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Biomedical subjects

R Sanchez

Publications and source records attributed to R Sanchez.

At least 55 records · Page 3Linked to original sources
PubMed1999

Progressive growth of infantile cutaneous hemangiomas is directly correlated with hyperplasia and angiogenesis of adjacent epidermis and inversely correlated with expression of the endogenous angiogenesis inhibitor, IFN-beta.

Cutaneous infantile hemangioma progresses through proliferation and involution phases. Since treatment with interferon, a negative regulator of angiogenesis, accelerates the involution phase, we hypothesized that cutaneous infantile hemangioma is associated with an imbalance between endogenous positive and negative regulators of angiogenesis. We examined 30 specimens of cutaneous hemangioma [proliferative phase (n=15), involuting phase (n=8), and involuted phase (n=7)] and control human skin (n=17), fixed in formalin and embedded in paraffin. Routine histology, immunohistochemistry, and an mRNA in situ hybridization technique were used to measure expression of the positive angiogenic molecules basic fibroblast growth factor (bFGF) and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), and an endogenous inhibitor of angiogenesis, interferon-beta (IFN-beta). Proliferative phase hemangiomas expressed high levels of bFGF and VEGF/VPF but not IFN-beta (mRNA and protein). The epidermis directly overlying proliferating hemangiomas was hyperplastic, contained numerous dividing cells, and expressed bFGF and VEGF/VPF but not IFN-beta. Epidermis from normal individuals and epidermis directly overlying involuted tumors or at sites distant to the proliferating hemangioma was not hyperplastic and expressed normal levels of bFGF, VEGF/VPF, and IFN-beta. These data suggest that the proliferation of cutaneous hemangiomas and adjacent epidermis is associated with an imbalance between positive and negative angiogenic factors expressed by the neoplasm and adjacent normal tissue.

Angiogenesis Inducing Agents↗
PubMed1998

HIV type 1 protease inhibitors fail to inhibit HTLV-I Gag processing in infected cells.

Protease inhibitors are currently the most effective antiviral agents against human immunodeficiency virus type 1 (HIV-1). In this study we determined the effect of four HIV-1 protease inhibitors on human T cell leukemia virus type 1 (HTLV-I). Rhesus monkey cells infected with HTLV-I were treated with different concentrations of indinavir, saquinavir, ritonavir, or nelfinavir. The effect of these inhibitors was monitored through their effect on the processing efficiency of the viral Gag protein in cells, the natural substrate for the viral protease. These inhibitors failed to block processing of HTLV-I Gag. To confirm these findings, human cells were cotransfected with plasmids encoding infectious copies of HIV-1 and HTLV-I, and the cells were subsequently treated with these same HIV-1 protease inhibitors. At concentrations between 5 and 50 times the IC50 for inhibition of HIV-1 replication, inhibition of HIV-1 Gag cleavage was apparent. In contrast, no effect on HTLV-I Gag processing was seen. At higher concentrations, HIV-1 Gag processing was essentially completely inhibited whereas HTLV-I Gag cleavage was still unaffected. Thus, these inhibitors are not effective inhibitors of HTLV-I Gag processing. Sequence alignments of the HIV-1 and HTLV-I viral proteases and processing sites suggest that the active site of the HTLV-I protease may have subtle differences in substrate recognition compared with the HIV-1 protease.

Amino Acid Sequence↗
PubMed1998

A medium-copy-number plasmid for insertional mutagenesis of Streptococcus mutans.

We have constructed a plasmid useful for insertional mutagenesis in Streptococcus mutans. The molecule, pSU20Erm, is based on a derivative of pACYC184 known as pSU20. The plasmid described here is approximately 3.7 kb in size and has the following properties: it replicates in Escherichia coli, does not replicate in S. mutans, contains an erythromycin-resistance marker which can be selected in E. coli or the streptococci, contains a multiple cloning site with few restriction sites in the remainder of the molecule, and can be screened on X-Gal-containing medium for the presence of insertions into the multiple cloning site. We have used the plasmid to construct a library of S. mutans DNA in E. coli and show that the clones can be reintegrated into the S. mutans chromosome via homologous recombination, thereby interrupting native genes. The plasmid has been used to clone part of a homologue of the E. coli drpA gene, encoding a global regulatory element for RNA synthesis. Further, we have identified an element closely linked to drpA in S. mutans with high homology to IS861.

