Hippocampal expression of the calcium sensor protein visinin-like protein-1 in schizophrenia

Hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. Amongst the chemical components being abnormal in brains of schizophrenics are altered calcium concentrations and reduced expression of the neurotrophin receptor, trkB. We studied by immunohistochemical methods the distribution of visinin-like protein-1 (VILIP-1), which is a calcium sensor protein and at the same time a trkB mRNA binding protein, in hippocampi of nine schizophrenic patients and nine matched control subjects. In normal hippocampi VILIP-1 immunoreactivity was found in multiple pyramidal cells and interneurons. A portion of VILIP-1 immunoreactive interneurons co-express calretinin (60%) and parvalbumin (<10%). In schizophrenics fewer pyramidal cells but more interneurons were immunostained. Our data point to an involvement of the protein in the altered hippocampal circuitry in schizophrenia.     

Mammography uptake predictors in older women

BACKGROUND: In women aged under 65 years, socio-economic factors and general health behaviours are important predictors of mammography uptake. Little is known about whether these factors are important in older women. OBJECTIVE: To examine a broad range of mammography uptake predictors in women aged 65 and older registered with a London (UK) practice. METHODS: A survey of all female patients aged 65 and over (n = 613) in a south London practice included questions on mammography and cervical screening, general health and functional ability, socio-economic factors, mental health, health behaviours, and attitudes to health. Associations between mammography uptake and other factors were examined using logistic regression. RESULTS: The response rate was 70% (432/613). Increased age was strongly associated with decreased mammography uptake. Additionally, socio-economic factors and general health behaviours (previous cervical smear, drinking alcohol and being a non-smoker) were independently predictive of mammography uptake. Measures of physical and mental health and health attitudes were not independent predictors. Restricting analyses to the oldest women, outside the national screening programme, gave very similar results. CONCLUSIONS: In this sample of older women, socio-economic factors and general health behaviours were more predictive of mammography uptake than measures of physical and mental health or attitudes to health. Knowledge of these predictors is of increasing importance as the screening programme in the UK is extended up to age 70.     

Immunogenicity of anti-Haemophilus influenzae type b CRM197 conjugate following mucosal vaccination with oligodeoxynucleotide containing immunostimulatory sequences as adjuvant

Most vaccines are delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to a reduction of mucosal colonization and of contaminated syringes. However, most vaccines are unable to induce immune responses when administered mucosally, and require the use of strong adjuvant or effective delivery systems. Synthetic oligodeoxynucleotides (ODN) containing CpG immunostimulatory sequences (ISS) have been shown to act as potent adjuvants of type-1 immune responses also when mucosally co-administered with protein or peptide vaccines. We have shown that ISS can increase the anti-polysaccharide polyribosyl ribitol phosphate (PRP) antibody titres and anti-diphtheria toxin neutralizing antibody, if used as adjuvant of anti-Haemophilus influenzae type b (Hib) PRP vaccine conjugated with cross-reacting material (CRM) of diphtheria toxin in mice. Here, we show that ISS have the potential to increase host local and systemic antibody response against both the PRP and the protein component of a conjugated vaccine when mucosally administered in mice. Mucosal administration of Hib-CRM vaccine induced anti-PRP and neutralizing anti-diphtheria toxin antibodies of all the IgG subclasses, with a predominance of type-1 immune response-associated IgG2a and IgG3. At odds with systemic administration, the mucosal delivery of Hib-CRM induced anti-PRP and anti-diphtheria toxin mucosal IgA. These data envisage the feasibility of a mucosal vaccination with an already licensed Hib-CRM vaccine to achieve both an anti-H. influenzae and -diphtheria effective protection.     

Oxidised mannan-listeriolysin O conjugates induce Th1/Th2 cytokine responses after intranasal immunisation

Clearance of infectious organisms does not always require polarised Th1 or Th2 responses and it may be advantageous for both Th1 and Th2 responses to be elicited for effective protection against an invading pathogen. It was the aim of this study to investigate oxidised mannan as a possible Th1/Th2 adjuvant. Oxidised mannan was conjugated to two candidate antigens and delivered intranasally to mice. Immunisation with the oxidised conjugate resulted in significant antigen specific proliferative responses, IL-2, IFN-gamma and IL-4 production when compared to unconjugated controls.     

Effects of walnut consumption as part of a low-fat,low-cholesterol diet on serum cardiovascular risk factors

Serum components, such as lipoproteins, coagulation factors (factor VII, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), fibrinogen), and homocysteine have been associated with cardiovascular disease. Dietary intervention with a low-fat, low-cholesterol diet has favorably influenced cardiovascular disease and certain food, specifically the consumption of nuts, has been associated with reduced cardiovascular risks. The effects of walnuts, as part of a low-fat, low-cholesterol diet, on serum cardiovascular risk factors were determined. Sixty-seven (67) outpatients with borderline high total cholesterol following a low-fat, low-cholesterol diet for six weeks before being randomly assigned to continue the diet or have 64 grams/day of walnuts in conjunction with the diet. After six weeks, the patients' diets were switched. Therefore, all patients consumed 64 grams/day of walnuts for six weeks during part of the trial as part of a low-fat, low cholesterol diet. Serum lipids demonstrated a significant reduction in triacyglycerols and favorable trend with decreases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and a slight increase in high-density lipoprotein (HDL) cholesterol. No statistical effects on homocysteine or the coagulation factors were observed. However, there was a slight favorable trend for tPA and PAI-1. This study demonstrated that walnuts, when consumed as part of a low fat, low-cholesterol diet, have a beneficial effect on serum cardiovascular risk factors. However, these changes may not explain all of the beneficial effects that walnut consumption has on cardiovascular disease.     

