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Biomedical subjects

A Matilla

Publications and source records attributed to A Matilla.

At least 19 recordsLinked to original sources
PubMed2006

Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis.

Endoglin, a transforming growth factor (TGF)-beta1 co-receptor, has been associated with renal and cutaneous fibrosis, as overexpression of this protein has been observed in biopsies from patients with glomerulosclerosis and scleroderma, respectively. Our aim was to evaluate whether endoglin may be associated with hepatic fibrosis featuring chronic hepatitis C virus (HCV) infection. Fifty-two anti-HCV+ patients, five anti-HCV- patients and 27 healthy subjects were studied. Western blot and immunohistochemistry were used to quantify the expression levels of endoglin and TGF-beta1 in liver biopsy samples, and serum concentrations of endoglin and hyaluronic acid were determined by enzyme-linked immunosorbent assays (ELISAs). In patients with advanced fibrosis, intrahepatic expression levels of endoglin and TGF-beta1 were significantly higher than those in patients with early fibrosis (mean: 3- and 5.8-fold, respectively) and normal liver (mean: 3.9- and 12-fold, respectively). Interestingly, activated hepatic stellate cells as well as portal and septal myofibroblasts expressed endoglin. Serum levels of endoglin were also significantly higher in patients with advanced fibrosis than in those with early fibrosis (55.5 +/- 1.6 vs 47.5 +/- 0.9 ng/mL, P < 0.001), showing a positive correlation with serum hyaluronic acid concentrations (r = 0.57, P = 0.01). In conclusion, increased intrahepatic endoglin and TGF-beta1 expression is significantly associated with progressive hepatic fibrosis in chronic HCV infection. Circulating endoglin levels are elevated in HCV patients showing a significant correlation with histological and serum markers of hepatic fibrosis. These data suggest an active role for endoglin in the fibrotic process featuring chronic HCV infection.

Adult↗
PubMed2003

Liver transplantation for fulminant and subfulminant hepatic failure.

AIMS: The aim of this study was to assess the long-term course and outcome after liver transplantation (LTX) for fulminant/subfulminant hepatic failure (FSHF) to determine which factors relate to outcome. PATIENTS AND METHODS: Between April 1990 and October 2002, 30 adult patients with FSHF underwent LTX. King's College criteria were used to decide which patients needed LTX. Pretransplantation parameters (age, sex, degree of hepatic encephalopathy, etiology, and time between onset of symptoms and LTX) were examined as risk factors for LTX outcome. RESULTS: Mean age at LTX was 40.4+/-13.9 years and 46.7% were men. The most frequent causes of FSHF were virus B in 23.3%, autoimmune hepatitis in 23.3%, and cryptogenic in 20%. Fifty percent of the patients with a survival longer than 15 days suffered episodes of acute rejection; chronic rejection occurred in 25%. One- and five-year patient and allograft survival rates for FSHF were 56.3% and 54.7%, respectively. Autoimmune hepatitis was the only factor associated with better posttransplantation outcome, although there were no differences in posttransplant course. Patient survival rates increased during the study period. During the first 5 years (1990-1995) the survival rates were 53.3% (1-year and 5-year), whereas they were 60% at 1 and 5 years in the second interval (1996-2002). CONCLUSIONS: The mortality rate of FSHF is high during the first year post-LTX. LTX for FSHF of autoimmune etiology showed better outcomes with increasing patient survival rates during the study period.

Adolescent↗
PubMed2001

Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7.

Adenosine Triphosphatases↗
PubMed2001

[Predictive factors of the mortality of digestive hemorrhage caused by esophageal varices in elderly patients].

