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991.
Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population. 总被引:6,自引:0,他引:6
D J Niehaus C J Kinnear V A Corfield P L du Toit J van Kradenburg J C Moolman-Smook J B Weyers A Potgieter S Seedat R A Emsley J A Knowles P A Brink D J Stein 《Journal of affective disorders》2001,65(1):61-65
BACKGROUND: It has been proposed that the catechol-o-methyl transferase gene (COMT) may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Whereas studies in a North American population showed that the low activity (L) allele of a functional polymorphism in COMT was associated with OCD in male patients, this result was not supported by studies in a Japanese population. The present association study assessed the risk for OCD conferred by this COMT polymorphism in a geographically different patient group, namely, the relatively genetically homogeneous Afrikaner population of South Africa. METHODS: Fifty-four unrelated OCD patients and fifty-four sex-matched controls were recruited from the same Afrikaner community. Patients and controls were phenotyped (DSM-IV) and genotyped for a NlaIII polymorphism with H (high activity) or L (low activity) alleles in the COMT gene. RESULTS: The H/L genotype was significantly more common than expected in the OCD patient group (P = 0.0017). LIMITATIONS: Replication studies with related individuals may be useful in discovering factors underpinning the H/L genotype abundance in the Afrikaner population. CONCLUSIONS: These results emphasise the need for further studies in genetically homogeneous populations to help define the complex etiology of this disease. 相似文献
992.
Constitutive expression of p35 and p40 IL-12 mRNA was detected in splenic
macrophages isolated from aged mice. Macrophages were also implicated as
the cell type responsible for the dysregulated IL-6 and tumor necrosis
factor (TNF)-alpha commonly observed to be constitutively produced by
lymphoid cells from aged donors. A role for IL-12 in the aging process was
suggested when it was found that recombinant IL-12 (rIL-12) directly
stimulated splenic CD5+ B cells to secrete IL-10, and both CD5+ and CD5- B
cells could be directly induced to produce IL-6 in response to rIL-12.
Furthermore, splenocytes from aged animals cultured in the presence of
anti-IL-12 antibodies demonstrated a significant reduction in spontaneous
IL-6, IL-10 and IFN- gamma production. Based on these observations it was
concluded that IL- 12 might be responsible for the dysregulated production
of IL-10 and IFN-gamma known to occur in aged animals. Treatment of aged
animals with low doses of dehydroepiandrosterone sulfate, previously
established to be immunocorrective in immunosenescent animals, reduced the
age-associated alterations in IL-12 mRNA and protein expression. The
mechanisms responsible for the abnormal constitutive expression of
inflammatory cytokines by the macrophages of aged animals may play an
important afferent role in establishing the immunosenescent phenotype.
相似文献
993.
ABH antigens are present on platelets from individuals of the corresponding red cell phenotype, but the extent to which these antigens are intrinsic or adsorbed remains undefined. To evaluate platelets for intrinsic H substance, an IgM mouse monoclonal antibody against type 2H chain (the intrinsic H structure found on erythrocytes) was labeled with 125I and incubated with platelets from donors of different ABO type. The antibody showed dose-response saturation curves, and binding to platelets paralleled that of the red cell ABO type, with O greater than B greater than A1 greater than A1B greater Oh cells, giving a single factor variance F of 190 (P less than .0005). Passive adsorption of A antigens by platelets has been previously reported. To verify this phenomenon for A and B antigens and to quantitate the elution of A and B antigens from platelets, the following assay system was used. Platelets from group A1 and B donors were incubated in plasma from group O donors, and platelets from group O donors were incubated in plasma from different ABO, Lewis, and presumed secretor-type donors. Human IgG anti-A or anti-B was added to the platelets. The amount of antibody bound was determined with a 125I- labeled mouse monoclonal anti-human IgG. When incubated for 96 hours in group O plasma, group A1 platelets showed a 45% to 50% decrease in binding of anti-A. There was no significant change in the level of type 2H antigen on these platelets during the same incubation period. Group O platelets incubated in A or B plasmas rapidly acquired the antigens, but if returned to their original plasma, 95% of this passively adsorbed antigen eluted off within 18 hours. The maximum uptake of A and B substances was influenced by the Lewis and secretor type of donor plasma. Our present study demonstrates that ABH antigens on platelets consist of type 2H chains, which are presumably intrinsic as when found on red cells, and of passively adsorbed ABH structures, which are presumably type 1H chains. 相似文献
994.
