Showing papers by "Saint Francis University published in 1991"

Transforming growth factor-beta and remodeling of bone.

Abstract: The transforming growth factor-betas are polypeptide growth factors encoded by a family of closely related genes that are expressed in numerous tissues and species. Bone was one of the first tissues in which locally produced molecules with transforming growth factor-beta-like activity appeared to regulate normal cellular function, and the skeletal matrix probably comprises the largest reservoir of transforming growth factor-betas in the organism. In vitro and in vivo studies have indicated that the transforming growth factor-betas can have either stimulatory or inhibitory effects on replication, lineage development, and differentiated phenotypic function in many types of skeletal tissue cells. These effects may be biphasic in the sense that low concentrations of transforming growth factor-beta stimulate proliferation of cells, whereas high concentrations inhibit proliferation. Even within the same cell lineage, opposite effects have been noted with different concentrations of transforming growth factor-beta, or with skeletal cells at different developmental stages. In fetal tissue, transforming growth factor-beta stimulates differentiation of mesenchymal cells, proliferation of osteoblasts, and synthesis of matrix, but it may also induce maturation into and through the osteoblast, chondrocyte, and osteoclast lineages. Furthermore, a number of other local and systemic factors can regulate expression of transforming growth factor-beta or receptor-binding by bone cells or can increase release of transforming growth factor-beta from the skeletal matrix. Some activities ascribed to the transforming growth factorbetas may overlap with those produced by osteoinductive factors and other less closely related members of the transforming growth factor-beta gene family. Consequently, a thorough understanding of activity, synthesis, and receptors of transforming growth factor-beta may result in the rational use of these or related molecules to enhance growth of bone or repair of fractures.

Prostaglandin E2 stimulates insulin-like growth factor I synthesis in osteoblast-enriched cultures from fetal rat bone.

Abstract: Prostaglandin E2 (PGE2) affects both bone resorption and formation, but its mechanism of action remains unclear. PGE2 is known to elevate intracellular cAMP levels in a variety of culture systems. Agents that increase cAMP in primary osteoblast-enriched (Ob) cultures enhance the synthesis of skeletal insulin-like growth factor I (IGF-I), a potent anabolic factor for bone. A 5 min exposure to PGE2 at 0.01-1 microM enhanced cAMP synthesis in Ob cultures by 8- to 54-fold, and within 6 h produced up to a 3- fold increase in steady state prepro-IGF-I transcripts. The stimulatory effect of PGE2 on IGF-I messenger RNA was first evident within 4 h of treatment and remained elevated for at least 24 h. Furthermore, 0.01-1 microM PGE2 increased immunoreactive IGF-I polypeptide accumulation by 1.9- to 4.7-fold. In contrast PGE2 did not elevate steady state IGF-II mRNA or polypeptide levels within this time frame. Although PTH increase cAMP, intracellular calcium, and PGE2 production by bone cells, our previous studies indicate that the stimulatory effect of PTH on IGF-I production is cAMP, but not calcium dependent. Inhibition of PGE2 synthesis by exposure to indomethacin did not alter basal or PTH-stimulated IGF-I levels, substantiating that the effect of PTH on IGF-I is not PGE2 dependent. These studies indicate that PGE2 production, a feature common to many agents that enhance bone resorption, could contribute to the coupling of bone resorption and new bone formation, by way of its ability to increase cAMP and, consequently, IGF-I synthesis by the osteoblast.

Growth Factors and Cytokines in Bone Cell Metabolism

Abstract: Growth factors regulate the growth and differentiated function of cells. Skeletal cells synthesize fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor beta, and additional cytokines. Some of the growth factors produced by bone cells primarily stimulate bone cell replication, whereas others also affect the differentiated function of the osteoblast. Skeletal growth factors also may play a role in the pathogenesis and therapy of metabolic bone disease.

Glucocorticoid regulation of transforming growth factor beta 1 activity and binding in osteoblast-enriched cultures from fetal rat bone.

