The continuity of physical activity--a retrospective and prospective study among older people

This study investigated the continuity of life‐span physical activity by examining the predictors of the maintenance of a high level of physical activity over 8 years among subjects aged 65–84 years at the baseline, in 1988, in Jyväskylä, Finland. Age, education, marital status and chronic conditions and past physical activity were studied at the baseline. In men and women, self‐reported competitive sport participation from as early as 10–19 years of age was a significant predictor for maintaining activity in old age. Also women’s participation in recreational sports at the age of 40–64 years predicted activity. We concluded that past physical activity is strongly connected to maintaining a high level of physical activity in old age regardless of chronic conditions that may develop.     

Low cdc27 and high securin expression predict short survival for breast cancer patients

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase–anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow‐up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti‐mitotic drug development.     

Histamine H(1) and H(3) receptors in the rat thalamus and their modulation after systemic kainic acid administration

In rat thalamus, histamine H(1) receptor and isoforms of H(3) receptor were expressed predominantly in the midline and intralaminar areas. Correspondingly, higher H(1) and H(3) receptor binding was also detected in these areas. All isoforms of H(3) receptor were expressed in several thalamic nuclei, but there were minor differences between their expression patterns. H(1) mRNA expression was high in the ventral thalamus, but the H(1) binding level was low in these areas. Since increased brain histamine appears to have an antiepileptic effect through the H(1) receptor activity, kainic acid (KA)-induced status epilepticus in rat was used to study modulation of H(1) and H(3) receptors in the thalamus following seizures. After systemic KA administration, transient decreases in mRNA expression of H(1) receptor and H(3) receptor isoforms with full-length third intracellular loops were seen in the midline areas and the H(1) receptor mRNA expression also decreased in the ventral thalamus. After 1 week, a robust increase in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop was found in the ventral posterior, posterior, and geniculate nuclei. The changes indicate a modulatory role of H(3) receptor in the sensory and motor relays, and might be involved in possible neuroprotective and compensatory mechanisms after KA administration. However, short-term increases in the H(3) receptor binding appeared earlier (72 h) than the increases of H(3) mRNA expression (1-4 w). The elevations in H(3) binding were evident in the intralaminar area, laterodorsal, lateral posterior, posterior and geniculate nuclei, and were likely to be related to the cortical and subcortical inputs to thalamus.     

Pain- and morphine-associated transcriptional regulation of neuropeptide FF and the G-protein-coupled NPFF2 receptor gene

Neuropeptide FF (NPFF) is involved in pain modulation, especially plasticity during inflammatory and neuropathic pain, and opiate interactions. Its nociceptive functions may be mediated by the NPFF2 receptor. To elucidate the role of the NPFF system in plasticity associated with pathologic pain, we studied the changes of NPFF mRNA and NPFF2 receptor mRNA in rat models of acute colonic inflammation, inflammatory pain, and neuropathic pain. Furthermore, we studied the mRNA levels of both NPFF and NPFF2 receptor in morphine-tolerant rats and after acute morphine injections. We found an activation of spinal NPFF and NPFF2 receptor during early inflammatory pain. Supraspinally, we found an up-regulation of NPFF2 receptor mRNA during acute colonic inflammation and neuropathic pain. Acute, but not chronic, morphine activated the genes supraspinally. The results give further evidence for the involvement of the NPFF system in pain modulation and may provide new therapeutic opportunities for pathologic pain.     

Underlying factors in the association between depressed mood and mobility limitation in older people

