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Biomedical subjects

A Cruz

Publications and source records attributed to A Cruz.

At least 37 records · Page 2Linked to original sources

Selective labeling of pulmonary surfactant protein SP-C in organic solution.

Pulmonary surfactant protein SP-C has been isolated from porcine lungs and treated with dansyl isothiocyanate in chloroform:methanol 2:1 (v/v) solutions,under conditions optimized to introduce a single dansyl group covalently attached to the N-terminalamine group of the protein without loss of its native thioesther-linked palmitic chains. The resulting derivative Dans-SP-C conserves the secondary structure of native SP-C as well as the ability to promote interfacial adsorption of DPPC suspensions and to affect the thermotropic behavior of DPPC bilayers. This derivative can be used to characterize lipid-protein and protein-protein interactions of a native-like SP-C in lipid/protein complexes.

Animals↗

The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for estrogen receptor negative breast cancers.

The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor (EGF)-stimulated estrogen receptor negative (ER-) breast cancer cells in vivo and role of nuclear factor kappa B (NF-kappaB) on tumorogenesis have been investigated. This was studied in an animal model by implanting ER- mouse mammary epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of tumors and caused extensive necrotic degeneration and regression of the tumors without causing any microscopically detectable damage to the vital organs liver and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit (dnIkkbeta) of the inhibitory kappa B (IkappaB) kinase (dnIkk) that selectively blocked activation of NF-kappaB caused loss of tumorigenic potential of CSMLO cells. Stable expression of dnIkkbeta also blocked phorbol 12-myristate 13-acetate (PMA)-induced activation of NF-kappaB and overexpression of cyclin D1, concomitantly with the loss or reduced tumorigenic potential of these cells. Thus, results from in vivo and in vitro experiments strongly suggest the involvement of NF-kappaB in ER- mammary epithelial cell-mediated tumorigenesis. We propose that blocking NF-kappaB activation not only inhibits cell proliferation, but also antagonizes the antiapoptotic role of this transcription factor in ER- breast cancer cells. Thus, NF-kappaB is a potential target for therapy of EGFR family receptor-overexpressing ER- breast cancers.

Animals↗

Melatonin protects against renal oxidative stress after obstructive jaundice in rats.

The goals of this study were to analyze the renal oxidative status in experimental biliary obstruction and to evaluate the impact of melatonin on renal oxidative stress. Cholestasis was done by double ligature and section of the extra-hepatic biliary duct. Melatonin was injected i.p. (500 microg/kg/day). Malondialdehyde, reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione transferase were determined in the renal tissue. After biliary obstruction, an increase in malondialdehyde (P<0.0001) and a fall in reduced glutathione (P<0.0001) were seen. Moreover, the scavenger enzyme activity had significantly diminished. After melatonin administration, the malondialdehyde fell significantly (P<0.0001), whereas reduced glutathione showed an important increase (P<0.0001) compared with the ligated bile duct group. Experimental bile duct obstruction was associated to an increase of renal oxidative stress. Treatment with melatonin decreased the renal lipid peroxidation, and both the reduced glutathione as well as the scavenger enzyme activity recovered.

Animals↗

Epidemiology of HPV infection among Mexican women with normal cervical cytology.

Cervical cancer is caused by human papillomavirus (HPV) and is the most common cancer among Mexican women, but no population-based studies have reported the prevalence and determinants of HPV infection in Mexico. A population-based study was carried out between 1996 and 1999, based on an age-stratified random sample of 1,340 women with normal cytologic diagnoses from 33 municipalities of Morelos State, Mexico. The prevalence of cervical HPV DNA was determined by reverse line blot strip assay to detect 17 cancer-associated and 10 non-cancer-associated HPV types. Two peaks of HPV DNA prevalence were observed. A first peak of 16.7% was observed in the age group under 25 years. HPV DNA prevalence declined to 3.7% in the age group 35-44 years, then increased progressively to 23% among women 65 years and older. Cancer-associated HPV types were the most common in all age groups; non-cancer-associated HPV types were rare in the young and became more common linearly with age. Twenty-four types of HPV were detected; HPV 16, HPV 53, HPV 31 and HPV 18 were the most common, but none was present in more than 1.7% of subjects. The main determinant of infection with both cancer-associated and non-cancer-associated HPV types was the number of sexual partners in all age groups. Less-educated women were at an increased risk of infection with cancer-associated but not with non-cancer-associated HPV types; low socioeconomic status was associated with detection of non-cancer-associated HPV types. Among young women an increasing number of pregnancies was associated with lower HPV detection and among older women low socioeconomic status was related to increased HPV detection, particularly for the age group 35-54 years. Among women with cancer-associated HPV types, there was a higher intensity of polymerase chain reaction signal in younger than in older age groups (p < 0.001). We present additional evidence for the sexually transmitted nature of HPV infection, regardless of age group and HPV type. We confirm previous findings of a second peak of high-risk HPV infections in postmenopausal women, in this case with a clear predominance of cancer-associated HPV types. In populations with this pattern, which can be related to reactivation of latent HPV infections or high previous exposure in older women, screening with HPV testing can have a reduced specificity among older women if proper cut-off points for HPV positivity are not used. Longitudinal studies of immune responses to HPV infection in different age groups are warranted.

