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Biomedical subjects

A Rosen

Publications and source records attributed to A Rosen.

At least 19 recordsLinked to original sources
PubMed2006

Distinct recognition of antibodies to centromere proteins in primary Sjogren's syndrome compared with limited scleroderma.

BACKGROUND: Anticentromere antibodies are characteristically observed in scleroderma but have recently been reported in other autoimmune rheumatic disorders, including Sjögren's syndrome. It is not known whether distinct centromere proteins (CENP) are targeted in primary Sjögren's syndrome (pSS) and scleroderma. OBJECTIVE: To determine whether antibodies to CENP-B and CENP-C are present in these two disorders. METHODS: Sera from 45 patients with pSS and 33 with limited scleroderma were studied. All patients met classification criteria for pSS and scleroderma, respectively. Sera were used to immunoprecipitate in vitro translated CENP-B and CENP-C. The proportions recognising CENP-B or CENP-C were compared. RESULTS: 10 of 45 patients (22%) with pSS and 18 of 33 (55%) with scleroderma had antibodies recognising CENPs (p = 0.004). Seven of 10 (70%) CENP positive patients with pSS recognised CENP-C alone, compared with one of 18 (6%) CENP positive patients with scleroderma (odds ratio (OR) = 40 (95% confidence interval (CI), 3.5 to 450) (p = 0.003). In contrast, the majority (15 of 18 (83%)) of CENP positive scleroderma sera recognised both CENP-B and CENP-C, compared with none of 10 pSS sera (OR = 93 (95% CI, 4.4 to 1979) (p = 0.0001). CONCLUSIONS: The pattern of CENP recognition differs markedly in pSS and limited scleroderma. While patients with pSS predominantly recognise CENP-C alone, dual recognition of CENP-B and CENP-C is most frequent in scleroderma. These findings suggest that obtaining antibodies to specific centromere antigens is useful diagnostically, and imply that distinct mechanisms underlie the unique patterns of centromere autoreactivity in pSS and scleroderma.

Adult↗
PubMed2006

The Australian experience of deinstitutionalization: interaction of Australian culture with the development and reform of its mental health services.

OBJECTIVE: To describe the Australian experience of deinstitutionalization of the Australian National Mental Health Strategy in the context of the history of mental health services in Australia, and of Australian culture. METHOD: The development of Australian Mental Health Services is described with reference to developments in both psychiatric intervention research and Australian culture. The effects and achievements of national mental health reforms are described and critically examined. RESULTS: The relationship in Australia between the development of mental health services and the development of Australian society includes the stories of colonization, gold rush, suppression of indigenous peoples' rights, incarceration of mentally ill people, and incompatible state service systems. Mental health services required reform to provide consistent services and support for full citizenship and rights for such individuals who are still on the margins of society. Recent national developments in service models and service system research have been driven by the Australian National Mental Health Strategy. The translation of national policy into state/territory mental health service systems has led to a 'natural' experiment between states. Differing funding and implementation strategies between states have developed services with particular strengths and limitations. CONCLUSION: The effects of competition for limited resources between core mental health service delivery and the shift to a population-based public health approach (to prevention of mental illness and promotion of mental health), leaves our services vulnerable to doing neither particularly well. The recent loss of momentum of these reforms, due to failure of governments to continue to drive and fund them adequately, is causing the erosion of their considerable achievements.

Australia↗
PubMed2005

Immunosuppressive treatment options in renal transplantation.

An overview of the first 4 decades of clinical kidney transplantation would characterize progress primarily in the development of new immunosuppressive agents designed to reduce the incidence and severity of acute rejection to improve short-term outcomes, but with less marked effects on long-term patient and graft survival. The new trend of immunosuppressive therapy is to facilitate long-term allograft and patient survival, and to help to maintain a good quality of life after renal transplantation. To achieve these goals, transplant physicians need to determine the immunosuppressive protocols that will best minimize risk factors associated with reduced allograft/patient survival and quality of life. Recent protocols and clinical experience with modern immunosuppression strategies, as well as the efficacy and safety of various combination protocols, will be reviewed.

Adrenal Cortex Hormones↗
PubMed2004

Altered autoantigen structure in Sjögren's syndrome: implications for the pathogenesis of autoimmune tissue damage.

The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.

Animals↗
PubMed2004

Recurrent transverse myelitis associates with anti-Ro (SSA) autoantibodies.

Transverse myelitis (TM) is an idiopathic inflammatory disorder of the spinal cord. The authors observed cases of recurrent TM in patients where anti-Ro (SSA) antibodies were present and therefore performed a case-control study to examine the frequency of anti-Ro autoantibodies in patients with recurrent TM and control subjects. Antibodies to 52-kd Ro were demonstrated in 77% of cases (10/13) compared with only 33% of control subjects (4/12).

Adolescent↗
PubMed2003

Effect of raloxifene on sexual function in postmenopausal women.

OBJECTIVE: To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream. METHODS: A total of 187 naturally postmenopausal women, 42-80 years of age, with signs of genitourinary atrophy were enrolled in this 6-month, multicenter, parallel-group study. Subjects were randomized to oral raloxifene HCl 60 mg daily or matching placebo; the same subjects were also randomized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months, followed by conjugated estrogen cream for 3 months. Both investigators and subjects were masked to the identity of the oral medication. The vaginal preparations were administered in an open-label fashion. The Sexual Activity Questionnaire (SAQ) was administered at baseline and at 3 and 6 months. Safety was assessed throughout the study. RESULTS: A total of 102 women were sexually active at baseline and, of these, 82 were also sexually active at the 6-month end-point. At 6 months, raloxifene and placebo, in the presence of vaginal conjugated estrogen cream, were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity. There were no significant differences between raloxifene and placebo groups in any SAQ item. Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo. No difference in adverse events was observed between groups. CONCLUSION: Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream.

