the most common clinical diagnosis at age 5 years, nephrotic syndrome was the most frequent diagnosis at age 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age.To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.

Objective: Causes and risk factors of neurodevelopmental disorders originate in the prenatal and perinatal periods. Several studies have demonstrated a relationship between prenatal and perinatal medical records, including maternal and paternal age at pregnancy, and the neurodevelopmental disorders, especially attention deficit/hyperactivity disorder and autism spectrum disorder. However, previous studies showed an association between specific learning disorders and environmental toxins such as lead and tobacco smoke, but not parental age. Patients and Methods: This study included 993 university freshmen, and their prenatal and perinatal medical data was collected from maternal and child handbooks. A mental health assessment questionnaire consisting of 24 items covering symptoms associated with neurodevelopmental disorders was administered, corresponding to aspects of attention deficit/hyperactivity disorder, autism spectrum disorder, and learning disorders. The relationship between prenatal and perinatal medical data and questionnaire results was statistically analyzed. Results: The number of available records was 881 (88.7%). Using Spearman's rank correlation coefficient analysis and trend analysis, a weak but statistically significant relationship was confirmed between paternal age at pregnancy and the score for learning disorder difficulties. Conclusion: Error accumulation in meiosis during spermatogenesis may be one of the risk factors of learning disorders.

Background Clinical trials are essential components of modern health care for the process of translating basic research into clinical practice. However, there is not well known about patients׳ information needs of clinical trials. Objective The purpose of our study was to understand the information-seeking behavior of patients about clinical trials and to determine what information patients׳ desire on websites. Methods We conducted a questionnaire survey between March and April 2013 of outpatients at three National Center hospitals in Japan and members of seven self-help groups for mainly intractable diseases. The questionnaire consisted of subjects׳ demographics, usage of general medical information, usage of clinical trial information, and desired items of clinical trial information on websites. Results Of the 2400 outpatient questionnaires, 1621 (67.5%) were returned and 1351 (56.3%) with valid information about demographic variables were eligible for analysis. In addition, of 2324 self-help group member questionnaires, 910 (39.2%) were returned and 850 (36.6%) were analyzed. The usage trends of general medical and clinical trial information were similar between the outpatients and self-help group members. However, the rate of access to clinical trial websites was not high. Conclusions Channels of clinical trial information used by patients were similar to those used for general medical information. If clinical trial information can be as an extension of general medical information, “tie-ins” between general medical information and clinical trial information should be reinforced at offering on websites for user convenience.

Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.

Background/Purpose The intracellular enzymes present in the saliva have been studied as markers of periodontal disease. The aim of this study was to establish procedures for using salivary biomarkers as an alternative to the Community Periodontal Index (CPI) for community-based screening for periodontal disease. Materials and methods The study included 101 adults aged between 19 and 77 years who were undergoing treatment for periodontal disease. We applied analysis of covariance (ANCOVA) to analyze the relationship between Community Periodontal Index (CPI) and levels of salivary factors for the 101 volunteers. Results Demographic characteristics, including age, number of remaining teeth, and smoking habits, showed a significant correlation with CPI. An overall correlation was shown between CP and both salivary lactate dehydrogenases (LD) and hemoglobin (Hb) levels, when analyzed using continuous demographic variables as covariates. Conclusion Results indicated that screening with statistical modeling can be an effective tool for detecting periodontal disease.

The aim of this study was to determine the association of dental health behavior with health awareness, oral condition, and subjective symptoms in Japan. The present study included 1699 individuals who underwent dental checkups at the public health center of Miura City. All those who underwent dental checkups were asked to fill out a questionnaire. The correlation between having a regular dentist and each of the other items was analyzed. Undergoing regular checkups was significantly related to having a regular dentist. To analyze the correlation of dental health behavior with Subjective symptoms and Health awareness, structured equation modeling was performed following factor analysis. As a result, only the regression weight between dental health behavior and health awareness was found to be statistically significant. The present survey indicates that dental health behavior was significantly related to Health awareness but not to Subjective symptoms.

