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Biomedical subjects

M Santamaria

Publications and source records attributed to M Santamaria.

At least 19 recordsLinked to original sources

Pharyngeal carriage of serogroup W135 Neisseria meningitidis in Hajjees and their family contacts in Morocco, Oman and Sudan.

In 2000 the global outbreak that began in Saudi Arabia was caused by a W135:2a:P1.5,2 strain of Neisseria meningitidis belonging to the ET-37 complex and to ST-11. There was concern that introduction of this epidemic clone (EC) might lead to a wave of outbreaks in the African meningitis belt. The WHO therefore initiated studies of meningococcal carriage among pilgrims and their family contacts in Morocco, Oman and Sudan, 3 to 12 months after the Hajj 2000. In Morocco, 1186 persons were swabbed 3 times. Ninety-five meningococcal strains were isolated from 2.7% of the specimens. Pulsed-field gel electrophoresis showed that 32 (33.6%) were identical with the EC. In Sudan, 5 strains identical with the EC were obtained after sampling 285 persons. In Oman, among 18 meningococcal strains isolated from 399 subjects, 11 (61.1%) belonged to the EC. The important pharyngeal carriage of W135 (EC) and its role in the 2001-2002 outbreaks in Burkina Faso argues for the necessity of reinforcing surveillance, and adapting and planning responses in Africa and the Middle East using the most appropriate vaccine.

Carrier State↗

[Inflammation, atherosclerosis and acute coronary syndromes].

Inflammatory mechanisms play a pivotal role in the atherosclerotic process. At the base of atherogenesis there are complex interactions between macrophages, T lymphocytes and smooth muscle cells. A growing body of experimental evidences suggest that inflammation is involved in the pathogenesis of acute coronary syndromes (ACS) and influences their clinical evolution. In fact, in patients with ACS, coronary atherosclerotic plaques are characterized by an abundant inflammatory infiltrate. Moreover, in these patients systemic signs of inflammatory reaction can be observed: activated circulating inflammatory cells (neutrophil, monocytes and lymphocytes) and increased concentrations of pro-inflammatory cytokines, such as interleukin (IL)-1 and 6, and of acute phase reactants, in particular C-reactive protein (CRP). Recent data demonstrate that CRP is a strong independent predictor of adverse cardiac events and death in patients with ACS, but also in patients with stable ischemic heart disease and in apparently healthy men and women. Furthermore, CRP is an important prognostic index, for early and late outcome, in patients undergoing percutaneous coronary interventions, and may be useful in choosing the therapeutic management of the patient. Although the causes of inflammation in patients with ACS are not yet clear, this new line of research may open the way to a different clinical approach for these patients.

Acute Disease↗

The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer.

LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have explored a role for LMO4, initially described as a human breast tumor autoantigen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy. Consistent with a role in proliferation, forced expression of this gene inhibited differentiation of mammary epithelial cells. Overexpression of LMO4 mRNA was observed in 5 of 10 human breast cancer cell lines. Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LMO4 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.

Adaptor Proteins, Signal Transducing↗

SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice.

Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma (IFN gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar development in the mammary gland during late pregnancy and precocious lactation. Significantly, the lactogenic defect in prolactin receptor heterozygous females could be rescued by deletion of a single SOCS1 allele. These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition.

Alleles↗

The promoter of a basic PR1-like gene, AtPRB1, from Arabidopsis establishes an organ-specific expression pattern and responsiveness to ethylene and methyl jasmonate.

