RESUMEN
BACKGROUND/AIMS: Pulmonary arterial hypertension (PAH) frequently accompanies childhood congenital heart disease (CHD) and may persist into adult life. The advent of specific PAH therapies for PAH prompted formation of a national Australian and New Zealand registry in 2010 to document the incidence, demographics, presentation and outcomes for these patients. METHODS: This multicentre, prospective, web-based registry enrols patients with CHD-associated PAH being followed in a tertiary centre. The inclusion criteria stipulated patient age ≥16 years, a measured mean pulmonary arterial pressure >25 mmHg at rest or echocardiographical evidence of PAH or a diagnosis of Eisenmenger syndrome, and followed since 1 January 2000. A single observer collected standardised data during a series of site visits. RESULTS: Of the first 50 patients enrolled, 30 (60%) were female. The mean age (standard deviation (SD)) at the time of PAH diagnosis or confirmation in an adult centre was 27.23 (10.07) years, and 32 (64%) patients are currently aged >30 years. Fourteen (28%) patients were in World Health Organization Functional Class II and 36 (72%) in Class III at the time of diagnosis. Forty-seven of 50 (94%) had congenital systemic-pulmonary shunts, and 36 (72%) never underwent intervention. Thirteen (26%) had Down syndrome. Confirmation of PAH by recent cardiac catheterisation was available in 30 (60%) subjects. During follow up, a total of 32 (64%) patients received a PAH-specific therapy. CONCLUSIONS: CHD associated with PAH in adult life has resulted in a new population with unique needs. This registry will allow documentation of clinical course and long-term outcomes for these patients.
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Cardiopatías Congénitas/epidemiología , Hipertensión Pulmonar/epidemiología , Sistema de Registros , Adulto , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/terapia , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Evaluation of the size of the pituitary gland on magnetic resonance imaging (MRI) may be difficult, considering the wide variation in normal gland morphology. Given the paucity of age-related biometric data, our purpose was to obtain standard normal reference values for pituitary volumes in prepubertal children using three-dimensional MRI data. METHODS: Children under the age of 10 yr undergoing brain MRI for seizures or idiopathic developmental delay and who had no endocrine abnormality were recruited prospectively over 2 yr. All MRI studies included a three-dimensional sequence. Only subjects with normal studies were included. One hundred thirty-nine children were eligible (mean age, 5.2 yr). Direct pituitary volumes were measured from contiguous 1-mm thick reconstructed coronal and sagittal images. Estimated pituitary volumes were calculated using pituitary height, width, and length. RESULTS: Volumes obtained from reconstructions in either plane were essentially identical. There was a linear increase in log-transformed pituitary volume with age, but relatively weak correlations with height or body mass index. There was no gender difference and only weak correlations between pituitary height and pituitary volume and between estimated pituitary volume calculation and measured pituitary volume. We provide age-related reference ranges for pituitary volumes in graphical and tabular forms.
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Imagen por Resonancia Magnética/métodos , Hipófisis/anatomía & histología , Hipófisis/fisiología , Estatura , Índice de Masa Corporal , Encéfalo/anatomía & histología , Niño , Preescolar , Discapacidades del Desarrollo/diagnóstico , Humanos , Lactante , Convulsiones/diagnósticoRESUMEN
BACKGROUND: Various methodologies have been proposed for analysis of continuous glucose measurements. These methods have mainly focused on the proportion of low or high glucose readings and have not attempted to analyze other dimensions of the data obtained. This study proposes an algorithm for analysis of continuous glucose data including a novel method of assessing glycemic variability. METHODS: Mean blood glucose and mean of daily differences (MODD) assessed the degree that the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA) trace was representative of the 3-month glycemic pattern. Percentages of times in low, normal, and high glucose ranges were used to assess marked glycemic excursion. Continuous overall net glycemic action (CONGA), a novel method developed by the authors, assessed intra-day glycemic variability. These methods were applied to 10 CGMS traces chosen randomly from those completed by children with type 1 diabetes from the Royal Children's Hospital, Melbourne, Victoria, Australia and 10 traces recorded by healthy volunteer controls. RESULTS: The healthy controls had lower values for mean blood glucose, MODD, and CONGA. Patients with diabetes had higher percentages of time spent in high and low glucose ranges. There was no overlap between the CONGA values for patients with diabetes and for controls, and the difference between controls and patients with diabetes increased markedly as the CONGA time period increased. CONCLUSIONS: We advocate an approach to the analysis of CGMS data based upon a hierarchy of relevant clinical questions alluding to the representative nature of the data, the amount of time spent in glycemic excursions, and the degree of glycemic variation. Integrated use of these algorithms distinguishes between various patterns of glycemic control in those with and without diabetes.