Complications of liver cirrhosis are increasingly frequent in elderly patients due to increased life expectancy and better management of cirrhotic patients. However, the influence of this condition on the evolution of variceal bleeding has not been well established. The aim of the present study was to determine the characteristics of esophagogastric variceal bleeding in elderly patients and the possible influence of advanced age on hemorrhage-related mortality. We analyzed 321 episodes of variceal bleeding in 227 cirrhotic patients. One hundred and thirteen (35.2%) episodes occurred in patients older than 65 years. No differences were found among patients older or younger than this age in terms of bleeding characteristics or Child-Pugh score. Patients older than 65 years more frequently presented serious associated diseases, hepatocellular carcinoma and hepatic encephalopathy during the episode (52.7% vs. 14%, p < 0.001; 19.7% vs. 8.7%, p = 0.01 and 17.4% vs. 10%, p = 0.09 respectively). Although hemorrhage-related mortality was higher in elderly patients (23.2% vs. 13.5%, p = 0.04), only the Child-Pugh score, definitive hemostasis, hepatocellular carcinoma and the development of encephalopathy or bacterial infection were independent predictive factors of mortality. A considerable proportion of the patients with esophagogastric variceal bleeding were older than 65 years. Advanced age does not independently influence mortality due to variceal bleeding.

Aged↗
PubMed2000

Merkel cell (neuroendocrine) carcinoma of the vulva. A case report with immunohistochemical and ultrastructural findings and review of the literature.

A new case of primary Merkel cell carcinoma (MCC) of the vulva is reported and the literature reviewed for noting its clinical presentation, microscopic, immunohistochemical and ultrastructural features, as well as for establishing the role of immunohistochemistry in the ultimate diagnosis of this uncommon and aggressive tumor. The lesion occurred in a 79 year old patient. Histologically, the tumor was composed of intradermal small cells with high mitotic index and frequent apoptosis. The immunohistochemical study showed positivity for wide spectrum and low molecular weight cytokeratins, epithelial membrane antigen, neurofilaments, neuron specific enolase and chromogranin A. Electron microscopy revealed intermediate filaments in a typical globular paranuclear arrangement. The coexpression of cytokeratins (including cytokeratin 20) and neurofilaments, both in typical globular paranuclear arrangement, made possible the diagnosis of MCC, differentiating it from other malignant small cell tumors such as neuroendocrine metastatic carcinoma.

Aged↗
PubMed2000

Molecular evolution and intratumor heterogeneity by topographic compartments in muscle-invasive transitional cell carcinoma of the urinary bladder.

Superficial transitional cell carcinomas (TCC) of the urinary bladder have been shown to be monoclonal. However, no combined study of clonality and tumor suppressor genes (TSG) is available to date for muscle-invasive TCC. Forty-four muscle-invasive TCC of the urinary bladder selected from women were included in this study. Tumor cells located above and below the muscularis mucosa zone were systematically microdissected and used for DNA extraction. Hha-I digested and undigested samples were used to study the methylation pattern of androgen receptor alleles and undigested samples were used for microsatellite analysis of TSG (TP53, RB1, WT1, and NF1). Both loss of heterozygosity (LOH) and single nucleotide polymorphism (SNP) analyses were performed using optimized denaturing gradient gel electrophoresis. The expression of p53, pRB, and p21WAF1 was assessed by immunohistochemistry. Appropriate controls were run in every case. All except two TCC showed a monoclonal pattern with the same allele inactivated in both compartments. Microsatellite analysis of TSG revealed the same LOH/SNP pattern in both tumor compartments in 30 cases (involving more than 1 TSG locus in 8) and genetic heterogeneity in 14 cases. From the latter group, 9 cases expressed more genetic changes in the deep compartment (involving TP53 gene in all cases, WT1 gene in 2, and NF1 in 1), whereas in 4 cases the superficial compartment showed more genetic changes (three involving NF1 and one involving both RB and TP53). No statistical difference in the immunoexpression was detected, although it tended to be higher in the superficial compartment than in the deep compartment. These concordant data in polymorphic DNA regions indicate that bladder-muscle-invasive TCC are monoclonal proliferations with homogeneous tumor cell selection. Heterogeneous tumor cell selection by topography defined two different genetic compartments: superficial, NF1-defective, and deep, TP53-defective. No differences in the immunohistochemical expression were observed, precluding a more extensive clinical application.