BACKGROUND: Depressed mood may either precede mobility limitation or follow from mobility limitation. OBJECTIVE: To compare mood status among people with manifest mobility limitation, those with preclinical mobility limitation and those without mobility limitation and investigate factors explaining the association between depressed mood and mobility limitation. DESIGN: Cross-sectional. Subjects: 645 community-living 75- to 81-year-old people. METHODS: Depressed mood was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D, cut-off score 16); difficulty walking 500 m was assessed by self-report. Those reporting difficulty were categorised as having manifest mobility limitation. Those with no difficulty but reporting task modifications, such as reduced frequency of walking, were categorised as having preclinical mobility limitation. The association between depressed mood and mobility limitation was analysed using logistic regression analysis with gender, age, economic situation, the availability of a confidant, chronic conditions, and widespread pain as covariates. RESULTS: Depressed mood was found in 34% of subjects with manifest mobility limitation, in 26% of those with preclinical mobility limitation, and in 13% of those without mobility limitation. The unadjusted odds ratio for depressed mood was 3.43 (95% CI 2.04-5.76) among subjects with manifest mobility limitation and 2.38 (95% CI 1.52-3.73) among those with preclinical mobility limitation, compared to those without mobility limitation.Adjustment for covariates reduced the risks to 2.10 (95% CI 1.15-3.82) and 1.99 (95% CI 1.24-3.20), respectively. Widespread pain explained 28% of the increased risk of depressed mood among those with manifest mobility limitation. CONCLUSION: The dose-response relationship between depressed mood and mobility limitation suggests that both conditions may progress simultaneously and may share aetiology, at least in part. Pain may be an underlying factor in both depressed mood and mobility limitation.     

Nicotine use and dependence and their association to psychiatric disorders in a large sample of adolescent psychiatric inpatients

The purpose of this research was to evaluate the level of nicotine dependence (ND) and to examine its association to psychiatric disorders in a representative clinical sample of adolescent psychiatric inpatients. The modified Fagerstrom Tolerance Questionnaire (mFTQ) was used to assess the level of ND. Psychiatric DSM-IV diagnoses were obtained by using the Schedule for affective disorder and schizophrenia for school-age children (K-SADS-PL). Of the total of 342 inpatients in the study sample, 259 (75.7%) reported to be current smokers. A sum score 6 or higher in the mFTQ, indicating a high level of ND, was found in 37.9% of all smokers. An increased likelihood for high level of ND was associated with substance related disorders (OR 5.1, 95% CI 2.8-9.3), conduct disorder and oppositional defiant disorders (OR 2.4, 95% CI 1.4-4.4). The usefulness of mFTQ in measuring ND among adolescent inpatients is apparent. Therefore, it can be recommended to be used as a routine screening instrument for ND among adolescents hospitalized due to psychiatric disorders.     

EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer

Background:

Only 40–70% of metastatic colorectal cancers (mCRCs) with wild-type (WT) KRAS oncogene respond to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. EGFR amplification has been suggested as an additional marker to predict the response. However, improved methods for bringing the EGFR analysis into routine laboratory are needed.

Methods:

The material consisted of 80 patients with mCRC, 54 of them receiving anti-EGFR therapy. EGFR gene copy number (GCN) was analysed by automated silver in situ hybridisation (SISH). Immunohistochemical EGFR protein analysis was used to guide SISH assessment.

Results:

Clinical benefit was seen in 73% of high (⩾4.0) EGFR GCN patients, in comparison with 59% of KRAS WT patients. Only 20% of low EGFR GCN patients responded to therapy. A high EGFR GCN number associated with longer progression-free survival (P<0.0001) and overall survival (P=0.004). Together with KRAS analysis, EGFR GCN identified the responsive patients to anti-EGFR therapy more accurately than either test alone. The clinical benefit rate of KRAS WT/high EGFR GCN tumours was 82%.

Conclusion:

Our results show that automated EGFR SISH, in combination with KRAS mutation analysis, can be a useful and easily applicable technique in routine diagnostic practise for selecting patients for anti-EGFR therapy.     

Histamine in brain development and tumors

Histamine is found in developing mammalian brain in both neurons and mast cells. Under normal conditions, histamine H1 and H2 receptors are found in neural, glial and endothelial cells, and H3 receptors at least on neurons. Experimental brain tumors display both H1 and H2 receptors, and histamine increases permeability in the tumors and in the neighboring areas. Many studies have addressed histaminergic signalling mechanisms in cell lines originating from brain tumors. However, the role of histamine in normal development of brain structures, proliferation and differentiation of neurons and glial cells, and growth of malignant tumors in situ is still poorly understood.