Antimicrobial proteins are a key feature underlying the deployment of both pre-formed and inducible defence responses. Probably the most well characterised class are the pathogenesis-related (PR) proteins, which are found in both basic and acidic isoforms. Here we describe the isolation and characterisation of a gene, designated AtPRB1, encoding a basic PR1-like protein from Arabidopsis. This protein showed high amino acid sequence identity with basic and acidic PR1 proteins from other plant species, for example PRB1 from Nicotiana tabacum and PR1 from Brassica napus, at 64% and 78% identity respectively. A genomic DNA fragment containing 2345 bp upstream from the putative transcriptional start site was fused to the gene encoding the luciferase (LUC) gene from Photinus pyralis in order to test for promoter activity. The resulting construct was transformed into Arabidopsis accession Col-0 and analysis of LUC activity, using an ultra-low-light imaging camera system, revealed that the AtPRB1 promoter established an exquisite organ-specific expression pattern. LUC activity was observed in flowers, stems and roots but not in leaf tissue. Superimposed upon this organ-specific expression pattern was responsiveness, in root tissue, to ethylene and methyl jasmonate (MeJA), important cues during the establishment of plant disease resistance. In contrast, AtPRB1::LUC gene expression was repressed in response to salicylic acid treatment. Analysis of a limited series of AtPRB1 5'-promoter deletion mutants, identified a number of promoter regions important for both the establishment of organ-specific expression and responsiveness to ethylene and MeJA. While AtPRB1 gene expression was not induced in response to an avirulent isolate of Peronospora parasitica in leaf tissue, this gene may contribute to horizontal resistance in other tissues and/or to MeJA- and ethylene-dependent defence responses engaged against necrotrophic pathogens in root tissue. It is anticipated that transgenic plants containing AtPRB1-based promoter::reporter constructs will provide useful tools for the future dissection of the cognate signalling networks regulating the expression of this gene.

Acetates↗

Neuropsychological functioning in first-episode psychosis--evidence of specific deficits.

Neuropsychological impairment is ubiquitous in schizophrenia even at the first presentation of psychotic symptoms. We sought to elucidate the nature of the neuropsychological profile at the onset of the illness by examining the neuropsychological functioning of 40 patients experiencing their first episode of psychosis and 22 matched controls. All participants completed a battery of neuropsychological tasks designed to assess attention, verbal learning/memory, non-verbal memory, spatial ability, psychomotor speed, and executive function. First-episode patients showed significant impairment on tasks of executive function, including those requiring the ability to form and initiate a strategy, to inhibit prepotent responses, and to shift cognitive set, and also on tasks of verbal fluency. Memory impairments were seen on verbal learning and delayed non-verbal memory only. Impairment on tasks of psychomotor speed suggests that there may be a significant amount of cognitive slowing even at the first onset of psychosis. We suggest that our patients may be experiencing difficulty in specific aspects of executive functions, including the ability to form and execute a strategy, and these difficulties may be mediating the deficits observed on tasks of verbal learning.

Adolescent↗

Features of structural brain abnormality detected in first-episode psychosis.

OBJECTIVE: Structural magnetic resonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. METHOD: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T(1)-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. RESULTS: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. CONCLUSIONS: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.

Adult↗

Experience of caregiving: relatives of people experiencing a first episode of psychosis.

BACKGROUND: There has been relatively little research on caregivers of people experiencing their first episode of psychosis. AIMS: To investigate dimensions of caregiving and morbidity in caregivers of people with first-episode psychosis. METHOD: Caregivers of 40 people with first-episode psychosis were interviewed at home about their experience of caregiving, coping strategies and distress. RESULTS: Caregivers used emotional and practical strategies to cope with participants' negative symptoms and difficult behaviours and experienced more worry about these problems. They increased supervision when the participants displayed difficult behaviours. Twelve per cent of caregivers were suffering from psychiatric morbidity as defined by the General Health Questionnaire. Those living with the participant had more frequent visits to their general practitioner. CONCLUSIONS: At first-episode psychosis, caregivers are already having to cope with a wide range of problems and are developing coping strategies. Caregivers worried most about difficult behaviours and negative symptoms in participants.

Adaptation, Psychological↗

Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals.

Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals.

Antigens, CD↗

The enzymatic properties of Octopus vulgaris hemocyanin: o-diphenol oxidase activity.

Hemocyanin and tyrosinase are dinuclear copper proteins capable of reversibly binding dioxygen. Despite the great similarity of structure and properties of their active site, the two proteins perform different biological functions (oxygen transport/storage versus monooxygenase and oxidase activity). In this paper, we show that Octopus vulgaris hemocyanin exhibits a tyrosinase-like activity; namely, it is capable of utilizing dioxygen for the oxidation of o-diphenol to quinone. The reaction is specific for this isomer of diphenol, the meta and para isomers being unreactive, and is strongly controlled by steric factors. Dioxygen represents a cosubstrate of the reaction, and it is involved in the catalytic turnover by binding to the dinuclear copper site of the protein to form, under steady-state conditions, oxy-Hc, which is the active species. The generation of semiquinone radicals, detected by EPR and by their reaction with N,N,N',N'-tetramethyl-1,4-phenylenediamine, strongly supports a reaction mechanism in which such radicals represent the reaction products of one-electron oxidation of the substrate, quinone being generated by dismutation of semiquinones. Met-Hc is regenerated by the substrate to the deoxy form. To close the catalytic cycle, the proposed reaction mechanism also involves the participation of two transient protein forms with the total oxidation state of the active site (V and IV) intermediate between that of oxy-Hcy, [CuIIO22-CuII]VI, and deoxy-Hc, [CuICuI]II. A mathematical model has been elaborated to describe the reaction kinetics. The differences in reaction mechanisms between hemocyanin and tyrosinase are discussed in terms of accessibility to exogenous molecules of their active sites.

