Decreased cerebral Irp-1B limits impact of social isolation in wild type and Alzheimer's disease modeled in Drosophila melanogaster.

Environmental factors, such as housing conditions and cognitively stimulating activities, have been shown to affect behavioral phenotypes and to modulate neurodegenerative conditions such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder affecting cognitive functions. Epidemiological evidence and experimental studies using rodent models have indicated that social interaction reduces development and progression of disease. Drosophila models of Aß42-associated AD lead to AD-like phenotypes, such as long-term memory impairment, locomotor and survival deficits, while effects of environmental conditions on AD-associated phenotypes have not been assessed in the fly. Here, we show that single housing reduced survival and motor performance of Aß42 expressing and control flies. Gene expression analyses of Aß42 expressing and control flies that had been exposed to different housing conditions showed upregulation of Iron regulatory protein 1B (Irp-1B) in fly brains following single housing. Downregulating Irp-1B in neurons of single-housed Aß42 expressing and control flies rescued both survival and motor performance deficits. Thus, we provide novel evidence that increased cerebral expression of Irp-1B may underlie worsened behavioral outcome in socially deprived flies and can additionally modulate AD-like phenotypes.

Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel.

BACKGROUND: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. METHODS: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. RESULTS: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. CONCLUSION: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Difficulties in organ procurement and transplantation in the aboriginal minority people in Taiwan.

BACKGROUND: Aboriginal people (AP) are a minority group in Taiwan. Little information on their perspectives on organ transplantation (OT) is available. Their rights for organ donation (OD) and as OT recipients (OTR) are constrained as a vulnerable population in society. This research sought to explore various Highland Aborigine Tribes beliefs systems and concepts related to OT. METHODS: We employed a qualitative design on a purposive sample including seven categories of Taiwanese AP. Data collected by face-to-face interviews were evaluated by content analysis. RESULTS: Seventy-five informants (45 female and 30 males) of 18 to 82 years from seven tribes completed interviews: Bunun (n = 20), Shao (n = 18), Tsou (n = 15), Amis (n = 12), Truku (n = 4), Rukai (n = 3), and Puyuma (n = 3). Of there, 33% had no idea of OT. All informants reported lack of knowledge of OD, organ procurement, and OTR. Eighty percent (45-82 years) had no willingness for OD or OTR; others might consult family members and health professionals (HP) to learn about OT. Seven hindering factors were identified: (1) having no background of OT; (2) limited impressions obtained from television news reports; (3) negative concepts of donating one's organs to others; (4) OT concepts contrast with cultural meanings of death; (5) possibility of being stigmatized; (6) fear of being rejected by others; and (7) HP had never mentioned OT. CONCLUSIONS: Taiwan APs' perspectives of OT concepts showed the majority to be unfamiliar with the concept and benefits of OT. Future research is necessary to explore the possible avenues to facilitate communications between HP and AP leaders, as well as elders in each AP category in Taiwan.

Late toxicities in concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy plus weekly cisplatin for locally advanced cervical cancer: a historical cohort comparison against two previous different treatment schemes.

PURPOSE: To determine the long-term toxicity of concurrent chemoradiotherapy (CCRT), using high-dose rate intracavitary brachytherapy (HDRICB) compared to radiation (RT) alone in patients with advanced cervical cancer using a control-cohort study. METHODS: A total of 332 cases of Stage IIB-III disease were included in this comparative study. Seventy-three patients were treated with a 3-insertion schedule and labeled group A, whereas the other 146 patients with a 4-insertion schedule became group B. One hundred and thirteen patients treated by a 4-insertion protocol with concurrent weekly cisplatin were labeled group C. RESULTS: The cumulative rate of grade 2 or above rectal complication was 13.7% for group A, 9.6% for the group B and 15.9% for group C (p = 0.76), whereas the grade 3 to 4 non-rectal radiation-induced intestinal injury was 6.8% for group A, 6.2% for group B and 9.7% for group C (p = 0.20). Grade 2 to 4 late bladder toxicity was higher in group C, with the cumulative rate being 5.5% for group A, 4.8% for group B and 15.0% for group C (p = 0.004). The independent factor for a rectal complication was the occurrence of a bladder complication (p = 0.01, hazard ratio 3.06). The independent factors for bladder complications were the use of CCRT (p = 0.01, hazard ratio 2.08), and the occurrence of rectal complications (p = 0.02, hazard ratio 2.77). CONCLUSIONS: When treating advanced cervical cancer, HDRICB consisting of four 6 Gy insertions and weekly cisplatin shows a trend of increasing late bladder complications. The interval between drug administration and HDRICB should be kept long enough to avoid any synergistic effect of both regimens.