Base Sequence↗
PubMed1999

Involvement of calcium in ACC-oxidase activity from Cicer arietinum seed embryonic axes.

Both in vivo and in vitro ACC-oxidase activities as well as ethylene production from embryonic axes of chickpea seeds were strongly inhibited by EGTA, a selective extracellular Ca2+ ion chelator, indicating that the influx of Ca2+ is important for enzymatic activity. EGTA inhibition was restored by exogenous Ca2+. Treatments of embryonic axes with either Verapamil and LaCl3 (both Ca2+ channel blockers) or TMB-8 (an intracellular Ca2+ antagonist) provoked an inhibition of both ACC-oxidase activity and ethylene production. These results suggest an involvement of calcium fluxes and intracellular calcium levels in the activity of the last step of the ethylene biosynthetic pathway, which is, in turn, intimately correlated with germination of Cicer arietinum seeds.

Amino Acid Oxidoreductases↗
PubMed1998

Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired-pulse facilitation.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the function of the SCA1 gene product ataxin-1, a novel protein without homology to previously described proteins, we generated mice with a targeted deletion in the murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate decreased exploratory behavior, pronounced deficits in the spatial version of the Morris water maze test, and impaired performance on the rotating rod apparatus. Furthermore, neurophysiological studies performed in area CA1 of the hippocampus reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term and post-tetanic potentiations are normal. These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and point to the possible role of ataxin-1 in learning and memory.

Analysis of Variance↗
PubMed1998

Urgent transjugular intrahepatic portosystemic shunt for control of acute variceal bleeding.

OBJECTIVE: Endoscopic sclerotherapy and pharmacological therapy are widely used in the treatment of acute variceal hemorrhage. However, they fail at arresting acute bleeding in 20-30% of bleeding episodes. The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the prevention of recurrent variceal bleeding has been proved recently, but the effectiveness and safety of urgent TIPS in the treatment of acute variceal bleeding refractory to conventional therapy are still under evaluation. METHODS: Over 4.5 yr, 358 variceal hemorrhage episodes were treated in our hospital. Pharmacological and endoscopic therapy failed to control hemorrhage in 93 episodes. Thirty-two patients died because of uncontrolled massive bleeding. In 56 patients, TIPS (Strecker stent) was performed after temporary control of the episode with balloon tamponade. RESULTS: Eleven of 56 patients with urgent TIPS belonged to Child-Pugh class A, 22 to class B, and 23 to class C. The mean time between indication and insertion was 17 +/- 10 h (range 4-24 h). Control of bleeding was achieved in 53 patients (95 %). Eight patients had recurrent bleeding at 1 month after TIPS, seven of them during the first week after the procedure. The 1-month actuarial probability of rebleeding was 22%. The main complications of the procedure were massive hemoperitoneum (n = 1), cardiorespiratory arrest (n = 2), cardiac failure (n = 1), acute renal failure (n = 2), and bacteremia (n = 7). Operative mortality (30 days) was 28%. The actuarial probability of survival at 30 days was significantly lower in Child-Pugh class C than in class A or B (48% vs 90%; p < 0.001). The presence of ascites, hepatic encephalopathy, and serum albumin level before TIPS were independent prognostic factors associated with the risk of operative mortality. CONCLUSIONS: Urgent TIPS is an effective alternative for the treatment of acute variceal bleeding refractory to endoscopic and pharmacological therapy, but sometimes is associated with major complications. Because of the high operative mortality rate in patients with severe liver failure, careful selection of patients is required before TIPS.

Actuarial Analysis↗
PubMed1997

The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. SCA1 belongs to a growing group of neurodegenerative disorders caused by expansion of CAG repeats, which encode glutamine. Although the proteins containing these repeats are widely expressed, the neurodegeneration in SCA1 and other polyglutamine diseases selectively involves a few neuronal subtypes. The mechanism(s) underlying this neuronal specificity is unknown. Here we show that the cerebellar leucine-rich acidic nuclear protein (LANP) interacts with ataxin-1, the SCA1 gene product. LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCA1. The interaction between LANP and ataxin-1 is significantly stronger when the number of glutamines is increased. Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures. The features of the interaction between ataxin-1 and LANP, their spatial and temporal patterns of expression, and the colocalization studies indicate that cerebellar LANP is involved in the pathogenesis of SCA1.

