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Biomedical subjects

A M Costa

Publications and source records attributed to A M Costa.

At least 19 recordsLinked to original sources

HLA-DRB1*04 and HLA-DQB1*03 association with the atrophic but not with the goitrous form of chronic autoimmune thyroiditis in a Brazilian population.

Autoimmune chronic lymphocytic thyroiditis appears in two forms, goitrous and atrophic. The evidence available is not enough to prove that the goitrous precedes the atrophic form, but immunogenetic analysis suggests that they may be distinct entities. The distribution of HLA class II alleles DRB1* and DQB1* was verified in patients from the region of Campinas, São Paulo, Brazil with both forms of thyroiditis. Ninety-one patients with primary hypothyroidism through autoimmune thyroiditis were classified as goitrous - 54 patients, 42.27 +/- 11.72 years old, having had hypothyroidism for 8.57 +/- 6.63 years - or atrophic - 37 patients, 42.72 +/- 12.01 years old, hypothyroidism for 6.73 +/- 4.07 years. The distribution of class II alleles was determined, DRB1* and DQB1* were genotyped after purifying DNA blood samples using the DNAzol technique, and the low-resolution PCR-SSP system was utilized for determination of generic alleles. Chi-square and Fisher's exact test were utilized to compare the distribution frequency of HLA alleles and the significant p-values were subjected to Bonferroni correction. We have demonstrated that the DRB1*04 allele is associated with autoimmune thyroiditis, and that there are genotypic differences regarding the presentation forms with a strong association between DRB1*04 and DQB1*03 and the atrophic form only.

Adolescent↗

A special ionisation chamber for quality control of diagnostic and mammography X ray equipment.

A quality control program for X ray equipment used for conventional radiography and mammography requires the constancy check of the beam qualities in terms of the half-value layers. In this work, a special double-faced parallel-plate ionisation chamber was developed with inner electrodes of different materials, in a tandem system. Its application will be in quality control programs of diagnostic and mammography X ray equipment for confirmation of half-value layers previously determined by the conventional method. Moreover, the chamber also may be utilised for measurements of air kerma values (and air kerma rates) in X radiation fields used for conventional radiography and mammography. The chamber was studied in relation to the characteristics of saturation, ion collection efficiency, polarity effects, leakage current, and short-term stability. The energy dependence in response of each of the two faces of the chamber was determined over the conventional radiography and mammography X ray ranges (unattenuated beams). The different energy response of the two faces of the chamber allowed the formation of a tandem system useful for the constancy check of beam qualities.

Equipment Design↗

Expression and cellular localization of fibrillin-1 in normal and pathological human liver.

BACKGROUND: The expression and the distribution of fibrillin-1 and elastin were studied in normal and pathological human liver samples. METHODS: As controls, histologically normal/subnormal liver samples (n = 24) were used. Pathological samples corresponded to seven cirrhosis and eight hepatocellular carcinomas (HCC) developed on cirrhotic (four) or noncirrhotic (four) liver. RESULTS: In normal liver, fibrillin-1 and elastin co-localized in vessel walls and portal tract connective tissue. Fibrillin-1 alone was detected along sinusoids and in portal spaces at the interface with the limiting hepatocytic plates and close to the basement membrane of bile ducts. By transmission electron microscopy, typical bundles of microfibrils were detected both in Disse space and in portal zones. Cirrhotic nodules were usually rich in fibrillin-1 along sinusoids; fibrillin-1 and elastin were co-localized in fibrotic septa surrounding nodules. In HCC, fibrillin-1 was present between tumoral hepatocytes; stromal reaction around the tumors contained both fibrillin-1 and elastin. CONCLUSIONS: Fibrillin-1 was associated with elastin in portal mesenchyme and vessel walls of normal liver, in fibrotic septa around cirrhotic nodules and stromal reaction around HCC, but was expressed alone in the perisinusoidal space. The functional roles for fibrillin-1 in non-elastic tissues, such as the liver, remain to be elucidated.

Adult↗

Early activation of hepatic stellate cells and perisinusoidal extracellular matrix changes during ex vivo pig liver perfusion.

