Pancreatic expression of keratinocyte growth factor leads to differentiation of islet hepatocytes and proliferation of duct cells.
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Keratinocyte growth factor, (KGF), a member of the fibroblast growth factor (FGF) family, is involved in wound healing. It also promotes the differentiation of many epithelial tissues and proliferation of epithelial cells as well as pancreatic duct cells. Additionally, many members of the highly homologous FGF family (including KGF), influence both growth and cellular morphology in the developing embryo. We have previously observed elevated levels of KGF in our interferon-gamma transgenic mouse model of pancreatic regeneration. To understand the role of KGF in pancreatic differentiation, we generated insulin promoter-regulated KGF transgenic mice. Remarkably, we have found that ectopic KGF expression resulted in the emergence of hepatocytes within the islets of Langerhans in the pancreas. Additionally, significant intra-islet duct cell proliferation in the pancreata of transgenic KGF mice was observed. The unexpected appearance of hepatocytes and proliferation of intra-islet duct cells in the pancreata of these mice evidently stemmed directly from local exposure to KGF. (+info)
Prolactin receptor expression in the developing human prostate and in hyperplastic, dysplastic, and neoplastic lesions.
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In situ hybridization and immunohistochemistry were used to localize and compare the expression of the long form of the human prolactin receptor in fetal, prepubertal, and adult prostate. Results were then compared with hyperplastic, dysplastic, and neoplastic lesions. Both receptor message and protein were predominately localized in epithelial cells of the fetal, neonatal, prepubertal, and normal adult prostate. In hyperplastic lesions the expression of the receptor was unchanged with respect to normal epithelial cells. Irrespective of grade, markedly enhanced expression of the receptor was evident in dysplastic lesions. In lower Gleason grade carcinomas the intensity of receptor signal at the message and protein levels approximated that found in normal prostatic epithelium. However, in foci within higher grade cancers, receptor expression appeared diminished. Results from our study suggest that prolactin action plays a role in the development and maintenance of the human prostate and may also participate in early neoplastic transformation of the gland. Diminution of receptor expression in high grade neoplasms could reflect the emergence of a population of cells that are no longer responsive to the peptide hormone. (+info)
Another set of responses and correlated responses to selection on age at reproduction in Drosophila melanogaster.
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Ageing is the decline in survival probability and fertility later in adult life. It can evolve through mutation accumulation and pleiotropy. Artificial selection by age at reproduction is a useful method for detecting the effects of pleiotropy, and for producing lines that differ in their rate of ageing for further analysis. However, the approach has encountered difficulties from gene-environment interaction and inadvertent selection. We have produced a new set of selection lines in Drosophila melanogaster, breeding from either 'young' or 'old' adults, and avoiding some of the difficulties present in previous studies. Breeding from older adults resulted in an evolutionary increase in survival but, contrary to all previous studies using this method, in no increase in late-life fertility. The increase in survival was accompanied by an evolutionary decline in fertility early in adult life, confirming the importance of pleiotropy in the evolution of ageing. Contrary to previous studies, there were no correlated responses to selection in the pre-adult period; development time, larval competitive ability and adult size achieved did not differ between the lines from the two selection regimes. (+info)
Exercise gas transport determinants in elderly normotensive and hypertensive humans.
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This study examined the effect of the phenylalkylamine calcium channel blocker verapamil, on resting left ventricular (LV) function and O2 uptake rate (VO2) during exercise at maximal and submaximal work rates. Nine older hypertensive (71 years; OH), 10 older sedentary normotensive (69 years; OS), 10 older active (71 years; OA) and 10 young (24 years; Y) individuals volunteered. Studies were completed in the control condition and 4-6 h following 240 mg verapamil SR per os. Resting LV systolic (fractional shortening; FS) and diastolic (early: late (E/A) flow velocity ratio and isovolumic relaxation time (IVRT) were measured by Doppler echocardiography. Maximal oxygen uptake (VO2,max) and, on subsequent test days, four transitions to and from a 6 min square wave exercise perturbation at a sub-anaerobic threshold intensity of 40 W (OH, OS, OA) or 100 W (Y) for determination of VO2 kinetics were performed on a cycle ergometer. Breath-by-breath VO2 transients were fitted with a monoexponential equation, starting at phase 2 of the response, while heart rate (HR) was fitted from phase 1, for the determination of the time constant of VO2 (tau VO2) and HR (tau HR). Baseline left ventricular FS was significantly greater in the OS (32%), OA (34%) and Y (34%) than in the OH (23%) groups, while E/A was significantly greater in the OA (1.16) and Y (2.34) than in the OH (0.9) and OS (0.82) groups (P < 0.05). Baseline VO2,max was higher and tau VO2 faster in the young (41.4 ml kg-1 min-1; 25.2 s) than in the older groups and in the OA (28.8 ml kg-1 min-1; 44.3 s) than in both OH (20.8 ml kg-1 min-1; 71.3 s) and OS (22.0 ml kg-1 min-1; 59.5 s) groups (P < 0.05). Heart rate kinetics showed similar differences to VO2 kinetics among the groups. After verapamil, no significant changes in FS, E/A or IVRT were observed in the OA and Y groups. In the OH group, FS (32%) and E/A (1.15) increased while IVRT decreased significantly (from 0.103 to 0.07; P < 0.05). In the OS group, only E/A increased significantly (0.82 to 1.0; P < 0.05). None of the exercise variables (VO2,max, tau VO2 or tau HR) were altered for the OA or Y groups. VO2,max increased (from 20.8 to 22.8 ml kg-1 min-1) in the OH and (from 22.0 to 24.1 ml kg-1 min-1) in the OS (P < 0.05). tau VO2 was accelerated from 71.3 to 49.2 s in the OH group and from 59.5 to 48.2 s in the OS group (P < 0.05). These results suggest that VO2 responses at maximal and submaximal work rates may be dependent upon the initial cardiac pump function of the study population. (+info)
Structural maturation of neural pathways in children and adolescents: in vivo study.