Lipoprotein glomerulopathy (LPG) is a rare hereditary disease characterized by the accumulation of much thrombi material consisting of lipoproteins at the glomerular capillary lumen. Most patients show nephrotic syndrome; nearly half progress to chronic renal failure. Intensive therapy with lipid-lowering agents reportedly engenders clinical remission with histological resolution. We report the case of a 14-year-old Japanese female patient who had been in a nephrotic condition with hematuria from 4 years old and who had been diagnosed based on pathological and molecular examination at 7 years old. We initially treated the patient with probucol, enalapril (angiotensin-converting enzyme inhibitor: ACEI), and dipyridamole from age 7, but achieved no improvement in her nephrotic status. Subsequently, we replaced probucol with bezafibrate at age 11 and added atorvastatin calcium hydrate and valsartan (angiotensin II receptor blocker: ARB) the following year. The next 3 years' treatment improved her nephrotic status, decreased serum apolipoprotein E, and markedly decreased intraglomerular lipoprotein thrombi. Early and intensive therapy with antilipidemic drugs combined with ACEI and ARB is inferred to be effective for LPG.

Background: The number of people eighty years of age and older in developed countries is increasing, with a concomitant increased demand for total hip replacement. We analyzed the outcomes of total hip arthroplasty for patients in this age group using data from the Finnish National Arthroplasty Registry. Methods: Data from the Finnish Arthroplasty Registry on 6540 patients (6989 hips) who were eighty years of age or older at the time of a total hip arthroplasty, performed between 1980 and 2004, were evaluated with use of survival analyses. Factors affecting survivorship rates were sought, and the reasons for revision were identified. Results: The mean age of the patients undergoing a primary total hip arthroplasty was 82.7 years. The mean longevity of 3065 patients who died following total hip arthroplasty was 5.1 years. With revision total hip arthroplasty for any reason as the end point, Kaplan Meier survivorship was 97% (95% confidence interval, 96% to 97%) at five years (2617 hips) and 94% (95% confidence interval, 93% to 95%) at ten years (532 hips). Of the 195 hip replacements that required revision, 183 had information on the reason for revision. Eighty-four (46%) were revised for aseptic loosening; thirty-six (20%), for recurrent dislocation; twenty-four (13%), for a periprosthetic fracture; and twenty-three (13%), for infection. Seven hundred and twenty-nine patients had undergone hybrid fixation (a cemented stem and a cementless cup). The survivorship of these replacements was significantly better than that for replacements with cementless fixation in 399 patients (p < 0.05). Conclusions: In patients who had a total hip arthroplasty when they were more than eighty years old, the prevalence of aseptic loosening was less than that encountered in younger patients, but recurrent dislocation, periprosthetic fracture, and infection were more common in this age group. Cementation of the femoral stem demonstrated better long-term results than cementless fixation, indicating that it may provide better initial fixation and, therefore, longer life-in-service. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in ~20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment.

Background: Many studies have reported on the information need and the seeking behavior of health professionals. However, there have been few reports on clinical trial information usage. Objectives: The purpose of our study was to understand the information-seeking behavior of health professionals and examine the desired provision of clinical trial information with a focus on Internet usage. Methods: The questionnaire was distributed to health professionals between March and April 2013 at three National Center hospitals in Japan and member hospitals of the Center for Clinical Trials of the Japan Medical Association. Results: Physicians mostly used the information provided by academic societies or medical journals, nurses mostly used information from colleagues and pharmacists, and CRCs mostly used information from the Internet. Although the proportion of the use of general medical information was higher than clinical trial information for each information source, the trend of information usage was similar between general medical information and clinical trial information among health professionals. Conclusions: It is suggested that the method of conveying information about clinical trials could be different ways among health professionals for its effectiveness.

