Predictive Association of Smoking with Depressive Symptoms: a Longitudinal Study of Adolescent Twins

Prevention Science - Longitudinal, genetically informative studies of the association between cigarette smoking and depressive symptoms among adolescents are limited. We examined the longitudinal...     

Impaired executive performance in healthy siblings of schizophrenia patients in a population-based study

There is increasing evidence that healthy siblings of schizophrenia patients have similar, although milder, neuropsychological deficits than their affected family members. However, the interpretation of these findings has been complicated by methodological differences, for example the selection of relatives studied and the sensitivity of tests used. We studied neuropsychological functioning in schizophrenia families in representative, population-based samples of schizophrenia patients (n=81) and healthy siblings (n=78) from 58 families, and control subjects (n=70). We found that the healthy sibling group was impaired in tests measuring performance speed and executive functions. The patients were significantly impaired in all neuropsychological variables studied when compared with the control subjects, and also when compared with the healthy siblings. The effects of age, sex and education were controlled for. In conclusion, in a study of representative, population-based sample the healthy siblings of schizophrenia patients demonstrated deficits in processing speed and executive functions.     

Depression: an important comorbidity with metabolic syndrome in a general population

OBJECTIVE—There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components.RESEARCH DESIGN AND METHODS—Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004–2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25–84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure.RESULTS—Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12–3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76–3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06–3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression.CONCLUSIONS—Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.Recent definitions of metabolic syndrome (1,2) specify the following quantitative criteria: large waist circumference, high blood pressure, dyslipidemia (high triglycerides and low HDL cholesterol), and fasting hyperglycemia with underlying insulin resistance as the likely mechanism. The combination of these components is a strong predictor of cardiovascular disease and type 2 diabetes. Understanding the mechanisms involved and factors associated with the metabolic syndrome is of great interest given the pandemic of obesity and increasing prevalence of the metabolic syndrome (32% in the U.S. adult population in 1999–2000 [3] using the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III [NCEP ATP III] [1], criteria and 28% in our region [4]).There is an increasing interest in the association between metabolic syndrome and depression and whether causal relationships are involved. The proposed link is consistent with reports that depression is associated with development of diabetes and with poor glycemic control in established diabetes (5). For instance, Björntorp (6) has hypothesized that psychological problems are associated with metabolic disorders via visceral fat accumulation. The postulated role of the hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of central adiposity and metabolic syndrome has led to the conceptualization of the metabolic syndrome as a neuroendocrine disorder (7).To investigate the link between metabolic syndrome and depression, several studies have been conducted with results generally supporting an association of metabolic syndrome with depression. However, the groups studied were not representative samples from the general population with metabolic syndrome, being either relatively young (8,9), men only (10), premenopausal women only (11,12), or a clinically targeted population (13) (

Maintenance therapy in cutaneous T-cell lymphoma: Who,when, what?

The aim of current therapy for cutaneous T-cell lymphoma (CTCL) is to induce clinically meaningful remission, provide symptom relief, improve patient quality of life (QoL) and prolong disease-free and overall survival. A key research question is whether such remissions or minimal disease status can be maintained in the long term. There have been few formal studies of maintenance therapy in CTCL. Some skin-directed therapies such as total-skin electron-beam therapy and high-dose psoralen plus ultraviolet A may not be considered suitable, because of the risk of long-term cumulative toxicities. Other therapies such as nitrogen mustard, interferon (IFN)-alpha and bexarotene have demonstrated positive effects in prolonging remissions in small numbers of patients. Large longitudinal studies are required to investigate the efficacy of maintenance treatments in CTCL and their impact on patients' QoL and overall survival. Of the systemic therapies currently approved for the treatment of CTCL, bexarotene and IFN-alpha are obvious candidates for testing, because they can be self-administered by the patient and provide good long-term tolerability.     

Systemic efficacy of oncolytic adenoviruses in imagable orthotopic models of hormone refractory metastatic breast cancer

Conditionally replicating oncolytic adenoviruses represent a promising developmental strategy for the treatment of cancer refractory to current treatments, such as hormone refractory metastatic breast cancer. In clinical cancer trials, adenoviral agents have been well tolerated, but gene transfer has been insufficient for clinical benefit. One of the main reasons may be the deficiency of the primary adenovirus receptor, and therefore viral capsid modifications have been employed. Another obstacle to systemic delivery is rapid clearance of virus by hepatic Kupffer cells and subsequent inadequate bioavailability. In this study, we compared several capsid-modified oncolytic adenoviruses for the treatment of breast cancer with and without Kupffer cell inactivation. Replication deficient capsid-modified viruses were analyzed for their gene transfer efficacy in vitro in breast cancer cell lines and clinical samples and in vivo in orthotopic models of breast cancer. The effect of Kupffer cell depleting agents on gene transfer efficacy in vivo was evaluated. An aggressive lung metastatic model was developed to study the effect of capsid-modified oncolytic adenoviruses on survival. Capsid-modified viruses displayed increased gene transfer and cancer cell killing in vitro and resulted in increased survival in an orthotopic model of lung metastatic breast cancer in mice. Biodistribution of viruses was favorable, tumor burden and treatment response could be monitored repeatedly. Kuppfer cell inactivation led to enhanced systemic gene delivery, but did not increase the survival of mice. These results facilitate clinical translation of oncolytic adenoviruses for the treatment of hormone refractory metastatic breast cancer.     

Specific cellular immune response and neutralizing antibodies in goats immunized with native or recombinant envelope proteins derived from human T-lymphotropic virus type IIIB and in human immunodeficiency virus-infected men.

