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Biomedical subjects

M Caballero

Publications and source records attributed to M Caballero.

At least 19 recordsLinked to original sources
PubMed2004

Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases.

AIMS: Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely. METHODS AND RESULTS: All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High-molecular-weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12-35 months). CONCLUSIONS: ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.

Adult↗
PubMed2003

[Analysis of cerebrospinal fluid related complications (hydrocephalus, fistula, pseudomeningocele and infection) following surgery for posterior fossa tumors].

INTRODUCTION: Hydrocephalus, cerebrospinal fluid (CSF) leak, pseudomeningocele and CSF infection are potential complications related to surgical treatment of posterior fossa tumors. The objectives of this study were to review the incidence of such complications and to identify contributing factors related to them. MATERIAL AND METHODS: This study is based on a retrospective review of the medical records of 71 consecutive patients who underwent posterior fossa surgery for a tumor between the period January 1997 and December 2001. Postoperative hydrocephalus was defined as enlargement of the ventricles and the subsequent clinical worsening requiring surgical treatment. Criteria for CSF leakage were:observed leak of CSF through the wound, rhinorrhea or otorrhea. Pseudomeningocele was determined when there was a large epidural CSF collection diagnosed in the postoperative period or by magnetic resonance imaging performed at least three months after posterior fossa surgery. Finally, CSF infection was defined on clinical ground and positive biochemical examination, but not necessarily positive cultures. RESULTS: The series included 84 operations for resection of posterior fossa tumors on 71 patients. There were CSF related complications in 31% (26/84)with the following detailed incidence: 9.5% (8/84) postoperative hydrocephalus; 14.3% (12/84) CSF leak, 7.1% (6/84) pseudomeningocele; 8.3% (7/84) CSF infection. The mortality rate is 5.9% (5/84). The tumor size was the only statistically significant factor associated with the occurrence of CSF related complications (mean 39.43 mm, SD 18.51 mm vs.29.80 mm, SD 14.12 mm, p=0.015). In the subgroup of patients, in which hydrocephalus was managed preoperatively, the election of an external ventricular drain vs.other strategies (subcutaneous reservoir, definite shunt or endoscopic third ventriculostomy) was associated with a higher occurrence of CSF related complications (p=0.006). The mortality rate was associated with age (mean 63.60 years, SD 5.86 years vs.49.18 years, SD 16.39 years; p=0.002). The occurrence of CSF related complications also influenced mortality (p=0.030), particularly postoperative hydrocephalus (p< 0.001). Inpatient hospital stay was longer in the subgroup of patients who developed CSF related complications (p=0.002). CONCLUSIONS: Tumor size was the only factor associated with the development of CSF related complications after surgery for posterior fossa tumors. In the subgroup of patients in which hydrocephalus was surgically treated preoperatively, the election of an external ventricular drain compared to other surgical modalities was associated with a higher rate of CSF related complications. The development of such complications, particularly hydrocephalus, was related with mortality.

Bacterial Infections↗
PubMed2003

[Evaluation of microsurgical treatment in a series of 121 intracranial aneurysms].

OBJECTIVE: The results obtained with therapy of intracranial aneurysms, in terms of morbidity and mortality, are very important when the patient has to choose between microsurgical techniques or endovascular management. The aim of this paper is to review the information regarding current microsurgical treatment of intracranial aneurysms, and presenting our experience over the last five years. MATERIAL AND METHODS: We studied 101 consecutive patients with 121 intracranial aneurysms admitted between 1996 and 2000 with the initial diagnosis of subarachnoid hemorrhage. We paid special attention to the day of admission from the onset of the symptomatic hemorrhage to the grade of Hunt&Hess scale and the possibility of early or delayed microsurgical treatment. The diagnosis was based on four vessels cerebral angiography and in a few cases with CT-angiography. All patients were treated by microsurgical technique and such treatment was completed by nimodipine, intensive care unit management and in some cases of postoperative suspected vasospasm, induced arterial hypertension was applied. Post surgical angiography was carried out in all patients to confirm the clipping of the cerebral aneurysm. The 12 months assessment was based on the Glasgow Outcome Scale (GOS). RESULTS: The 92.1% of the patients were admitted with a grade equal or below III in the Hunt&Hess scale. A 80% were operated within the 72 hours of admission and in the remaining cases, the surgical treatment was delayed due to a grade IV or V or to a medical contraindication. Four patients died (3.9%). At 12 months follow up, 88.9% presented a score I or II in the GOS. CONCLUSION: According to our results, there are a substantial improvements in the microsurgical treatment of cerebral aneurysms, specially in patients admitted early after the onset of the symptoms of their hemorrhage, who have a grade I to III in the Hunt&Hess scale and showed a good level of consciousness. We think that the improvement of our results are due to: l. the high percentage of patients admitted with grades I to III. 2. the high percentage of patients operated within the first 72 hours from the onset of their symptomatic hemorrhage. 3. surgery was always carried out by the same two experienced vascular neurosurgeons. 4. intraoperative measures taken to prevent the rupture of the aneurysm. 5. early administration of nimodipine, ICU management, doppler studies and in seldom cases, induced hypertension therapy to treat the vasospasm and postoperative hypotension.

