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Biomedical subjects

E Muñoz

Publications and source records attributed to E Muñoz.

At least 127 records · Page 7Linked to original sources

Human papillomavirus DNA as a factor determining the survival of bladder cancer patients.

The natural history of transitional cell carcinoma (TCC) of the urinary bladder is somewhat variable, with a significant number of tumour recurrences that occasionally evolve towards an infiltrating disease. The aim of this study was to investigate the presence of human papillomavirus (HPV) DNA in 76 TCC specimens, and then correlate such findings with the overall patient survival. However, other classical prognostic clinical and pathological variables such as pathological grade and stage, koilocytosis, age and sex were also tested. HPV DNA was investigated by means of the highly sensitive polymerase chain reaction (PCR). DNA primers specific for HPV types 6, 11, 16 and 18 were used. Our results showed that 7 (9.21%) out of 76 such cases were reactive for HPV 16 DNA; one of them also reacted with HPV 6 DNA. The statistical analysis was done by the Kaplan-Meier method, Wilcoxon's generalised test for studying the differences in survival curves and Cox's regression analysis for independent prognostic factors. A significant P-value was found for pathological grade (P < 0.0001) and stage (P < 0.0001), HPV 16 DNA (P = 0.0418) and koliocytosis (P = 0.0140). Thus, pathological grade was the only independent factor in the bladder cancer survival. These observations may prove useful in prognostic stratification of patients with TCC of the bladder.

Age Factors↗

Labelling pattern obtained by non-isotopic in situ hybridization as a prognostic factor in HPV-associated lesions.

In the study of infection of the lower female genital tract caused by human papillomavirus (HPV), one of the main concerns is the search for prognostic factors to predict the evolution of premalignant low- and high-grade squamous intraepithelial lesions. This study has evaluated the prognostic usefulness of the patterns of positive reaction obtained by non-isotopic in situ hybridization (NISH), referred to as diffuse, punctate, or mixed 'labelling patterns'. The study examined 141 vulvar and uterine cervical biopsy specimens that were positive for HPV by a NISH screening technique and that had the following histological diagnoses: low-grade squamous intraepithelial lesion (LSIL; n = 87); high-grade squamous intraepithelial lesion (HSIL, n = 40); and squamous cell carcinoma (SCC n = 14). Typing of all the specimens was carried out by NISH with DNA probes specific for HPV types 6/11 (low risk), 16/18 (high risk), and 31/33/51 (intermediate risk), and the labelling pattern observed in each specimen was recorded. Statistical analysis of the results showed that there was a significant difference in the distribution of labelling patterns, both by lesion diagnosis (P < or = 0.004) and by infecting viral type (P < or = 10(-6)). Lesions with a punctate or mixed pattern are considered more likely to undergo malignant evolution and consequently have a worse prognosis than lesions with a diffuse pattern.

Carcinoma, Squamous Cell↗

Penicillium brevicompactum as the cause of a necrotic lung ball in an allogeneic bone marrow transplant recipient.

The non-Candida, non-Aspergillus fungal infections are being reported with increasing frequency in BMT patients. One of these agents is Penicillium which has rarely been implicated as a pathogen in these patients. Only a few cases of isolated fungemias have been reported to date. We present the first documented case of invasive lung infection due to Penicillium brevicompactum in an allogeneic BMT recipient. As this case shows, the diagnosis of non-Candida, non-Aspergillus fungal infections may be incorrect if only histologic findings are available, mainly because misdiagnosis with other more common fungus can occur. A positive culture is required in order to make an accurate diagnosis.

Adult↗

Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha-responsive elements.

The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor. Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli, in vivo it is mainly expressed by T-lymphocytes located in the inflammatory infiltrates of several human diseases. To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes, we isolated the promoter region of the CD69 gene and carried out its functional characterization. Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors (NF-kappa B, Egr-1, AP-1), which might mediate the inducible expression of this gene. Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate-inducible transcription of the CD69 gene. Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate. We also found that tumor necrosis factor-alpha (TNF-alpha) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene, suggesting that this cytokine may regulate in vivo the expression of CD69.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Reaction time and acoustic startle in normal human subjects.

We studied the effects of collision between a voluntary command and the startle response by interrupting a simple visual reaction time task with an acoustic startle. We observed two main effects. First, the reaction time was markedly shortened when the startle was delivered at intervals of 0-75 ms after the 'go' signal. Second, the startle response elicited when the subject's attention was focused onto reacting to the visual 'go' signal involved more muscles and induced larger EMG responses than when the startling stimulus was delivered unexpectedly. Startle response and voluntary commands may share a number of structures along the motor path. Reaction time can be shortened up to the latency of a startle response if the voluntary command is issued a short time after the startling stimulus. Facilitation of the startle responses during motor preparation may be due to the excitability enhancement that occurs in various neural structures along the motor path before the onset of EMG activity.

Acoustic Stimulation↗

Human herpesvirus-6 and the course of human immunodeficiency virus infection.

