Showing papers by "Saint Francis University published in 1995"
TL;DR: The ability of cortisol to downregulate α1(I) procollagen transcripts was sensitive to cycloheximide treatment, suggesting that the gene is under “secondary control” by glucocorticoids.
Abstract: Glucocorticoids decrease osteoblast proliferation and type I collagen production, and this may play a role in the development of glucocorticoid-induced osteoporosis. Osteoblast-enriched cultures derived from fetal rat calvaria were used to determine the mechanisms by which cortisol decreases α1(I) procollagen expression in bone cells. A 24 h treatment with cortisol decreased collagen synthesis in these cultures in a dose-dependent manner. Cortisol decreased α1(I) procollagen transcripts in a dose- and time-dependent manner as well. Repression of α1(I) procollagen transcripts was evident as early as 2 h of treatment and was maximal after 48 h of treatment. Nuclear run-off assays showed that cortisol downregulated transcription of the α1(I) procollagen gene. In addition, pretreatment with cortisol decreased the stability of α1(I) procollagen mRNA in transcription-arrested osteoblast cultures. The ability of cortisol to downregulate α1(I) procollagen transcripts was sensitive to cycloheximide treatment, suggesting that the gene is under “secondary control” by glucocorticoids. Since cortisol decreases α1(I) procollagen gene transcription in osteoblasts but does not affect α1(I) procollagen gene transcription in fibroblasts, we suggest that the mechanisms controlling glucocorticoid repression of collagen expression are cell-type specific.
161 citations
TL;DR: Oral transmucosal fentanyl is safe and effective for use in relieving the pain of pediatric procedures, but frequency of vomiting may restrict its clinical usefulness.
Abstract: Objective To investigate the efficacy and safety of oral transmucosal fentanyl (OTFC) in providing analgesia and sedation for painful diagnostic procedures in children. Design Randomized, placebo-controlled clinical trial. Method Forty-eight children referred to the University Connecticut Division of Pediatric Hematology/Oncology for bone marrow aspiration or lumbar puncture were randomized to receive either OTFC (15 to 20 micrograms/kg) or a placebo lollipop. Thirty minutes after administration, the procedure was begun. An anesthesiologist monitored the child's heart rate, blood pressure, and oxygen saturation every 10 minutes. At the conclusion of the procedure, the nurse, the child's parent, and all children over 8 years of age were asked to rate the pain associated with the procedure using a 1 to 10 visual analogue scale. Young children (less than 8) used a modified scale, the Oucher, yielding a 0 to 5 score. Results Significant differences in pain ratings between the OTFC and placebo groups were noted on the pain scores of the parents (P = .005), nurses (P = .001), younger children (P = .006), and older children (P = .013), and median pain scores in the OTFC group were reduced to tolerable levels. Vomiting (P = .003) and itching (P = .001) were more common in the OTFC group, but no clinically significant vital sign deviations occurred. Conclusion OTFC is safe and effective for use in relieving the pain of pediatric procedures, but frequency of vomiting may restrict its clinical usefulness.
152 citations
TL;DR: In conclusion, cortisol inhibits the transcription of IGF-I in osteoblasts, an effect that may be relevant to the actions of cortisol in bone.
Abstract: Insulin-like growth factor I (IGF-I) is an abundant autocrine and paracrine growth factor secreted by osteoblasts. It promotes osteoblast proliferation and expression of their differentiated phenotype. Glucocorticoids decrease IGF-I production by osteoblasts, which may mediate some actions of the steroid on bone in both normal and pathological states. The mechanisms by which the glucocorticoid cortisol down-regulates IGF-I transcripts were explored using cultures of osteoblast-enriched cells derived from fetal rat calvaria (Ob cells). Repression of IGF-I transcripts was apparent after 8 h of treatment, was sustained for at least 24 h, and was not altered by cotreatment with cycloheximide. Cortisol did not alter the stability of IGF-I messenger RNAs in transcriptionally arrested Ob cells. Cortisol decreased IGF-I heterogeneous nuclear RNA and gene transcription, as determined by reverse transcription-linked polymerase chain reaction and nuclear run-on assay, respectively. Transient transfection of Ob cells with constructs containing portions of the rat IGF-I exon 1 promoter and 5'-flanking DNA linked to the reporter gene luciferase were performed to determine glucocorticoid-responsive region of the rat IGF-I exon 1 promoter was localized to 34 to 192 relative to the first start site of transcription. In conclusion, cortisol inhibits the transcription of IGF-I in osteoblasts, an effect that may be relevant to the actions of cortisol in bone.
