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Biomedical subjects

M Suarez

Publications and source records attributed to M Suarez.

At least 19 recordsLinked to original sources

Activation of nuclear factor-kappa B is linked to resistance to neoadjuvant chemotherapy in breast cancer patients.

The nuclear factor (NF)-kappaB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kappaB in breast cancer, we aimed to study the value of basal NF-kappaB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kappaB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kappaB/p65 subcellular expression. We studied NF-kappaB/p65, a well-characterised member of the NF-kappaB family that undergoes nuclear translocation when NF-kappaB is activated. Activation of NF-kappaB (i.e. nuclear NF-kappaB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kappaB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kappaB/p65 nuclear staining. Moreover, the number of patients with NF-kappaB/p65 activation increased after chemotherapy exposure. It is concluded that NF-kappaB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kappaB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kappaB inhibitors to prevent or overcome chemoresistance in breast cancer.

Adult↗

Increased immunohistochemical expression of thrombomodulin at placental perivascular myofibroblast in severe preeclampsia (PE).

The presence of pro-coagulant and anti-coagulant components of the placental vascular endothelium and syncytiotrophoblast are essential for homeostasis. Vascular endothelium prevents blood clot formation in vivo by involving a cell surface thrombin-binding glycoprotein, thrombomodulin (TM), that activates plasma anti-coagulant protein C. The TM levels increase during pregnancy, but the fibrinolytic capacity diminishes. Since vascular lesions with placental coagulation disorders can be associated with preeclampsia (PE), we hypothesized that TM expression in the stem villous vasculature and syncytiotrophoblast of the placenta are impaired in PE. Plasma and placental tissue samples were collected from PE (n=12) and normotensive pregnant patients (n=11). Patient's gestational age was 35.7+/-1.2 (normotensive) and 30.6+/-1.5 weeks (PE). Blood samples were drawn 30 min before delivery. Serum PAI-1 and PAI-2 antigens were determined by enzyme-linked immunoabsorbent assay (ELISA). A monoclonal antibody specific for TM was used for immunohistochemical tissue staining (ABC) and the staining was quantified by semi quantitative scores. Results show no intensity differences at the apical syncytiotrophoblast between the two groups. However, in preeclamptic placenta, TM expression diminished in the endothelium of the stem villi arteries and increased in the perivascular and stromal myofibroblats in cases of severe PE. TM changes were associated with an increased PAI-1/PAI-2 ratio. It is suggested that in severe PE, the decreased placental blood flow may be due to structural and functional impairment of the endothelium of the stem villi vessels and the surrounding perivascular and stromal myofibroblast, by increasing TM expression which may modulate fetal blow flow in the villous tree.

Actins↗

Simple sequence repeat marker diversity in cassava landraces: genetic diversity and differentiation in an asexually propagated crop.

Cassava (Manihot esculenta) is an allogamous, vegetatively propagated, Neotropical crop that is also widely grown in tropical Africa and Southeast Asia. To elucidate genetic diversity and differentiation in the crop's primary and secondary centers of diversity, and the forces shaping them, SSR marker variation was assessed at 67 loci in 283 accessions of cassava landraces from Africa (Tanzania and Nigeria) and the Neotropics (Brazil, Colombia, Peru, Venezuela, Guatemala, Mexico and Argentina). Average gene diversity (i.e., genetic diversity) was high in all countries, with an average heterozygosity of 0.5358 +/- 0.1184. Although the highest was found in Brazilian and Colombian accessions, genetic diversity in Neotropical and African materials is comparable. Despite the low level of differentiation [F(st)(theta) = 0.091 +/- 0.005] found among country samples, sufficient genetic distance (1-proportion of shared alleles) existed between individual genotypes to separate African from Neotropical accessions and to reveal a more pronounced substructure in the African landraces. Forces shaping differences in allele frequency at SSR loci and possibly counterbalancing successive founder effects involve probably spontaneous recombination, as assessed by parent-offspring relationships, and farmer-selection for adaptation.

Alleles↗

Expression of a plant-derived peptide harboring water-cleaning and antimicrobial activities.

Drinking water is currently a scarce world resource, the preparation of which requires complex treatments that include clarification of suspended particles and disinfection. Seed extracts of Moringa oleifera Lam., a tropical tree, have been proposed as an environment-friendly alternative, due to their traditional use for the clarification of drinking water. However, the precise nature of the active components of the extract and whether they may be produced in recombinant form are unknown. Here we show that recombinant or synthetic forms of a cationic seed polypeptide mediate efficient sedimentation of suspended mineral particles and bacteria. Unexpectedly, the polypeptide was also found to possesses a bactericidal activity capable of disinfecting heavily contaminated water. Furthermore, the polypeptide has been shown to efficiently kill several pathogenic bacteria, including antibiotic-resistant isolates of Staphylococcus, Streptococcus, and Legionella species. Thus, this polypeptide displays the unprecedented feature of combining water purification and disinfectant properties. Identification of an active principle derived from the seed extracts points to a range of potential for drinking water treatment or skin and mucosal disinfection in clinical settings.