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Glucemia/análisis , Diabetes Mellitus/sangre , Adolescente , Adulto , Algoritmos , Glucemia/metabolismo , Niño , Interpretación Estadística de Datos , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Monitoreo FisiológicoRESUMEN
In the period 1988-1992, 74 consecutive radically resected patients with NSCLC were randomised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival. There were 61 males and 13 females, aged 35-80 years, median 59 years. Their distribution by stage was as follows: pT1N2 = 19, pT2N2 = 54, pT3N2 = one patient; histology: 32 squamous, 32 adeno and 10 large cell carcinomas; surgery: atypical resection in six, lobectomy in 27, bilobectomy in ten, and pneumonectomy in 31 patients. In 27 patients, only one lymph node in a single mediastinal lymph node site was affected; in 31 patients more than one lymph node in one site; in 16 patients more sites were affected. In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed. On December 31, 1994, 19 patients (26%) were still alive; 39/55 patients died of the following causes: locoregional failure-10(26%), distant metastases- 25 (64%), other tumor-unrelated causes-four patients (10%). Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex, pTNM stage, histology and frequency of locoregional failure. The number of metastatic mediastinal lymph nodes was the only significant prognostic factor (P < 0.005) in both randomised groups.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Active plasma kallikrein (Mr = 90,000) can be separated by reduction of the disulfide bridges into a heavy-chain (Mr = 45,000) and a light-chain (Mr = 36,000). A partially active fragment, corresponding to the light-chain, was isolated during the purification of active human plasma kallikrein. Bovine trypsin can form a fragment corresponding to the heavy-chain when incubated with plasma kallikrein; plasmin also causes the formation of the heavy-chain but at a slower rate. High molecular weight kininogen decreases the rate of cleavage of kallikrein by both enzymes. Light-chain does not accumulate during incubation with these proteases and the heavy-chain, after prolonged incubation is also digested. Incubation of labelled active kallikrein with plasma causes formation of fragments corresponding to the heavy- and the light-chain.
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Fibrinolisina/metabolismo , Calicreínas/sangre , Fragmentos de Péptidos/metabolismo , Tripsina/metabolismo , Humanos , Hidrólisis , Sustancias Macromoleculares , Peso MolecularRESUMEN
From 1963 to 1980, intrathoracic bypass anastomosis was performed in 42 patients with nonresectable esophageal carcinoma. In this study 25 patients are reported on; of these, seven presented with midthoracic and one with lower thoracic esophageal tumor, 13 with carcinoma of the cardia and four with recurrences on the esophagogastric anastomosis. Seven underwent left, and eight right intrathoracic esophagogastrostomy, whereas ten underwent left intrathoracic esophagojejunostomy. Exclusion of the esophagus was not performed in any of these cases. Dehiscence occurred in three (12%) anastomoses. Nine patients (36%) died in the early postoperative period. The majority of surviving patients (12/18) were able to consume solid food. The mean survival period was 6.3 months (min. 1 mo, max. 14 mos). Most patients died of cachexia. A bypass anastomosis is the best palliative procedure in nonresectable esophageal carcinoma. A relatively high mortality, however, necessitates a strict selection of patients.