Adult↗

Melatonin versus vitamin E as protective treatment against oxidative stress after extra-hepatic bile duct ligation in rats.

The aims of the present study were first to compare the effects of melatonin and vitamin E on the cholestasis syndrome and their protective effect on liver injury, and second, to evaluate the activity of antioxidant enzymes after treatment with these antioxidant drugs. Cholestasis was achieved in adult male Wistar rats by double ligature and section of the extra-hepatic biliary duct. Hepatic and plasma oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and reduced glutathione (GSH) in plasma and homogenates of hepatic tissue. Serum bilirubin, alkaline phosphatase (AP), and gamma-glutamyl-transpeptidase (GGT) were used to evaluate the severity of cholestasis, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Both vitamin E and melatonin were administrated 1 day before and 7 days after bile duct ligation. Acute ligation of the bile duct was accompanied by a significant increased in MDA and a decrease in GSH levels in both plasma and liver, as well as a significant reduction in antioxidant enzymes activities. The overall analysis of both treatments showed that melatonin (500 microg/kg daily) offered significantly better protection against cholestasis and a superior protective effect on hepatic injury than did vitamin E (15 mg/kg daily). Although vitamin E treatment resulted in a reduction of parameters of oxidative stress, the results were significantly better after a much lower daily dose of melatonin. Moreover, melatonin treatment was associated with a significant recovery of antioxidative enzymes. In conclusion, the present paper demonstrates a correlation between the intensity of biliary tract obstruction and increased free radical generation, as well as a direct correlation between the level of oxidative stress and the biochemical markers of liver injury. Melatonin (at a much lower dose than vitamin E) was much more efficient than vitamin E in reducing the negative parameters of cholestasis, the degree of oxidative stress and provided a significantly greater hepatoprotective effect against the liver injury secondary to the acute ligation of the biliary duct.

Animals↗

Synthesis and hypolipidemic activity of modified side chain alpha-asarone homologues.

A series of homologues of alpha-asarone (1), containing variable size and functionality on the side chain attached to the aromatic ring, has been subjected to a study of structure-activity relationship. For most of the prepared derivatives, either with a carbonyl (8a-8e), a hydroxy group (9a-9e), or with a conjugated double bond (10a-10d), significant effects on serum lipoprotein cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were displayed. The results showed an enhancement of the hypocholesterolemic activity as the length of the chain is decreased. Theoretical conformational and electrostatic potential analyses of I and olefins 10 suggest unfavorable steric interactions in the bulky superior side-chain homologues as the deactivating biological effect.

Allylbenzene Derivatives↗

Perinatal management of fetal cardiac anomalies in a specialized obstetric-pediatrics center.

Perinatal teams dealing with fetal heart disease frequently wonder which pregnancies might be terminated, and when delivery should take place in a specialized surrounding. We present a retrospective study of 229 fetuses, in which prenatal ultrasound showed a cardiac anomaly not compatible with a standard maternity ward delivery. One hundred nineteen pregnancies were terminated (group I) while 110 pregnancies led to the birth of a live baby (group II). Pathology in group I was discovered earlier than in group II (24 vs. 29.3 weeks' gestation; p <0.01), and associated malformations or chromosomal anomalies were much more frequent in group I (80/119 vs. 9/110; p <0.001). Among live born babies, three infants with transposition of the great arteries underwent Rashkind atrioseptostomy in the delivery room. With a minimum follow-up of 12 months, 69 children (63%) have undergone surgery. Among 92 survivors (1 child is lost to follow-up), 78 (71%) are asymptomatic and 14 symptomatic. Early prenatal diagnosis of fetal heart anomalies significantly facilitates prenatal work-up and perinatal care. We present the types of pathology having led to termination and define the situations in which children are at risk of perinatal hemodynamic compromise.

