Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Improving access to disability benefits among homeless persons with mental illness: an agency-specific approach to services integration

OBJECTIVES: This study evaluated a joint initiative of the Social Security Administration (SSA) and the Department of Veterans Affairs (VA) to improve access to Social Security disability benefits among homeless veterans with mental illness. METHODS: Social Security personnel were colocated with VA clinical staff at 4 of the VA's Health Care for Homeless Veterans (HCHV) programs. Intake assessment data were merged with SSA administrative data to determine the proportion of veterans who filed applications and who received disability awards at the 4 SSA-VA Joint Outreach Initiative sites (n = 6709) and at 34 comparison HCHV sites (n = 27 722) during the 2 years before and after implementation of the program. RESULTS: During the 2 years after the initiative began, higher proportions of veterans applied for disability (18.9% vs 11.1%; P < .001) and were awarded benefits (11.4% vs 7.2%, P < .001) at SSA-VA Joint Initiative sites. CONCLUSION: A colocation approach to service system integration can improve access to disability entitlements among homeless persons with mental illness. Almost twice as many veterans were eligible for this entitlement as received it through a standard outreach program.     

Role of radiology in the treatment of malignant hilar biliary strictures 2: 10 years of single‐institution experience with percutaneous treatment

We reviewed the results of percutaneous intervention of hilar biliary malignancy over a 10‐year period at a single institution: the Royal Melbourne Hospital. Ninety‐nine patients (100 treated in total) were included. Information was retrieved by retrospective examination of patient notes and radiology, combined with interviews with family and relevant physicians. Sixty‐nine patients were treated with insertion of semipermanent stents, 19 had external drain tubes, and 25 received percutaneous access for Iridium brachytherapy. Adequate drainage was achieved in 87% of the patients stented, and percutaneous access was successful in 96% of patients planned for brachytherapy. Of those patients undergoing endoprosthesis insertion, early complications occurred in 39% and late complications in 23%. Average survival for the entire patient population was 227.3 days, with a median of 167 days. Longer survival times (213 vs 142 days) and lower complication rates (44 vs 64%) are observed with metal stents in comparison with plastic stents. Percutaneous intervention is an important treatment option in hilar biliary malignancy, particularly in patients unfit for surgery. Reasonable survival with good palliation is the most common outcome, and most patients do not require further intervention.     

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.      

DNA vaccination using bacillus Calmette-Guerin-DNA as an adjuvant to enhance immune response to three kinds of swine diseases

In order to enhance the immune efficacy of DNA vaccination, experiments were conducted to investigate the regulating effects of Bacillus Calmette-Guerin （BCG）-DNA as an adjuvant on immune responses of mice against foot-and-mouth disease （FMD）, Aujeszky＇s disease （AID） and classical swine fever （CSF）. BCG-DNA was purified from BCG by ion-exchange chromatography. Three DNA vaccines （pVSG, pVgD and pVE2） against the respective infection were constructed, and BCGDNA was coimmunized to mice by muscle injection. The results showed that titres of specific immunoglobulin （Ig）G to the vaccines mounted remarkably in the sera of the adjuvant covaccinated mice （P〈0.01）. Antibody isotype IgG2a and IgG1 also increased, respectively, in mice coimmunized with BCG-DNA compared with those of the control groups （P〈0.01）. Cellular immune cytokine interferon-gamma and cytotoxic T lymphocytes were detected in coimmunized BCG-DNA groups （P〈0. 05）. Whereas interleukin-4, humoral immune cytokine, was not significant （P〉 0. 05）. These results suggest that codelivery of BCG-DNA with DNA vaccines against FMD, AjD and CSF can enhance the induction of antigen-specific, especially, cell-mediated immunity.     

Referral and housing processes in a long-term supported housing program for homeless veterans

OBJECTIVE: The study examined client characteristics, case management variables, and housing features associated with referral, entry, and short-term success in a Department of Veterans Affairs (VA) national intensive case management and rental assistance program for homeless veterans. METHODS: Information collected from homeless veterans at the time of initial outreach contact and from case managers during the housing search was used to create logistic regression models of referral into the program and successful completion of several stages in the process of obtaining stable independent housing. RESULTS: Overall, only 8 percent of the more than 65,000 eligible veterans contacted by outreach workers were referred to the program. Those referred were more likely to be female, to have more sources of income, to have recently used VA services (including residential treatment), and to have serious mental health problems. Once in the program, 64 percent of veterans eventually moved into an apartment, and 84 percent of those who obtained an apartment were stably housed one year later. In general, activities of case managers, such as accompanying the veteran to the public housing authority and securing additional sources of income, were associated with success in the housing process. The therapeutic alliance, clients' housing preferences, and the quality of housing were unrelated to retention of housing. CONCLUSIONS: This supported housing program was judged appropriate for a small percentage of eligible veterans. However, a large proportion of clients were successful in attaining permanent housing, which lends support to the effectiveness of the supported housing approach.     

Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis

The objective was to investigate the relationship between the presence of different types of antinuclear antibodies (ANA) in patients with systemic sclerosis (SSc) and the presence of clinical features. Sera from 230 patients with SSc were tested for the presence of ANA, including anticentromere antibodies (ab), antitopoisomerase I ab, anti- U1 RNP ab and antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP. Clinical features were registered prospectively in a clinical database. Eighty-two per cent of the patients were women. The median age was 58 yr (45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA were found in 86% of the patients (anticentromere: 34%; antitopoisomerase I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%; anti-U3 RNP: 3.5%; anti- U17 RNP: 0%). Anticentromere ab were found to be related to a high prevalence of calcinosis, telangiectasia, digital ulcers, acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary diffusing capacity, and a low prevalence of radiological evidence of pulmonary fibrosis. Antitopoisomerase I ab were associated with a high prevalence of digital joint deformity, distal osteolysis, radiological signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis and myositis, a low prevalence of calcinosis, and early disease onset. The presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was not significantly related to any particular clinical features in this study; possibly due to the small number of patients with these ab. The presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the serum was also found to have previously described clinical correlations in a group of Danish SSc patients.      

取样胶囊吸取胃液的模拟实验分析与研究

取样胶囊主要是吸取人体消化道内的消化液进行研究,本文以胃液为例,对取样胶囊吸取消化液进行探讨,分析在取样胶囊的研究中选取何种吸附材料最合适．首先对胃液成分进行分析,然后配置模拟胃液,选取六种不同吸附材料进行了吸附实验,并按实验结果绘制了不同的吸附曲线．由实验结果,对各种材料的吸附量、吸附稳定性和可靠性等进行了对比分析,同时还对取样机构模型设计的简单化因素进行分析．最后得出结论,认为德制胶棉在各个因素上都有明显的优势,适宜作为取样胶囊中的吸附材料．