Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia

We have investigated the alterations of p53 and ras genes including H-, K-, and N-ras genes in 22 acute lymphoblastic leukemia (ALL) cases and five cell lines carrying t(1;19) by use of polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and direct sequencing. The mutations of the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4 cases at relapse (100%), and 4 of the 5 cell lines (80%). Four of the five patients who died had missense mutations at codons 49, 177, 179, and 248. In cases examined sequentially, one had the same point mutation at codon 179 at both diagnosis and relapse, and another had the same p53 gene mutation at codon 240 both in leukemic cells at relapse and in a cell line derived at that time. The other case had no mutation at diagnosis but had the mutation at codon 177 at relapse and cell lines derived from blast cells at diagnosis, suggesting that a small number of leukemic cells with the p53 gene mutation at diagnosis might have escaped PCR-SSCP analysis. In cell lines, SCMC-L9 had three point mutations in the p53 gene at codons 175, 248, and 358, whereas SCMC-L10 had frame shift at codons 209-211. One case had a rare polymorphism at codon 11. We found only one mutation of the N-ras gene that was a 2-bp substitution of GGT(Gly) to GTC(Val) at codon 13 among 22 t(1;19)-ALL cases and five cell lines. This case showed no mutation of the p53 gene and has had a good course. These results suggest that in t(1;19)-ALL, mutations of the p53 and ras genes are infrequent at diagnosis and that p53 gene alterations may be associated with relapse phase or progression of t(1;19)-ALL.     

Increased macrophage colony-stimulating factor levels in patients with Graves’ disease

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves’ disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.     

Successful treatment of spinocerebellar ataxia 6 with medicinal herbs

A case of familial spinocerebellar ataxia 6 with typical symptoms is presented. A 60-year-old Japanese female suffered from gait disturbance, ataxia and dizziness. Head magnetic resonance imaging revealed a typical atrophic image in cerebellum. Genetic tests revealed an expanded allele of 22 CAG repeats at the spinocerebellar ataxia type 6 locus. She was diagnosed with spinocerebellar ataxia 6. Her mother was also diagnosed with the same disease. A mixture of 18 medicinal herbs (modified Zhengan Xifeng Tang) was given according to the differential diagnosis based on the guidelines of traditional Chinese medicine. All of the symptoms were remarkably improved after 60 days of the herbal treatment. One year after discontinuation of the treatment, she complained of gait ataxia. She was treated with the modified Zhengan Xifeng Tang for 60 days. Gait ataxia was markedly improved by the second treatment. Fifteen months after discontinuation of the second treatment, she complained of gait ataxia again. The same remedy was given for 60 days. Gait ataxia was remarkably reduced again. The results may imply therapeutic potential of the medicinal herbs for spinocerebellar ataxia 6.     

Granulomatous hypophysitis with meningitis and hypopituitarism.

We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis.     

Shoulder injuries in the athlete

Shoulder injuries are common in the athletic population. Injuries can be a result of repetitive overhead use or from direct trauma. Common injury sites include the rotator cuff, glenohumeral joint, acromioclavicular joint, biceps tendon, scapulothoracic articulation, and sternoclavicular joint. The identification, physical exam, and treatment options of these conditions will be discussed.     

结核感染若干年后特异性γ-干扰素应答减弱

假设：随着时间的流逝，结核感染者记忆性T细胞对特异性抗原的应答减弱。背景：很多证据表明特异性全血γ-干扰素（IFN-γ）检测试验Quanti—FERON～TB Gold（QFT—G）能够检测出近期结核感染者，并具有较高的灵敏度和特异性。目的：我们应用此项技术检测日本一个社区的成人群体以确定其流行病学应用价值。方法：1559例参加定期体检的健康志愿者入选本研究。结果：40～49岁人群QFT—G的阳性率为3．1％，50～59岁人群的阳性率为5．9％，60～69岁人群的阳性率为9．8％。作者根据一系列研究估计40～49岁、50～59岁、60～69岁的预期结核感染率分别为11．1％、29．6％、53．1％。预期阳性率与实际阳性率之间存在的巨大差异提示结核感染后随着时间的延长IFN-γ应答减弱。那些经胸部X线证实存在陈旧性结核病灶者阳性率大大低于100％。结论：特异性IFN—γ应答可能在结核感染后随着时间的推移大大地减弱。需要在感染者中长期地纵向研究细胞介导的免疫动力学。     

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF)

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.     

Profile Analysis of Sexual Assault Experiences among Adult Women and Their Implications for Mental Health

ObjectiveExtant studies indicate that just one characteristic of sexual assault cannot properly represent the whole experience of sexual assault and, especially, the severity of sexual assault. This study aimed to understand the totality of sexual assault experiences and elucidate subtypes of sexual assault victims based on the detailed characteristics of their sexual assault experiences and those relationships with mental health. MethodsA total of 255 adult sexual violence victims who used intervention services and a comparison group were included. Information on their sexual assault experiences was gleaned from case records data. ResultsThe following four distinctive profile groups were identified: “Sexual Touching” (19.6%), “Rape/Social Relation” (30.4%), “Intimate Partner Violence (IPV)” (18.8%), and “Rape/Stranger” (31.3%). The subgroups differed in terms of secondary victimization and adverse childhood experiences. The Rape/Social Relation and IPV subgroups most frequently experienced secondary victimization and childhood adversity. The four profile subgroups demonstrated different relationships with mental health outcomes, with a complicated pattern. The Rap/Social Relation and IPV subgroups scored higher on mental health problem screening measures compared to other groups. However, a considerable proportion of victims in the Sexual Touching subgroup also reported suicidal behaviors and self-injury. ConclusionBased on the results, theoretical and clinical implications were discussed.