Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium

OBJECTIVE: To localize vascular endothelial growth factor C (VEGF-C) and VEGF-D in synovial specimens in relation to their VEGFR-2 and VEGFR-3 receptors in blood and lymphatic vessels. METHODS: Immunohistochemical staining and messenger RNA analysis from control and arthritic synovial membrane specimens. RESULTS: Quantitative RT-PCR disclosed that VEGF-C mRNA copy numbers were higher than VEGF-D mRNA copy numbers in the rheumatoid arthritis (RA), osteoarthritis, and control patient groups studied (p < 0.01). Immunohistochemical staining localized VEGF-C to synovial lining cell layer, pericytes, and smooth muscle cells of blood vessels. The number of VEGF-C positive cells was increased in the synovial lining of ankylosing spondylitis (AS) and RA compared to control synovium. However, in contrast to control synovial lining, little if any VEGF-D was detected in AS or RA synovial lining. VEGFR-2 expressing stromal blood vessels, also positive for the vascular endothelial marker PAL-E and the basement membrane marker laminin, were more abundant in RA and AS than in controls. Interestingly, the lymphatic endothelial receptor VEGFR-3 was also expressed in most synovial vessels, especially in the sublining capillaries and venules. CONCLUSION: VEGF-C is strongly expressed in the hypertrophic synovial lining of arthritic joints, whereas VEGF-D expression is very low in AS and RA. The expression of VEGF-C and VEGF-D in pericytes and smooth muscle cells suggests that these factors may have a role in maintaining vascular homeostasis. The VEGF receptors VEGFR-2 and VEGFR-3 are present in most of the sublining blood vessels. The expression of the lymphatic marker VEGFR-3 in the sublining blood vessels may relate to fluid filtration and/or fenestrations. The relatively few lymphatic vessels along with increased vascular permeability in RA may contribute to the development of tissue edema and joint stiffness.     

Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study

Aims/hypothesis  

We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors.     

Body mass index, waist circumference, and waist-hip ratio on the risk of total and type-specific stroke

BACKGROUND: Adiposity is an established risk factor for cardiovascular disease, but the relationship of adiposity with the risk of cerebrovascular disease is still to some extent unclear. METHODS: We prospectively investigated the association of different indicators of adiposity (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared], waist circumference, and waist-hip ratio) with total and type-specific stroke incidence among 49 996 Finnish participants who were aged 25 to 74 years and free of coronary heart disease and stroke at baseline. RESULTS: During a 19.5-year follow-up, 3228 people developed an incident stroke event (674 hemorrhagic and 2554 ischemic). Compared with normal-weight men (BMI, 18.5-24.9), the multivariate-adjusted (age, study year, smoking, physical activity, educational level, family history of stroke, and alcohol drinking) hazard ratios among lean (BMI, < 18.5), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) men were 0.74 (95% confidence interval [CI], 0.18-2.96), 1.23 (95% CI, 1.10-1.37), and 1.59 (95% CI, 1.37-1.83) for total stroke, and 0.49 (95% CI, 0.07-3.50), 1.27 (95% CI, 1.12-1.44), and 1.70 (95% CI, 1.45-2.00) for ischemic stroke, respectively. Among women, the corresponding hazard ratios were 1.87 (95% CI, 1.12-3.14), 1.08 (95% CI, 0.95-1.22), and 1.30 (95% CI, 1.14-1.50) for total stroke, and 1.81 (95% CI, 0.97-3.41), 1.11 (95% CI, 0.96-1.28), and 1.41 (95% CI, 1.21-1.64) for ischemic stroke. Abdominal adiposity, defined as the highest quartile of waist circumference or waist-hip ratio, was associated with a greater risk of total and ischemic stroke in men but not in women. CONCLUSIONS: Body mass index was a risk factor for total and ischemic stroke in men and women. Abdominal adiposity was a risk factor for total and ischemic stroke only in men.     

Knowledge of memory aging and Alzheimer's disease in college students and mental health professionals

In this study, college students and mental health professionals completed the Knowledge of Memory Aging Questionnaire, Alzheimer's Disease Knowledge Test and the Fraboni Scale of Ageism before and after a lecture on normal and pathological memory issues in adulthood. Results confirmed that professionals were more knowledgeable about memory aging and Alzheimer's disease (AD) and less ageist than college students. Analyses of pre- and post-lecture response accuracy yielded comparable benefits in memory aging and AD knowledge for both groups. Correlation analyses provided modest evidence for the influence of ageist attitudes on the knowledge measures. Implications for memory education programs and psychology curriculum are considered.     

Expression of the Ste20-like kinase SLK during embryonic development and in the murine adult central nervous system

Cell growth and terminal differentiation are controlled by complex signaling cascades that regulate the expression of specific subsets of genes controlling cell fate and morphogenic processes. We have recently cloned and characterized a novel Ste20-like kinase termed SLK (Sabourin et al., Mol. Cel. Biol. 20 (2000) 684). However, the specific function of SLK is poorly understood. To gain further insights into the role of SLK we have characterized its activity, expression and distribution in the CNS during embryonic development and in the adult brain. Although SLK is expressed ubiquitously in adult tissues, our results show that it is expressed preferentially in neuronal lineages during development. We find that SLK is preferentially expressed in the neurons and neuroepithelium of the developing embryo and can be detected at 10.5 and 12.5 days post-coitum (dpc) in the forebrain, midbrain and hindbrain of the developing CNS. At later stages (14.5 dpc), SLK is expressed in the hypothalamus region, all layers of the neural tube, dorsal root ganglion and in the proliferating ependymal layers. Surprisingly, following middle cerebral artery occlusion, SLK expressing neuronal cells are lost and SLK is localized to phagocytic macrophages/microglia. These results suggest a functional role for SLK in early neuronal development as well as in the adult CNS.     

A case of mononucleosis complicated by acute nephritis

We report a case of mononucleosis in a 30-year old female patient which was complicated by acute, moderate renal failure presumably due to interstitial nephritis.     

Genetic regulation of growth from birth to 18 years of age: The Swedish young male twins study

Growth is a complex process, and only little is known on the genetic regulation of it. We analyzed the effect of genetic and environmental factors on growth in a longitudinal Swedish cohort of 231 monozygotic and 144 dizygotic twin pairs born 1973–1979 with length or height measured annually from birth to age 18. The data were analyzed by two different multivariate variance component models for twin data using the Mx statistical package. At birth and 1 year of age, a substantial part of the variation in length was because of common environment (50 and 57%, respectively) and the effect of genetic factors was minor. After 2 years of age, 91–97% of the variation of height could be explained by genetic differences whereas the rest was because of environmental variation not shared by twins. The genetic correlation between heights at ages 2 and 18 was 0.73 (95% confidence intervals 0.68–0.77) showing that 53% of the genes affecting height at these ages are the same or closely linked; with increasing age the correlation with genetic effects at age 18 become subsequently stronger. Especially in mid‐childhood, growth was largely regulated by the same genetic factors. During puberty new genetic factors started to affect height, but also genetic variation affecting height at previous ages remained. These results suggest that genetic regulation of growth is rather uniform, which is encouraging for further efforts to identify genes affecting growth. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.