Adolescent↗
PubMed2001

Lymphoid tissue viral burden and duration of viral suppression in plasma.

OBJECTIVES: To assess virological response in lymphoid tissue and its impact on the durability of response in plasma in HIV-1-infected persons who achieved sustained suppression of plasma viraemia with different antiretroviral regimens. METHODS: Consecutive patients on first-line antiretroviral therapy were included if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months and tonsillar tissue accessible for biopsy. First-line therapy contained two nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed until virus was detectable in plasma, they changed therapy or were lost to follow-up. RESULTS: Tonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10 patients: one in the PI group (9%), six (38%) in the NVP group and in all three patients in the 2NRTI group. Primary resistance mutations could be detected in only 2 of these 10 patients. After a median of 9 months after the biopsies, viral suppression in plasma had failed in 6 of these 10 patients whereas failure had only occurred in 1 out of 20 with initially undetectable viral load in lymphoid tissue (P = 0.01; log rank test). CONCLUSIONS: In patients with sustained viral suppression in plasma, triple therapy including a HIV-1 protease inhibitor was more potent than triple therapy containing nevirapine or dual therapy with nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response in lymphoid tissue could not be explained by local selection of resistance and was associated with a less durable virological response in plasma.

Adult↗
PubMed2001

Inefficient processing of an olfactomedin-deficient myocilin mutant: potential physiological relevance to glaucoma.

Mutations in TIGR/MYOC (myocilin), a secretory protein of unknown function, have been recently linked to glaucoma. Most known mutations map to the C-terminus, an olfactomedin-like domain. We have previously shown that, in contrast to the wild-type, a truncated form of myocilin lacking the olfactomedin domain is not secreted. In this study, we present evidence that the mutant protein is not correctly processed in the endoplasmic reticulum (ER) and accumulates into insoluble aggregates. In addition, we show that the presence of increasing amounts of mutant protein induces a fraction of the soluble, native myocilin to move to the insoluble fraction. Given the importance of such protein aggregates in the etiology of several aging-related diseases, we propose that olfactomedin-defective mutants might contribute to the pathology of glaucoma through a mechanism involving intracellular accumulation of misfolded proteins.

Adenoviridae↗
PubMed2001

Confirmation of the mapping of a 12-O-tetradecanoylphorbol-13-acetate promotion susceptibility locus, Psl1, to distal mouse chromosome 9.

Susceptibility to two-stage skin carcinogenesis in the mouse is affected by several genes. In addition, studies suggest that genes that modify the response of mice to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) also may influence histologic changes in the skin as the result of TPA treatment. One TPA susceptibility locus, Psl1, previously was mapped to distal chromosome 9. The mapping of this locus was confirmed by marker-based genotypic selection. Furthermore, Psl1 or a gene closely linked to Psl1 influenced epidermal hyperplasia and epidermal labeling index of mice treated with TPA.

Animals↗
PubMed2000

Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain.