The outcome and prognostic factors in patients with aspiration pneumonia during concurrent chemoradiotherapy for head and neck cancer.

This study aimed to investigate the outcome in patients with aspiration pneumonia during definitive concurrent chemoradiotherapy for head and neck cancer. The data of 595 patients with head and neck cancer treated by chemoradiotherapy were reviewed. Forty-one patients were identified as developing symptomatic aspiration pneumonia during treatment and were analysed for this study. The definition of symptomatic aspiration pneumonia fit three criteria: (1) at least one event of aspiration during the treatment or evidence of grade 2 or above dysphagia during treatment; (2) clinical or radiographic signs of pneumonia or pneumonitis; and (3) no evidence of grade 4 haematological toxicity before the outbreak of pneumonia. Termination of allocated radiotherapy was noted in 10 patients. A treatment break was observed in 26 patients, whereas irradiation was prolonged more than 1 week in 11 patients. Logistic regression analysis showed the dysphagia score during the treatment course and the chest roentgenography pattern following symptomatic aspiration pneumonia were found to independently influence the outcome. Aspiration pneumonia occurring during chemoradiotherapy for head and neck cancer has a detrimental effect on the treatment outcome. Intensive medical care is essential for this group of patients with a dysphagia score of 3 during treatment and an unfavourable chest film pattern.

Association of interleukin-18 promoter polymorphisms with WHO pathological classes and serum IL-18 levels in Chinese patients with lupus nephritis.

Accumulating evidence indicates that interleukin (IL)-18 has a central role in the pathogenesis of lupus nephritis (LN). Although two recent studies showed that IL-18 promoter gene polymorphisms might be associated with systemic lupus erythematosus (SLE), to our knowledge, there have not been any reports concerning their association with LN. The aim of our study was to investigate the association of IL-18 promoter polymorphisms with World Health Organization pathological classes and identify their functional correlations. Sequence-specific primer polymerase chain reaction and the restriction fragment length polymorphism method were used to analyse the genotypes of IL-18 promoter polymorphism at the position -607 in 101 unrelated patients with LN, 64 non-renal patients with SLE and 174 ethnically matched healthy controls. Serum IL-18 levels were determined using enzyme-linked immunosorbent assay during the active phase. Immunohistochemical analysis was performed for IL-18 expression on renal biopsies from 72 patients with LN. Our results showed that patients with non-renal SLE had significantly higher frequencies of SNP-607/AA when compared to patients with LN (37.5% vs 18.8%, P < 0.05). LN patients with the AA genotype had significantly lower levels of serum IL-18 than those with the CA or CC genotype (P < 0.01) and also had lower levels of glomerular IL-18 expression than those with the CC genotype (P < 0.05). Significantly, higher frequencies of the SNP-607/AA genotype were observed in LN patients with WHO class III than in those with class IV (34.6% vs 15.6%, P < 0.05). The SNP-607/AA genotype was not observed in patients with LN who progressed to end-stage renal failure that required haemodialysis or renal transplantation. In conclusion, the SNP-607/AA genotype that had lower IL-18 levels might be a genetically protective factor against renal involvement in Chinese patients with SLE and against development of severe nephritis in patients with LN.

Hypopharyngeal cancer treatment based on definitive radiotherapy: who is suitable for laryngeal preservation?

AIMS: To investigate prognostic factors for survival and locoregional control in patients with stage I-IVA hypopharyngeal cancer treated with laryngeal preservation radiotherapy. METHODS: This study was a retrospective analysis of 108 patients with stage I-IVA squamous cell carcinoma of the hypopharynx, treated with laryngeal preservation radiotherapy. Actuarial survival, disease-specific survival and local relapse-free survival were calculated, and multivariate analyses were performed using Cox's proportional hazards model. RESULTS: After a median follow-up duration of 39 months, the five-year local relapse-free survival rate was 35 per cent for all patients, 66 per cent for those with stage I-II disease, 46 per cent for those with stage III disease and 20 per cent for those with stage IVA disease (p = 0.004). Multivariate analyses showed that tumour and node stages were independent prognostic factors. CONCLUSIONS: Patients with stage I-II disease were suitable for laryngeal preservation radiotherapy. For most patients with stage III-IVA disease, other than those who were T1 N1 or T2 N1, the treatment results were poor.

Association of Epstein-Barr virus infection with systemic lupus erythematosus in Taiwan.

