The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain.

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

American Indian--Alaska Native youth health.

OBJECTIVE--To assess risk behaviors, health problems, worries and concerns, and resiliency-promoting factors among American Indian-Alaska Native adolescents. DESIGN--Survey. SETTING--Nonurban schools from eight Indian Health Service areas. PARTICIPANTS--A total of 13,454 seventh- through 12th-grade American Indian-Alaska Native youths. MAIN OUTCOME MEASURES--revised version of the Adolescent Health Survey, a comprehensive, anonymous, self-report questionnaire with 162 items addressing 10 dimensions of health. RESULTS--Poor physical health was reported by 2% of the study sample and was significantly correlated with social risk factors of physical and/or sexual abuse, suicide attempts, substance abuse, poor school performance, and nutritional inadequacies. Injury risk behaviors included never wearing seatbelts (44%), drinking and driving (37.9% of driving 10th through 12th graders), and riding with a driver who had been drinking (21.8%). Physical and sexual abuse prevalence was 10% and 13%, respectively, with 23.9% of females reporting physical abuse and 21.6% of females reporting sexual abuse by the 12th grade. Almost 6% of the entire sample endorsed signs of severe emotional distress. Eleven percent of the teens surveyed knew someone who had killed himself or herself, and 17% had attempted suicide themselves. Sixty-five percent of males and 56.8% of females reported having had intercourse by the 12th grade. Weekly or more frequent alcohol use rose from 8.2% of seventh graders to 14.1% by the 12th grade; for males, the survey noted an increase in regular alcohol use of 3% to 5% a year to 27.3% by the 12th grade. For each variable measured, rates are much higher for American Indian adolescents than those for rural white Minnesota youth, except for age at first intercourse and alcohol use. CONCLUSIONS--American Indian-Alaska Native adolescents reported high rates of health-compromising behaviors and risk factors related to unintentional injury, substance use, poor self-assessed health status, emotional distress, and suicide. Interventions must be culturally sensitive, acknowledge the heterogeneity of Indian populations, be grounded in cultural traditions that promote health, and be developed with full participation of the involved communities.     

Recombinant bone morphogenetic protein (BMP)-2 regulates costochondral growth plate chondrocytes and induces expression of BMP-2 and BMP-4 in a cell maturation-dependent manner

This study examined the effect of recombinant human bone morphogenetic protein-2 on several parameters of growth, differentiation, and matrix synthesis and on the endogenous production of mRNA of bone morphogenetic proteins 2 and 4 by growth plate chondrocytes in culture. Chondrocytes from resting and growth zones were obtained from rat costochondral cartilage and cultured for 24 or 48 hours in medium containing 0.05-100 ng/ml recombinant human bone morphogenetic protein-2 and 10% fetal bovine serum. Incorporation of [³H]thymidine, cell number, alkaline phosphatase specific activity, incorporation of [³H]proline into collagenase-digestible protein and noncollagenase-digestible protein, and incorporation of [³⁵S]sulfate were assayed as indicators of cell proliferation, differentiation, and extracellular matrix synthesis. mRNA levels T for bone morphogenetic proteins 2 andv4 were determined by Northern blot analysis. Recombinant human bone morphogenetic protein-2 increased the incorporation of [³H]thymidine by quiescent resting-zone and growth-zone cells in a similar manner, whereas it had a differential effect on nonquiescent cultures. At 24 and 48 hours, 12.5-100 ng/ml recombinant human bone morphogenetic protein-2 caused a dose-dependent increase in cell number and DNA synthesis in resting-zone chondrocytes. No effect was seen in growth-zone cell Recombinant human bone morphogenetic protein-2 stimulated alkaline phosphatase specific activity in resting-zone chondrocytes in a bimodal manner, causing significant increases between 0.2 and 0.8 ng/ml and again between 25 and 100 ng/ml. In contrast, alkaline phosphatase specific activity in growth-zone chondrocytes was significantly increased only between 12.5 and 100 ng/ml. Recombinant human bone morphogenetic protein-2 increased the production of both collagenase-digestible protein and noncollagenase-digestible protein by resting-zone and growth-zone cells, but incorporation of [³⁵S]sulfate was unaffected. Administration of recombinant human bone morphogenetic protein-2 also increased incorporation of [³H]uridine in both resting-zone and growth-zone chondrocytes; these cells produced mRNA for bone morphogenetic proteins 2 and 4. Bone morphogenetic protein-2 mRNA levels in both resting-zone and growth-zone chondrocytes increased in the presence of recombinant human bone morphogenetic protein-2; however, bone morphogenetic protein-4 mRNA levels in growth-zone cells decreased under its influence, and those in resting-zone cells were upregulated only with a dose of 10 ng/ml. This indicates that recombinant human bone morphogenetic protein-2 regulates chondrocyte proliferation, differentiation, and matrix production, and the effects are dependent on the stage of cell maturation. Resting-zone chondrocytes were more sensitive, suggesting that they are targeted by bone morphogenetic protein-2 and that this growth factor may have autocrine effects on these cells.     

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. III. Epithelial tumors of low malignant potential in white women. Collaborative Ovarian Cancer Group.

Epithelial ovarian neoplasms of low malignant potential, also called borderline ovarian tumors, have various features of malignancy, but they do not invade the ovarian stroma. Women with these tumors usually are younger when diagnosed and have better prognoses than do women with invasive tumors. There have been few epidemiologic studies of borderline tumors, and it is unclear whether there are etiologic differences between the two types of tumor behavior. Combined data from nine case-control studies, conducted from 1974 to 1986 and representing 327 white women with tumors of low malignant potential and 4,144 white controls, were used to evaluate the relation between these tumors and personal characteristics related to invasive ovarian cancer. The risk profile for tumors of low malignant potential was found to be similar to that for invasive tumors, with two exceptions: Compared with that of invasive tumors, risk of borderline tumors was less clearly reduced among women who had used oral contraceptives and more clearly elevated among women with a history of infertility.     

Corticosteroid therapy in Riedel's thyroiditis.

We report a case of Riedel''s thyroiditis presenting with a systemic illness, life-threatening stridor and a stony hard goitre. Diagnosis was confirmed by open thyroid biopsy. Treatment with corticosteroid resulted in a dramatic improvement. A possible autoimmune mechanism in the pathogenesis of Riedel''s thyroiditis is discussed.     

Sex-specific effects for body mass index in the new Norwegian twin panel

Sex-specific effects for body mass index (BMI) were explored in a newly established, population-based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health-related behaviors, well-being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike-sexed pairs. Alternate sets of models testing for either sex-specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex-specific additive genetic effects, as well as genetic and non-shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male-female genetic correlation was 0.622. The series of models specifying sex-specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex-specific effects for BMI and sex differences in health outcomes. ©1995 Wiley-Liss, Inc.