TIGR/MYOC, a novel 504 amino acids (aa) protein of unknown function, has recently been linked to glaucoma. The protein is both intra- and extracellular and most known mutations map to its C-terminus, an olfactomedin-like domain. To investigate the properties of a TIGR/MYOC peptide lacking this important domain, we constructed a replication-deficient adenovirus with the first 344 aa and over-expressed the truncated protein in primary human trabecular meshwork cells and perfused human anterior segment cultures. The truncated mutant contains the entire N-terminus plus 98 aa of the olfactomedin-like domain. We found that the delivered truncated mutant accumulates inside the cell, reduces secretion of endogenous TIGR/MYOC and induces an increase in outflow facility at 48 h post-infection. Based on these findings, we hypothesize that TIGR/MYOC might have a dual role in trabecular meshwork function. This dual role might be that of an intracellular modulator of vesicular transport as well as that of a secreted protein involved in extracellular matrix conformation. Both functions could have a direct effect in maintaining aqueous humor outflow facility.

Adenoviridae↗
PubMed2000

Characterization of human immunodeficiency virus type 1 vif gene in long-term asymptomatic individuals.

We have determined the sequence of the human immunodeficiency virus type 1 (HIV-1) vif genes from a cohort of 42 long-term nonprogressors (LTNP) and compared these sequences to those of 8 late progressors. The coding potential of the vif open reading frame directly derived by nested PCR from uncultured peripheral blood mononuclear cell DNA was conserved in all 50 individuals. The nucleotide distances between vif sequences were not significantly different between LTNP and late progressors, indicating similar selections of viruses within both types of long-term HIV-1-infected subjects. However, a statistically significant correlation between an amino acid signature at position 132 of Vif and the viral load was found within LTNP. Namely, amino acid Ser was associated with low viral load and amino acid Arg with high viral load. This signature was also observed when LTNP with low viral load were compared to progressors. The Ser132 signature was introduced in place of Arg132 present in the HIV-1 YU-2 Vif prototype into chimeric viruses to assess the impact of Vif signature on the virus. While the replication properties in the SupT1 cell line were unmodified, the mutagenized virus revealed a fivefold decreased replication in activated PBMC, suggesting a possible role of this Vif signature for viral production in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Development of a microparticle-enhanced nephelometric immunoassay for quantitation of human lysozyme in pleural effusion and plasma.

A microparticle-enhanced nephelometric immunoassay, based on polystyrene beads coated with antihuman lysozyme antibody, has been developed for lysozyme quantification in sera and pleural effusions. The standard curve extends from 0.58 mg/l to 18.75 mg/l and no antigen effect was observed. The results showed a good serial precision. The intra-assay precision (n = 20) expressed as CV was between 2.2 and 4.2 in three different concentrations. The inter-assay precision, with different calibration curves (n = 12) was between 6.4 and 7.1. The analytical assay showed a sufficient linearity (r > 0.999). There were no interferences either with haemoglobin (up to 4 g/l), lipids (up to 0.5%, expressed as 1% Lipofundina content), or bilirubin (up to 5 mg/dl). The analytical sensitivity was lower than 0.6 mg/l. The correlation with a Micrococcus lysodeikticus turbidimetric assay showed a correlation coefficient of 0.915. We have studied 92 patients with pleural effusion. In each case, pleural fluid adenosine deaminase activity and pleural fluid to plasma lysozyme ratio were determined. The lysozyme ratio showed similar clinical sensitivity and specificity as to adenosine deaminase.

Adenosine Deaminase↗
PubMed1998

Infectious agents associated with diarrhoea of calves in the canton of Tilarán, Costa Rica.

A case-control study of calves under 3 months of age was carried out by weekly visits to 15 farms in the canton of Tilarán, Costa Rica. Most farms were dedicated to beef or dual-purpose (DP) production. Faecal samples were collected over a 6-month period from a total of 194 calves with clinical signs and from 186 animals without clinical signs of diarrhoea as assessed by a scoring system. The samples were investigated for the presence of viruses, bacteria and parasites. Torovirus was detected for the first time in Costa Rica and was present in 14% of calves with diarrhoea and in 6% of the controls. Coronavirus and Rotavirus were less frequently encountered in either one of the groups (in 9 and 7% of scouring calves and in 1 and 2% of controls, respectively). Escherichia coli was detected in 94% of all the faecal samples, but isolates from only three samples from calves with diarrhoea contained the K99 antigen. Similarly, Salmonella was found only in scouring calves. Cryptosporidium oocysts were detected in animals with signs of diarrhoea, while other coccidia oocysts, Strongylida and Strongyloides eggs were frequently found in animals both with and without diarrhoea. A conditional logistic regression (CLR) analysis to compare healthy and scouring calves showed a significant difference with regard to the presence of Torovirus, Rotavirus and Coronavirus.