Administration, Intravaginal↗
PubMed2002

Tumor progression, histologic grading and DNA-ploidy as predictive factors of lymphogenous metastasis in primary carcinoma of the Fallopian tube.

UNLABELLED: The bad prognosis of primary carcinoma of the Fallopian tube (FTC), with 5-year overall survival rates of only 35%, is particularly ascribed to lymphogenous metastasis. Yet, we know very little on the pathophysiologic factors on which this lymphogenous metastasis is based. The present study, therefore, aims at evaluating the influence of intra-abdominal tumor progression and tumor-cell anaplasia on lymphogenous metastasis in FTC. We studied 41 cases of FTC, who had been subjected to radical lymphadenectomy during primary operation in a retrospective analysis. Staging was done by International Federation of Gynecology and Obstetrics-classification. Histologic grading and nuclear DNA-content (DNA-index) were used for evaluating tumor-cell anaplasia. Histologic grading discriminated between highly differentiated (G1), moderately dedifferentiated (G2), and dedifferentiated (G3) tumors. According to their DNA-indices, tumors were separated into three groups: DNA-index < or =1.1 (euploid cases), DNA-indices between 1.1 and 2.0 (cases of intermediate ploidy), and DNA-index >2.0 (aneuploid cases). The overall incidence of lymph node metastases was 43.9%. There was no correlation between histologic grading and DNA-index (P=0.98). Lymphogenous metastasis set in after the tumor had transgressed the tube (intra-abdominal stage II). Further intra-abdominal tumor progression (including omentum, liver, or peritoneum) significantly increases the incidence of lymph node metastases (P=0.02). There was only a single G1-tumor that had already disseminated into the lymph, all other cases of lymph node metastases were found in G2- or G3-tumors. DNA-index and the extent of lymphogenous metastases were not found to be correlated (P=0.74). CONCLUSIONS: The extent of lymphogenous metastases in FTC depends above all on intra-abdominal tumor progression. This fact has clinical consequences as the indication for lymphadenectomy can be obtained directly during operation. The results of histologic grading are of no impact on the surgical proceedings; the determination of DNA-ploidy is negligible.

Adult↗
PubMed2002

Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS).

Monoclonal expansion of B cells and plasma cells, producing antibodies against 'self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström's macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein--Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-lambda type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

Aged↗
PubMed2002

Structure characterization of human serum proteins in solution and dry state.

The present report describes application of advanced analytical methods to establish correlation between changes in human serum proteins of patients with coronary atherosclerosis (protein metabolism) before and after moderate beer consumption. Intrinsic fluorescence, circular dichroism (CD), differential scanning calorimetry and hydrophobicity (So) were used to study human serum proteins. Globulin and albumin from human serum (HSG and HSA, respectively) were denatured with 8 m urea as the maximal concentration. The results obtained provided evidence of differences in their secondary and tertiary structures. The thermal denaturation of HSA and HSG expressed in temperature of denaturation (Td, degrees C), enthalpy (DeltaH, kcal/mol) and entropy (DeltaS kcal/mol K) showed qualitative changes in these protein fractions, which were characterized and compared with fluorescence and CD. Number of hydrogen bonds (n) ruptured during this process was calculated from these thermodynamic parameters and then used for determination of the degree of denaturation (%D). Unfolding of HSA and HSG fractions is a result of promoted interactions between exposed functional groups, which involve conformational changes of alpha-helix, beta-sheet and aperiodic structure. Here evidence is provided that the loosening of the human serum protein structure takes place primarily in various concentrations of urea before and after beer consumption (BC). Differences in the fluorescence behavior of the proteins are attributed to disruption of the structure of proteins by denaturants as well as by the change in their compactability as a result of ethanol consumption. In summary, thermal denaturation parameters, fluorescence, So and the content of secondary structure have shown that HSG is more stable fraction than HSA.

Blood Proteins↗
PubMed2001

Nociceptin/orphanin FQ into the rat periaqueductal gray decreases the withdrawal latency to heat and loading, an effect reversed by (Nphe(1))nociceptin(1-13)NH(2).

The present study investigated the effect of intraperiaqueductal grey injection of nociceptin/orphanin FQ (N/OFQ) and an antagonist (Nphe(1))nociceptin(1-13)NH(2) on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. N/OFQ (5 nmol) significantly decreased the nociceptive thresholds in both tests and 1, 5 and 10 nmol of (Nphe(1))nociceptin(1-13)NH(2) significantly reversed this effect in a dose dependent way. Our results demonstrate, that N/OFQ has a nociceptive action, possibly through inhibition of PAG neurons. This effect is blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) probably via ORL1 receptors in the periaqueductal grey.

Animals↗
PubMed2001

Six-year clinical effect of donor bone marrow infusions in renal transplant patients.

BACKGROUND: To date, several single- and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. METHODS: Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The immunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01x10(8)+/-1.9x10(8) (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. RESULTS: There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P = <0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3+/-0.36% (SE) most recently. This has not occurred in the controls. CONCLUSIONS: There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

Adolescent↗