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Biomedical subjects

A Fausto

Publications and source records attributed to A Fausto.

At least 19 recordsLinked to original sources
PubMed2006

One-shot CT and MR arthrography of the shoulder with a mixture of iodinated and paramagnetic contrast agents using arthroscopy as a gold standard.

PURPOSE: Our aim was to perform computed tomography arthrography (CTA) and magnetic resonance arthrography (MRA) of the shoulder as a one-shot examination and to evaluate its value on the basis of arthroscopy as a gold standard. MATERIALS AND METHODS: Fifteen men and 16 women with planned arthroscopy for chronic (n=17) or traumatic tear of the rotator cuff (n=8), congenital atraumatic (n=1) or traumatic glenohumeral instability (n=2), traumatic tear of the rotator cuff with glenohumeral instability (n=1), or "frozen shoulder" (n=2) underwent plain helical CT in neutral position and intra-articular CT-guided injection of a mixture of iodinated and paramagnetic contrast agents (gadodiamide at 1:250 and iobitridol 350 at 1:5 in 20 ml of saline solution). CT helical scans in intra- and extrarotation and T1-weighted MRA scans in the neutral position were obtained. CTA and MRA were evaluated separately and jointly (CTA-MRA) in different blinded sessions, giving a 0-3 score to the agreement of CTA, MRA, and CTA-MRA with arthroscopy. RESULTS: The injected volume of the solution ranged from 10 to 24 ml. No side effects were observed. CTA obtained a score of 2.33+/-0.62, MRA 2.47+/-0.52, and CTA-MRA 2.67+/-0.49. Significant differences were found for CTA-MRA versus CTA (p=0.0281) and MRA (p=0.0277). There was no significant difference for CTA versus MRA. CONCLUSIONS: CTA and MRA can be performed as a one-shot exam. CTA-MRA seems to give more information than CTA or MRA separately.

Adult↗
PubMed2006

Dynamic breast magnetic resonance imaging without complications in a patient with dual-chamber demand pacemaker.

Mammography and ultrasound indicated a cancer of the right breast in a 77-year-old woman with a dual-chamber demand pacemaker. The patient was not pacemaker-dependent. She underwent breast 1.5T magnetic resonance imaging (MRI) (dynamic gradient echo sequence with Gd-DOTA 0.1 mmol/kg). Before the patient entered the MR room, the configuration of the device was changed (the response to magnet was switched from asynchronous to off and the rate-responsive algorithm was disabled). No relevant modifications of heart rhythm or rate were observed during the MR examination. No symptom was reported. Immediately after the examination, the pacemaker interrogation showed neither program changes nor alert warnings. MRI detected a bifocal cancer in the right breast which allowed tailored breast-conserving treatment to be initiated. Histopathology confirmed a bifocal invasive ductal carcinoma.

Aged↗
PubMed2002

Contrast agents and temporal resolution in breast MR imaging.

The article summarizes the technique of dynamic Gd-enhanced breast magnetic resonance (MR) imaging and the established clinical indications to this examination. The main features of the four different non-selective Gd-chelates today available for contrast-enhanced MR breast imaging are described. Their typical two-compartment (vascular/interstitial) distribution is related to the temporal resolution used for the MR acquisition; the gain in specificity obtained increasing the temporal resolution during the first phase after the contrast intravenous injection (using both, rapid T1-weighted sequences or ultrafast T2*-weighted perfusion imaging) is discussed. Moreover, a survey of new contrast agents is supplied, including a high T1-relaxivity Gd-chelate, blood pool agents, and lymph node targeted agents. In conclusion, future directions are delineated.

Breast↗
PubMed2001

Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells.

Extracellular signal-regulated kinases (Erks), members of the mitogen-activated protein kinase superfamily, play an important role in cell proliferation and differentiation. In this study we employed a dominant negative approach to determine the role of Erks in the regulation of human osteoblastic cell function. Human osteoblastic cells were transduced with a pseudotyped retrovirus encoding either a mutated Erk1 protein with a dominant negative action against both Erk1 and Erk2 (Erk1DN cells) or the LacZ protein (LacZ cells) as a control. Both basal and growth factor-stimulated MAPK activity and cell proliferation were inhibited in Erk1DN cells. Expression of Erk1DN protein suppressed both osteoblast differentiation and matrix mineralization by decreasing alkaline phosphatase activity and the deposition of bone matrix proteins. Cell adhesion to collagen, osteopontin, and vitronectin was decreased in Erk1DN cells as compared with LacZ cells. Cell spreading and migration on these matrices were also inhibited. In Erk1DN cells, expression of alphabeta(1), alpha(v)beta(3), and alpha(v)beta(5) integrins on the surface was decreased. Metabolic labeling indicated that the synthesis of these integrins was inhibited in Erk1DN cells. These data suggest that Erks are not only essential for the growth and differentiation of osteoblasts but also are important for osteoblast adhesion, spreading, migration, and integrin expression.