Amino Acid Sequence↗
PubMed1998

Granulomatous epididymo-orchitis: sonographic features and clinical outcome in brucellosis, tuberculosis and idiopathic granulomatous epididymo-orchitis.

PURPOSE: We reviewed and analyzed sonographic findings in granulomatous epididymo-orchitis in an attempt to differentiate this rare inflammatory entity from other causes of enlarged scrotum, such as tumors. MATERIALS AND METHODS: We retrospectively reviewed sonographic features of 9 patients a mean of 41 years old with specific and nonspecific granulomatous epididymo-orchitis, including brucellosis in 7, tuberculosis in 1 and idiopathic granulomatous epididymo-orchitis in 1. Histological confirmation was obtained in 3 cases, and in the remaining 6 positive clinical manifestations and laboratory tests for brucellosis were accepted as the main criteria for the diagnosis of brucellar epididymo-orchitis. RESULTS: The most notable echographic finding was an enlarged and heterogeneous epididymis, predominantly in the body and tail. Testicular involvement consisted of a diffusely hypoechoic testis or focal intratesticular areas. Thickening of the scrotal wall and tunica albuginea, and moderate hydrocele were also noted occasionally. Followup scans revealed intratesticular abscesses in 3 patients. CONCLUSIONS: These echographic findings may suggest the diagnosis of granulomatous epididymo-orchitis in the appropriate clinical setting, and help to avoid unnecessary orchiectomy for benign disease.

Adult↗
PubMed1998

Epidemiology of elderly patients' burns in the South West of France.

A retrospective study of 716 patients aged 60 years and above (324 men, 392 women) was undertaken in order to determine quality control in burns management in the South West of France. The following epidemiological data was obtained: high hospitalization rate (7 per cent of the general admissions); monthly and seasonal periodicity; predominance of indoor accidents (86 per cent) with domestic accidents being more frequent in women (63 vs. 37 per cent). Outdoor accidents were mainly recreational and were five times more frequent in men than in women. The overall mortality was 39 per cent and was influenced by the burns extent, depth, predisposing factors and early management. More burns occurred in urban areas (53 per cent) but mortality was higher in patients from rural areas (62 vs. 38 per cent). It was observed that delay in management, especially fluid resuscitation of patients from the rural areas, was partly responsible for this outcome. Propositions were made to diffuse more information on the importance of early management of burns in rural areas.

Age Distribution↗
PubMed1998

Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence.

It was determined whether the expression level of several genes that regulate different steps of metastasis in formalin-fixed paraffin-embedded archival specimens of human gastric cancers correlated with disease recurrence and metastasis. The steady-state mRNA expression level for epidermal growth factor receptor (EGF-R), basic fibroblast growth factor (bFGF), E-cadherin, type IV collagenase and multidrug resistance (MDR-1) were examined by a colorimetric in situ hybridisation (ISH) technique, concentrating on reactivity at the periphery of the lesions. All patients were operated on for cure. 15 cases were disease-free and 10 had disease recurrence by 4.5 years after resection of the primary tumours. The expression of EGF-R and bFGF type IV collagenase was higher and expression of E-cadherin was lower in the disease-recurrence cases than in the disease-free cases. The ratio between the expression level of collagenase type IV and E-cadherin at the periphery of the surgical specimens differed significantly between the disease-free cases and the recurrent-metastatic cases. These data show that multiparametric ISH analysis for several metastasis-related genes may allow prediction of disease recurrence of gastric cancer.

Cadherins↗
PubMed1998

Epidural anesthesia in cardiac surgery: is there an increased risk?

OBJECTIVE: To assess the risk of hemorrhagic complications associated with epidural anesthesia in patients undergoing coronary artery bypass grafting. DESIGN: A prospective study. SETTING: A cardiac surgical center associated with a university. PARTICIPANTS: Five hundred fifty-eight consecutive patients scheduled for coronary artery bypass surgery. INTERVENTIONS: A Tuohy 18G epidural catheter was inserted the day before surgery in all patients. MEASUREMENTS AND MAIN RESULTS: Preoperative coagulation tests, such as platelet count and prothrombin time, were performed. No patient was on oral anticoagulation therapy or had coagulation disorders. Four hundred three (72%) patients were on antiplatelet therapy, which was terminated at least 1 week before surgery. The epidural catheter was left in situ for up to 5 days. All patients were observed daily for signs of spinal cord compromise, such as radicular back pain or progressive sensory or motor deficits. There were no documented spinal hematomas. CONCLUSION: By following certain guidelines, the risk for the development of epidural hematoma is not increased in patients undergoing epidural anesthesia during cardiac surgery.