117 citations
TL;DR: It is demonstrated that glucocorticoids regulate collagenase gene expression in a novel tissue-specific manner, further highlighting the differences in gene regulation between osteoblastic and fibroblastic cells.
113 citations
TL;DR: IGF-I and RA modify the synthesis and secretion of IGFBP-5 in rat Ob cells through pathways that may involve increased transcription and elongation and/or altered processing of heterogenous nuclear RNA.
Abstract: The insulin-like growth factor (IGF) regulatory system has a major impact on bone physiology. Among the modulators of IGFs, a family of structurally related proteins, the IGF-binding proteins (IGFBPs), have been shown to either potentiate or inhibit IGF actions on bone growth. However, the regulation of IGFBP expression in bone cells is not completely understood. In the present study, the expression of IGFBP-5 was analyzed in primary osteoblastic cells (Ob cells) isolated from 22-day-old fetal rat calvariae. Treatment of Ob cells with either IGF-I or all-trans-retinoic acid (RA) caused a time- and dose-dependent increase in IGFBP-5 messenger RNA (mRNA) levels, as determined by Northern blot analysis. Stimulation of IGFBP-5 mRNA was obtained at 100 nM IGF-I between 6 and 16 h (2- to 2.5-fold) and 100 nM RA between 16 and 24 h (3- to 4-fold). Concomitant treatment of Ob cells with IGF-I and RA revealed an additive effect and a 5- to 7-fold increase in IGFBP-5 mRNA levels after 16-24 h. The effect of IGF-I a...
78 citations
TL;DR: PDGF BB stimulates IL- 6 expression in Ob cells, a response that is PKC and calcium dependent, and the increase in IL-6 expression may be relevant to the actions of PDGF BB on bone resorption.
Abstract: Platelet-derived growth factor (PDGF) increases bone resorption and the number of osteoclasts in calvarial sections, and it may regulate local cytokines involved in bone remodeling. Interleukin-6 (IL-6), a cytokine secreted by osteoblasts, osteoclasts, and stromal cells, is known to increase osteoclast recruitment. We tested the effects of PDGF on IL-6 expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with PDGF BB caused a time- and dose-dependent induction of IL-6 messenger RNA (mRNA), as determined by Northern blot analysis. The effect was maximal after 1 h of treatment and was observed with PDGF BB at 0.3-3.3 nM. Treatment with PDGF BB for 24 h also increased IL-6 polypeptide levels in the culture medium, as determined by a specific bioassay. Although PDGF AA increased IL-6 mRNA levels, its effect was less pronounced than that of PDGF BB. Phorbol 12-myristate 13-acetate (PMA) induced IL-6 transcripts, and the effect of PDGF BB was ...
69 citations
TL;DR: The authors found that there are individual differences in motivation as a function of goal discrepancy or congruence, and that being motivated should lead to better performance when a person is focused on positive outcomes, or to worse performance if he or she was focused on negative outcomes (success-oriented vs. failure-threatened in Studies 1 and 2, ideal vs. ought discrepancy in Study 3).
Abstract: Reducing discrepancies between performance and goals was predicted to motivate uncertainty-oriented people, but maintaining congruence was predicted to be more motivating for certainty-oriented people. Being motivated should lead to better performance when a person is focused on positive outcomes, or to worse performance if he or she is focused on negative outcomes (success-oriented vs. failure-threatened in Studies 1 and 2, ideal vs. ought discrepancy in Study 3). Three studies tested these hypotheses: an experiment that used bogus performance feedback, a field study of examination performance as a function of prior discrepancies from desired grades, and an experimental priming of standards associated with a discrepancy or with no discrepancy. All 3 studies revealed the predicted interaction, supporting the hypothesis that there are individual differences in motivation as a function of goal discrepancy or congruence
61 citations
TL;DR: BFGF may modulate degradation of collagenous bone matrix by inhibiting collagen as well as stimulating collagenase and TIMPs by osteoblasts.