Abstract: Transforming growth factor beta (TGF-beta) enhances replication and bone matrix protein synthesis and associates with distinct binding sites in osteoblast-enriched cultures from fetal rat bone. In the organism high levels of or sustained exposure to glucocorticoids alters bone cell activity and decreases bone mass, effects that may be mediated in part by changes in local TGF-beta actions in skeletal tissue. Preexposure of osteoblast-enriched cultures to 100 nM cortisol reduced the stimulatory effects of TGF-beta 1 on DNA and collagen synthesis by 40 to 50%. Binding studies showed that cortisol moderately enhanced total TGF-beta 1 binding, but chemical cross-linking and polyacrylamide gel electrophoretic analysis revealed an increase only within Mr 250,000 (type III) TGF-beta-binding complexes, which are thought to represent extracellular TGF-beta storage sites. In contrast, a decrease in TGF-beta 1 binding was detected in Mr 65,000 (type I) and 85,000 (type II) complexes, which have been implicated as signal-transducing TGF-beta receptors. Our present studies therefore indicate that glucocorticoids can decrease the anabolic effects of TGF-beta 1 in bone, and these may occur in part by a redistribution of its binding toward extracellular matrix storage sites. Alterations of this sort could contribute to bone loss associated with glucocorticoid excess.

Individual Differences in Children's Response to Pain: Role of Temperament and Parental Characteristics

Abstract: Sixty-five families were enlisted in a study exploring factors associated with distress behavior in 5-year-old children receiving diphtheria-tetanus-pertussis immunizations. At a home visit 1 month before the immunization, the following measures were obtained: (1) the Behavioral Style Questionnaire, a measure of temperament: (2) parental self-reports of medically related attributes (eg. "good patient"); (3) parental attitudes toward pain in children and responsiveness to their child's pain; and (4) parental prediction of distress at upcoming immunization. The child's distress behavior during the immunization was evaluated using a modification of the Procedure Rating Scale-Revised and, after the procedure, the child's assessment of his or her pain was elicited using the Oucher. Children's mean Procedure Rating Scale-Revised score was 2.57 of a possible 11. Thirty-one (48%) had low (less than or equal to 1) and 7 (11%) had high distress scores (greater than or equal to 2 SD above the mean). Factors positively correlated with distressed behavior included more "difficult child" cluster characteristics, the individual temperamental dimension of adaptability, but few parental attitudes and attributes. Parent's predictions of distress were the strongest correlates. These findings document the variation that children demonstrate in response to pain and offer some insight into associated innate and environmental factors. These results imply that treatment strategies derived from parental knowledge and tailored to individual characteristics of the child may be most effective in alleviating pain-related distress in medical settings.

Activin-A binding and biochemical effects in osteoblast-enriched cultures from fetal-rat parietal bone.

Abstract: Activin, a disulfide-linked polypeptide dimer first isolated from gonadal tissue extracts, has amino acid sequence and structural homology with transforming growth factor beta (TGF beta). Along with other activities, TGF beta regulates replication and differentiation and interacts with a defined set of binding sites on isolated bone cells. To determine if activin shares these properties, recombinant human activin-A (A-chain homodimer) was examined in osteoblast-enriched cultures obtained from fetal-rat parietal bone. After 23 h of treatment, 60 to 6,000 pM activin-A increased the rate of [3H]thymidine incorporation into DNA 1.5- to 4.0-fold, and at 600 to 6,000 pM, it enhanced the rate of [3H]proline incorporation into collagen and noncollagen protein by up to 1.7-fold. Like earlier studies with TGF beta in primary osteoblast-enriched cultures, the stimulatory effects of activin-A on DNA and protein synthesis were opposed by parathyroid hormone, and the influence of activin-A on collagen synthesis was independent of cell replication. Binding studies with 125I-activin-A indicated approximately 8,000 high-affinity (Kd = 0.4 nM) and 300,000 low-affinity (Kd = 40 to 50 nM) binding sites per cell. Polyacrylamide gel analysis revealed 125I-activin-A-binding complexes of Mr greater than 200,000 and 73,000 which did not appear to correspond to primary TGF beta-binding sites. These results indicate that activin-A produces TGF beta-like effects in bone and that some of these effects may be mediated, at least in part, by distinct activin receptors on bone cells.

Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone

Abstract: Platelet-derived growth factor (PDGF) exists as a homodimer or a heterodimer comprising either PDGF-A or PDGF-B subunits, and each isoform occurs in various tissues, including bone. Although the stimulatory effects of PDGF-BB have been studied in cultures of bone cells and intact bone fragments, the influence of other isoforms that may arise locally or systemically in vivo, has not been reported. Therefore recombinant human PDGF-BB, PDGF-AB, and PDGF-AA were evaluated in osteoblast-enriched cultures from fetal rat bone. Within 24 hours these factors produced a graded response in bone cell DNA and protein synthesis, with half-maximal effects at approximately 0.6, 2.1, and 4.8 nM PDGF-BB, PDGF-AB, and PDGF-AA, respectively. Increases in collagen and noncollagen protein synthesis were abrogated when DNA synthesis was blocked with hydroxyurea. Furthermore, each factor reduced alkaline phosphatase activity, PDGF-BB being the most inhibitory. Binding studies with 125I-PDGF-BB or 125I-PDGF-AA and each unlabeled PDGF isoform produced discrete ligand binding and displacement patterns: 125I-PDGF-BB binding was preferentially displaced by PDGF-BB (Ki ≈0.7 nM), less by PDGF-AB (Ki ≈2.3 nM) and poorly by PDGF-AA. In contrast, 125I-PDGF-AA binding was measurably reduced by PDGF-AA (Ki ≈4.0 nM), but was more effectively displaced by PDGF-BB or PDGF-AB (each with Ki ≈0.7 nM). These studies indicate that each PDGF isoform produces biochemical effects proportional to binding site occupancy and suggest that receptors that favor PDGF-B subunit binding preferentially mediate these results in osteoblast-enriched bone cell cultures.

Regulation of Insulin-Like Growth Factor-II Production in Bone Cultures*

Abstract: Although bone matrix is a rich source of insulinlike growth factor-II (IGF-II), little is known about the regulation of its synthesis by bone cells. This is due in part to the lack of simple and reliable assays to measure IGF-II. We have developed a method to dissociate IGF-II from its binding proteins by acidification and ultrafiltration, and quantitated IGF-II by RIA in 24- to 72-h cultures of 21-day-old fetal rat calvariae. The coefficient of variation of the assay was 13.8% or less; the recovery of IGF-II was 30–50%, and IGF-I cross-reacted 1% or less in the assay compared to IGF-II standards. The IGF-II concentrations in calvarial culture medium were in the 1- to 3- nM range, and these levels were suppressed by cycloheximide (3.6 μM) by almost 80%. Continuous treatment with placental lactogen, PTH, GH, insulin, or T3 did not modify IGF-II concentrations in 24- to 72-h cultures. Treatment with 17β-estradiol, testosterone, and 1,25-dihydroxyvitamin D3 also had no effect on IGF-II levels, whereas cortis...

Community hospital level II trauma center outcome.

Abstract: Currently, level II trauma center standards allow trauma surgeons to take call out-of-hospital. To address the concern that this practice may adversely influence outcome, we tested the hypothesis that the survival of injury victims treated at a level II trauma center is significantly different from that predicted by the Major Trauma Outcome Study (MTOS). In addition, we examined the impact of trauma surgeons taking call out-of-hospital on the survival of patients with severe thoracoabdominal injury. Over a 26-month period, a total of 3,689 consecutive injured patients who were treated at a community hospital level II trauma center were entered into this study. There was no significant difference between the MTOS survival and the actual survival in the overall population (96% vs. 97%, respectively; Z statistic = ns). Among the patients with severe thoracoabdominal injury (i.e., Abbreviated Injury Scale score greater than or equal to 3), there was no significant difference in survival between the patients whose arrival time corresponded to the presence of an in-hospital surgeon (0700-1800 hours) versus those who arrived when a surgeon was generally out-of-hospital (1801-0659 hours), (76% vs. 81%, respectively; p = ns). From these data we conclude that there was no significant difference between the survival observed and that predicted by the MTOS at our community hospital, which complies with level II trauma center standards. Furthermore, in the cohort with severe thoracoabdominal injury, the response of trauma surgeons from out-of-hospital did not adversely influence survival.