Alkaline Phosphatase↗
PubMed2000

Regulation of alphaVbeta3 and alphaVbeta5 integrins by dexamethasone in normal human osteoblastic cells.

Long-term administration of pharmacological doses of glucocorticoids inhibits bone formation and results in osteoporosis. Since integrin-mediated cell-matrix interactions are essential for osteoblast function, we hypothesized that the detrimental effect of glucocorticoids on bone derived, at least in part, from decreased integrin-matrix interactions. Because alphavbeta3 and alphavbeta5 integrins can interact with several bone matrix proteins, we analyzed the effects of dexamethasone (Dex) on the expression of these integrins in normal human osteoblastic cells. We found adhesion of these cells to osteopontin and vitronectin to be dependent on alphavbeta3 and alphavbeta5, respectively; this ligand specificity was not altered by Dex. The effects of Dex on the adhesion of human osteoblastic cells to osteopontin and vitronectin were biphasic with an increase after 2 days, followed by a decrease after 8 days of treatment. Consistently, surface alphavbeta3 and alphavbeta5 integrins, which were increased after 2 days of Dex treatment, were decreased after 8 days. Similarly, total cellular alphav, beta3, and beta5 proteins, which were increased by Dex early in the culture, were diminished after 8 days. Metabolic labeling studies indicated that Dex exhibited biphasic regulation on the biosynthesis of alphavbeta5, with stimulation observed during the second day of treatment, followed by inhibition during the 8th day of exposure. By contrast, the biosynthesis of alphavbeta3 was inhibited by Dex on day 1 and remained inhibited on day 8. Analysis of the mRNA indicated that alphav and beta5 levels were increased by Dex during early exposure (1-3 days), followed by inhibition after prolonged exposure (>/=7 days). By contrast, Dex decreased beta3 mRNA level at all the time points analyzed. Consistently, Dex decreased beta3 promoter activity after 1 day and persisted over 8-day period. By contrast, Dex stimulated beta5 promoter activity after 1 or 2 days but had no effect after 8 days. To further evaluate mechanism(s) leading to the decreased integrin expression after prolonged Dex treatment, mRNA stability was analyzed. Dex was found to accelerate the degradation of alphav, beta3 and beta5 mRNA after an 8-day treatment. Thus, the regulation of alphavbeta3 was dependent on transcription and posttranscriptional events whereas the expression of alphavbeta5 was dependent mainly on posttranscriptional events after prolonged Dex treatment. In conclusion, Dex exhibited time-dependent regulation on the expression of alphavbeta3 and alphavbeta5 integrins in normal human osteoblastic cells. Short-term exposure to Dex increased the levels of alphavbeta3 and alphavbeta5 on the surface and cell adhesion to osteopontin and vitronectin whereas long-term exposure to Dex decreased the expression of both integrins and inhibited the cell adhesion to matrix proteins.

Antigens, CD↗
PubMed2000

Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression.

Bone cells transduce mechanical signals into anabolic biochemical responses. However, the mechanisms of mechanotransduction are unknown. To address this issue, we performed studies in primary cells of the human osteoblast lineage grown on collagen/vitronectin-coated supports. We discovered that mechanical strain stimulated a redistribution of the alphavbeta3-integrin to irregular plaque-like areas at the cell-extracellular matrix surface. Proteins involved in integrin-matrix interactions in focal adhesions, vinculin and talin, did not localize to the plaque-like areas of alphavbeta3-expression, but signaling molecules such as focal adhesion kinase (FAK) did. Mechanical strain increased the number and size of the plaques defined by surface expression of alphavbeta3-integrin. Osteopontin was secreted as a cross-linked macromolecular complex, likely through the action of tissue transglutaminase that also was found in the plaques of alphavbeta3-integrin cell-matrix interaction. Mechanical strain increased mineralization of the extracellular matrix that developed in these plaques in alphavbeta3-integrin-dependent manner. Because the plaque-like areas of cell-matrix interaction exhibit macromolecular assembly and mineralization, we conclude that they may represent subcellular domains of bone formation and that alphavbeta3-integrin activation represents one mechanism by which mechanical strain stimulates bone formation.