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Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions. (+info)
Prospective analysis of traits related to 6-year change in sodium-lithium countertransport. Gubbio Population Study Research Group.
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Sodium-lithium countertransport (Na-Li CT) activity in red blood cells relates cross-sectionally and longitudinally to blood pressure and hypertension. Lifestyle and metabolic factors relate cross-sectionally to this sodium transporter. The aim of this study was to conduct a prospective analysis of 6-year Na-Li CT change and of traits related to Na-Li CT change. In 2183 participants in the Gubbio Population Study (972 men and 1211 women; baseline ages, 18 to 74 years), the following data collected at baseline and 6-year follow-up were analyzed: Na-Li CT; gender; age; body mass index (BMI); blood pressure; antihypertensive treatment; alcohol intake; smoking habits; urinary sodium-to-potassium ratio; and plasma cholesterol, glucose, uric acid, sodium, potassium, and triglycerides (measured only at follow-up). Six-year changes were defined as follow-up minus baseline values. Na-Li CT was higher at follow-up than at baseline in both genders (P<0.001). Baseline Na-Li CT; baseline and change values of BMI; and change values of alcohol intake, plasma potassium, and plasma glucose related to Na-Li CT change significantly and independently with control for other variables. Follow-up plasma triglyceride levels also related independently to Na-Li CT change. Coefficients were positive for BMI, alcohol intake, and plasma glucose and triglyceride levels and were negative for baseline Na-Li CT and plasma potassium levels. Baseline and change values of other variables did not relate significantly to Na-Li CT change. In conclusion, in prospective analyses, BMI, alcohol intake, plasma glucose, and lipids were directly related to Na-Li CT change; baseline Na-Li CT and plasma potassium levels were inversely related. The data support the concept that lifestyle and related metabolic factors influence Na-Li CT. (+info)
Caregiver behaviors and resources influence child height-for-age in rural Chad.
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The purpose of this study was to identify caregiver characteristics that influence child nutritional status in rural Chad, when controlling for socioeconomic factors. Variables were classified according to the categories of a UNICEF model of care: caregiving behaviors, household food security, food and economic resources and resources for care and health resources. Sixty-four households with 98 children from ages 12 to 71 mo were part of this study. Caregivers were interviewed to collect information on number of pregnancies, child feeding and health practices, influence on decisions regarding child health and feeding, overall satisfaction with life, social support, workload, income, use of income, and household food expenditures and consumption. Household heads were questioned about household food production and other economic resources. Caregiver and household variables were classified as two sets of variables, and separate regression models were run for each of the two sets. Significant predictors of height-for-age were then combined in the same regression model. Caregiver influence on child-feeding decisions, level of satisfaction with life, willingness to seek advice during child illnesses, and the number of individuals available to assist with domestic tasks were the caregiver factors associated with children's height-for-age. Socioeconomic factors associated with children's height-for-age were the amount of harvested cereals, the sources of household income and the household being monogamous. When the caregiver and household socioeconomic factors were combined in the same model, they explained 54% of the variance in children's height-for-age, and their regression coefficients did not change or only slightly increased, except for caregiver's propensity to seek advice during child illnesses, which was no longer significant. These results indicate that caregiver characteristics influence children's nutritional status, even while controlling for the socioeconomic status of the household. (+info)
Depletion of cutaneous peptidergic innervation in HIV-associated xerosis.
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Severe xerosis occurs in approximately 20% of human immunodeficiency virus seropositive patients. Changes in cutaneous innervation have been found in various inflammatory skin diseases and in xerotic skin in familial amyloid. We have therefore carried out a quantitative examination of the cutaneous peptidergic innervation in human immunodeficiency virus-associated xerosis. Immunohistochemistry and image analysis quantitation were used to compare total cutaneous innervation (protein gene product 9.5), calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at two sites in the skin of human immunodeficiency virus-associated xerosis patients (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each type was carried out for each subject in the epidermis and papillary dermis, and around the sweat glands. Immunostained mast cells in these areas were counted. Epidermal integrity and maturation were assessed by immunostaining for involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in total lengths of protein gene product 9.5 fibers in both epidermis/papillary dermis and sweat gland fields; of calcitonin gene-related peptide innervation in the epidermis/papillary dermis; and of substance P innervation of the sweat glands. There were no differences in the distribution of mast cells, or in the epidermal expression of involucrin. Depletion of the calcitonin gene-related peptide innervation may affect the nutrient blood supply of the upper dermis, and the integrity and function of basal epidermis and Langerhans cells. Diminished substance P innervation of the sweat glands may affect their secretory activity. Both of these changes may be implicated in the development of xerosis. (+info)