Adult↗
PubMed1998

Molecular regulation of UVB-induced cutaneous angiogenesis.

We determined whether cutaneous angiogenesis induced by exposure of mice to ultraviolet-B (UVB) radiation is associated with an imbalance between positive and negative angiogenesis-regulating molecules. Unshaved C3H/HeN mice were exposed to a single dose (15 kJ per m2) of UVB. At various times, the mice were killed, and their external ears were processed for routine histology and immunohistochemistry. Antibodies against proliferating cell nuclear antigen and bromodeoxyuridine identified dividing cells. Antibodies against CD31/ PECAM-1 identified endothelial cells, and antibodies against basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor, and interferon-beta (IFN-beta) identified angiogenesis-regulating molecules. Epidermal hyperplasia was documented by 48 h and reached a maximum on day 7 after exposure to UVB. The expression of bFGF increased by 24 h, whereas the expression of IFN-beta decreased by 72 h after exposure to UVB. The expression of vascular endothelial growth factor/vascular permeability factor increased slightly after irradiation. The altered balance between bFGF and IFN-beta was associated with increased endothelial cell proliferation (bromodeoxyuridine + CD31 + cells) within existing blood vessels, leading to telangiectasia and new blood vessels. UV-induced epidermal hyperplasia and cutaneous angiogenesis were highest in IFN-alpha/beta receptor knockout mice. These results demonstrate that in response to UVB radiation, dividing keratinocytes produce a positive angiogenic molecule (bFGF) but not a negative angiogenic molecule (IFN-beta), and that this altered balance is associated with enhanced cutaneous angiogenesis.

Animals↗
PubMed1998

Evaluation of a bioabsorbable physical barrier for guided bone regeneration. Part I. Material alone.

This study evaluates a prototype bioabsorbable physical barrier material for guided bone regeneration. Nonspacemaking dehiscence-type defects were surgically created in the right and left mandibles of six adult dogs. Each animal received six root-form threaded titanium implants. The osseous defects were randomized to receive treatment by either the prototype bioabsorbable barrier composed of a copolymer of lactide and glycolide, an expanded polytetrafluoroethylene nonresorbable barrier, or no barrier (control), Clinical and histologic results after 3.5 months of wound healing indicated that exposed threads were covered when treated with the expanded polytetrafluoroethylene barrier. Minimal thread coverage was evident with the bioabsorbable barrier and the control.

Alveolar Bone Loss↗
PubMed1998

Evaluation of a bioabsorbable physical barrier for guided bone regeneration. Part II. Material and a bone replacement graft.

Part I of the evaluation of a prototype bioabsorbable physical barrier composed of a copolymer of lactide and glycolide for treatment of bone defects in the guided bone regeneration procedure indicated that the prototype bioabsorbable physical barrier did not possess sufficient spacemaking characteristics to prevent collapse of the barrier into the defect or against the threads of the titanium implants. The purpose of Part II was to evaluate this bioabsorbable physical barrier in combination with a supporting material to prevent barrier collapse. Posterior mandibular teeth in three dogs were extracted and allowed to heal for 3 months. This produced localized alveolar ridge defects with a narrow buccolingual width. Six titanium threaded implants were placed in the right and left mandibles of each dog so that nonspacemaking dehiscencetype defects were produced. Two defects in each animal were randomly treated with the prototype bioabsorbable physical barrier and decalcified freeze-dried bone allograft; two defects were treated with a nonbioabsorbable expanded polytetrafluoroethylene barrier with decalcified freeze-dried bone allograft; and one defect each was treated with prototype bioabsorbable physical barrier alone or by flap access with no barrier or bone replacement graft. The results demonstrated that both the bioabsorbable and the nonbioabsorbable barrier combined with decalcified freeze-dried bone allograft produce comparable amounts of new bone with percent bone-to-implant contact, height, width, and area. Defects treated with the prototype bioabsorbable physical barrier alone or no barrier demonstrated unfavorable results. It is suggested that a bone replacement graft is indicated when treating defects with a nonspacemaking morphology.

Alveolar Bone Loss↗
PubMed1998

[Vascular dysfunction in hypertension evaluated by nonivasive assessment of arterial impedance].