An association between Epstein-Barr virus (EBV) infection and systemic lupus erythematosus (SLE) has been suggested from previous serologic evidence. Since most adults in Taiwan are EBV-infected, seroepidemiologic studies based on standard assays for EBV are unlikely to dissociate SLE patients and control groups. We reexamine this question by using novel methodologies in which IgA anti-EBV-coded nuclear antigens-1 (EBNA-1) and IgG anti-EBV DNase antibodies were analysed by ELISA, and EBV viral loads were detected by real-time quantitative PCR for 93 adult SLE patients and 370 age-, sex- and living place-matched healthy controls in Taiwan. The specificities of antibodies for extractible nuclear antigens were determined by Western blot. Our results show that IgA anti-EBV EBNA1 antibodies were detectable in 31.2% SLE patients but only in 4.1% of controls (odds ratio [OR] = 10.72, 95% confidence interval [CI] = 5.19-22.35; P < 10(-7)), IgG anti-EBV DNase antibodies were detected in 53.8% SLE patients but only in 12.2% controls (OR = 8.40, 95% CI = 4.87-14.51; P < 10(-7)). EBV DNA was amplifiable from the sera of 41.9% SLE patients but from only 3.24% controls (P < 0.05). A significant association of IgG anti-EBV DNase antibodies with anti-Sm/RNP antibodies was observed (P < 0.005). The higher seroreactivity and higher copy numbers of EBV genome indicated association of EBV infection with SLE in Taiwan.

Use of a recombinant protein containing major epitopes of hnRNP G to detect anti-hnRNP G antibodies in dogs with systemic lupus erythematosus.

The objective of this study was to express major epitopes of heterogeneous nuclear ribonucleoprotein G (hnRNP G) for detecting anti-hnRNP G antibodies in dogs with systemic lupus erythematosus (SLE). HnRNP G cDNA clone was isolated from HEp-2 cells, and a DNA fragment encoding immunodominant region (residues 189-272) of hnRNP G (hnRNP Gi) was subcloned into pET32 vector to construct a prokaryotic expression plasmid named pEThnRNPGi. After induction, Escherichia coli carrying pEThnRNPGi expressed a recombinant protein of 28 kDa, comprising recombinant hnRNP Gi and fusion tag. Purified recombinant hnRNP Gi protein was further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its identity was confirmed. Western blot analysis showed that recombinant hnRNP Gi was specifically recognized by anti-hnRNP G positive sera of SLE dogs, and not by negative control sera. In conclusion, recombinant hnRNP Gi protein expressed in this study may serve as a useful reagent to assist in the immunological diagnosis of canine SLE.

Multiparametric analysis of cerebral substrates and nitric oxide delivery in cerebrospinal fluid in patients with intracerebral haemorrhage: correlation with hemodynamics and outcome.

BACKGROUND: There is no information regarding the possible role of cerebral substrates in the pathogenesis of neuronal injury in intracerebral haemorrhages (ICHs). Purposes of this prospective study were to clarify whether changes in substrates are the consequence of the initial brain damage in ICH and to elucidate the relationship among the biochemical mechanisms and clinical course of patients with ICH. METHOD: During a period of two years, patients (GCS < or =8) who had ICH secondary to an aneurysm (SAH), stroke (sICH), or trauma (tICH) and underwent ventriculostomy with ICP monitoring and/or underwent cranial surgery were randomly enrolled in this study. Extracellular concentrations of glutamate, aspartate, glycine, GABA, lactate, lactate/pyruvate ratio, and glucose in the CSF were measured by use of high-performance liquid chromatography (HPLC). The nitric oxide (NO) concentration in the CSF was analyzed by chemiluminescence. FINDINGS: There were 75 patients (38 women and 37 men) with ICH included in this study. Twenty-one patients had SAH, 28 sICH, and 26 tICH. In tICH patients, there was a 30-fold increase in glutamate and a 10-fold in aspartate over reference values. The levels of glutamate, aspirate, GABA, lactate, glucose, and NO differed significantly among the three groups (p<0.001). There were no significant differences in glycine and L/P ratio among the groups. The initial GCS, the mean CPP and outcome six months after the insult were all significantly correlated with the concentration of substrates (p<0.01), both within groups and among the total sample. The CSF levels of glutamate lactate, NO and glucose correlated significantly with outcome (p<0.005). CONCLUSIONS: This study confirms the correlation between the level of EAAs and the outcome of ICHs, suggesting that neurochemical monitoring of these substances may have a role in caring for patients.

Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still's disease.