Bone Marrow Cells↗
PubMed1998

Regulation of insulin-like growth factors I and II and their binding proteins in human bone marrow stromal cells by dexamethasone.

Glucocorticoids inhibit the proliferation, but induce the differentiation, of bone marrow stromal cells into osteoblast-like cells. The mechanisms, however, are still conjectural. Since insulin-like growth factors (IGFs) have profound effects on osteoblast growth and differentiation, it is possible that glucocorticoids exert their effects on bone marrow stromal cells in part via regulation of IGFs. Therefore, we analyzed the effects of dexamethasone (Dex) on the expression of IGF I and IGF II in cultured preosteoblastic normal human bone marrow stromal cells (HBMSC). Whereas Dex decreased the concentration of IGF I in the conditioned medium since early in the treatment, the concentration of IGF II was increased progressively as culture period lengthened. As the activities of IGF I and IGF II are regulated by the IGF binding proteins (IGFBPs), we analyzed the effects of Dex on the expression of IGFBPs. Dex increased IGFBP-2 in a time-dependent manner. The increase in IGFBP-2, however, was only to the same extent as that of IGF II at most, depending on the length of treatment. Therefore, the increase in IGFBP-2 would dampen, but not eliminate, the increased IGF II activities. By contrast, Dex decreased IGFBP-3 levels, the latter increasing the bioavailability of IGF II. Although IGFBP-4 mRNA levels were stimulated by Dex, IGFBP-4 concentration in the conditioned medium was unchanged as measured by RIA. IGFBP-5 and IGFBP-6 mRNA levels were decreased by Dex in a time-dependent fashion. IGFBP-5 protein level was also decreased 1-4 days after Dex treatment. IGFBP-1 mRNA was not detectable in HBMSC. These accumulated data indicate that Dex regulates IGF I and IGF II and their binding proteins differentially in normal human bone marrow stromal cells. The progressive increase in IGF II may contribute to Dex-induced cell differentiation.

Blotting, Northern↗
PubMed1998

Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension.

In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25 (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were not observed until week 32 in uneventful pregnancies, but were present by week 24 (p = 0.002) in patients who later developed hypertensive complications. A net individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8 times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at week 32 predicted the development of hypertensive complications with 80% accuracy. Serial pTM determinations can be useful to select pregnancies who may benefit from early pharmacological intervention.

Adult↗
PubMed1997

An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats.

Intermittent administration of parathyroid hormone (PTH) peptides increases bone density in animal and human models of osteoporosis. In vitro studies have demonstrated that PTH analogs lacking the first two amino acids can stimulate cell proliferation in certain cell systems, whereas fragments with an intact N terminus can be antimitogenic. We have tested whether the truncated PTH(3-38) fragment may be a better "anabolic analog" than PTH(1-38) by monitoring bone density and biomechanical properties of the femur in 6-month-old ovariectomized (OVX) rats. Either PTH fragment was administered subcutaneously (8 micrograms/100 g of body weight) 5 days/week, for 4 weeks, starting 1 week after surgery. During the entire study, untreated OVX rats lost 12.1 +/- 4.4% of their initial bone density. PTH(1-38) reversed the initial bone loss, leading to complete restoration of presurgery values after 4 weeks of treatment. Conversely, administration of PTH(3-38) resulted in 13.2 +/- 5.8% bone loss, while continuous estrogen infusion (10 micrograms/kg/day) prevented bone loss but did not reverse it. Sham-operated animals also experienced significant bone loss in the vehicle and PTH(3-38)-treated groups (-4.5 +/- 6.7%, and -7.6 +/- 2.8%, respectively), whereas a significant gain in bone density (+4.4 +/- 5.6%) was observed in the rats treated with PTH(1-38). A bone quality factor (index of strain energy loss) and the impact strength (resistance to fracture) were 25% and 44% lower in femurs explanted from OVX animals treated with either vehicle or PTH(3-38), compared with sham-operated animals. On the contrary, no difference was observed between OVX and control animals after treatment with PTH(1-38), indicating a preservation of the capacity to withstand mechanical stress. Thus, PTH(1-38) counteracts estrogen-dependent loss of mineral density and bone biomechanical properties and increases bone density in estrogen-replete animals. An intact N terminus sequence is necessary for this anabolic action of PTH.

Amino Acid Sequence↗
PubMed1994

Expression of metalloproteinases and tissue inhibitors of metalloproteinases in human osteoblast-like cells: differentiation is associated with repression of metalloproteinase biosynthesis.