The effects of high blood pressure on arterial vessels has become an important topic of research. These effects can be evaluated by analyzing three major components: systemic vascular resistance, arterial compliance and wave reflection. The increase in systemic vascular resistance and arterial stiffness produces modifications of left ventricular afterload and morphologic changes of pressure and flow waves. These effects can eventually cause structural changes of the left ventricle, an increase in oxygen consumption and a decrease in coronary perfusion. Until recently, invasive methods were the only means to evaluate arterial function. The aim of this review is to assess the usefulness of non invasive methods to determine the components of arterial impedance in order to evaluate the hemodynamic changes due to high blood pressure.

Arteries↗
PubMed1997

Aqueous extracts of cigarette smoke promote the oxidation of low density lipoprotein by peroxidases.

Oxidation of low density lipoprotein (LDL) by cigarette smoke has been considered a potential mechanism by which smoking may promote atherosclerosis. We report in this study that cigarette smoke extract (CSE) inhibited copper-induced oxidation of LDL suggesting the presence of antioxidants in CSE. It is currently believed that peroxidases may oxidize LDL in vivo and during such oxidations antioxidants become pro-oxidants. Accordingly, when LDL was oxidized by peroxidase in the presence of CSE there was an increase in the oxidation of LDL. This is the first study suggesting that smoking may promote atherosclerosis by enhancing peroxidase-catalyzed lipid peroxidation.

Copper↗
PubMed1997

Ornithine carbamoyltransferase from the extreme thermophile Thermus thermophilus--analysis of the gene and characterisation of the protein.

The ornithine carbamoyltransferase (OTC) gene from Thermus thermophilus was cloned from a lambda-ZAP genomic library. An ORF of 903 bp was found coding for a protein of Mr 33,200. The coding region has a very high overall G+C content of 68.0%. T. thermophilus OTC displays 38-48% amino acid identity with other OTC, the most closely related proteins being OTC from the archaeon Pyrococcus furiosus and from Bacillus subtilis. The enzyme was expressed in Escherichia coli and purified to homogeneity using a thermoshock followed by affinity chromatography on delta-N-phosphonoacetyl-L-ornithine-Sepharose. The native enzyme has an Mr of about 110,000, suggesting a trimeric structure, as for most anabolic OTC from various organisms. T. thermophilus OTC exhibits Michaelis-Menten kinetics for carbamoyl phosphate and ornithine with a Km(app) of 0.10 mM for both substrates. The pH optimum was dependent on ornithine concentration with an optimum at pH 8 for ornithine concentrations around Km values. Higher concentrations shift the optimum towards lower pH. The optimal temperature was above 65 degrees C and the activation energy 39.1 kJ/mol. The enzyme is highly thermostable. In the presence of its substrates the half-life time was several hours at 85 degrees C. Ionic and hydrophobic interactions contribute to the stability. The expression of T. thermophilus OTC was negatively regulated by arginine.

Amino Acid Sequence↗
PubMed1997

Blockade of the stimulatory effect of estrogens, OH-tamoxifen, OH-toremifene, droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells.

Although temporary benefits of tamoxifen therapy are observed in up to 40% of women with breast cancer, this compound, which is known to possess mixed estrogenic and antiestrogenic activities, has been associated with increased risk of endometrial carcinoma. This study compares the effects of the novel nonsteroidal pure antiestrogen EM-800 and related compounds with those of a series of antiestrogens on the estrogen-sensitive alkaline phosphatase (AP) activity in human endometrial adenocarcinoma Ishikawa cells. Exposure to increasing concentrations of up to 1000 nM EM-800 or its active metabolite EM-652 alone failed to affect basal AP activity. In contrast, incubation with 10 nM (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, or raloxifene increased the value of this estrogen-sensitive parameter by 3.3-, 3.5-, 2.2-, and 1.6-fold, respectively, a stimulatory effect that was completely reversed by simultaneous exposure to 30 nM EM-800. Moreover, the stimulation of AP activity induced by 1 nM 17beta-estradiol was completely reversed by EM-800, EM-652, or ICI-182780, at the IC50 value of 1.98 +/- 0.23, 1.01 +/- 0.16, and 5.64 +/- 0.59 nM, respectively, whereas the partial blockade exerted by (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, or raloxifene was observed at IC50 values of 13.5 +/- 3.80, 41.0 +/- 7.2, and 3.74 +/- 0.43 nM, respectively. Thus, as assessed by their activity in the human Ishikawa endometrial carcinoma cells, EM-800 and EM-652 are the most potent known antiestrogens in Ishikawa cells, and, most importantly, they are devoid of the estrogenic activity observed in these human endometrial cancer cells with (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, and raloxifene.