A common autoepitope near the carboxyl terminus of the 60-kD Ro ribonucleoprotein: sequence similarity with a viral protein.

Abstract: The Ro ribonucleoprotein is composed of hY RNA and a 60.7-kD peptide that is antigenic for autoantibodies produced by many patients with systemic lupus erythematosus or Sjogren's syndrome and mothers of newborns with complete congenital heart block. A major immunoreactive fragment (13 kD) of the 60-kD Ro is bound by 28 of 45 (62%) of the anti-Ro sera tested. Amino acid sequence analysis localizes this fragment to the carboxyl end of the 60-kD Ro peptide. All possible overlapping octapeptides of this 13-kD peptide of 60-kD Ro have been assessed for antigenicity. Sera that bind the 13-kD peptide fragment in immunoblot generally also bind the octapeptides of Ro spanning the sequence AIALREYRKKMDIPA (P<0.01). Inhibition studies with synthetic peptides and purified Ro have established specificity for reference serum antibody binding to an antigenic octapeptide, EYRKKMDI, from this region. The closely related sequence EYRKKLMD is found in the nucleocapsid protein of vesicular stomatitis virus and may portend an immunologic link to this or a related viral antigen. These results also demonstrate that despite fine specificity variation between human sera, there are recurring patterns of anti-Ro binding shared by some patients who have precipitating anti-Ro autoantibodies.

Photogrammetric evaluation in clinical genetics: theoretical considerations and experimental results.

Abstract: As newer mathematical approaches are applied to the field of clinical genetics accurate methods of craniofacial measurement are increasingly necessary. If photogrammetric techniques are to be used certain theoretical and practical issues must be taken into account. Errors due to projection are particularly important, but systematic and random errors must also be considered. We discuss theoretical aspects of projection errors along with experimental measurements. Systematic errors in excess of 20% were found during simulations of typical clinical conditions, although smaller errors were obtained using techniques practical in a clinical setting. Photogrammetric measurements are potentially valuable in the field of clinical genetics but must be used cautiously.

Effects of desamino-(1-3)-insulin-like growth factor I on bone cell function in rat calvarial cultures.

Abstract: Insulin-like growth factor (IGF) I, a polypeptide synthesized by skeletal cells, and its amino terminus truncated derivative desamino-(l–3)-IGF I (des-IGF I) were compared for their effects on bone formation in vitro. Des-IGF I and IGF I were studied for their effects on DNA and collagen synthesis in cultures of intact fetal rat calvariae and of osteoblast-enriched (Ob) cells from fetal rat parietal bone, and for their ability to bind to IGF receptors in Ob cells and to IGF binding proteins (IGF-BPs) from calvariae. Des-IGF I and IGF I increased [3H] thymidine incorporation into DNA, [3H]proline incorporation into collagen and noncollagen protein, and the mitotic index in intact calvariae. Both factors had similar actions in calvariae. Des-IGF I stimulated all parameters studied at 1 nM, and IGF I was effective on the labeling of DNA at 1 nM, but concentrations of 10 nM were required to observe changes in collagen and noncollagen protein synthesis and in the mitotic index. The effect of des-IGF I on colla...

Recognizing and responding to adolescent depression.