Animals↗
PubMed1997

Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract. Work presented here describes the behavioral and neuropathological course seen in mutant SCA1 transgenic mice. Behavioral tests indicate that at 5 weeks of age mutant mice have an impaired performance on the rotating rod in the absence of deficits in balance and coordination. In contrast, these mutant SCA1 mice have an increased initial exploratory behavior. Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has divergent effects on the motor behavior of juvenile animals: a compromise of rotating rod performance and a simultaneous enhancement of initial exploratory activity. With age, these animals develop incoordination with concomitant progressive Purkinje neuron dendritic and somatic atrophy but relatively little cell loss. Therefore, the eventual development of ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but the result of cellular dysfunction and morphological alterations that occur before neuronal demise.

Alleles↗
PubMed1996

[The molecular pathology of RET protooncogene in families with multiple endocrine neoplasia type 2A].

BACKGROUND: Multiple endocrine neoplasm type 2A (MEN 2A) is an autosomal dominantly inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. Mutations have been identified in the extracellular domain of the RET proto-oncogen product (10q11.2) in MEN 2A patients. In each case a single base pair substitution results in replacement of cysteine with another amino acid. Most MEN 2A patients have mutations of codon 634. PATIENTS AND METHODS: Sixty-five unrelated MEN 2A patients from seven families were studied. Polymerase chain reaction, segregation, sequence analysis and restriction enzyme digestion were performed. RESULTS: Of seven families, four had the TGC to TAC transition, two families the TGC to TGG transversion and one family the TGC to CGC transition in codon 634 of RET. CONCLUSIONS: We found all the mutations in codon 634. The characterization of MEN 2A mutations allows early and presymptomatic diagnosis in this syndrome.

Base Sequence↗
PubMed1996

Cis-Dichloro(diaminosuccinate diethyl ester)palladium (II) as Pd(II)/Pt(II) model compound for DNA-binding and antitumor properties: solution equilibria of their aqua-, hydroxo-, and/or chloro-species.

Cis-Dichloro(diaminosuccinic acid)palladium(II), cis-[Pd(H2dasa)Cl2] (I), or cis-dichloro(diaminosuccinate diethyl ester)palladium(II), cis-[Pd(Et2dasa)Cl2] (II) reacts with two equivalents of AgClO4 to give insoluble Pd(dasa) or an aqueous solution of [Pd(Et2dasa) (H2O)2](ClO4)2, respectively. Three solutions of this salt were titrated with NaOH (I = NaClO4 (0.15M),37 degrees C), and 133 E(H+) data (3.5 < or = pH < or = 7) were treated by SUPERQUAD to fit log beta pqr of cis-aquahydroxo-(pqr = 10-1, -5.25(3)) and di-mu-hydroxo-species (20-2, -6.55(1)). At pH > 7 the ester hydrolysis prevents the calculation of log beta 10-2 for the cis-dihydroxo-complex. Another three solutions of such salt were titrated (I = 0.15M (NaClO4), 37 degrees C) with NaOH and NaCl simultaneously using two potentiometric systems (which measure H+ or Cl-). From 147 E(H+) and E(Cl-) data pairs and the above fixed log beta pqr, SUPERQUAD calculations yield log beta pqr for cis-chloro-aqua (pqr = 110, 3.65(1)), cis-chloro-hydroxo (11-1, -2.68 (4)), and cis-dichloro-species (120, 5.86(3)). Simulated and experimental titrations are in good agreement. Circular dichroism spectra of native DNA and drug:DNA complexes suggest that cis-Pd(H2dasa) and cis-Pd(Et2dasa) chelate moieties induce an opening and rotation of the stacked bases in the double helix. This finding is explained by the abundance of each one and of the total neutral and charged species of II in the tested CD solution.