Background: National and regional arthroplasty registries have been used to study the results of primary total knee arthroplasties. The purpose of this paper was to present the results of revision total knee replacements and describe predictors of survival of those replacements, with repeat revision as the end point. Methods: The nationwide Finnish Arthroplasty Registry included 2637 revision total knee arthroplasties from 1990 through 2002. Survivorship of the revision total knee arthroplasties was analyzed, with repeat revision as the end point. The survivorship analyses comprised evaluations of the proportional hazards assumption followed by calculations of univariate and multivariate statistics and model diagnostics as appropriate. Results: The survival rate following the revision total knee arthroplasties was 95% (95% confidence interval, 94% to 96%) at two years (1874 knees), 89% (95% confidence interval, 88% to 90%) at five years (944 knees), and 79% (95% confidence interval, 78% to 81%) at ten years (141 knees). Multivariate regression analysis showed the most significant predictors of prosthetic survival to be the age of the patient and the life in service of the primary total knee replacement (that is, the time between the primary total knee replacement and the revision). Survivorship was also significantly predicted by the year of the first revision total knee arthroplasty and the reason for the revision. Conclusions: An age greater than seventy years, revision five years or more after the primary arthroplasty, and absence of patellar subluxation are positive indicators of survival of a revision total knee replacement. We believe that normal aging as well as the deconditioning effect of disease (osteoarthritis and rheumatoid arthritis) and its treatment (primary total knee replacement) may lead to a reduced activity level, which, together with a presumed reluctance to operate on elderly patients, protects against repeat revisions. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

It is known that information regarding clinical research/trials is not easily available to the public in Japan. To improve the current clinical research/trial information portals, we could consider combining them with intelligible clinical information; moreover, we could explore how best to provide trial-related information to patients and medical professionals. To this end, we conducted a questionnaire survey; self-administered questionnaires were administered by post to medical facilities in Japan. The responses to a few questions were statistically significant with regard to the distribution of clinical research/trial information. We confirmed that several medical facilities have provided clinical research/trial information to the public. However, we need to consider the distribution of the information content expected by the patients and citizens. For greater awareness, it is necessary that medical facilities consider the method of information delivery from the viewpoints of patients and citizens, regardless of whether they are a small or large facility.

Background It is well known that information about clinical trials is not easily accessible by the public. In Japan, clinical trial information can be accessed by the general public through online registries; however, many people find these registries difficult to use. To improve current clinical trial registries, we propose that combining them with clinical information phrased in lay terms would be beneficial to other interested professionals such as journalists and clinicians, as well as the general public. Therefore, this study aimed to examine the current pattern of distribution of clinical trial information from the primary World Health Organization (WHO) registries. Based on the results of this assessment, we then aimed to build and evaluate a prototype of the Japan Primary Registries Network (JPRN) portal that would be easily accessible to patients and the public, while still remaining useful for professionals. Methods We assessed a total of 14 primary clinical trial registries listed on the WHO International Clinical Trials Registry Platform between January and February 2013. Website content was accessed and checked against a series of items that looked at usability, communication, design and accessibility of the sites. We excluded registries that were not active or were not on the approved WHO registry list at the time of our assessment. We also examined only the English versions of the websites as native-language registries may offer more functionality or different content than the English version of the same website. Results All registries examined had a function allowing users to search the registry data and that displayed the related information from the search, including the clinical trial registration data. However, few websites were found to be user-friendly, and there was little integration with social media. Conclusions We confirmed that there are few websites providing useful clinical trial information to patients and their families. However, information gleaned from some of the more advanced online registries could be used to improve the content and functionality of the JPRN portal.

We report how scapholunate (SL) lesions found during arthroscopy were treated using a new palmar operation based on the use of a tendon loop formed using the palmaris longus tendon, with promising preliminary results. Scapholunate instability induced by hyperextension injury was diagnosed and graded arthroscopically. Volar capsuloplasty was then done by free tendon graft in the same session in 31 patients with grades II-IV scapholunate instability. Half of the patients operated on had a normal range of movement, and all except one had flexion-extension of at least 75% of the normal. Half of the patients had no pain or limitations of the use of the wrist, and although half the patients had some pain on exertion, not one had severe pain. These results are comparable to, or even better than, those reported using other methods of repair. The combined procedure saves money, diminishes the total recuperation time and, as autologous tissues are used for the repair, secondary operations for removal of the implant are unnecessary. This method seems to be a useful adjunct to the types of operative treatment available, although it is apparently not suitable in static grade IV SL instability.

Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 +/- 3.1 yr and mean age at renal transplantation was 10.4 +/- 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GCC to GCT) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2-5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.