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Neoplasias Esofágicas/cirugía , Esófago/cirugía , Yeyuno/cirugía , Cuidados Paliativos , Estómago/cirugía , Adulto , Anciano , Cardias , Trastornos de Deglución/terapia , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Neoplasias Gástricas/cirugíaRESUMEN
This article presents a case of pseudocyst of the pancreas, clinically manifested as a benign tumor of the mediastinum. The cyst had spread from the retroperitoneum into the posterior lower mediastinum behind the oesophagus. The diagnosis was proved by the histological examination of the Wall and by analysis of amylase of the cyst contents, for the intraoperatively discovered cyst of the pancreas, the wide drainage into the pleural cavity has been an effective procedure. According to the data of the literature the mediastinal location of the pseudocyst of the pancreas is very rare.
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Quiste Mediastínico/diagnóstico , Quiste Pancreático/diagnóstico , Diagnóstico Diferencial , Drenaje , Humanos , Masculino , Quiste Mediastínico/cirugía , Persona de Mediana Edad , Quiste Pancreático/cirugíaRESUMEN
In seven years we have operated eleven patients with the benign stricture of the distal part of esophagus secondary to the gastroesophageal reflux. We have made Thal's fundoplastic operation in the combination with the fundoplication operation. We are contented with the late results of the operation in eight observed patients. In five cases results of the operation are very good and patients consume food without difficulties. In three cases we have observed stenosis after the operation, successfully treated by dilatation. All these patients were rentogenologically examined and thus patent anastomosis without gastroesophageal reflux was prooved. High mortality (two patients) and morbidity ater the operation are conditional with the age of patients, their bad physical condition due to the malnutrition and the extensive operation. Thus clear indication and the utilization of the conservative treatment of strictures is demanded.
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Estenosis Esofágica/cirugía , Esófago/cirugía , Estómago/cirugía , Anciano , Esofagoplastia/métodos , Femenino , Humanos , Masculino , Métodos , Persona de Mediana Edad , Complicaciones PosoperatoriasRESUMEN
In a group of 245 cases of primary carcinoma of the esophagus the authors found three cases of adenoid cystic carcinoma (ACC). Clinical and pathologic data of those patients (one female and two male; age range, 49-74 years) were analyzed. Tumors were localized in the middle third of the esophagus. One patient lived 15 months after surgery. Another is a case of early ACC who has been living 4.5 years after surgery and is without specific symptoms. The third patient had not had surgery and died 13 months after the onset of dysphagia. An autopsy showed only a locally invasive tumor growing into the surroundings of the esophagus, and regional lymph node metastases without distant parenchymal metastases. These findings support pathologic and biologic similarities between ACC of the esophagus and ACC of the salivary glands. There are synchronous tumors of the esophagus and the vital localization which makes the prognosis of ACC of the esophagus worse than ACC of the salivary glands.
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Carcinoma Adenoide Quístico/patología , Neoplasias Esofágicas/patología , Anciano , Antígenos de Neoplasias/análisis , Antígeno Carcinoembrionario/análisis , Carcinoma Adenoide Quístico/secundario , Colágeno/análisis , Femenino , Humanos , Hialina/química , Inmunohistoquímica , Queratinas/análisis , Laminina/análisis , Metástasis Linfática , Masculino , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Mucina-1 , Proteínas S100/análisisRESUMEN
AIMS: To determine whether intra-individual measures of diabetes control deteriorated through adolescence and whether HbA1c in late childhood was predictive of HbA1c after adolescence. METHODS: Retrospective analysis of sequential 3-6 monthly data including HbA1c, height, weight, and total daily insulin dosage in 118 patients with Type 1 diabetes aged between 8.00 and 17.99 years between 1983 and 1999. RESULTS: In females mean body mass index (BMI) increased sharply during adolescence but there was no significant increase in males. The mean total daily dose of insulin/weight (TDDI/W) increased sharply for females through puberty. Males exhibited a constant rate of increase in mean TDDI/W from pre- to post-puberty. There was a constant increase in mean HbA1c for females, with an estimated increase from pre- to post-puberty of 0.92%. In males there was only a slight increase from pre- to peri-puberty and no change subsequently. Comparing pre-puberty (8-9.99 years) and post-puberty (15-17.99 years) in the total group, 47% of patients remained in the same mean HbA1c grouping, 37% had worsened control and 16% had improved control. Analysis of change in the absolute value of mean HbA1c showed that the majority of patients had mean HbA1c values that remained within +/- 1% (54%) or +/- 2% (82%) from pre- to post-puberty. A significant proportion showed significantly worsening control with only a minority showing improved metabolic control from pre- to post-puberty. CONCLUSIONS: The likelihood of a significant improvement in HbA1c from late childhood to adolescence is remote, with the majority of patients having either constant or deteriorating metabolic control.