Abstract: Basic fibroblast growth factor (bFGF) is a bone cell mitogen that affects osteoblastic function by suppressing type I collagen synthesis. The investigators in this study examined whether bFGF also regulates interstitial collagenase and tissue inhibitors of metalloproteinases (TIMPs) in osteoblast-enriched cells isolated from 22-day fetal rat calvariae. After exposure to 600 pM bFGF, interstitial collagenase messenger RNA (mRNA) levels, as determined by Northern hybridization analysis, increased after 2 h and were maximally stimulated to approximately 13-fold at 6 h. Exposure of osteoblast-enriched cells to 0.06-6 nM bFGF increased collagenase mRNA in a dose-dependent manner, and bFGF also increased immunoreactive collagenase measured in the culture medium by Western blot analysis. The protein synthesis inhibitor cycloheximide, as well as two inhibitors of protein kinase C, staurosporine and sangivamycin, prevented the bFGF induction of collagenase transcripts, whereas indomethacin, an inhibitor of prostag...
61 citations
TL;DR: The purpose of this survey was to identify the national treatment practices for oral mucositis, mucocutaneous Herpes simplex virus infections, and oral candidiasis, and to compare them to the NIH guidelines.
54 citations
TL;DR: It is shown that basic fibroblast growth factor, TGF β1, and PDGF BB inhibit IGFBP-5 expression in Ob cells independently of their mitogenic activity and through mechanisms that involve decreased transcription.
53 citations
TL;DR: The regulation of IGF-I synthesis by PGE2 in osteoblast-enriched (Ob) cells from fetal rat calvaria is examined and it is concluded that regions involved in IGF-i regulation by P GE2 are contained within the IGF- I promoter.
Abstract: Insulin-like growth factor I (IGF-I) is a widely expressed abundant autocrine and paracrine factor that regulates the proliferation and differentiation of a variety of cell types. Prostaglandin E2 (PGE2) is a potent stimulator of IGF-I synthesis in bone. We examined the regulation of IGF-I synthesis by PGE2 in osteoblast-enriched (Ob) cells from fetal rat calvaria. PGE2 treatment of Ob cells at 1 microM for 2 h resulted in a 5-fold increase in heterogeneous nuclear RNA levels, as measured by a reverse transcriptase-polymerase chain reaction assay, suggesting an increase in IGF-I gene transcription. RNase protection analysis was used to map the transcriptional start sites in the IGF-I gene that are used in Ob cells. Consistent with other extrahepatic tissues, initiation of transcription occurs primarily at three sites within the 5'-regions of exon 1 of the IGF-I gene. PGE2 treatment did not alter start site usage. The regions upstream of these transcriptional start sites were analyzed by transiently transf...
TL;DR: Cortisol decreases transcription of the IGF-II receptor in Ob cell cultures, an effect that could mediate selected actions of glucocorticoids in bone.
Abstract: Glucocorticoids have a number of effects on bone cell function, some of which might be mediated by changes in the synthesis or activity of insulin-like growth factors (IGFs). Glucocorticoids inhibit IGF-I, but not IGF-II, synthesis in osteoblasts and decrease the expression of selected IGF-binding proteins. The effects of glucocorticoids on IGF-I and -II receptor messenger RNA (mRNA) expression in osteoblasts are not known, and changes in IGF-I or -II receptor levels could result in changes in IGF activity. We examined the effects of glucocorticoids on IGF-I and -II receptor mRNA expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Cortisol at 1 microM for 2-48 h did not alter IGF-I receptor transcripts, as determined by Northern blot analysis and ribonuclease protection assay. In contrast, cortisol caused a time- and dose-dependent inhibition of IGF-II receptor mRNA levels. The effect was maximal at 0.1-1 microM for 24-48 h and was accompanied by a decrease ...
TL;DR: BMP-2 inhibits IGFBP-5 expression in Ob cells through pathways that are independent of its mitogenic activity and through mechanisms that may involve decreased transcription or altered RNA processing.