Abstract: We have seen that depression is increasingly recognized as a problem which affects adolescents as well as adults. Race by itself is not a factor which increases vulnerability to depression, but the multitude of sociodemographic, biological, and personal factors contributing to the development of depression are not fully understood. Research is needed to better understand how these factors interact in order to better develop prevention strategies and treatment modalities. With regard to treatment, adolescents are truly underserved. There is an awkward fit between the traditional mental health system and the developmental needs of adolescents. Unlike the majority of depressed adults who receive some treatment from general practitioners and medical clinics, adolescents do not tend to visit their pediatricians when they are depressed. One proposed solution is the adolescent comprehensive health care clinic providing a holistic approach to assessment, early intervention, and collaborative treatment between primary provider and mental health worker. Data from our adolescent program suggest that this approach has been successful in dealing with the problem of depression, especially in its early stages. Again, more research is needed to support these preliminary findings, but we believe that the adolescent comprehensive health care approach can be an effective, efficient way of addressing the health needs, mental and physical, of our teens at risk. Federal money for research must be made available, liberalization of health insurance must occur, and state-sponsored services must be developed so that these programs can be made more effective and can be brought to more of the adolescents who need them.

Postprandial glycemic response to orange juice and nondiet cola: is there a difference?

Abstract: The purpose of this study was to compare the effects of unsweetened fruit juice and regular, decaffeinated soda on postprandial serum glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) when these liquids are ingested separately as part ofmixed meals. Eighteen individuals with NIDDM consumed three test breakfasts calculated using the diabetic exchange meal-planning system. Foods were identical in each ofth e breakfasts except for foods in the fruit exchange. Carbohydrate- equivalent amounts offresh orange slices, unsweetened orange juice, and regular, decaffeinated Coke were consumed in breakfasts 1, 2, and 3, respectively. Serum glucose samples were drawn at fasting and 1, 2, and 3 hours postprandially. No difference wasfound in the postprandial serum glucose response when Coke versus orange juice was consumed in the breakfast. These findings question the appropriateness of using unsweetened fruit juices in routine meal planningfor individuals with NIDDM.

The use of intravenous immunoglobulin (IVIG) to prevent infections in bronchopulmonary dysplasia: report of a pilot study.

Abstract: The incidence and severity of pneumonia, sepsis, and other infections was evaluated in a group of 30 premature infants with moderate to severe bronchopulmonary dysplasia (BPD), half of whom were randomly treated with intravenous immunoglobulins (group A). The patients were treated until the age of 6 months. They were compared with an untreated control group (group B). The number of pneumonic episodes (5 in group A and 15 in group B) and other infections, excluding sepsis (1 in group A and 7 in group B), were significantly reduced in the treated group (P less than .05). The number of episodes of sepsis, suspected sepsis, and necrotizing enterocolitis were similar in the two groups. The decrease in the number of respiratory and other infections in BPD infants treated with IVIG requires verification by a larger trial.

Application of D'Arcy Thompson's coordinate transformation approach to clinical genetics photographs using image processing techniques.

Abstract: The coordinate transformation approach outlined by D'Arcy Thompson for analysing biological shape was extended using modern computerised image processing techniques so that it could be applied to photographs for the study of patients with syndromes of altered facial morphogenesis. Photographs digitised at a resolution of 512 by 480 pixels were subjected to 'rubbersheeting' transformations using a fast microcomputer. Starting with a photograph of a normal child, a single application of the rubbersheeting algorithm produced features such as an upturned nose quite simply. Other facial anomalies may also be recreated with multiple applications. Preliminary results suggest that this technique may be a useful tool in attempts to understand and analyse the changes in facial configuration in a variety of syndromes with facial anomalies.

Ulnar tunnel syndrome.

Abstract: The ulnar tunnel syndrome is a relatively uncommon condition resulting from compression of the ulnar nerve as it passes through the loge de Guyon, or ulnar tunnel, in the wrist. The syndrome may cause weakness and atrophy of the intrinsic hand muscles and loss of sensation in the ulnar nerve distribution of the hand. The most common cause of ulnar tunnel syndrome is chronic occupational trauma, either from pressure exerted over the hypothenar eminence by a tool or from the use of the heel of the hand as a hammer. Nonoccupational etiologies include congenital, inflammatory, neoplastic, vascular, metabolic, degenerative and traumatic disorders. Diagnosis often requires neurophysiologic evaluation, in addition to a careful history and physical examination. Conservative treatment aimed at protecting the ulnar tunnel from trauma frequently is effective. Occasionally, surgical decompression of the ulnar tunnel is required.