Arthroscopy offers a welcome and reliable supplement to the current tool set for the diagnosis of lunotriquetral (LT) instability. This study reports the findings of LT-lesions during arthroscopy and the clinical results obtained after using dorsal stabilisation in its surgical management using extensor retinacular split. LT-instability of grade I-III was diagnosed in 26 patients. Imaging results were normal, Reagan's ballottement and Watson tests were positive in 47% and 79%, respectively. After arthroscopic diagnosis, the procedure was immediately continued with an open repair utilising an 8-10 mm wide and radial-based extensor retinacular split for dorsal capsular reinforcement. At 39 months (range: 14 to 84) follow-up, 64% had no or only occasional mild pain and 36% had pain with overuse or lifting. Overall scoring encompassing pain, patient satisfaction, range of motion and grip strength, was excellent in 24% and good in 64%. Only three patients had fair results, one after a further injury leading to distal radio-ulnar joint (DRUJ) instability, and two with concurrent DRUJ-stabilisation. One further patient required a secondary procedure. Arthroscopy seems to allow accurate diagnosis of LT-instability and can be continued in the same session using a straightforward reconstruction procedure providing satisfactory results.

National and regional arthroplasty registries have been used to study the results of primary total knee arthroplasties. The purpose of this paper was to present the results of revision total knee replacements and describe predictors of survival of those replacements, with repeat revision as the end point.The nationwide Finnish Arthroplasty Registry included 2637 revision total knee arthroplasties from 1990 through 2002. Survivorship of the revision total knee arthroplasties was analyzed, with repeat revision as the end point. The survivorship analyses comprised evaluations of the proportional hazards assumption followed by calculations of univariate and multivariate statistics and model diagnostics as appropriate.The survival rate following the revision total knee arthroplasties was 95% (95% confidence interval, 94% to 96%) at two years (1874 knees), 89% (95% confidence interval, 88% to 90%) at five years (944 knees), and 79% (95% confidence interval, 78% to 81%) at ten years (141 knees). Multivariate regression analysis showed the most significant predictors of prosthetic survival to be the age of the patient and the life in service of the primary total knee replacement (that is, the time between the primary total knee replacement and the revision). Survivorship was also significantly predicted by the year of the first revision total knee arthroplasty and the reason for the revision.An age greater than seventy years, revision five years or more after the primary arthroplasty, and absence of patellar subluxation are positive indicators of survival of a revision total knee replacement. We believe that normal aging as well as the deconditioning effect of disease (osteoarthritis and rheumatoid arthritis) and its treatment (primary total knee replacement) may lead to a reduced activity level, which, together with a presumed reluctance to operate on elderly patients, protects against repeat revisions.Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

ATP-binding cassette (ABC) transporters comprise a superfamily of similar proteins involved in transmembrane transport of various substances. ABC transporter family members in the liver participate in bile formation and lipid metabolism. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for determination of the expression of ABC transporter genes in the liver, we compared ABC transporter gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured ABCA1, A2, B1-B4, C1 degrees C5, G1 and G2 gene expression levels in PBL, and cancerous and non-cancerous portions of liver from patients with hepatocellular carcinoma by means of real time reverse-transcription (RT)-PCR. We could not detect ABCC5 expression in any tissue of the liver. Close correlations between ABCA2, C1 and G1 in PBL and in non-tumor tissues of the liver were found. Compared with the non-tumor part, HCC tissue expressed lower levels of ABCA1, B4 and G2. We think monitoring of ABCA2, C1 and G1 gene expression levels in PBL will be useful for selection of anti-cancer agents and monitoring of drug resistance of HCC. Administration of chemotherapeutic agents which are substrates of ABCA1, B4 and G2 should be effective for the treatment of HCC.

Cytochromes p450 (CYPs) compose a superfamily of similar proteins involved in detoxification and elimination, as well as activation of a wide variety of compounds. Most CYP family members are localized in the liver. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for the determination of CYP gene expression levels in the liver, we compared CYP gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, 3A7, 4A11, 4B1 and CYP27 gene expressions in PBL and in the liver by real-time reverse-transcription (RT)-PCR. We could detect expression of CYP1A1, 1A2, P1B1, 2A6, 2B6 and 2E1 genes in PBL and all the genes except for CYP2F1 in the liver. Although gene expression levels within each subfamily were closely correlated within PBL and within the liver, a clear correlation of gene expression levels between PBL and liver tissues was found only for CYP4B1. Although inter-individual variation of the expression level of each CYP gene was wide, the induced level was proportional to the basal expression level. Therefore, monitoring of CYP gene expression levels in PBL, especially those of CYP4B1, could be available as a biomarker for monitoring of exposure to environmental pollutants and assessing the associated risk. Compared with non-tumor tissue, HCC tissues tended to show overexpression of multiple CYP genes, indicating that individualized selection and more effective administration of chemotherapeutic agents could perhaps be based on the pattern of CYP overexpression.