To more clearly define the expression of metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) within the human osteoblast (hOB) lineage, normal hOB and human osteogenic sarcoma cells possessing various levels of alkaline phosphatase (a marker of commitment to the osteoblast lineage) were treated with bone-resorbing agents to determine their effect on the production of interstitial collagenase, stromelysin, 72-kilodalton (kDa) gelatinase, 92-kDa gelatinase, TIMP-1, and TIMP-2. The results revealed that 1) normal hOB release copious amounts of 72-kDa gelatinase, TIMP-1, and TIMP-2; 2) hOB production of 72-kDa gelatinase and TIMP-2 is not regulated by agents that promote bone resorption (e.g. phorbol-12-myristate 13-acetate, recombinant human interleukin-1 beta, tumor necrosis factor-alpha, PTH, and vitamin D3); 3) normal hOB fail to secrete collagenase, stromelysin, or 92-kDa gelatinase when cultured on plastic or a type I collagen substratum, even in response to bone-resorptive agents or mononuclear cell-conditioned medium; 4) in contrast, certain of the osteogenic sarcoma cell populations produce collagenase, stromelysin, and 92-kDa gelatinase, especially when exposed to bone-resorbing stimuli; 5) in general, the capacity for metalloenzyme production by osteogenic sarcoma cell lines varies inversely with their alkaline phosphatase expression; and 6) the most committed (highest alkaline phosphatase) osteogenic sarcoma cell line, SAOS-2, precisely mimics the metalloproteinase profile of normal hOB. The results suggest that the expression of most metalloproteinases is under strict repression within the differentiated normal hOB, and cellular development is associated with diminished capacity to elaborate such enzymes.

Cell Differentiation↗
PubMed1994

Improving vaccination coverage in urban areas through a health communication campaign: the 1990 Philippine experience.

From March to September 1990 the Philippine Department of Health, with the assistance of the HEALTHCOM Project, carried out a national mass-media communication campaign to support routine vaccination services. The essential elements of the campaign strategy were as follows: focusing on measles as a way to get mothers to bring their children to the health centre; emphasizing logistic knowledge in the mass-media messages, in particular popularizing a single day of the week as "vaccination day" and giving clear information about the age for measles vaccination; and focusing on urban areas, which had lower vaccination rates than rural areas. Evaluation of the effects of the campaign indicates an increase in vaccination coverage and a substantial increase in the timeliness of vaccination that can be attributed to improvement in carers' knowledge about vaccination. Furthermore, most of the observed increase in knowledge was related to exposure to the mass-media campaign. There was no evidence of any programmatic change that could account for the increase in vaccination or evidence that increased health education efforts at health centres could account for the change in knowledge. These results indicate that when countries meet certain conditions--a high level of access to the media, sufficient expertise and funds available to develop and produce high-quality radio and television advertisements, and a routine system that is able to serve the increased demand--a mass communication campaign can significantly improve vaccination coverage.

Communication↗
PubMed1992

Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems.

Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Effect of dihydrotachysterol on bone induction in ovariectomized rats.

We have demonstrated via marrow stromal cell cultures and the osteoinductive response to demineralized bone grafts (DBM) that the cortical bone deficit in the ovariectomized (OVX) rat (6 weeks postop) is primarily due to impaired osteoprogenitor cell proliferation, and that dihydrotachysterol (DHT) treatment can be protective. In cultured marrow stromal cells from OVX rats, short-term DHT-Rx exaggerated the already subnormal pattern of marrow stromal cell proliferation. However, in DBM grafts, DHT treatment benefited the time-course of mesenchymal cell DNA synthesis as measured by tritiated thymidine incorporation and osteogenic cell maturation as measured by alkaline phosphatase concentration, and established a suggestive trend toward normalization of bone formation/mineralization (24 h 45Ca incorporation). The data from this animal model infer that DHT could moderate the bone loss normally seen in ovariectomized rats via an activation of the osteoprogenitor cell population.

Alkaline Phosphatase↗
PubMed1989

Parathyroid hormone-related peptide transiently increases cytosolic calcium in osteoblast-like cells: comparison with parathyroid hormone.