Morphologic transformation of follicular lymphoma is associated with somatic mutation of the translocated Bcl-2 gene 总被引:5,自引:1,他引:5
Follicular lymphoma (FL) is a low-grade B-cell non-Hodgkin's lymphoma (NHL) that frequently transforms into diffuse aggressive NHL. The majority of FLs display a t(14; 18) translocation that places the bcl-2 gene into juxtaposition with the lg heavy-chain (H) gene locus. Morphologically transformed malignant FL cells retain their t(14;18) translocation and may acquire additional genetic abnormalities. We analyzed serial biopsy specimens from eight patients with FL for secondary alterations of the rearranged bcl-2 gene in the breakpoint and open reading frame (ORF) regions. Two cases of FL showed no histologic alteration in the second biopsy, and six cases of FL showed morphologic transformation to diffuse large-cell lymphoma (DLL) in the second biopsy. Polymerase chain reaction (PCR) amplification, cloning, and sequencing of the junctional region of the hybrid bcl-2/IgH genes showed identical nucleotide sequences in multiple biopsy specimens of FL that did not show morphologic transformation. In patients in whom FL cells underwent morphologic transformation, FL and autologous DLL cells displayed identical bcl-2/IgH gene nucleotide sequences in five cases and different sequences in one case. In the case for which FL and DLL cells showed different bcl-2/IgH junctional sequences, DLL cells incorporated larger bcl-2 and Ig-joining (JH) gene fragments than the corresponding FL cells, suggesting that DLL clones developed by a distinct t(14; 18) translocation rather than by alteration of the hybrid bcl-2/IgH gene detected in the FL cells. In all eight cases, neither FL nor DLL cells showed alterations of bcl-2 gene sequences in the breakpoint region, suggesting high conservation of the bcl-2 gene during both t(14; 18) translocation and morphologic transformation of the FL cells. PCR single-strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the ORF region corresponding to the 239-amino acid p26-bcl-2 alpha protein. A total of 11 point mutations of the ORF were detected in DLL cells of three transformed NHLs, but no alteration of the ORF was detected in FL cells. Four of 11 mutations, at positions 29, 46, 59, and 106, yielded amino acid replacements. These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells may be associated with somatic point mutations of the bcl-2 proto- oncogene ORF sequence resulting in alteration of the p26-bcl-2 alpha gene product. 相似文献
995.
Donaldson VH; Wagner CJ; Tsuei B; Kindness G; Bing DH; Harrison RA; Rosen FS 《Blood》1987,69(4):1096-1101
Purified preparations of normal C1(-)-inhibitor (C1(-)-INH) formed high mol wt complexes with plasma kallikrein that were stable during sodium dodecyl sulfate (SDS)-gel electrophoresis, but most of the dysfunctional C1(-)-INH proteins isolated from plasma of patients with type II hereditary angioneurotic edema (HANE) did not. Two of eight dysfunctional C1(-)-INH proteins were cleaved to lower mol wt forms that were not seen following the reaction of normal C1(-)-INH with equimolar amounts, or less, of plasma kallikrein. Only the higher mol wt component of normal C1(-)-INH (106,000 mol wt) appeared to form a stable complex with the plasma kallikrein, whereas both the 106,000 and 96,000 mol wt forms made stable complexes with C1-s. When a preparation of normal C1(-)-INH containing a homogeneous single band of C1(-)-INH was exposed to C1-s or kallikrein, a "doublet" form evolved in which the heaviest band was in the original position of native C1(-)-INH; C1- s cleavage provided a second band of 96,000; and cleavage by kallikrein, a second band of 94,000 mol wt. We conclude that dysfunctional C1(-)-INH proteins from plasma of persons with type II hereditary angioneurotic edema have impaired interactions with plasma kallikrein and are heterogeneous with respect to these interactions. Moreover, the requirements for the formation of stable complexes between normal C1(-)-INH and plasma kallikrein differed from those for stable complex formation with C1-s. The doublet form of C1(-)-INH, which purified preparations frequently demonstrate, may be due to prior cleavage by C1-s or kallikrein. 相似文献
996.