Amino Acid Sequence↗

Sclerosing mesenteritis in small bowel transplantation: possible manifestation of acute vascular rejection.

BACKGROUND: Acute rejection of human small bowel allografts is characterized by clinical symptoms combined with characteristic morphologic alterations. The typical geographic distribution of acute rejection in the bowel is involvement of the intestinal parenchyma, which can be transmural, particularly when the rejection is more severe. However, little is known concerning the potential for donor-derived soft tissue adjacent to the bowel to become involved by the host alloimmune response. METHODS: We describe a male patient who, several weeks after combined small bowel and liver transplantation, demonstrated sclerosing mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The vascular lesions in the mesentery demonstrated increased IgG deposition and the patient developed an alloantibody to the donor. CONCLUSIONS: The changes described herein may represent a novel presentation of acute vascular rejection.

Acute Disease↗

Mass spectral fragmentation patterns of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones

The electron impact mass spectra of new 5-acetyl-4-aryl-6-methyl-2(1H)pyridones have been studied. A dominant peak in all the spectra is due to cleavage of the CO-NH bond of the amido group with charge retention on the carbonyl group. This fragmentation is followed by a hydrogen rearrangement to the nitrogen atom forming ketene intermediates; this pathway leads to a highly stabilized ion which constitutes the base peak in the spectra in most of the compounds studied. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

Foreign body granuloma mimicking intracranial meningioma: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Intracranial foreign body granulomas are rare. We describe a case of an intracranial foreign body granuloma found in a 17-year-old female patient 9 years after she underwent a craniotomy for a tumor of unknown type. Postoperative imaging of patients who have undergone neurosurgical procedures can often reveal enhancing masses, and foreign body granuloma should be included in the differential diagnosis. CLINICAL PRESENTATION: The patient presented with a history of developmental delay, panhypopituitarism, and chronic headache. Admission resulted from an acute increase in the severity of her headache. INTERVENTION: Imaging studies, including computed tomography and magnetic resonance imaging, demonstrated a 1.5 x 2 cm round, enhancing anterior interhemispheric mass, appearing to arise from the falx and causing mild mass effect. A nonenhancing cystic mass was also noted in the suprasellar region but was without mass effect. The patient underwent a craniotomy and removal of the anterior mass without complication, and her headache resolved. A pathological examination of the specimen confirmed the diagnosis of foreign body granuloma. CONCLUSION: Although rare, foreign body granuloma should be included in the differential diagnosis of previously operated intracranial masses. The importance of accurate historical information and guidelines that may assist in diagnosis are discussed.

Adolescent↗

Improved outcome of cytomegalovirus retinitis in AIDS patients after introduction of protease inhibitors.

The objective of this study was to evaluate the influence of protease inhibitor therapy on the rate of progression and survival of 17 AIDS patients with stable Cytomegalovirus retinitis, who were receiving anti-CMV therapy. CD4+ count, HIV load, and CMV antigenemia assay were determined at baseline, at the first month, and every 3 months thereafter. Median CD4+ count increased from 11 to 87 cells/mm3, and median HIV RNA level decreased from 4.96 to 3.28 log10 copies/ml, after 6 months on therapy. Although 9 patients (53%) relapsed in a median time of 97 days (range, 15-152 days), no further episodes were observed during a median follow-up of 17 months (range, 5-18 months). Thus, the probability of remaining free of relapse was twofold higher than that observed in matched patients who did not receive protease inhibitors. Median CD4+ count at the 3rd month was higher in those individuals who went on to progress (p = .03), and a positive result to a CMV antigenemia test was associated with progression of retinitis (relative hazard, 4.45; p = .04). Survival rate was 94% at 17 months (89% increase). Therefore, protease inhibitor therapy reduces retinitis progression and improves survival. However, the immunologic response may not provide initial sufficient protection to avoid, or even may play a role on, early CMV progression.

AIDS-Related Opportunistic Infections↗

Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherichia coli DinB homolog confers UV radiation sensitivity and altered mutability.