OBJECTIVE: To determine the type 1 T helper (Th1)/type 2 T helper (Th2) balance in the peripheral blood (PB) and pathological tissues of patients with active untreated adult onset Still's disease (AOSD). METHODS: The percentages of interferon gamma (IFNgamma)- and interleukin (IL)4-producing Th cells in the PB of 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls were determined by intracellular staining and flow cytometry. Serum levels of IL18 and soluble IL2 receptor were measured by enzyme linked immunosorbent assay. Levels of IFNgamma and IL4 messenger (m) RNA expression were examined by real time quantitative polymerase chain reaction in biopsy specimens of evanescent rash and synovitis from 8 patients with AOSD. RESULTS: Significantly higher IFNgamma-producing Th cells and Th1/Th2 ratio in PB were found in patients with AOSD than in healthy controls. Percentages of IFNgamma-producing Th cells and Th1/Th2 ratio in PB correlated significantly with clinical activity score and serum IL18 levels in patients with AOSD. Increased ratio of Th1/Th2 cytokine transcripts was seen in the biopsy specimens of evanescent rash and synovitis from patients with AOSD compared with normal skin controls and patients with OA. Th cell cytokine pattern in PB and cytokine mRNA expression in synovium were similar for patients with AOSD and with RA. After 3 months' treatment, clinical remission was associated with a marked decrease in the percentages of cytokine-producing Th1 cells, but not of the Th2 cells. CONCLUSION: A predominance of Th1 cytokine may precipitate the pathogenesis of AOSD.

Pet dogs owned by lupus patients are at a higher risk of developing lupus.

The aim of this study is to determine whether pet dogs owned by patients with systemic lupus erythematosus (SLE) are at a higher risk of developing SLE. Diagnosis of canine SLE was mainly based on the 11 diagnostic criteria for human SLE and two marked immunological features of canine SLE. Among 59 pet dogs owned by 37 SLE patients, 11 (18.64%) were ANA positive, and three (5.08%) had SLE. In contrast, of 187 pet dogs owned by non-SLE households, nine (4.81%) were ANA positive, and none (0%) had SLE. Among 650 outpatient dogs registered in the veterinary hospital, 34 (5.23%) were ANA positive, and six (0.92%) had SLE. Frequency of ANA and SLE among pet dogs owned by SLE patients was significantly higher than in pet dogs owned by non-SLE households (P = 0.001 for ANA; P = 0.013 for SLE) and in outpatient dogs (P < 0.001 for ANA; P = 0.032 for SLE). With respect to canine SLE development, the relative risk or risk ratio (R) of human SLE contact varied from 5.5 (compared with outpatient dogs) to near the infinite (compared with dogs owned by non-SLE households). The prevalence of canine SLE among pet dogs of SLE patients was therefore estimated to be 508 per 10 000 [95% confidence interval (95% CI), 0-1068]. In conclusion, pet dogs with human SLE contact were at a higher risk of developing SLE. Our results indicate that a common environmental factor or zoonotic agent may be involved in the development of human and canine SLE.

Early stage cervical cancer with negative pelvic lymph nodes: pattern of failure and complication following radical hysterectomy and adjuvant radiotherapy.

PURPOSE OF INVESTIGATION: The objective was to optimize the adjuvant treatment for patients with lymph node negative cervical cancer by analyzing patterns of failure and complications following radical hysterectomy and adjuvant radiotherapy. METHODS: From September 1992 to December 1998, 67 patients with lymph node negative uterine cervical cancer (FIGO stage distribution: 50 Ib. 17 IIa), who had undergone radical hysterectomy and postoperative adjuvant radiotherapy with a minimum of three years of follow-up were evaluated. All patients received 50-58 Gy of external radiation to the lower pelvis followed by two sessions of intravaginal brachytherapy with a prescribed dose of 7.5 Gy to the vaginal mucosa. For 21 patients with lymphovascular invasion, the initial irradiation field included the whole pelvis for 44 Gy. The data were analyzed for actuarial survival (AS), pelvic relapse-free survival (PRFS), distant metastasis-free survival (DMFS), and treatment-related complications. Multivariate analysis was performed to assess the prognostic factors. RESULTS: The respective five-year AS, PRFS, and DMFS for the 67 patients were 79%, 93% and 87%. Multivariate analysis identified two prognostic factors for AS: bulky tumor vs non-bulky tumor (p = 0.003), positive resection margin (p = 0.03). The independent prognostic factors for DMFS was bulky tumor (p = 0.003), while lymphatic permeation showed marginal impact to DMFS (p = 0.08). The incidence of RTOG grade 1-4 rectal and non-rectal gastrointestinal complication rates were 20.9% and 19.4%, respectively. The independent prognostic factor for gastrointestinal complication was age over 60 years (p = 0.047, relative risk 4.1, 95% CI 1.2 approximately 11.7). The incidence of non-rectal gastrointestinal injury for the patients receiving whole pelvic radiation and lower pelvic radiation was 28.5% and 15.2%, respectively (p = 0.25). CONCLUSION: For patients with lymph node negative cervical cancer following radical hysterectomy, adjuvant lower pelvic radiation appears to be effective for pelvic control. It is also imperative to intensify the strategies of adjuvant therapy for some subgroups of patients.