PTH-related protein (PTHrP), similarly to PTH, stimulates cAMP production in target tissues. However, different potencies have been observed for the two peptides in some biological assays, suggesting that cAMP-independent second messenger pathways might be involved in PTHrP signal transduction. This hypothesis was tested in the osteogenic sarcoma cell line UMR 106-01. Addition of PTHrP-(1-34) to cell suspensions loaded with the Ca2+ indicator indo-1 produced a transient dose-dependent increase in intracellular calcium ([Ca2+]i), with a maximal effect at 2 x 10(-7) M and an ED0.5 at about 4 x 10(-8) M. The amplitude and duration of the transients were similar to those induced by equimolar concentrations of bovine PTH-(1-34) (bPTH), and the dose-responses of the two peptides completely overlapped. Both full-length peptides, PTHrP-(1-141) and bPTH-(1-84), produced effects identical to those observed with the 1-34 fragments. Homologous and heterologous desensitization to both PTHrP-(1-34) and PTHrP-(1-141) occurred when the cells were prestimulated with equimolar or 10-fold lower doses of either PTHrP-(1-34) or bPTH-(1-34). Desensitization to bPTH-(1-34) was also observed when cells were prestimulated with PTHrP-(1-34). Furthermore, pretreatment with either bPTH-(3-34) or [Nle8,18, Tyr34]bPTH-(3-34) amide did not affect [Ca2+]i, but reduced the response to PTHrP-(1-34) by 55 +/- 10% (n = 3) and 67 +/- 8% (n = 3), respectively. The PTHrP-(1-34)-induced [Ca2+]i transient was not substantially affected by either extracellular Ca2+ chelation by EGTA or pretreatment with diltiazem, and nitrendipine only partially inhibited the [Ca2+]i response to PTHrP-(1-34) by about 10%. These results indicate that in osteoblastic cells PTHrP mobilizes Ca2+ from an intracellular storage pool with potency equal to that of PTH, and that the two hormones interact with the same receptor.

Animals↗
PubMed1987

Stimulation of phosphatidylcholine biosynthesis in diabetic hypertrophic kidneys.

Choline metabolism and phosphatidylcholine biosynthesis were studied in renocortical slices of rats rendered diabetic with streptozotocin. The rates of [14C]choline incorporation into both acid-soluble and acid-insoluble fractions were increased in diabetic relative to control kidneys. While choline uptake into the control kidneys reached a plateau after 30 min of incubation, the tissue uptake of choline by the diabetic kidneys showed a time-dependent increase over 120 min, rising to a level exceeding that of control kidneys. In the control kidney, the oxidation of choline to betaine was similar to the level of phosphocholine accumulation during the first 30 min, while the formation of phosphocholine in the diabetic kidney was 1.9-fold higher than that in the control kidney (P less than 0.02) and 1.4-fold higher than the formation of betaine in diabetics (P less than 0.05). These data suggest that most of the choline transported into cells enters the Kennedy pathway by phosphorylation to phosphocholine in diabetic kidneys. The diabetic kidney also demonstrated a marked increase in the formation of three choline-containing phospholipids; phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The treatment of diabetes with insulin restored these abnormalities toward normal. The absolute content of phosphatidylcholine significantly increased in diabetic kidneys (P less than 0.05) while contents of other major phospholipids and total lipid phosphorus in diabetic kidneys were not different from those in control kidneys. Our results indicate that renal hypertrophy in experimental diabetes is associated with a stimulation of the biosynthesis of renal phosphatidylcholine, presumably caused by an enhanced tissue uptake of choline and a stimulation of choline kinase. Since an enhancement of the membrane phosphatidylcholine biosynthesis is one of the early responses to growth signals, an alteration in phosphatidylcholine biosynthesis may contribute to the development of renal hypertrophy in experimental diabetes.

Animals↗
PubMed1986

Effects of age and estrogen on calcium absorption in the rat.

In order to differentiate the relative effects of age and estrogen on rates of calcium absorption and serum levels of parathyroid hormone and calcitonin, the effect of oophorectomy with and without estrogen replacement (2 weeks) was studied in rats for 30- or 120-day periods. Whereas oophorectomy for 30 days resulted in a significant decrease in serum calcium and an increase in serum phosphate, no change in either calcium or phosphate was observed in the 120-day oophorectomized animals. iPTH decreased in both the 30- and 120-day oophorectomized animals although these changes were not significant at the .05 level. Whereas no significant change in basal circulating calcitonin occurred in the 30-day oophorectomized rats, it decreased significantly in the older animals following the ablative procedure. Forty-five days following estrogen deprivation, calcitonin release to a calcium secretagogue was significantly blunted. Intestinal calcium absorption decreased with age, and unlike the increments in calcium absorption observed in the younger estrogen-repleted, 30-day oophorectomized rat, no change in calcium absorption was observed when estrogens were administered to the older, 120-day oophorectomized rat. The accumulated data suggest that the effects of estrogen loss on the hormonal control of bone metabolism and calcium absorption are age dependent, and that estrogen contributes significantly to changes in calcium homeostasis observed in the maturing rat.

Aging↗