The dinB gene of Escherichia coli is an SOS-inducible gene of unknown function. Its mode of regulation and the amino acid sequence similarity of the predicted DinB protein to the UmuC protein of E. coli both suggest a role in cellular responses to DNA damage and probably in error-prone repair. Proteins with sequence similarity to DinB have been predicted from genes cloned from various prokaryotic and eukaryotic organisms, including Caenorhabditis elegans. Here we present the phenotypic characterization of a haploid Saccharomyces cerevisiae strain deleted for the ORF YDR419W, encoding a yeast DinB homolog. The deletion mutant is viable but is moderately sensitive to killing following exposure to ultraviolet (UV) radiation. Hence, we have named the gene RAD30. Steady-state levels of RAD30 transcripts are increased following UV irradiation. UV-induced locus-specific reversion of an ochre allele (arg4-17) is reduced in the rad30 deletion mutant. However, enhanced mutability was observed following treatment with the alkylating agent methylmethanesulfonate (MMS). Spontaneous mutability was also slightly increased. We conclude that RAD30 encodes an accessory function involved in DNA repair and mutagenesis. We speculate that the relatively weak phenotype and the opposite effects on mutability as a function of the type of DNA damage involved may derive from a functional redundancy of yeast proteins which facilitate replicative bypass of non-coding DNA lesions.

Amino Acid Sequence↗

A novel occlusive dressing for skin resurfacing.

BACKGROUND: Over the last decade the benefits of occlusive dressings have been appreciated. These dressings allow the epithelium to resurface easier. The wound heals quicker. OBJECTIVE: To evaluate a new silicone sheeting for immediate post-op wound care. Our objective was to determine its benefit in the wound care management after laser skin resurfacing. METHOD: The silicone sheeting was applied immediately after laser resurfacing in 35 individuals. This temporary skin replacement was held in place with 4 x 4 gauzes and tube gauze netting. Although the tube netting and the 4 x 4 gauzes were changed daily the silicone sheeting remained in place for 4 or 5 days. Following this, applications of a petrolatum-based ointment were continued for another 5 days. At day 10 the skin care program was changed to a moisturizing sunscreen. Bleaching cream was added at day 15 in darker complexed individuals. RESULTS: The dressing accelerated wound healing. Pain and swelling were minimized under the sheeting. Histologic examinations demonstrated a more rapid reepithelialization at these treated sites. Other than technical problems, such as the riding up of the dressing over the jawline or retraction of the dressing off the lips or off the eyelids, there were no adverse sequelae. The wound healed rapidly and allowed the rapid progression to the application of a moisturizer-sunscreen or a skin-bleaching cream. Other than these technical problems there were no complications. No wound infections were noted. CONCLUSION: The use of silicone sheeting following skin resurfacing facilitated a rapid reepithelialization of treated areas. There was a remarkable reduction in erythema and edema accompanying the use of the dressing. The program made it possible for patients to return to work in 12-15 days.

Dermatologic Surgical Procedures↗

Small volume fat transfer.

BACKGROUND: The use of autologous fat has been advocated for tissue augmentation for over a century. However, this technique remains controversial and many investigators have made suggestions to increase its potential. OBJECTIVES: To develop a less traumatic method to collect, purify, and reinject fat to obtain more dramatic augmentations for the cosmetic improvement of contours and tissue defects. METHODS: Fat was collected from the donor site following tumescent infiltration of tissue. A "vented" syringe with an atraumatic Mercedes tip was used to collect the fat and, after washing with lactated Ringers or saline, the fat was transferred to small syringes for controlled injections. Small filaments of fat were placed in multi-layers throughout the area of the defect or area of desired contour change. The unused fat was frozen for a second or third injection session. RESULTS: The fat transfer method yielded augmentations of 40%-120% of injected volume in the 339 areas treated. After 45-60 days, the implant was stabilized and remained for the length of our study (up to 10 years). In several cases excessive fat had to be removed. Other than slight bruising, occasional divots at the donor site, and three cases of bacterial infection, the autologous tissue transfer was an uncomplicated event. CONCLUSION: Fat grafting has proven to be a safe and effective procedure for correcting and enhancing tissue defects and contour deficiencies.

Adipocytes↗

Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children.

This study investigated whether a child's first infection with Cryptosporidium parvum had an acute effect on weight gain. Specifically, the authors compared monthly rates of weight gain between C. parvum-infected and noninfected children. Over a 2-year period (1989-1991), a cohort of Peruvian children aged 0-3 months at recruitment were followed twice weekly for assessment of daily diarrheal status, weekly for C. parvum stool examinations, and monthly for anthropometric measurements. Data on 207 children permitted the authors to examine the effect of C. parvum infection on weight gain. During the 2-year study period, 45% (94/207) of the children became infected with C. parvum for the first time. Weight gain intervals in 57 of the 94 infected children met criteria for analysis. Of these, 63 percent (36/57) were asymptomatic (i.e., had no diarrhea). On average, children with symptomatic cryptosporidiosis gained (i.e., grew) 342 g less (95% confidence interval 167-517) during the first month of infection than did children without diarrhea who were not yet infected. The effect of asymptomatic cryptosporidiosis was less severe: On average, children with asymptomatic infection gained 162 g less (95% confidence interval 27-297) during the first month of infection than did children without diarrhea who were not yet infected. Symptomatic cryptosporidiosis retarded weight gain more than did asymptomatic cryptosporidiosis, but the latter was twice as common. Since asymptomatic cryptosporidiosis is more prevalent, it may have more of an overall adverse effect on child growth in the community than symptomatic cryptosporidiosis.

