Maximizing worksite survey response rates through community organization strategies and multiple contacts

BACKGROUND. Worksites are natural settings for health promotion. In many cases, the effectiveness of such interventions is appraised by surveying employees to assess worksite-wide changes in the targeted behavior. Little attention has been paid to increasing worksite survey response rates. One way is to utilize community organization strategies, which involve enlisting the individuals within a group to work together with researchers to affect the social environment. METHODS. Community organization strategies and multiple contacts were used to obtain responses from employees in five worksites involved in a smoking cessation project. Employee Advisory Board members in each worksite reviewed, adapted, and revised the survey distribution method, the messages that accompanied the survey, and the survey content. Three major survey waves were undertaken: a worksite effort, a home mailing (in the pilot worksite only), and a telephone call to nonrespondents. RESULTS. Response rates to a worksite-wide survey in one worksite the first year and four additional worksites the next year yielded 99.3% and 98.4% response rates, respectively. In the pilot worksite, 273 employees were eligible for the survey with 366 eligible employees in the four other worksites. Chi-square or analysis of variance computations were used, as appropriate, to test for differences in characteristics of respondents in the various data collection waves. DISCUSSION. These results suggest that there may be merit in adapting such community organization intervention methods for research applications.     

The interaction between fluoropyrimidines and methotrexate,and [14C]-formate incorporation into nucleic acids and protein

Summary Changes are reported in [¹⁴C]-formate incorporation into nucleic acids and protein of Ehrlich ascites tumor cells during exposure to methotrexate (MTX) and fluoropyrimidines. The rate of [¹⁴C]-formate incorporation into RNA, DNA, and protein in the presence of only MTX was inhibited by 82%, 91%, and 75% respectively, when compared with control rates. However, in the presence of 5-fluorodeoxyuridine (FdUrd) plus MTX, formate incorporation into RNA, DNA, and protein was inhibited by 67%, 85%, and 66%. Incubation of cells in vitro with [³H]-dihydrofolate (DHF) results in its rapid conversion to [³H]-tetrahydrofolate (THF). The THF/DHF ratio from the soluble fraction of cells that were incubated with [³H]-DHF was 43% greater in the presence of FdUrd and MTX than in the presence of MTX alone. As the rate of [³H]-dUrd incorporation into DNA was reduced by 88% and 99% by pretreating cells with 0.1 M and 1 M FdUrd, respectively, the inhibitory effect of MTX on [¹⁴C]-formate incorporation into (a) RNA was decreased by 63% and 46%; (b) DNA was decreased by 74% and 61%; and (c) protein was decreased by 63% and 32%. These data suggest that fluoropyrimidines can antagonize the effects of MTX on purines or nucleic acid synthesis and protein synthesis by preventing the consumption of THF for dTMP synthesis.The abbreviations used are MTX methotrexate - FdUrd 5-fluorodeoxyuridine - Fura 5-fluorouracil - FdUMP 5-fluorodeoxyuridine monophosphate - dUrd deoxyuridine - dUMP deoxyuridine monophosphate - dTMP thymidylate - DHF dihydrofolate - THF tetrahydrofolate - 5,10-CH₂THF 5,10-methylene tetrahydrofolate - DHFR dihydrofolate reductase     

Modulation of tissue immunogenicity by organ culture. Comparison of adult islets and fetal pancreas

Uncultured mouse islet allografts (BALB/c to CBA) are rejected 2 to 4 weeks after transplantation. Allografts, cultured in 95% O2 and 5% CO2 for 7 days before transplantation, show no sign of rejection up to 3 months post-transplantation. However, the cultured allografts are rejected if the CBA recipient is given an i.v. injection of 10(5) peritoneal cells at the time of transplantation. Organ culture of BALB/c fetal pancreas (16 to 17 days gestation) under the same conditions failed to prevent allograft rejection. The immunogenicity of fetal pancreas is reduced if this tissue is cultured in 95% O2 and 5% CO2 for 17 days before transplantation.     

Evidence for the role of luteinizing hormone in Alzheimer disease

Epidemiological and experimental data supporting a role for luteinizing hormone in Alzheimer disease is accumulating. Paralleling the female predominance for developing Alzheimer disease, luteinizing hormone levels are significantly higher in females as compared to males and luteinizing hormone levels are higher still in individuals who succumb to Alzheimer disease. Importantly, luteinizing hormone, which is capable of modulating cognitive behavior, is not only present in the brain, but also has the highest receptor levels in the hippocampus, a key processor of cognition that is severely deteriorated in Alzheimer disease. These findings, together with data indicating that luteinizing hormone modulates amyloid-beta protein precursor processing in vivo and in vitro, suggests that luteinizing hormone may contribute to Alzheimer disease pathology through an amyloid-dependent mechanism. Indeed, abolishing luteinizing hormone, using a potent gonadotropin-lowering agent, leuprolide acetate, in the amyloid-beta protein precursor transgenic mice improved hippocampally-related cognitive performance and decreased amyloid-beta deposition. These promising findings support the importance of luteinizing hormone in Alzheimer disease and bring to the forefront an alternative, and much needed therapeutic avenue for the treatment of this insidious disease.     