Animals↗

Causes of cervical cancer in the Philippines: a case-control study.

BACKGROUND: Among the numerous human papillomavirus (HPV) types, only types 16 and 18 have been formally classified as human carcinogens. To evaluate the associations of 33 HPV types and other risk factors with squamous cell carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, case-control study in the Philippines. METHODS: The study included 356 case subjects who had histologically confirmed cervical cancer (323 incident cases of squamous cell carcinoma and 33 incident cases of adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. Information on risk factors was obtained by personal interview. HPV DNA was detected in exfoliated cervical cells and biopsy specimens by use of a polymerase chain reaction assay. RESULTS: HPV DNA was detected in 93.8% of case subjects with squamous cell carcinoma and in 90.9% of case subjects with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control subjects, giving age-adjusted odds ratios of 156 (95% confidence interval [CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were detected in squamous cell carcinoma, and six different HPV types were detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other than types 16 and 18, the associations of HPV with risk of squamous cell carcinoma were strongest for HPV45. In addition to HPV, high parity, low socioeconomic status, and smoking were also associated with both types of cervical cancer. CONCLUSIONS: As has been shown for squamous cell carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous carcinoma of the uterine cervix. The observed associations of less prevalent HPV types with cervical cancer have important implications for cervical cancer prevention strategies.

Adenocarcinoma↗

Risk factors for cervical cancer in Thailand: a case-control study.

BACKGROUND: Human papillomaviruses (HPV) types 16 and 18 are clearly involved in the etiology of cervical cancer, but the evidence for the carcinogenicity of other HPV types is limited. Cofactors involved in the progression from infection with HPV to high-grade precursors and cancer have not been clearly defined by the results of previous studies. METHODS: We conducted a hospital-based, case-control study of invasive cervical cancer to investigate risk in relation to HPV infection and its epidemiologic cofactors in Hat-Yai, Thailand. A total of 338 patients with squamous cell carcinoma, 39 patients with adenocarcinoma/adenosquamous carcinoma, and 261 control subjects were included in the study and were interviewed to obtain information with regard to cervical cancer risk factors. HPV DNA presence in cervical exfoliated cells or frozen biopsy specimens was determined by a polymerase chain reaction assay. RESULTS: HPV DNA was detected in 95% of patients with squamous cell carcinoma, 90% of those with adenocarcinoma/adenosquamous carcinoma, and 16% of control subjects. For patients with squamous cell carcinoma, the most common types of HPV found were type 16 (60% of the positives), type 18 (18%), type 58 (3%), type 52 (3%), and type 31 (2%). For patients with adenocarcinoma/adenosquamous carcinoma, the most common HPV types found were type 18 (60% of the positives), type 16 (37%), and type 45 (3%). The risk factors that remained associated with risk of both histologic types after adjustment for HPV and their mutual confounding effects were limited education, increasing number of sexual partners, history of venereal diseases, and interval since last Pap smear (i.e., cytologic) test. Among patients with squamous cell carcinoma, some association with smoking was also observed. CONCLUSION: New preventive strategies for cervical cancer will require the consideration of multiple HPV types.

Adenocarcinoma↗

Electrophoretic behavior and size distribution of the acidic polysaccharides produced by the bacteria Bradyrhizobium (Chamaecytisus) strain BGA-1 and Bradyrhizobium japonicum USDA 110.