The aim of this study is to investigate the relationship between human herpesvirus type 6 (HHV-6) and cytomegalovirus (CMV) infection and progression of AIDS disease. A group of 52 HIV-1-seropositive patients was examined for HHV-6 DNA expression in peripheral blood mononuclear cells and for CMV DNA in serum. We found that 21.1% (n = 52) and 12% (n = 25) of them tested positive for HHV-6 and CMV DNA, respectively. In contrast, only 3.3% (n = 29) and 0% (n = 29) of control healthy HIV-1-seronegative donors tested positive for HHV-6 and CMV, respectively. In light of these results, the possible role of HHV-6 as a cofactor in AIDS development has also been assessed by closely following, over 6 years, the course of an HIV-1-seropositive person who had a dramatic loss in the total number of CD4+ cells along with a spontaneous production of HIV-1 p24 antigen in vitro and who also showed progression to AIDS when coinfected with HHV-6. These observations have spurred our prospective analysis of the possible clinical significance of coinfection with HHV-6 and HIV.

Adult↗

Structural domains of streptokinase involved in the interaction with plasminogen.

Two fragments of recombinant streptokinase, comprising amino acids Val143-Lys293 (17-kDa rSK) or Val143-Lys386 (26-kDa rSK), were cloned and expressed in Escherichia coli, purified to homogeneity and their interactions with plasmin(ogen) were evaluated. Both 17-kDa rSK and 26-kDa rSK bound to plasminogen with a 1:1 stoichiometry and with affinity constants of 3.0 x 10(8) M-1 and 12 x 10(8) M-1, respectively, as compared to 6.3 x 10(8) M-1 for the binding of intact recombinant streptokinase to plasminogen. Binding of 17-kDa rSK to plasminogen-Sepharose was displaced by addition of increasing concentrations of recombinant streptokinase, whereas bound recombinant streptokinase was not displayed by 17-kDa rSK. In equimolar mixtures of plasminogen and 26-kDa rSK, the appearance of amidolytic activity as monitored with a chromogenic substrate, was significantly delayed compared to the equimolar mixture with recombinant streptokinase (60% of the maximal activity after 30 min, compared to maximum activity within < or = 2 min). In contrast, no amidolytic activity was generated in equimolar mixtures of plasminogen and 17-kDa rSK. Plasminogen was rapidly activated by catalytic amounts (1:100 molar ratio) of recombinant streptokinase (60-70% within 10-15 min), whereas only 4% of the plasminogen was activated within 60 min with 26-kDa rSK, and no plasmin was generated with 17-kDa rSK. Complexes of plasmin with 17-kDa rSK or with 26-kDa rSK were very rapidly inhibited by alpha 2-antiplasmin (apparent second-order inhibition rate constant of approximately 2 x 10(7) M-1 s-1), whereas the complex with recombinant streptokinase was resistant to inhibition. With 26-kDa rSK, inhibition by alpha 2-antiplasmin resulted in dissociation of the complexes and recycling of functionally active 26-kDa rSK to other plasminogen molecules; 17-kDa rSK, in contrast, remained associated with the plasmin-alpha 2-antiplasmin complex. These findings suggest that different regions of the streptokinase molecule are involved in binding to plasminogen, in active-site exposure, and in impairment of the inhibition of plasmin by alpha 2-antiplasmin. Thus, the 17-kDa region spanning Val143-Lys293 in streptokinase mediates its binding to plasminogen but does not induce activation. Furthermore, this region does not interfere with the inhibition of the complex with plasmin by alpha 2-antiplasmin.

Amino Acid Sequence↗

Vitamin B-12 deficiency and malabsorption are highly prevalent in rural Mexican communities.

Vitamin B-12 status of rural Mexicans was evaluated in two studies, 6 y apart. In the first, a single blood sample was collected from children and adults, including pregnant and lactating women. Prevalence of deficient plasma vitamin B-12 values ranged from 19% to 41% among groups, but plasma folate status was normal in all individuals. Breast milk vitamin B-12 concentration was low in 62% of samples. The second study was conducted in 219 children aged 18-36 mo in five communities, whose prevalence of deficient and low plasma vitamin B-12 concentrations, respectively, was 8% and 33% on entry, 3% and 22% 6 mo later, and 7% and 29% 12 mo later. Prevalence of low holotranscobalamin II concentrations, indicating malabsorption of the vitamin, averaged 18-40% across the three same periods. Both vitamin B-12 status indicators differed significantly between communities. The widespread vitamin B-12 deficiency was probably caused by malabsorption, perhaps exacerbated by low dietary intake and, for young children, maternal depletion of the vitamin.

Adult↗

Transitional cell carcinoma of the bladder: low incidence of human papillomavirus DNA detected by the polymerase chain reaction and in situ hybridization.