Abortion, Eugenic↗

High prevalence of antibodies to herpes simplex virus type 2 among middle-aged women in Mexico City, Mexico: a population-based study.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is among the most prevalent sexually transmitted diseases worldwide. In Mexico there is a lack of population-based HSV-2 surveys. GOALS: To determine population-based HSV-2 seroprevalence and risk factors among women in Mexico City. STUDY DESIGN: A random sample of 730 women was identified among the residents of Mexico City. Women ages 25 to 85 years were selected from 3,694 households. Western blot serology testing was conducted on serum samples to determine HSV-2 type-specific serostatus. A structured questionnaire was administered, and multivariate analyses were performed to identify risk factors for HSV-2 seropositivity, which were stratified into two age categories: younger than 50 years of age and 50 years of age or older. RESULTS: The HSV-2 seroprevalence among female participants was 29.8%, with a significant trend of increasing HSV-2 prevalence for each higher level of age (P < 0.001). Female participants had a median age of 46 years and were predominantly monogamous (82.6%). The overall population-based seroprevalence estimated in Mexico City among women was 35.8%. The independent risk factors for HSV-2 seropositivity included a history of two or more sexual partners (odds ratio [OR], 2.2; 95% CI, 1.4-3.4), two or more sexual partners before first pregnancy (OR, 2.3; 95% CI, 1.4-3.7), cohabitation with partner (OR, 2.5; 95% CI, 1.3-4.7), and current vaginal douching (OR, 1.7; 95% CI, 1.2-2.6). CONCLUSIONS: Population-based HSV-2 seroprevalence is endemically high among middle-age women in Mexico City, and clearly is correlated with higher-risk sexual behavior. This elevated HSV-2 seroprevalence may reflect unrecognized HSV-2 transmission throughout life.

Adolescent↗

A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis.

Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage ( approximately 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated.

Animals↗

A therapeutic target for hormone-independent estrogen receptor-positive breast cancers.

BACKGROUND: The action of the steroid hormone estradiol (E2) is mediated via interaction with a specific receptor (ER) that initiates a series of events downstream, leading to the modulation of hormone-responsive genes and cell proliferation. Antihormones also bind, but do not confer the active configuration to ER, thereby, blocking the transmission of E2-ER-initiated signals for cell proliferation. Although these compounds qualify for successful therapy of ER-positive [ER (+)] breast cancer patients, only a fraction of patients responds to antihormone treatment. In this study, the functional status of ER is determined to identify alternative targets for therapy of antihormone-resistant ER (+) breast cancers. METHOD: The interaction of ER with a specific DNA sequence, designated as E2 response element (ERE), was targeted to assess the functional state of ER. ER-ERE complex formation was measured by electrophoretic mobility shift assay (EMSA) and by a newly developed technique, based on the preferential binding of DNA-protein complex to a nitrocellulose membrane (NMBA) that measures both total and functional fraction of ER. RESULTS: The NMBA assay identified functional variants of ER among ER (+) breast cancer cell lines and breast tumor biopsy specimens. ER of (21PT) cells did not bind E2 and these cells were tamoxifen (TAM) resistant. However 21PT cells were sensitive to a calmodulin (CaM) antagonist, W7, that blocked ERE-ER complex formation. CONCLUSIONS: ER variants of the 21PT type were detected among breast cancer biopsy specimens, emphasizing the significance of an alternative therapeutic target for TAM-resistant ER (+) human breast cancers with compounds such as W7.

Adult↗

Biodegradation of disperse blue 79 using sequenced anaerobic/aerobic biofilters.

A sequential anaerobic/aerobic treatment process was used to biodegrade the azo dye disperse blue 79 (DB79). The integrated process was successfully tested and operated for the mineralization of the DB79 dye until a concentration of 120 mg/l in 96 h. In the first stage, the anaerobic biofilter biotransformed the DB79 to amines with efficiencies of decolorization higher than 95% in 72 h. The amines produced in the first stage were degraded in the aerobic biofilter with efficiencies of 65% in 24 h. It was observed that the use of a co-substrate on the anaerobic biofilter influenced the performance of the bioreactor only when the concentration of the DB79 was higher than 48 mg/l. It was found that the residual dye in the effluent of the anaerobic stage inhibits the performance of the aerobic microorganisms.