Acute Disease↗

Identification of peripheral vascular disease in elderly subjects using optical spectroscopy.

The purpose of this study was to determine the usefulness of near-infrared spectroscopy (NIRS) measurements to identify peripheral vascular disease (PVD). Usefulness was determined by the frequency of a successful test, as well as comparison with standard clinical assessments. Study subjects (N = 117, mean age = 67.8 +/- 8.1 yrs) responded to a free screening for PVD. NIRS was used to measure the relative O2 saturation of hemoglobin in the soleus muscle. The time to 1/2 recovery of O2 saturation (O2T1/2) was measured after 1 minute of repeated plantar flexions using a Cybex Eagle seated calf machine. O2T1/2 was used as many subjects had recovery curves that did not have an exponential line shape. The test was done on both legs and the worst leg was used for analysis. For comparative purposes, a clinical history and physical examination were performed by a physician or nurse practitioner, which included questions on intermittent claudication, examination of peripheral pulses, and questions to identify cardiovascular risk factors. NIRS signals were obtained on 105 of 117 subjects (89% success rate). Subjects with body mass index (BMI) values above 32 appeared to have NIRS O2T1/2 values that were less reliable than subjects with BMI values < or = 32 (77% success rate). The O2T1/2 was longer in subjects with claudication and reduced pulses than in subjects without these conditions. Sensitivity comparing O2T1/2 to claudication and reduced pulse varied from 51-76% and specificity from 65-80%, depending on the cutoff value for O2T1/2 that was used (normal value plus 1 or 2 SD). A longer O2T1/2 was significantly associated with incidence of diabetes, smoking, hypercholesterol, and coronary bypass surgery. In summary, successful NIRS O2T1/2 measurements were made in 77% of the subjects, with failure primarily occurring in obese subjects. NIRS O2T1/2 measurements showed reasonable although not strong agreements with clinical assessment of PVD, and with some risk factors for cardiovascular disease.

Aged↗

Use of folk healing practices by HIV-infected Hispanics living in the United States.

In the absence of a medical cure for AIDS, HIV-infected individuals may seek alternative treatments that are consistent with cultural and social beliefs. This paper examines beliefs about, and use of, folk healing practices by HIV-infected Hispanics receiving care at an HIV/AIDS clinic in inner-city New Jersey. Anonymous individual interviews were conducted with 58 male and 18 female HIV-infected Hispanics aged 23-55, primarily of Puerto Rican origin (61%) or descent (29%). The majority of respondents believed in good and evil spirits (73.7%); among the 56 believers, 48% stated that the spirits had a causal role in their infection, either alone or in conjunction with the AIDS virus. Two thirds of the respondents engaged in folk healing (spiritualism and/or santeria). The main desired outcomes of folk healing included physical relief (44%), spiritual relief (40%), and protection from evil (26%). A number of respondents (n = 9) stated that they hoped to effect a cure by engaging in folk healing. These results indicate that health care professionals treating HIV-positive Hispanics should be aware of the prevalence of folk beliefs and alternative healing practices in this population.

Adult↗

Morning reduction of cerebral vasomotor reactivity.

We measured cerebral vasomotor reactivity during normoventilation, hyperventilation (hypocapnia), and breathing of 6% CO2 (hypercapnia) in 20 normal subjects during the hours of 6 to 8 AM, 1 to 3 PM, and 7 to 9 PM. Cerebral vasomotor reactivity was calculated, using transcranial Doppler, as percent change in the mean blood flow velocity of the middle cerebral artery per mm Hg change in end-tidal CO2 during hypocapnia and hypercapnia. Vasomotor reactivity during hypercapnia was lower in the morning (1.72 +/- 0.66 %/mm Hg) than in the afternoon (2.34 +/- 0.74 %/mm Hg, p < 0.01) and evening (2.31 +/- 0.56 %/mm Hg, p < 0.001). Vasomotor reactivity during hypocapnia did not vary significantly during the three periods (2.34 +/- 0.59 %/mm Hg in the morning, 2.43 +/- 0.51 %/mm Hg in the afternoon, and 2.26 +/- 0.52 %/mm Hg in the evening). This reduced morning response to hypercapnia suggests diminished vasodilator reserve during this period, and may be related to the increased stroke risk during the morning hours.

Adult↗