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Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Adolescente , Índice de Masa Corporal , Niño , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/uso terapéutico , Estudios Longitudinales , Masculino , Pubertad , Análisis de Regresión , Caracteres Sexuales , Insuficiencia del TratamientoRESUMEN
Cleavage of the 45-kDa gelatin-binding fragment of human plasma fibronectin with fibronectinase resulted in the activation of two forms of metalloproteinase with different substrate specificities. The 40-kDa FN-type-IV collagenase A degrades heat-denatured type-I collagen, laminin and also native collagen type IV. The 27-kDa FN-type-IV collagenase B degrades native collagen type IV, but it does not cleave laminin and only poorly degrades gelatin. Both enzymes begin with the same N-terminal sequence VYQPQPH- (residues 262-268 of fibronectin) but, contrary to the FN-type-IV collagenase A, the FN-type-IV collagenase B has lost the C-terminal region of type I repeats, where the major gelatin-binding determinants of fibronectin are located. The FN-type-IV collagenases A and B are sequentially similar to the middle domain (domain II) of collagenase type IV, secreted by H-ras-transformed human bronchial epithelial cells. Substrate and inhibition specificity of FN-type-IV collagenase A and B are different from those of FN-gelatinase and FN-laminase, isolated previously from the central and C-terminal fibronectin domains, respectively. The substrate specificity of both enzymes, characterized in this study, is also different from that of already known matrix-degrading metalloproteinases.
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Colágeno/metabolismo , Fibronectinas/metabolismo , Colagenasa Microbiana/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Activación Enzimática , Fibronectinas/química , Calor , Humanos , Laminina/metabolismo , Colagenasa Microbiana/antagonistas & inhibidores , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/metabolismo , Desnaturalización Proteica , Ratas , Serina Endopeptidasas/metabolismo , Especificidad por SustratoRESUMEN
The N-terminal 70-kDa fragment of human plasma fibronectin, purified from a cathepsin D digest, is characterized by lack of stability. It is processed proteolytically during incubation in the presence of Ca2+ into 27-kDa N-terminal heparin-binding and 45-kDa collagen-binding domains. The N-terminal residue in the 27-kDa fragment was blocked as in native fibronectin. The 45-kDa fragments began with the sequences AAVYQP, AVYQP and VYQP (residues 260, 261, 262-265 of fibronectin) that correspond to the beginning of the collagen-binding domain. In the presence of Ca2+ the purified 27-kDa fragment underwent further processing finally leading to the cleavage of the bond K85-D86 and to the simultaneous appearance of a specific proteolytic activity. Inhibition studies suggests that the newly generated enzyme is a Ca(2+)-dependent serine proteinase. Among all assayed matrix proteins, the newly generated enzyme cleaves native fibronectin and its fragments. It is proposed that this fibronectinase may originate from the N-terminal domain of fibronectin.