In previous works, we observed during liver transplantation procedure, the early activation of hepatic stellate cells (HSC) which acquire alpha-smooth muscle (SM) actin expression. In this study, we evaluated changes in HSC and in perisinusoidal extracellular matrix during ex vivo pig liver perfusion. Under general anesthesia, pig livers were flushed and removed, and then perfused ex vivo for 6 h with homologous blood. Liver biopsies were taken before and after washout, at 5 min perfusion, and then hourly. Tissues were processed for immunohistochemistry, immunofluorescence, confocal microscopy, in situ hybridization and electron microscopy. Before and after liver washout, alpha-SM actin was present in vessel walls but in very few lobular HSC. After 1 h perfusion, a strong reactivity for alpha-SM actin was present in HSC, particularly along dilated sinusoids. At the ultrastructural level, numerous microfilament bundles appeared in HSC cytoplasmic processes. During perfusion, type I and type IV collagens, type III procollagen, and fibronectin acquired a looser organisation in relation with the enlargement of perisinusoidal spaces; laminin appeared in perisinusoidal spaces around portal areas and fibrillin deposits increased. In situ hybridization studies showed an increase of the type I procollagen mRNA expression mainly in portal tracts and septa. Ex vivo liver perfusion induces: 1) an early activation of HSC which acquire the expression of alpha-SM actin, and 2) significant changes in the perisinusoidal extracellular matrix. These results are compatible with the view that HSC function as liver specific pericytes participating in the regulation of sinusoidal blood pressure.

Actin Cytoskeleton↗

New protecting groups for 1,2-diols (boc- and moc-ethylidene). Cleavage of acetals with bases.

[reaction: see text] 1,2-Diols react at rt with alkyl propynoates, in the presence of 4-dimethylaminopyridine, to give cyclic acetals which are quite stable to acid-catalyzed hydrolysis or methanolysis. 1,3-Diols and 1, 4-diols do not form acetals with alkyl propynoates under the same conditions. Deprotection is accomplished with bases (via elimination and addition/elimination steps).

Journal Article↗

Role of myofibroblasts during normal tissue repair and excessive scarring: interest of their assessment in nephropathies.

Following injury, tissue repair process takes place involving inflammation, granulation tissue formation and scar constitution. Granulation tissue develops from the connective tissue surrounding the damaged area and contains vessels, inflammatory cells, fibroblasts and myofibroblasts. Myofibroblasts play an important role in many tissue injuries and fibrocontractive diseases. The process of normal wound repair after tissue injury follows a closely regulated sequence including the activation and the proliferation of fibroblastic cells. In pathological situations, the normal resolution stages are abrogated and the proliferation of myofibroblasts continues, inducing excessive accumulation of extracellular matrix. The differentiation of fibroblastic cells into myofibroblasts is an early event in the development of tissue fibrosis. Myofibroblastic cells express smooth muscle cytoskeletal markers (alpha-smooth muscle actin in particular) and participate actively in the production of extracellular matrix. The evaluation of myofibroblast differentiation in renal biopsies would be useful for histopathologists to appreciate the intensity of tissue injury and particularly to predict the long term outcome of some nephropathies. Immunohistochemical studies for alpha-smooth muscle actin should be made systematically in renal tissue biopsies. Myofibroblastic differentiation appears to play a significant role in the progression of renal failure and seems to be a useful marker of progressive disease.

Animals↗

[Human care: purification action].

This article was originated by a request of some professors of the Masters Course in Nursing. The theme "bath", as an act of care, was developed, initially, on the meaning of moves. The esthetic of body movement, to the sound of music, was represented graphically, allowing to reach constructs as: relationship, physical contact, sharing, pleasure, satisfaction, cleanliness, reaproximation. The concept of "bath", understood through research in different bibliography and idioms, was translated as "purification". The meaning of "purification" was studied with an anthropological view. Many practices and rituals were perceived through history and human experience and bring with them tools that may help Nursing to create and recreate the experience and concept of human care. These elements and some contributions to comprehend care are shown in this study.

Baths↗

Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars.