Helping tomorrow's doctors to gain a population health perspective - good news for community stakeholders

INTRODUCTION: The modernising agenda of the NHS and recommendations of professional bodies demand that all doctors achieve a basic understanding of a population health perspective. The principle of integrated learning and the logistics of provision make it inappropriate for such learning to be delivered solely by public health specialists, and community-based learning has been promoted as the best setting in which to assist this objective. However, there is little evidence from practice as to whether non-specialist staff are willing or able to play a role in orienting tomorrow's doctors to the needs of communities. METHODS: Semi-structured interviews, questionnaires and focus groups iterated the opinion of key stakeholders on their preferred contributions to community-oriented undergraduate medical education. Framework analysis was used to elicit key outcomes and process factors. RESULTS: There was consensus that community-based learning should be a core element of the medical curriculum as it can demonstrate the socioenvironmental context of care and the doctor's role in interagency working and preventive care. Effective academic/NHS partnerships were called for, with higher education leading the agenda on aims and objectives, creating collaborative structures, and reallocating resources to support new learning. Community-based stakeholders would offer the translation of theory into practice by demonstrating clinical and social diversity, models of teamworking, and a context for the application of prior learning. They also promoted recurrent contact with communities, and suggested an enhanced role in mentoring students through longer term relationships. CONCLUSION: Community-based personnel and NHS users are an under-used resource for medical education. Their proposed contributions strongly accord with the agenda for a population health perspective in basic training. Curriculum planners need to make long-term partnerships with community-based agencies, rather than using them as an intermittent provider of limited learning sessions with narrowly defined objectives.     

Changing incidence of non-Hodgkin lymphomas in the United States

BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has been rising in many regions and populations during the last few decades. Data from the Surveillance, Epidemiology, and End Results (SEER) Program show that age-adjusted rates of NHL increased through the 1980s but leveled off in the 1990s. METHODS: To determine whether the incidence of NHL stabilized in all population subgroups, particularly in age-defined groups with distinctive risks of NHL, the authors investigated trends in NHL incidence among persons aged 0-14 years, 15-24 years, 25-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years, and > 75 years by gender and race using 1973-1998 data from the SEER Program, which covered approximately 10% of the U.S. population. Joinpoint regression was used to assess changes in trends across the period. RESULTS: NHL incidence trends changed significantly among males aged 25-54 years, in whom rates began to decrease (6-16% per year) in the middle to late 1990s, as well as among most whites aged > or = 55 years, in whom rate increases slowed from 3-4% to 1-2% per year in the late 1980s. Incidence trends were steady in other groups, with uniform increases among whites aged 15-24 years (2-3% per year), women aged 25-54 years (1-6% per year), and blacks aged > or = 55 years (2-4% per year). Although recent age specific incidence rates were generally higher in males compared with females and in whites compared with blacks, among males aged 25-54 years, rates were significantly higher in black males compared with white males. CONCLUSIONS: There have been changes in the demographic groups impacted by NHL. The trends for human immunodeficiency virus probably are related to recent decreases in NHL incidence among males aged 25-54 years. The rate change in the older white population is unexplained but represents both an alleviation of the burden of NHL in this population and a potential opportunity to generate hypotheses regarding risk factors for the development of NHL.     

BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases

The anti-apoptotic molecules BCL-x(L) and BCL2 delay cell cycle entry from quiescence. We used serum induction and induction of a Myc-estrogen receptor fusion protein (MycER) in quiescent fibroblasts to investigate the mechanisms underlying the cell cycle activity of BCL-x(L) and BCL2. We demonstrate for the first time that BCL-xL and BCL2 delayed serum-induced and Myc-induced, but not E2F-induced, cell cycle entry. The cyclin-dependent kinase inhibitor p27 was elevated during serum deprivation and cell cycle entry in BCL-x(L) or BCL2-expressing NIH3T3 cells and a Rat1MycER cell line. Activation of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4) were delayed during progression to S phase, while the induction of cyclin D1 protein, as well as the levels of cyclin E, cdk2, and cdk4 were unaltered by BCL-x(L) or BCL2. Inhibition of cyclin/cdk activities in BCL-x(L) or BCL2 expressing cells was associated with excess p27 in the cyclin/cdk complexes. Neither BCL-x(L) nor BCL2 delayed S phase entry in cells deficient in p27, thus p27 is required for the cell cycle function of BCL-x(L) and BCL2. The cell cycle effects of BCL-x(L) and BCL2 were more profound in Myc-induced than in serum-induced cell cycle entry. Our results suggest that one possible mechanism by which BCL-x(L) and BCL2 delay cell cycle entry may be the inhibition of Myc activity through the elevation of p27.