Animals immunized with native or recombinant envelope proteins from the human immunodeficiency virus (HIV, formerly referred to as human T-lymphotropic virus type III) human T-lymphotropic virus type IIIB and naturally HIV-infected men were assessed for neutralizing antibodies and cell-mediated immunity toward the virus. Immunization of rabbits or goats with the native external envelope glycoprotein gp120 or with corresponding recombinant proteins elicited strictly type-specific neutralizing antibodies. A broad, group-specific cellular immune response to gp120 and to three different HIV isolates was seen in goats immunized with the native gp120 but not in animals immunized with the nonglycosylated recombinant envelope proteins. In HIV-infected people, no T-cell response was seen, even though their T-cell response toward other foreign antigens was intact. The results show type- and group-specific epitopes on gp120, some of which may be of importance for the development of a vaccine against HIV infection.     

A novel mutation in the third extracellular domain of the tumor necrosis factor receptor 1 in a Finnish family with autosomal-dominant recurrent fever

OBJECTIVE: To investigate the presence of TRAPS (tumor necrosis factor receptor-associated periodic syndrome), which is a recently defined, dominantly inherited autoinflammatory syndrome caused by mutations in the tumor necrosis factor receptor superfamily 1A gene (TNFRSF1A, CD120a), in a Finnish family with recurrent fever. METHODS: The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometry and enzyme-linked immunosorbent assay analyses were used to assess membrane expression and serum levels of the TNFRSF1A protein, respectively. RESULTS: A missense mutation in exon 4, located in the third extracellular domain of TNFRSF1A and resulting in an amino acid substitution (F112I) close to a conserved cysteine, was found in all 4 affected family members and in 1 asymptomatic individual. The mutation was clearly associated with low levels of soluble TNFRSF1A as well as with the clinical symptoms of recurrent fever and abdominal pain. Impaired shedding of TNFRSF1A after phorbol myristate acetate stimulation was detected in blood granulocytes and monocytes from the 3 adult family members with the mutation, but in the child bearing the mutation and showing clinical symptoms of recent onset, the shedding defect was less marked. CONCLUSION: TRAPS should be suspected in any patient who presents with a history of intermittent fever accompanied by unexplained abdominal pain, arthritis, or skin rash, particularly in the presence of a family history of such symptoms. Screening for low serum levels of soluble TNFRSF1A identifies individuals who are likely to have TNFRSF1A mutations.     

Clinical and laboratory characteristics of Finnish lupus erythematosus patients with cutaneous manifestations

Our objective was to characterize clinical features, laboratory findings, concomitant autoimmune diseases, and smoking habits of lupus erythematosus subgroups in genetically homogeneous patients from two Dermatology Departments of Finnish University hospitals. One hundred and seventy eight discoid lupus erythematosus, 55 subacute cutaneous lupus erythematosus, and 77 systemic lupus erythematosus patients were enrolled using patients' charts from institutional database (1995-2006) and during routine control visits. Clustering analysis was performed to reveal natural groupings. Smoking at the onset of disease was significantly more common in all subgroups (57% for discoid lupus erythematosus, 35% for subacute cutaneous lupus erythematosus, and 34% for systemic lupus erythematosus) compared with the age/gender-matched prevalence in the Finnish population, suggesting smoking to be a trigger factor for cutaneous lupus. Leukopenia (38%) and lymphopenia (52%) were observed more often in patients with systemic lupus erythematosus than reported previously. Photosensitivity characterized all groups, especially patients with subacute cutaneous lupus erythematosus (87%). Of the autoimmune diseases, Sj?gren's syndrome was the most common (22% of patients with systemic lupus erythematosus), followed by autoimmune thyroid disease (13% of patients with subacute cutaneous lupus erythematosus). The clustering analysis showed environmental factors (smoking) to be more involved in disease development in discoid lupus erythematosus, whereas immunological factors were more significant in initiating systemic lupus erythematosus. The high prevalence of autoimmune thyroid disease, together with photosensitivity, and the clustering profiles suggest that lupus erythematosus subtypes, especially discoid lupus erythematosus, are heterogeneic in their pathomechanisms.     

Presence of α -Naphthyl Acetate Esterase Activity in Human Haematopoietic Cell Lines and in Fresh Biopsy Specimens of Lymphoma and Myeloma

We have previously shown that non-proliferating human T- but not B-lymphocytes contain demonstrable amounts of acid α-naphthyl acetate esterase (ANAE). The usefulness of this histochemical marker for the diagnosis and classification of malignant lymphoid tumors was investigated by use of a panel of established normal and malignant human haematopoietic cell lines and fresh biopsy cells from malignant lymphomas and myelomas. The results showed that not only the T-cell derived acute leukaemia lines, but also histiocytic lymphoma and myeloma lines and some of the lymphoma (Burkitt and lymphocytic) and non-neoplastic lymphoblastoid cell lines with B-cell surface markers expressed strong ANAE reactivity. Some but not all of the immunoglobulin producing myeloma and lymphocytic lymphoma biopsies were ANAE-positive. Inhibition experiments with sodium fluoride and E-600 demonstrated that although the T-lymphocyte specific esterase is predominantly of ‘A’-type, the malignant lines contain also non-specific ‘B’ esterase and pseudocholinesterase. As the presence of the various esterases did not demonstrate any specific distribution pattern among he haematopoietic cell lines of different origin, we concluded that the ANAE marker is no longer T-specific when malignant lymphoid cells are considered, and that the usefulness of this marker in routine diagnostic work therefore is limited.