Reparative process of second and third degree burns usually results in hypertrophic scar formation that can be treated by pressure. Although this method is efficient, its mechanisms of action are not known. In this work, we have studied the histological organization of hypertrophic scars submitted to pressure. Skin biopsies were performed 2 to 7 months after the onset of treatment in two adjacent regions of the scar, non-pressure- or pressure-treated and analyzed by immunohistochemistry and transmission electron microscopy for extracellular matrix organization and cellular morphology. In non-pressure-treated regions, fibrillin deposits did not present the classical candelabra-like pattern under epidermis and were reduced in dermis; in pressure-treated regions the amount was increased compared to non-pressure-treated regions but the organization was still disturbed. In non-pressure-treated regions, elastin was present in patch deposits; in pressure-treated regions elastin formed fibers, smaller than in normal dermis. Tenascin was present in the whole dermis in non-pressure-treated regions, whereas in pressure-treated regions it was observed only under epidermis and around vessels, as in normal skin. alpha-Smooth muscle actin-expressing myofibroblasts were absent in normal skin, present in large amounts in non-pressure-treated regions, and almost absent in pressure-treated regions. The disturbed ultrastructural organization of dermal-epidermal junction observed in non-pressure-treated regions disappeared after pressure therapy; typical features of apoptosis in fibroblastic cells and morphological aspects of collagen degradation were observed in pressure-treated regions. Our results show that, in hypertrophic scars, pressure therapy restores in part the extracellular matrix organization observed in normal scar and induces the disappearance of alpha-smooth muscle actin-expressing myofibroblasts, probably by apoptosis. We suggest that the pressure acts by accelerating the remission phase of the postburn reparative process.

Adolescent↗

Effect of pentoxifylline on early proliferation and phenotypic modulation of fibrogenic cells in two rat models of liver fibrosis and on cultured hepatic stellate cells.

BACKGROUND/AIMS: During liver fibrosis, different fibroblastic cells, i.e. hepatic stellate cells (HSCs) or portal fibroblasts, are involved in the development of lesions, and acquire myofibroblastic differentiation. We investigated, in the rat, whether pentoxifylline can influence the early phase of fibrogenesis in two animal models of fibrosis induced by either carbon tetrachloride (CCl4) plus acetone (given twice) or bile duct ligation. METHODS: The fibroproliferative response and myofibroblastic phenotypic modulation were evaluated by PCNA and alpha-smooth muscle (alpha-SM) actin immunohistochemistry, respectively, in livers taken 24 h after the last CCl4 treatment or 72 h after bile duct ligation. Desmin expression was also measured, and inflammation was evaluated by ED-1 staining. Furthermore, proliferation and alpha-SM actin expression were studied in cultured HSCs after pentoxifylline treatment. RESULTS: In the CCl4-acetone groups, pretreatment with pentoxifylline decreased the proliferative response and expression of alpha-SM actin in the HSCs. Similarly, pentoxifylline reduced the proliferation and myofibroblastic differentiation of portal fibroblasts after bile duct ligation. Pentoxifylline reduced ED-1 expression, particularly in the CCl4 model, where there was significant inflammation. In cultured pentoxifylline-treated HSCs, both proliferation and alpha-SM actin expression were decreased. CONCLUSIONS: In both animal models of fibrosis, during the early stages of tissue injury, pentoxifylline was able to reduce fibroproliferation and myofibroblastic differentiation and to reduce hepatocellular damage and the inflammatory response, particularly in the toxin-induced model. In culture, alpha-SM actin expression decreased in both growing and quiescent HSCs treated with pentoxifylline, indicating that the drug may also exert a direct effect on hepatic fibrogenic cells.

Acetone↗

Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing.

Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant PEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by PEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-alpha1(VII) polypeptide chain. As a consequence, procollagen VII failed to be processed to mature collagen VII and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody. The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified. This represents the first report of a recessive deletion mutation in PEB and extends the range of EBD phenotypes associated with mutation 33563del14.

Adult↗

Long-term administration of interferon-alpha in non-responder patients with chronic hepatitis C: follow-up of liver fibrosis over 5 years.