Viral studies on mammalian urothelium have shown an association between the bovine papillomavirus and cancer of the bladder in cattle. However, the evidence for human papillomavirus (HPV) involvement in urinary bladder in man is less clear. The aim of this study was to investigate the association between HPV DNA and transitional cell carcinoma of the bladder, using the highly sensitive polymerase chain reaction (PCR) and non-isotopic DNA in situ hybridization of formalin-fixed paraffin-embedded tissues from 76 patients. An HPV type specific set of primers was localized on the E6-gene for HPV 16/18 DNA. The second and third set of primers were specific for HPV 6/11 DNA. A biotinylated DNA probe which recognizes HPV 6/11, 16/18, and 31/33/35 was used for in situ hybridization. Of the 76 cases investigated, PCR analysis showed positive signals in seven (9.2%) of cases--six for HPV 16 DNA, and one for HPV 16 DNA and HPV 6 DNA. Four (5.2%) were also reactive for HPV 16/18 DNA using in situ hybridization. Most transitional cell carcinomas (71.4%) associated with HPV DNA were of high pathological grade/stage. One case had koilocytosis. Our results suggest that HPV DNA in transitional cell carcinoma is probably a rare occurrence, although the finding on the high risk HPV 16 DNA may indicate a role for it in this tumour's aetiology.

Aged↗

Diagnosis of genital infection caused by human papillomavirus using in situ hybridisation: the importance of the size of the biopsy specimen.

AIM: To determine the size of a cervical biopsy specimen with human papillomavirus (HPV) infection required to enable in situ hybridisation to be carried out with a guarantee of a reliable result. METHODS: In situ hybridisation was carried out in 142 cervical uterine biopsy specimens classified histologically as low grade and high grade squamous intraepithelial lesions. Epithelial length at the level of the basal membrane was measured by image analysis. The specimens were divided into 10 groups based on epithelial length. RESULTS: Of the biopsy specimens, 61.2% were HPV positive. In specimens with an epithelial length below 5 mm 31.9% were HPV positive; in those between 5 and 9 mm in length 67.5% were HPV positive; and in those greater than 9 mm in length 81.8% were positive for HPV. For low grade squamous intraepithelial lesions (n = 90), 68.4% of specimens with an epithelial length greater than 5 mm were HPV positive. For high grade squamous intraepithelial lesions (n = 52), 86.8% of specimens with an epithelial length greater than 5 mm were HPV positive. CONCLUSIONS: For a diagnosis of HPV infection using in situ hybridisation, the minimum length of epithelium in a cervical biopsy specimen should be 5 mm. For high grade squamous intraepithelial lesions, specimens over 5 mm in length are suitable. For low grade squamous intraepithelial lesions, to minimise the number of false negative results, the ideal minimum length is 10 mm.

Biopsy↗

Stimulation of alpha 1 (I) procollagen gene expression in NIH-3T3 cells by the human T cell leukemia virus type 1 (HTLV-1) Tax gene.

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene (COL1A1) promoter. The results indicated that the promoter activity of the -804 to bp COL1A1 fragment increased up to 12-fold in cells expressing Tax. Deletion analysis revealed that the region of COL1A1 encompassing nucleotides -174 to -84 contained the Tax-responsive elements. A gene segment encompassing nucleotides -187 to -67, which contained this region, proved sufficient to confer Tax inducibility (2.5-fold) to a herpes simplex virus thymidine kinase promoter. Stably transfected NIH-3T3 cell clones that constitutively produce Tax displayed elevated levels of alpha 1(I) procollagen and fibronectin transcripts and increased production and accelerated processing of type I procollagen. These findings suggest that retroviral proteins may be involved in the pathogenesis of idiopathic diseases accompanied by collagen overproduction.

3T3 Cells↗

Pachydermodactyly: a case report.

Pachydermodactyly is an uncommon variant of digital fibromatosis that has previously been related to knuckle pads. It is a benign condition that needs no investigation for an underlying systemic disease. We present a new case of pachydermodactyly and comment on the available literature.

Adolescent↗

[Biochemical-histological study of the effects of lithium on various organs of vizcacha (Lagostomus maximus maximus)].

Considering that the vizcacha (Lagostomus maximus maximus) is a very Lithium sensitive rodent, we planned a biochemical-histological study injecting IP doses of 1 mEq/kg/day LiCl during one month to adult vizcachas, and they were divided into three lots: Lot I the optical microscopy revealed evident renal, gonadal, hyphophyseal and adrenal damages; the biochemical analysis showed that Li significantly decreased the female serum LH levels while testosterone and estradiol levels were not affected. The male Li serum values resulted to be significantly higher than those of female animals. The damage was greater in male specimens. Lott II: the tissue recovery from the damage observed in Lot I was the following: total in hyphophysis, partial in testis, the same in kidney and was enhanced in adrenal and ovary. The Li renal clearance was determined in Lot III verifying no changes in both sexs. According to our results, Li (1 mEq/kg/day during one month) produce modifications in different tissues probably the gonadal damage may be consequence of a direct Li effect and not for a hyphophysis alteration, since in male vizcacha the LH serum level was not changed. In regard to the selective effect in the suprarenal glomerulus structure, this Li effect is produced via hyphophysis. In conclusion, the selective effect of Li on adrenal and gonada organs of this rodent is a contribution in order to warm about the possible reproduction of such effects in human beings.

Adrenal Glands↗