Seroprevalence of Chlamydia pneumoniae infection in Taiwan.

OBJECTIVES: To survey the seroprevalence of Chlamydia pneumoniae (C. pneumoniae) infection in healthy subjects in Taiwan. MATERIALS AND METHODS: We used microimmunofluorescence antibody assay to survey the prevalence of antibodies to C. pneumoniae in 620 serum samples from healthy subjects aged 6 months to 86 years in Taiwan. RESULTS: The mean prevalence (+/-SD) of IgG antibodies against C. pneumoniae at titer greater than or equal 1:16 was 55.8% (range 7.8-81.8%). The antibody prevalence was low in children under the age of 10 years (7.8%), and increased rapidly with age. Most individual acquired infection during the second and third decades of life with highest antibody prevalence reached up to 81.8% at fifth decade of life and remained high (70%) thereafter. CONCLUSIONS: Chlamydia pneumoniae infection is highly endemic in Taiwan. These data contribute to the understanding of asymptomatic infections with C. pneumoniae in general population and should serve as a basis for studies on the role of C. pneumoniae infections and their related diseases.

Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells.

During development, calcium (Ca) is actively transported by placental trophoblasts to meet fetal nutritional and the skeletal mineralization needs. Maternal exposure to estrogenic pesticides, such as 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and methoxychlor (MTC), has been shown to result in reproductive disorders and/or abnormal fetal development. In this study, we have examined the effects of exposure of trophoblastic cells to MTC and DTT, in comparison to 17beta-estradiol (E2) and diethylstilbestrol (DES), to test the hypothesis that cellular Ca handling is a target for these endocrine disruptive components. Treatment with DDT, MTC, DES, or E2 increased cellular Ca uptake, and the expression of trophoblast-specific human Ca binding protein (HCaBP) was down-regulated by both MTC and DDT. Treatment with MTC, DDT, and DES inhibited cell proliferation, induced apoptosis, and suppressed expression of several trophoblast differentiation marker genes. These effects were reversed by overexpression of metallothionein IIa, a gene highly responsive to cadmium and other metals. These results strongly suggest that trophoblast Ca handling functions are endocrinally modulated, and that their alteration by candidate endocrine disruptors, such as MTC and DDT, constitutes a possible pathway of the harmful effects of these components on fetal development.

Idiopathic inflammatory myopathy with diffuse alveolar damage.

Interstitial lung disease (ILD) in patients with myositis is defined by the presence of interstitial changes on radiographic examination. The reported prevalence of ILD varies from 0% to nearly 50%. However, only rarely has the pathological pattern of diffuse alveolar damage (DAD) associated with idiopathic inflammatory myopathy (IIM) been reported. We report five patients with IIM (one with dermatomyositis, one with polymyositis, and three with amyopathic dermatomyositis) and respiratory failure. Four underwent open lung biopsy with pathological proof of diffuse alveolar damage (DAD). Despite intensive immunosuppressive therapy, all of them died. In addition to the case reports, we discuss DAD in patients with IIM.

Comparing whole body (18)F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer.

PURPOSE: At present, bone metastases are usually assessed using conventional technetium-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with (18)F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved specificity. We attempted to evaluate the usefulness of FDG-PET for detecting bone metastases in breast cancer and to compare FDG-PET results with bone scan findings. PATIENTS: The study group comprised 48 patients with biopsy-proven breast cancer and suspected of having bone metastases who underwent bone scan and FDG-PET to detect the bone metastases. The final diagnosis of bone metastases was established by operative, histopathological findings or during a clinical follow-up longer than 1 year by additional radiographs or following FDG-PET/bone scan findings showing progressive widespread bone lesions. RESULTS: A total of 127 bone lesions including 105 metastatic and 22 benign bone lesions found by either FDG-PET or bone scan were evaluated. Using FDG-PET, 100 metastatic and 20 benign bone lesions were accurately diagnosed, and using bone scan 98 metastatic and 2 benign bone lesions were accurately diagnosed. The diagnostic sensitivity and accuracy of FDG-PET were 95.2% and 94.5%, and of bone scan were 93.3% and 78.7%, respectively. CONCLUSIONS: Our findings suggest that FDG-PET shows a similar sensitivity and a better accuracy than bone scan for detecting bone metastases in patients with breast cancer.