Animals↗
PubMed1998

Measles virus fusion protein is palmitoylated on transmembrane-intracytoplasmic cysteine residues which participate in cell fusion.

[3H]palmitic acid was metabolically incorporated into the viral fusion protein (F) of Edmonston or freshly isolated measles virus (MV) during infection of human lymphoid or Vero cells. The uncleaved precursor F0 and the F1 subunit from infected cells and extracellular virus were both labeled, indicating that palmitoylation can take place prior to F0 cleavage and that palmitoylated F protein was incorporated into virus particles. [3H]palmitic acid was released from F protein upon hydroxylamine or dithiothreitol treatment, indicating a thioester linkage. In cells transfected with the cloned MV F gene, in which the cysteines located in the intracytoplasmic and transmembrane domains (Cys 506, 518, 519, 520, and 524) were replaced by serine, a major reduction of [3H]palmitic acid incorporation was observed for F mutated at Cys 506 and, to a lesser extent, at Cys 518 and Cys 524. We also observed incorporation of [3H]palmitic acid in the F1 subunit of canine distemper virus F protein. Cell fusion induced by cotransfection of cells with MV F and H (hemagglutinin) genes was significantly reduced after replacement of Cys 506 or Cys 519 with serine in the MV F gene. Transfection with the F gene with a mutation for Cys 518 abolished cell fusion, although less mutant protein was detected on the cell surface. These results suggest that the F protein transmembrane domain cysteines 506 and 518 participate in structures involved in cell fusion, possibly mediated by palmitoylation.

Acylation↗
PubMed1998

Evaluation of a hand-held electrical conductivity meter for detection of subclinical mastitis in cattle.

OBJECTIVE: To assess, under field conditions, whether a hand-held electrical conductivity (EC) meter could be used to detect subclinical mastitis caused by pathogens most commonly associated with mastitis in dairy cows. ANIMALS: 425 lactating cows on 15 dairies in Costa Rica. PROCEDURE: Immediately prior to milking, milk samples from each quarter were tested, using a hand-held EC meter. A milk sample from the quarter with the highest score was submitted for bacteriologic culture. Results of bacteriologic culture were compared with highest absolute EC score for each cow and with differential EC score (ie, difference between the highest and lowest absolute EC scores for the 4 quarters of each cow). RESULTS: Absolute EC score for cows with subclinical mastitis was significantly higher than that for cows without subclinical mastitis, and absolute EC score was significantly associated with detection of subclinical mastitis. If absolute EC score > or = 7 was considered indicative of subclinical mastitis, sensitivity was 0.43, specificity was 0.83, predictive value of a positive result was 0.39, and predictive value of a negative result was 0.85. Differential EC score for cows with mastitis was significantly higher than that for cows without subclinical mastitis. If differential EC score > or = 2 was considered indicative of subclinical mastitis, sensitivity was 0.53, specificity was 0.77, predictive value of a positive result was 0.37, and predictive value of a negative result was 0.87. CLINICAL IMPLICATIONS: A hand-held EC meter may be used to screen cows for subclinical mastitis.

Animals↗
PubMed1997

Sequence divergence of measles virus haemagglutinin during natural evolution and adaptation to cell culture.

Phylogenetic analysis of the sequence of the H gene of 75 measles virus (MV) strains (32 published and 43 new sequences) was carried out. The lineage groups described from comparison of the nucleotide sequences encoding the C-terminal regions of the N protein of MV were the same as those derived from the H gene sequences in almost all cases. The databases document a number of distinct genotype switches that have occurred in Madrid (Spain). Well-documented is the complete replacement of lineage group C2, the common European genotype at that time, with that of group D3 around the autumn of 1993. No further isolations of group C2 took place in Madrid after this time. The rate of mutation of the H gene sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low (5 x 10(-4) per annum for a given nucleotide position). This is an order of magnitude lower than the rates of mutation observed in the HN genes of human influenza A viruses. The ratio of expressed over silent mutations indicated that the divergence was not driven by immune selection in this gene. Variations in amino acid 117 of the H protein (F or L) may be related to the ability of some strains to haemagglutinate only in the presence of salt. Adaptation of MV to different primate cell types was associated with very small numbers of mutations in the H gene. The changes could not be predicted when virus previously grown in human B cell lines was adapted to monkey Vero cells. In contrast, rodent brain-adapted viruses displayed a lot of amino acid sequence variation from normal MV strains. There was no convincing evidence for recombination between MV genotypes.