Anthraquinones↗

Tripodal ionophore with sulfate recognition properties for anion-selective electrodes.

Ionophore topology has a profound effect on the behavior of ion-selective electrodes. This is demonstrated with a new class of ionophores that incorporates aminochromenone moieties linked through urea spacers to different scaffolds that preorganize the ionophore binding cleft into tripodal topologies. Tris(2-aminoethylamine) and cis-1,3,5-tris(aminomethyl)cyclohexane were employed as the scaffolds. The two differ in their rigidity and in the size of ionophore cavity that they create. The electrodes based on the ionophore that incorporates the tris(2-aminoethylamine) scaffold show anti-Hofmeister behavior with an improved selectivity for sulfate. In contrast, the ionophore with the cis-1,3,5-tris(aminomethyl)cyclohexane scaffold exhibits a more Hofmeister-like response.

Anions↗

Thermal stimulation of taste.

The first electrophysiological recordings from animal and human taste nerves gave clear evidence of thermal sensitivity, and studies have shown that as many as half of the neurons in mammalian taste pathways respond to temperature. Because temperature has never been shown to induce sensations of taste, it has been assumed that thermal stimulation in the gustatory system is somehow nulled. Here we show that heating or cooling small areas of the tongue can in fact cause sensations of taste: warming the anterior edge of the tongue (chorda tympani nerve) from a cold temperature can evoke sweetness, whereas cooling can evoke sourness and/or saltiness. Thermal taste also occurs on the rear of the tongue (glossopharyngeal nerve), but the relationship between temperature and taste is different there than on the front of the tongue. These observations indicate the human gustatory system contains several different types of thermally sensitive neurons that normally contribute to the sensory code for taste.

Body Temperature↗

Restrictive endothelial barrier function during normal angiogenesis in vivo: partial dependence on tyrosine dephosphorylation of beta-catenin.

Differentiation of a restrictive endothelial barrier in the chick chorioallantoic membrane (CAM) occurs between Day 4.5 and Day 5.0 of the normal 21-day gestation. Whether molecular changes in the endothelial cell-cell junctional protein complex contribute to the ontogeny of barrier function represents the principal focus of this study. VE-cadherin has been shown to contribute to the regulation of endothelial cell monolayer permeability in vitro. Accordingly, VE-cadherin is complexed to the cytosolic catenins, and changes in monolayer permeability have been linked to alterations of the cadherin/catenin complex. Currently, a CAM endothelial VE-cadherin/beta-catenin complex was identified, and phosphotyrosine labeling of beta-catenin was decreased concurrently with the abrupt increase in CAM endothelial selectivity between Day 4.5 and Day 5.0. Further, inhibition of protein tyrosine phosphatases impeded regular tyrosine dephosphorylation of beta-catenin at Day 5.0 and this served to partially restore macromolecular extravasation to elevated levels normally present at Day 4.5. Thus, differentiation of selective barrier function in the angiogenic CAM endothelium in vivo is dependent, in part, on tyrosine dephosphorylation of beta-catenin.

Allantois↗

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers.

Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems.

1,2-Dipalmitoylphosphatidylcholine↗

High prevalence of serum antibodies to Ras and type 16 E4 proteins of human papillomavirus in patients with precancerous lesions of the uterine cervix.

Serum samples from 38 healthy women and 55 women with different types of cervical lesions were investigated for the presence of antibodies to Ras and against E4 and E7 proteins of human papillomavirus type 16 (HPV-16). Our results showed that anti-E7 antibodies were closely associated with cervical cancer (75%), as previously reported. Interestingly, E4 antibodies showed higher prevalence in condyloma lesions (79%; 11/14) than in cervical cancer (60%; 12/20). We also identified 11% (4/38) of healthy individuals as positive for E4 antibodies, which suggests an early immune recognition of this protein. Patients with condyloma and cervical intraepithelial neoplasia (CIN) also showed higher prevalences of Ras antibodies (approximately 40%) than cervical cancer patients (10%; 2/20). By sequencing part of the ras genes and using different Ras antigens, we showed that serum antibodies from patients were not directed to a Ras mutation, since wild-type cHa-Ras protein was recognized by these antibodies. In addition, patients positive for Ras antibodies (94%) were also positive for E4 antibodies, suggesting an association between these. The high prevalence of antibodies against Ras and E4 proteins in pre-malignant lesions opens the possibility of using both antibodies as early markers for potential cervical cancer patients.

Adult↗