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Fibronectinas/metabolismo , Heparina/metabolismo , Fragmentos de Péptidos/metabolismo , Serina Endopeptidasas/aislamiento & purificación , Secuencia de Aminoácidos , Sitios de Unión , Electroforesis en Gel de Poliacrilamida , Humanos , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/aislamiento & purificación , Inhibidores de Serina Proteinasa/farmacología , Especificidad por SustratoRESUMEN
By their endoproteinase activities, cathepsins B, G, H and L can generate matrix-degrading proteolytic system from fibronectin. All four cathepsins studied cleaved fibronectin in fragments that were either proteolytically active or activated after incubation at pH 7.4 and in the presence of Ca2+. The highest enhancement of the matrix protein-degrading activity was observed after a gelatin-affinity chromatography of each digest. These results suggest that the effect of cathepsins at physiological pH in vivo may be enhanced by the activation of a matrix-degrading proteolytic system from fibronectin.
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Catepsinas/farmacología , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Péptido Hidrolasas/metabolismo , Cromatografía de Afinidad , Endopeptidasas/metabolismo , Activación Enzimática , Gelatina , Humanos , Concentración de Iones de HidrógenoRESUMEN
Human plasma fibronectin contains a latent proteinase that after activation cleaves gelatin and fibronectin. The autoactivation propensity of the two purified cathepsin D-produced fragments of fibronectin (190 and 120 kDa) was compared. Both polypeptides were spontaneously activated in the presence of Ca2+. This activation was inhibited by EDTA. The active gelatinase was isolated from the autodigest of the 190-kDa fragment. Among various protein substrates, including laminin and native type I and IV collagens, the purified enzyme degraded only gelatin and fibronectin. We have named this proteinase FN-gelatinase. FN-gelatinase is inhibited by phenylmethanesulfonyl fluoride and also by pepstatin A like retroviral aspartic proteinases. The amino-acid composition of the purified enzyme (35 kDa) was compared with the entire fibronectin sequence using the computer programme FIT. The optimal fit indicated that the 35-kDa fragment corresponds to the stretch # 1043-1404. This sequence contains a 93-residue segment (# 1140-1233) analogous to retroviral aspartic proteinases, comprising the sequence DTG of their putative active site.
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Aminoácidos/análisis , Endopeptidasas/aislamiento & purificación , Fibronectinas/análisis , Gelatina/metabolismo , Pepsina A/aislamiento & purificación , Fragmentos de Péptidos/análisis , Secuencia de Aminoácidos , Colágeno/metabolismo , Endopeptidasas/sangre , Activación Enzimática , Gelatinasas , Humanos , Datos de Secuencia Molecular , Pepsina A/sangre , Inhibidores de Proteasas , Retroviridae/enzimología , Especificidad por SustratoRESUMEN
The purified 190-kDa fibronectin fragment produced by cathepsin D can be spontaneously activated in the presence of CaCl2. This activation generates new proteolytic activities and also results in the formation of several subfragments. One of them exhibits the activity of FN-gelatinase that preferentially splits type I denatured collagen and fibronectin (see preceding paper). In this work we describe the purification and characterization of another fragment (25 kDa), issued from the same autodigest. This fragment may be activated to yield another proteinase, that splits preferentially laminin and denatured collagen type I. This enzyme will be referred as FN-laminase. Purified FN-laminase specifically reacted with antibodies against fibronectin. The specificity of bond cleavage by FN-laminase was studied with various synthetic peptides analogous to collagen repeats. FN-laminase cleaves the Ala-Gly bond in the sequence GPAGPR; the arginine residue in position P3' is important for this cleavage. The enzyme is inhibited by pepstatin A and phenylmethanesulfonyl fluoride, like retroviral aspartic proteinases. It is also inhibited by EDTA. No inhibition was obtained with 1,10-phenanthroline or 4-chloromercuribenzoate, inhibitors of Zn-metalloproteinases or cysteine proteinases, respectively.