To elucidate the genetic alterations that are specific to Thorotrast-induced liver cancers and their possible roles in tumorigenesis, we analyzed loss of heterozygosity (LOH) at 37 loci. Our previous study of liver cancers that were not associated with Thorotrast found LOH at 9 of these loci to be characteristic of intrahepatic cholangiocarcinoma (ICC), at 19 to be characteristic of hepatocellular carcinoma (HCC), and at 9 to be common to both ICC and HCC. LOH analysis was also performed in tissues of cholangiolocellular carcinoma, which is thought to originate from a common stem cell progenitor of hepatocytes and bile duct epithelial cells. We found frequent LOH at D4S1538, D16S2624 and D17S1303 to be common to all the subtypes of liver cancers, independent of the specific carcinogenic agent. In contrast, LOH at D4S1652 generally was not observed in Thorotrast-induced ICC. LOH analysis revealed that Thorotrast-induced ICC shares some LOH features with both ICC and HCC that were not induced by Thorotrast; however, it is more similar to ICC than to HCC in terms of genetic changes. This study could narrow down the crucial chromosomal loci whose deletions are relevant to hepatobiliary carcinogenesis irrespective of the carcinogenic agent. The study of LOH at loci other the those crucial ones may help us understand how the phenotype of liver cancers is determined.

Background: Treatment of steroid-resistant (SR) primary focal segmental glomerulosclerosis (FSGS) remains a major challenge in nephrology. A prospective study was conducted to clarify the therapeutic role of low-density lipoprotein apheresis (LDL-A) in 11 nephrotic children with SR and cyclosporine A (CsA)-resistant primary FSGS. Methods: Based on entry criteria, all 11 eligible patients had biopsy-proven primary FSGS presenting with nephrotic syndrome (NS) and were resistant to steroid and conventional-dose CsA therapy. LDL-A was performed twice a week for 3 weeks (first course), then weekly for 6 weeks (second course). Beginning from the second LDL-A course, a dosage of 1 mg/kg/d of prednisone was administered for 6 weeks, then tapered. Results: Seven patients experienced remission of NS, 5 of whom achieved complete remission within 4 weeks after initiating prednisone therapy with LDL-A. These 5 patients maintained normal renal function during follow-up (median, 4.4 years). Of 2 patients with partial remission, 1 patient maintained stable renal function during follow-up (4.5 years), whereas the other patient showed a gradual decline in renal function and progressed to end-stage renal failure (ESRF) 7.8 years after LDL-A therapy. Four patients who were considered to experience treatment failure had persistent NS and progressed to ESRF in 1.3 years (median) after LDL-A therapy. Complete remission (n = 5) was associated with significantly more highly selective proteinuria compared with treatment failure (n = 4). Conclusion: This study suggests that combined LDL-A and prednisone therapy can be a valuable addition to therapeutic options for treating patients with SR-FSGS. The role of LDL-A in treating these patients deserves to be assessed further in larger randomized controlled trials.

A novel recombinant congenic mouse strain, McRA1lpr/lpr, which was established by the intercrosses between MRL/Mp/-lpr/lpr and C3H/HeJ-lpr/lpr strains throughout more than F50 generations by means of selection based on swelling of ankle joints, manifested severe arthritis, followed by ankylosis, pathologically resembling rheumatoid arthritis in humans. To clarify the genetic mechanisms on the development of arthritis in this strain, we newly prepared "GTree" for analyzing the pedigree of pathological phenotypes of arthritis, splenomegaly and lymphadenopathy based on the collected data from over 700 McRA1-lpr/lpr mice collected and arranged by Shiro MORI. The data themselves are now dealt with by a PostgreSQL Linux server administered by Hideki SAWADA. We explain the algorithm of the program and its complexity, and show the pathological peculiarity of spleens and axillary lymph nodes which appear only in the group of RA mice.