Animals↗
PubMed1996

Isolation and identification of bacteria associated with the screwworm fly Cochliomyia hominivorax, coquerel and its myiasis.

We studied eight different myiasis of sheep caused by screwworm flies under laboratory conditions. Swabs were taken from the wound, before, during, and after the myiasis. Seven hundred and thirty-one samples were streaked on different bacteriological media. All samples were identified by Api System (bioMerieuex). We found thirty-eight different bacterial species in the exudates from the myiasis (before, during, and after the parasitic cycle). The analysis of bacterial flora of the screwworm showed, on larvae stage 1, 10 different bacterial species, on larvae 2, 12 bacterial species; larvae 3, 15 bacterial species; crawl off, 15 bacteria species, pupa, 9 bacterial species; and adults, 2 bacterial species and on the pioneer fly, 14 different bacterial species were isolated and identified.

Animals↗
PubMed1996

Identification of two amino acids in the hemagglutinin glycoprotein of measles virus (MV) that govern hemadsorption, HeLa cell fusion, and CD46 downregulation: phenotypic markers that differentiate vaccine and wild-type MV strains.

We have used site-directed mutagenesis of the hemagglutinin (H) glycoprotein of measles virus (MV) to investigate the molecular basis for the phenotypic differences observed between MV vaccine strains and recently isolated wild-type MV strains. The former downregulate CD46, the putative cellular receptor of MV, are positive for hemadsorption, and are fusogenic in HeLa cells, whereas the latter are negative for these phenotypic markers. CD46 downregulation in particular, could have profound consequences for the immunopathology of MV infection, as this molecule protects the cell from complement lysis. Mutagenesis of two amino acids, valine and tyrosine at positions 451 and 481, respectively, in the H protein from the vaccine-like Hallé MV strain to their counterparts, glutamate and asparagine, in the H protein from the wild-type Ma93F MV strain (creating the V451E/Y481N double mutation) abrogated CD46 downregulation, HeLa cell fusion, and hemadsorption. The converse double mutagenesis of the Ma93F H protein (E451V/N481Y) transferred the CD46-downregulating, fusogenic, and hemadsorption functions to this protein. The data provide the first mapping study of the functional domains of MV H. The consequences of these results for MV vaccine design and the role of CD46 in MV infection are discussed.

Animals↗
PubMed1996

Two novel mutations in the Norrie disease gene associated with the classical ocular phenotype.

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness due to a degenerative and proliferative dysplasia of the neuroretina and, occasionally, by deafness and mental handicap. Here, we report two novel mutations detected in patients with the classical eye features of ND. Both the one-base pair insertion in exon II (544/545 insA) and the two-base pair deletion in the start codon (418delTG) of the ND gene predict a functional 'null allele', i.e. the complete absence of the corresponding gene product.

Alleles↗
PubMed1995

Temporal and geographical distribution of measles virus genotypes.

The nucleotide sequence encoding the C terminus of the nucleocapsid protein of measles virus (MV) is the most variable in the genome. The sequence of this region is reported for 21 new MV strains and for virus RNA obtained from cases of subacute panencephalitis (SSPE) tissue. The nucleotide sequence of a total of 65 MV strains has been analysed using the CLUSTAL program to determine the relationships between the strains. An unrooted tree shows that eight different genotypes can be discerned amongst the sequences analysed so far. The data show that the C-terminal coding sequence of the nucleocapsid gene, although highly variable between strains, is stable in a given strain and does not appear to diverge in tissue culture. It therefore provides a good 'signature' sequence for specific genotypes. The sequence of this region can be used to discriminate new imported viruses from old 'endemic' strains of MV in a geographical area. The different genotypes are not geographically restricted although some appear to be the mainly 'endemic' types in large areas of the world. In global terms there appears to be at least four cocirculating genotypes of MV. The low level of divergence in the Edmonston lineage group isolated before 1970 indicates that some isolates are probably laboratory contaminants. This applies to some SSPE isolates such as the Hallé, Mantooth and Horta-Barbosa strains as well as some wild-type isolates from that period.

Amino Acid Sequence↗