Amino Acids, Diamino↗
PubMed1996

Multizone versus monozone in the treatment of high and moderate myopia with an excimer laser.

BACKGROUND AND OBJECTIVE: Numerous modifications have been proposed to photorefractive keratectomy (PRK) in the treatment of myopia in excess of 6.00 diopters (D). One of the techniques employed in an attempt to achieve better refractive results and to avoid, above all, the appearance of an intense haze, is the technique known as multizone. PATIENTS AND METHODS: We have attempted, in a prospective study, to compare the refractive results and the complications of monozone and multizone techniques for the treatment of moderate and high myopia. We performed 139 monozone PRKs and 30 multizone PRKs with a one-year follow-up. RESULTS: We did not find statistically significant differences between the two groups either in the degree of correction obtained nor in the final visual acuity. A statistically significant difference was found only in the number of cases with severe haze (greater than 3) which proved more frequent in the monozone group. CONCLUSION: Our results suggest the techniques are comparable in predictability and effectiveness. However, the incidence of severe haze was lower in the multizone group, which may render its use preferable in the treatment of myopias in excess of 6.00 D.

Corneal Opacity↗
PubMed1996

[Treatment with interferon alfa-2b in patients with chronic hepatitis caused by hepatitis C virus: predictive factors for the response, relapse and early development to cirrhosis after treatment].

UNLABELLED: The treatment of chronic hepatitis C is interferon (IFN). Diverse predictive factors influence a complete response. The aim of this study was to determine the response to IFN-alpha therapy and factors that may predict a sustained response before and after the first month of treatment. Likewise, it evaluates the relapse and liver cirrhosis evolution after therapy. PATIENTS AND METHODS: We have treated 155 consecutively patients with chronic hepatitis C. Nine left therapy because of severe side effects. We studied the patients who had had persistently elevated serum aminotransferase concentrations, HBsAg negative, HIV negative and antiHCV positive with polymerase chain reaction confirmation, and without any other liver disease. The schedule of IFN-alpha 2b therapy was 5 MU three times per week for 3 months, and later, 3 MU three times per week for 6 more months. There were two groups of response: A) Complete response, if serum aminotransferase levels were normal and RNA-HCV negative, B) No response, if it didn't meet these conditions. The sustained response was complete response during follow-up. The relapse described as aminotransferase increase after suppression therapy with or without positive RNA-HCV, or positive RNA-HCV only. RESULTS: A complete response was obtained in 34.9%. Ten variables were statistically significant (p < 0.05) on univariate analysis: weight, corporal surface, dosage IFN/m2, bilirubin and total protein pretreatment; polymorphonuclears/mononuclears cells, AST, ALT, AST/ALT, and gamma GT in the first therapy's month. In multivariate analysis, serum AST levels < 40 U/l (odds ratio 0.15, 95% CI 0.04-0.52), and AST/ALT ratio > 0.75 (odds ratio 3.05, 95% CI 1.04-8.9) in the first month, were correlated independently with complete response. Incidence of relapse was 47% of responders, with mean appearance period a of 2.7 +/- 2.1 months. Therefore, a sustained response was obtained in 27 patients (18.5%). Seventeen of 115 patients (14.6%) without cirrhosis initially, developed liver cirrhosis after a second biopsy. Two variables were statistically significant in multiple regression analysis: RNA-HCV positive after treatment (odds ratio 2.99, 95% CI 0.9-2.99), and platelet count < 180,000/mm3 before therapy (odds ratio 17.7, 95% CI 3.7-83.2) were correlated independently with cirrhosis development. CONCLUSIONS: A 9 months course of IFN therapy is effective in a third of patients, but almost half of them have relapsed within 6 months after treatment's suppression. The AST levels and AST/ALT ratio in the first of month therapy were correlated independently with complete response. Liver cirrhosis appears in a small percentage. Platelet count before therapy and RNA-HCV positive at the end treatment, were predictor variables of this evolution.

Adult↗
PubMed1995

Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.

A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.

Adolescent↗