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Fibronectinas/análisis , Laminina/metabolismo , Fragmentos de Péptidos/análisis , Secuencia de Aminoácidos , Colágeno/metabolismo , Activación Enzimática , Humanos , Inmunoglobulina G/inmunología , Datos de Secuencia Molecular , Inhibidores de Proteasas , Retroviridae/enzimología , Especificidad por SustratoRESUMEN
AIMS: To evaluate a systematic approach to the development and implementation of evidence based asthma management guidelines. METHODS: Comparative study of children (2-18 years) with acute asthma; a control cohort (cohort 1) was recruited before implementation of the guidelines and two cohorts were recruited after implementation (cohorts 2 and 3). RESULTS: There was no difference in the proportion of patients who reattended in the six months following initial presentation for cohort 1 (21.5%), cohort 2 (27.8%), or cohort 3 (25.4%) and no difference in readmission rates (11.4%, 11.3%, 11.0% respectively). There was no difference in measures of asthma morbidity between the cohorts at 3 and 6 months across three domains: interval symptoms, exercise limitation, and bronchodilator use. Of those who did not have a management plan before presentation, one was provided to 46.9% of cohort 1, 74.8% of cohort 2, and 81.1% of cohort 3. There was no difference comparing cohort 2 or cohort 3 with cohort 1 regarding quality of life for either the subjects or their parents. CONCLUSIONS: Implementation of our evidence based guidelines was associated with the improved provision of asthma management plans, but there was no effect on reattendance or readmission to hospital, asthma morbidity, or quality of life. Future efforts to improve asthma management should target specific components of asthma care.
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Asma/terapia , Medicina Basada en la Evidencia , Guías de Práctica Clínica como Asunto , Enfermedad Aguda , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Morbilidad , Aceptación de la Atención de Salud , Readmisión del Paciente , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: The importance of nitric oxide (NO) in hypoxic pulmonary hypertension has been demonstrated using nitric oxide synthase (NOS) knockout mice. In that model NO from endothelial NOS (eNOS) plays a central role in modulating pulmonary vascular tone and attenuating hypoxic pulmonary hypertension. However, the normal regulation of NOS expression in mice following hypoxia is uncertain. Because genetically engineered mice are often utilized in studies of NO, we conducted the present study to determine how hypoxia alters NOS expression in wild-type mice. METHOD: Mice were exposed to sea level, ambient conditions (5280 feet) or severe altitude (17,000 feet) for 6 weeks from birth, and hemodynamics and lung NOS expression were assessed. RESULTS: Hypoxic mice developed severe pulmonary hypertension (right ventricular systolic pressure [RVsP] 60 mmHg) as compared with normoxic mice (27 mmHg). Using quantitative reverse-transcription PCR, it was found that expressions of eNOS and inducible NOS (iNOS) increased 1.5-fold and 3.5-fold, respectively, in the lung. In addition, the level of lung eNOS protein was increased, neuronal NOS (nNOS) protein was unchanged, and iNOS was below the limit of detection. Immunohistochemistry demonstrated no change in lung iNOS or nNOS staining in either central or peripheral areas, but suggested increased eNOS in the periphery following hypoxia. CONCLUSION: In mice, hypoxia is associated with increases in lung eNOS, possibly in iNOS, but not in nNOS; this suggests that the pattern of lung NOS expression following hypoxia must be considered in studies using genetically engineered mice.
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Hipertensión Pulmonar/enzimología , Hipoxia/enzimología , Óxido Nítrico Sintasa/biosíntesis , Regulación hacia Arriba/fisiología , Animales , Presión Sanguínea/fisiología , Western Blotting , Hematócrito , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipoxia/complicaciones , Hipoxia/patología , Inmunohistoquímica , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Función Ventricular DerechaRESUMEN
Fibronectin is one of the major adhesive glycoproteins and bears interaction sites for both cell receptors and the extracellular matrix. Disappearance of fibronectin is the first step of cellular transformation in carcinogenesis. This phenomenon has been ascribed to increased proteolysis of fibronectin or of its cellular receptor. Results obtained during previous studies by the authors have shown that the fibronectin molecule has latent proteolytic activities which become apparent only after the action of other external proteases. Two proteinases, FN-gelatinase and FN-laminase, were identified in cathepsin D fibronectin digest. The acute activity of these two proteases is responsible for degradation of the extracellular matrix. Furthermore, the sequences and functions of both enzymes share a number of features with retroviral proteases.