The electrophoretic behavior in polyacrylamide gels of the acidic polysaccharides produced by the soil bacteria Bradyrhizobium (Chamaecytisus) strain BGA1 and Bradyrhizobiumjaponicum USDA1 10 has been studied. Both polysaccharides were polydisperse, producing a ladder-like pattern after fixation with Alcian Blue and silver staining of the gel. The polysaccharide molecules were separated according to their size, and they behaved as a collection of flexible random coils of different size and similar charge/mass ratio. The electrophoretic behavior was not affected by the presence of acetyl groups in the polysaccharide. The range of molecular weights of the exopolysaccharide produced by B. japonicum USDA110 was wider and with larger molecules than that of the polysaccharide produced by strain BGA1. The resolution was dependent on the electrophoresis buffer; the best results were achieved with Tris-borate; in Tris-glycine buffer, the resolution was worse, and it was not improved by the addition of sodium dodecyl sulfate (SDS).

Bradyrhizobium↗

Transient energy coupling between rhizobia and legume cells mediated by the peribacteroid membrane ATPase proton pump.

We present a model for the metabolic coupling between rhizobia and plant cell in the nitrogen-fixing legume root nodules. The symbiosome, an organelle-like structure formed by the modified rhizobia (the bacteroids) enclosed by a plant cell derived peribacteroid membrane, is an unique structure in which two energized membranes are closely packed: the inner bacteroid membrane and the peribacteroid membrane that possesses an ATPase proton pump. The model is based on the following points: (i) The permeability for hydrogen ions of the outer membrane of the rhizobia. (ii) The reversibility of the ATPase proton pump of the peribacteroid membrane [Szafran, M.M. and Haaker, H. (1995) Plant Physiol. 108, 1227-1232]. (iii) The relative affinites for oxygen of the bacteroid and plant mitochondria terminal oxidases, and the prevailing oxygen concentration inside the nodule, which results in aerobic metabolism for the bacteroid, but in quite fermentative catabolism for the host plant cell. We propose that the bacteroid can transiently supply free energy to the plant cell in the form of protonmotive force by the movement of hydrogen ions from the bacteroid periplasmic space to the plant cytoplasm through the peribacteroid membrane ATPase. The proposed hydrogen ion flux could be dependent on the phosphorylation potential in both the plant cell cytoplasm and the bacteroid, and the simultaneous ion movements to avoid the development of opposite delta psi. It could be important in situations of transient ATP depletion inside plant cell, which involves the block of ammonia assimilation and, subsequently, the inhibition of bacteroid nitrogenase.

Adenosine Triphosphatases↗

Meningococcal disease: public health burden and control.

Meningococcal disease which is increasing globally is still associated with a high mortality and persistent neurological defects, particularly among infants and young children. Sporadic meningococcal meningitis occurs throughout the world, with seasonal variations, and accounts for 10-40% of endemic bacterial meningitis. Epidemic meningitis occurs in any part of the world but the largest and most frequently recurring epidemics have been in the semi-arid area of sub-Saharan Africa where the current pandemic is associated with attack rates exceeding 500 per 100,000 population and thousands of deaths. In the Americas and Europe serogroup B is the predominant agent causing systemic disease, followed in frequency by serogroup C. Serogroup A meningococcus was historically the main cause of epidemic meningococcal disease globally and still predominates in Africa and Asia. A range of internal and external factors predispose for epidemics such as strain virulence, carriers, humoral immunity, co-infections, low humidity and drought, population movements and crowding. To respond to the current situation and the expected spread of the disease, WHO, in collaboration with its Member States and various governmental and non-governmental agencies, has developed a sustainable plan of action for preparedness and control of meningitis.

Adolescent↗

Inter-observer variation in cytological and histological diagnoses of cervical neoplasia and its epidemiologic implication.

Inter-observer variation in cytohistological diagnosis was assessed for 1506 cervical smears and 883 histological slides from four case-control studies on cervical neoplasia. The kappa statistic among a panel of three cytopathologists was highest for diagnosis of invasive cancer (0.70 for cytology and 0.74 for histology), followed by normal/inflammatory in cytology (0.68) and CIN III in histology (0.58). There was also nearly perfect agreement between the final panel diagnoses and the original diagnoses made by local cytopathologists, except for those of CIN III. Inter-observer variation in diagnosis for CIN III was inversely associated with age, number of children (in histology) and sexual activity (in cytology). However, the odds ratios for CIN III calculated by each cytopathologist's diagnosis were not different from each other for any etiologic factor. These results indicate that the diagnoses of invasive cancer and of normal/inflammatory changes are highly reproducible and that the inter-observer variation does not have much impact on the etiologic risk estimates.

Adult↗

Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients.

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.

Adolescent↗