Etiology of acute myeloid leukemia in the elderly

The biologic and epidemiologic study of acute myeloid leukaemia (AML) in the elderly is in its infancy. Most epidemiologic data attempting to ascertain the etiology of AML have been obtained from younger cohorts or patients with therapy-related AML. The increasing prevalence of deletional and complex karyotypes in elderly AML patients implies a cumulative genotoxicity over time for this subgroup, given the similar spectrum of abnormalities following exposure to known genotoxic agents such as alkylating chemotherapeutic drugs. Exposure to benzene, radiation, and tobacco smoke are clear but weak risk factors for AML. Polymorphic variants in several genes responsible for genomic protection and integrity are now also weak risk factors for AML. Future epidemiologic studies should correlate exposure data with well-defined biologic subtypes of AML.     

Neuropathology of Alzheimer disease: pathognomonic but not pathogenic

Neuropathological changes in subjects with dementia are, by definition, end-stage phenomena. While such changes allow case characterization and lend themselves to disease classification and modeling, the lesions themselves are not etiological. This truth would appear to be self-evident, yet the medical and scientific literature suggests otherwise. Indeed it is now customary to view amyloid plaques in Alzheimer disease as primary etiological, neurotoxic lesions and, hence, removing them (e.g., by immunotherapy) is believed to lead to clinical improvement. The foundation for this line of thinking lies in the existence of rare kindreds with mutations in amyloid-β, or mutations believed to be involved in the processing of amyloid-β, and then the extrapolation of the inherited condition to sporadic disease. We believe that this overall construct ignores early events that are more critical to onset and progression of sporadic disease. Likewise, we have studied subjects with sporadic Alzheimer disease, as well as early onset familial Alzheimer disease and Down’s syndrome, over a spectrum of ages, and have found that markers of oxidative stress precede amyloid deposits in all three conditions. Amyloid and neurofibrillary pathology in the Alzheimer brain show a decrease in oxidative stress relative to vulnerable but morphologically intact neurons, suggesting that neurodegenerative lesions are compensatory phenomena, and thus manifestations of cellular adaptation. The pathology of neurodegenerative diseases should be viewed as the end-stage consequence, as opposed to cause, of the disease processes, so that early disease processes that are amenable to intervention can be properly recognized and treated.Drs. Rudy J. Castellani and Hyoung-gon Lee contributed equally to this work.     

A novel mitochondrial transfer RNA(Asn) mutation causing multiorgan failure

BACKGROUND: Mitochondrial cytopathies are a heterogeneous group of disorders with a broad spectrum of clinical symptoms. OBJECTIVE: To characterize a novel mutation in the transfer RNA(Asn) (m.5728A>G) identified in a 13-year-old boy with multiorgan failure. DESIGN: Biochemical and immunocytochemical studies were performed in combination with transmitochondrial cybrid analysis. SETTING: A university hospital. Molecular and biochemical analyses were performed in collaboration between 2 other university hospitals. PATIENT: Thirteen-year-old boy with multiorgan failure. RESULTS: In the patient's muscle tissue and cultured skin fibroblasts, a combined deficiency of complexes I and IV was found, using spectrophotometric analysis and activity staining in the gel following blue native polyacrylamide gel electrophoresis. An identical biochemical profile was seen in transmitochondrial cybrids carrying more than 55% mutant mitochondrial DNA. CONCLUSION: These data suggest that the m.5728A>G transition is a pathogenic mutation and is the cause of the respiratory chain dysfunction in the propositus.     

Neurone specific regulation of dendritic spines in vivo by post synaptic density 95 protein (PSD-95)

Post synaptic density protein 95 (PSD-95) is a postsynaptic adaptor protein coupling the NMDA receptor to downstream signalling pathways underlying plasticity. Mice carrying a targeted gene mutation of PSD-95 show altered behavioural plasticity including spatial learning, neuropathic pain, orientation preference in visual cortical cells, and cocaine sensitisation. These behavioural effects are accompanied by changes in long-term potentiation of synaptic transmission. In vitro studies of PSD-95 signalling indicate that it may play a role in regulating dendritic spine structure. Here, we show that PSD-95 mutant mice have alterations in dendritic spine density in the striatum (a 15% decrease along the dendritic length) and in the hippocampus (a localised 40% increase) without changes in dendritic branch patterns or gross neuronal architecture. These changes in spine density were accompanied by altered expression of proteins known to interact with PSD-95, including NR2B and SAP102, suggesting that PSD-95 plays a role in regulating the expression and activation of proteins found within the NMDA receptor complex. Thus, PSD-95 is an important regulator of neuronal structure as well as plasticity in vivo.