Abstract: Previous work from our laboratory indicated that bone morphogenetic protein-2 (BMP-2) enhances the synthesis of insulin-like growth factor-I (IGF-I) and IGF-II by skeletal cells. The activity of IGF-I and -II is regulated by six known IGF-binding proteins (IGFBPs). Although most IGFBP's inhibit the actions of IGF on bone growth, IGFBP-5 is stimulatory, and its synthesis correlates with changes in osteoblast cell growth. We tested the effects of BMP-2 on IGFBP-5 expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with BMP-2 caused a time- and dose-dependent decrease in IGFBP-5 messenger RNA (mRNA) levels, as determined by Northern blot analysis. The effect was maximal after 24 h of treatment and occurred at BMP-2 concentrations of 0.03-3.3 nM. Treatment with BMP-2 for 24 h also decreased IGFBP-5 polypeptide levels in the extracellular matrix, as determined by Western blot analysis. The effects of BMP-2 on IGFBP-5 transcripts were indepen...
TL;DR: Growth factors such as IGF I could be considered for the systemic treatment of various bone disorders, or drugs could be developed to modify the synthesis or activity of the locally produced factors.
Journal Article•
TL;DR: Twenty-two cases of severe necrotizing soft-tissue infections (SNSTIs), seen by the infectious disease service from 1983 to 1988 in a community teaching hospital, are described and compared with previously reported series.
Abstract: Twenty-two cases of severe necrotizing soft-tissue infections (SNSTIs), seen by the infectious disease service from 1983 to 1988 in a community teaching hospital, are described and compared with previously reported series. Clinical findings were distinguishable from cellulitis at the time of surgery in only 45% of the patients who had either necrosis, crepitus, vesicle or bullae, and/or an abnormal air pattern on x-ray studies. Patients with "cellulitis" were not less sick than patients with "necrosis" findings (ie, presence of shock, leukocytosis with left shift, fever, or anion gap). Despite the fact that all but one of the patients were seen by the infectious disease service preoperatively, and 55% underwent surgical intervention within 48 hours of admission, patient mortality (18%) was not better than some reported in earlier series. However, the epidemiology of SNSTI was different: in our series there were more diabetic patients (64%) and fewer postsurgical infections (14%). Among the diabetic patients, SNSTI developed more frequently at a site not related to peripheral vasculopathy or neuropathy. Abdominal wall involvement was 10 times more likely be diagnosed as cellulitis (5/8 vs 2/14 with involvement elsewhere, P < 0.02).
TL;DR: Fetal neuron cell cultures from 22 day gestation and 18 day gestation fetal rabbit brain were studied for the presence of insulin-like growth factor I (IGF I), which may promote cell survival in early stages of brain development, and may be of exogenous origin.
TL;DR: An on-screen method to determine fetal cardiac axis by use of multiple calipers is described, comparable to a protractor-measured Fetal cardiac axis.
TL;DR: Homelessness should alert prenatal care providers to the expected coexistence of numerous additional psychosocial and health risk factors in young pregnant teens.
Abstract: Study Objective: Homelessness is a major complication to adolescent pregnancy. We hypothesized that homelessness was associated with an increased incidence of other psychosocial and health risk factors for young pregnant teens. Design, Setting, Participants: We conducted a nationwide study of homeless young pregnant teens living in group residential facilities and of a control population of young pregnant teens living at home with their families. Clinical social workers involved in services for these patients were located by consulting a national directory of maternity homes and through contact with hospital-based social service departments randomly selected through long-distance telephone information. After a telephone conversation detailing the nature of the project, questionnaires were mailed to each social worker. They were to complete a questionnaire for each of the two youngest pregnant teens cared for at their facility in the previous 12 months. The data from the returned questionnaires were evaluated by chi-square analysis and Fisher's exact test. Main Outcome Measures: We distributed 736 questionnaires and collected data on 509 subjects (278 homeless, 231 controls) from 191 cities throughout the United States. The return rates were 69.1% from each group. There were no significant differences between the two groups in median age (14 years), race (50 and 42% white, 32 and 39% black, 10 and 14% Hispanic), school grade level (8th), or dropout rates (19 and 18%). Results: Findings included a greater likelihood for those in the homeless group to be under the guardianship of a social service agency (29 vs. 3%, p p p p p p p p p Conclusions: Homelessness should alert prenatal care providers to the expected coexistence of numerous additional psychosocial and health risk factors in young pregnant teens.