Adenocarcinoma↗
PubMed1997

Structure-function relationships of 3 beta-hydroxysteroid dehydrogenase: contribution made by the molecular genetics of 3 beta-hydroxysteroid dehydrogenase deficiency.

The transformation of delta 5-3 beta-hydroxysteroids into the corresponding delta 4-3-keto-steroids is an essential step for the biosynthesis of all classes of active steroids: progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. These steroid hormones play a crucial role in the differentiation, development, growth, and physiological function of most human tissues. The structures of several cDNAs encoding 3 beta-HSD isoenzymes have been characterized in human and several other vertebrate species: human types I and II; macaque; bovine; rat types I, II, III, and IV; mouse types I, II, III, IV, V and VI; hamster types I, II, and III; and rainbow trout. Their transient expression reveals that 3 beta-HSD and delta 5-delta 4-isomerase activities reside within a single protein. Distinct approaches have been used for a better understanding of the structure-function relationships of these 3 beta-HSD enzymes: i) affinity radiolabeling studies of the human type I 3 beta-HSD; ii) identification and the functional consequences of the human type-II 3 beta-HSD mutations detected in patients with 3 beta-HSD deficiency. Taken together, all of these data were examined to determine whether the relationship between the genotype and the phenotype of these patients were consistent with in vitro mutagenesis studies. 3 beta-HSD deficiency, transmitted in an autosomic recessive disorder, is characterized by varying degrees of salt wasting; in genetic males, fetal testicular 3 beta-HSD deficiency causes an undervirilized male genitalia (male pseudohermaphroditism); females exhibit either normal sexual differentiation or mild virilization. All mutations were detected in the type II 3 beta-HSD gene, which is expressed almost exclusively in the adrenals and gonads. No mutation was detected in the type I 3 beta-HSD gene, which is expressed in peripheral tissues. The finding of a normal type I 3 beta-HSD gene explains the elevated delta 5-steroids and mild virilization of affected girls at birth. To date, 24 mutations have been identified in 25 distinct families with 3 beta-HSD deficiencies. All nonsense and frameshift mutations introducing a premature termination codon were associated with the classical salt-losing form. The locations of these nonsense mutations suggest that at least the first 318 amino acids out of 371 are required for 3 beta-HSD activity. The consequences of the missense mutations on some domains of the 3 beta-enzyme, such as membrane-spanning domains, cofactor-binding site, and steroid-binding site, were reviewed. The future crystallization of the overexpressed normal and mutant-type II-3 beta-HSD enzymes should contribute to a better understanding of the structure-function relationships of this enzyme, especially for missense mutations located outside the putative functional regions.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Mammalian cell expression of dimeric small immune proteins (SIP).

We have designed and expressed bivalent small immune proteins (SIP) based on scFv fragments connected through a short linker of four amino acids to the CH3 domain of the human immunoglobulin gamma 1 H-chain. Three different versions have been designed and expressed in mammalian cells. In one construct a cysteine residue was included in the last amino acid of the flexible 15-amino acid long linker connecting the V(L) and V(H) domains, thus creating a disulphide bond stabilized molecule. A version with a shorter (five amino acids) V(L)/V(H) linker was also produced and shown to be efficiently assembled and secreted. All three SIPs form dimers retaining their antigenic specificity in Western blotting and having a comparable functional affinity (avidity) as determined by ELISA.

Animals↗
PubMed1997

Cutaneous verruca with genital human papillomavirus in a 2-year-old girl.

Human papillomavirus (HPV) is the etiologic agent of warts and condyloma acuminatum (CDA). Condyloma acuminatium is believed to result from sexual transmission of HPV types 6 and 11 in adults. In contrast, nonsexual transmission of CDA occurs frequently between children and caregivers. Nonsexual-CDA are present almost exclusively in the mucosal epithelium in children. The authors analyzed a rapidly growing cutaneous wart on the thigh of a two-year-old girl for the presence of oncogenic and nononcogenic HPV types by in situ hybridization. This cutaneous wart was found to have the HPV types commonly found in CDA, namely types 6 and/or 11. This is an unusual finding and suggests that verruca vulgaris may result from papillomavirsuses other than HPV 2 in children.

Child, Preschool↗