Zimmer WD; Berquist TH; McLeod RA; Sim FH; Pritchard DJ; Shives TC; Wold LE; May GR 《Radiology》1985,155(3):709-718
The magnetic resonance (MR) imaging characteristics of bone tumors are described and the clinical utility of MR imaging in patient evaluation is reported. Fifty-two patients with skeletal lesions were examined with a Picker MR imager (0.15-T resistive magnet). Twenty-five patients had primary malignancies, seven had benign bone neoplasms, 15 had skeletal metastases, and five had neoplasm simulators. Forty-five patients had CT scans available for comparison. For demonstrating the extent of tumor in marrow, MR was superior to CT in 33% of cases, about equal to CT in 64%, and inferior to CT in 2%. For delineating the extent of tumor in soft tissue, MR was superior to CT in 38% of cases and about equal to CT in 62%. CT was superior in all cases for demonstrating calcific deposits and pathologic fractures. In four patients with metal prostheses or surgical clips, MR was superior to CT in documenting recurrent tumor because of artifactual degradation of the CT image. Direct sagittal and coronal images from MR permit accurate assessment of the relationship of tumor to adjacent normal structures, including the physis, joints, and neurovascular structures. MR is useful in the evaluation of bone tumors: it is of greatest value in evaluations of the peripheral skeleton, the medullary canal, soft tissues, and postoperative tumor recurrence. With a 0.15-T magnet, MR is less useful in the evaluation of the axial skeleton and cortical bone. 相似文献
997.
O Abbas N Marrouch MM Kattar S Zeynoun AG Kibbi RA Rached GF Araj S Ghosn 《Journal of the European Academy of Dermatology and Venereology》2011,25(1):33-42
Background Only a few studies characterized cutaneous non‐tuberculous Mycobacterium (NTM) infections in this region of the world . Objective The aim of this study was to describe the epidemiological, clinical and histological findings of cutaneous NTM infections in Lebanon. Patients/Methods Retrospective study of 17 patients (19 histological specimens) diagnosed with cutaneous NTM infections and confirmed by culture‐based partial sequencing of the 16S rRNA gene at the American University of Beirut Medical Center between 2005 and 2008. Results Of 17 cases, 14 were caused by Mycobacterium marinum. All patients were immunocompetent except for one. Clinically, the most common presentation was multiple sporotrichoid lesions over an extremity (8/17). Many patients had peculiar presentations including bruise‐like patches, herpetiform lesions, annular ulcerated plaques, symmetrical nodules over the buttocks and locally disseminated lesions with surrounding pale halo. Almost all patients cleared their infection on either minocycline or clarithromycin monotherapies. Histologically, a dermal small vessel proliferation with mixed inflammation (granulation tissue‐like changes) was identified in 58% of specimens. The most common type of granulomatous inflammation was the suppurative (47%) followed by the tuberculoid (30%), sarcoidal (11%), and palisading (5%) types. Lichenoid granulomatous dermatitis was noted in 42% of cases. Special staining highlighted mycobacteria in only two specimens. Conclusions The incidence of cutaneous NTM infections is high in our area. Many patients had peculiar clinical presentations. Our study is the second to report the common presence of granulation tissue‐like changes as a good histological indicator of cutaneous NTM infections. Minocycline and clarithromycin remain the drugs of choice in our area. 相似文献
998.
999.
1000.
PurposeEvidence for the recommendation to deliver Cognitive Behavioural Therapy (CBT) and Family Interventions (FI) to under-18s with psychosis derives from adult research, and no previous study has focused exclusively on an adolescent population. We evaluated adaptations of these therapies for adolescent inpatients with psychosis (CBTpA and FIpA), delivered as an adjunct to inpatient standard care (SC).Subjects and methodsThirty adolescent inpatients with psychotic symptoms on admission were sequentially allocated to receive CBTpA + SC (n = 10); FIpA + SC (n = 10) or SC alone (n = 10). Psychotic symptoms and functioning were measured at admission and discharge.ResultsGroup comparisons did not reach conventional significance, but effect sizes in this pilot study showed a promising impact of CBTpA compared to SC alone, in reducing symptoms (ES: d = 0.6), with smaller effect sizes for functioning (d = 0.2) and for FIpA (symptoms, d = 0.1 and functioning, d = 0.4). There was no advantage of either additional treatment in reducing length of stay, but self-report satisfaction ratings were higher for both psychological therapies.Discussion and conclusionsThe study is the first to focus on an exclusively adolescent population, using appropriately adapted therapy protocols. Findings suggest that the interventions are feasible, acceptable and helpful for adolescents with psychosis. Larger randomised controlled trials are now needed. 相似文献