In chronic hepatitis C, previous data have shown that short-term treatment with interferon-alpha (IFN-alpha) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non-responder patients, the long-term effect of IFN-alpha on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non-responder patients with chronic hepatitis C retreated with successive courses of IFN-alpha. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN-alpha treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN-alpha therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow-up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow-up period in all patients (P = 0.045). Long-term treatment with IFN-alpha is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.

Adult↗

Interstitial alpha-smooth muscle actin: a prognostic marker in membranous nephropathy.

AIM: Membranous nephropathy in adults causes 20% of nephrotic syndromes. Spontaneous outcome of this glomerulopathy is difficult to evaluate from clinical and histological data. Some patients can achieve complete remission, while others develop progressive renal failure. In this study we assessed alpha-smooth muscle actin (alpha-SMA) expression in renal interstitial myofibroblasts as a marker to predict the outcome of membranous nephropathy. PATIENTS AND METHODS: Renal function tests in tandem with alpha-SMA immunolabelling were performed on 25 patients with a mean follow-up of 7.2+/-5.6 years. The intensity of interstitial alpha-SMA (ialpha-SMA) immunostaining was compared to changes in glomerular filtration rate (GFR) evaluated by inulin clearance, between the time of diagnosis (GFR1) and the end of follow-up (GFR2). RESULTS: A significant correlation (r = 0.62, p<0.001) was found, between the intensity of interstitial myofibroblasts, immunolabeling and GFR at the end of follow-up. Moreover, the annual GFR variation and the annual percentage of GFR variation were correlated to interstitial myofibroblast labeling (respectively r = 0.62, p<0.001; r = 0.67, p<0.001). In addition, the importance of proteinuria, initial GFR impairment and fibrosis were confirmed as prognostic criteria. CONCLUSION: This study strongly shows that ialpha-SMA expression is a useful and early prognostic marker in the evolution of membranous nephropathy.

Actins↗

[Interdisciplinary actions: perception of the participants of a promotional and health care program].

The authors analyze the perceptions that participants of a promotional and health care program have about the meaning, the professional profile, advantages and difficulties of the interdisciplinary work. In a qualitative approach, the data have been collected through semi-structured interviews with professionals and students of nursing, nutrition and psychology, categorized with the technique of content analysis. It was perceived that the subjects characterize their practice as an interdisciplinary interaction. However, they need to overcome institutional, epistemological, psychosocial, cultural and material obstacles, in order to develop a methodology for the interdisciplinary work in a more explicit and effective way.

Attitude of Health Personnel↗

Quantification of the intrahepatic biliary tree during human fetal development.

Development and differentiation of bile ducts have been studied for the understanding of pathogenesis of biliary atresia and other diseases of the intrahepatic biliary tree. The aim of this study is to correlate the type of biliary structure with the size of the portal tract and the gestational age. Twenty-four human livers were studied. Fetuses were assigned to four gestational age groups: group I, up to 20 postfecundation weeks (PFW); group II, from 21-26 PFW; group III, from 27-32 PFW; and group IV, from 33-38 PFW. In each specimen, 30 portal tracts were classified as small, medium, or large according to the diameter of the portal vein. In order to identify the bile duct cells, the sections were immunolabeled with anti-cytokeratin antibody, and the biliary structure was classified as absent (bile ducts (BD) = 0), presence of bile duct cells without lumen (BD = 1), or presence of bile duct with lumen (BD = 2). In the small portal tracts, either there were no biliary structures or just a few. There was a substantial increase in the number of medium portal tracts that included a bile duct as a function of gestational age. The majority of large portal tracts exhibited a bile duct. In human fetus up to 20 PFW, it is possible to find 70% of portal tracts without bile ducts, and at 38 PFW it is expected that more than 50% of the portal tract has a BD > 0. We suggest the use of the diameter of the portal vein and the gestational age for the quantification of biliary structures and the evaluation of maturity of intrahepatic biliary tree.

Bile Ducts, Intrahepatic↗

Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts: variable expression of multiple pilosebaceous cysts within an affected family.

BACKGROUND: Steatocystoma multiplex (SM) and eruptive vellus hair cysts (EVHC) are conditions characterized by numerous cutaneous cysts with a clinical resemblance, such as age of onset, location, appearance of the lesions and mode of inheritance, but with distinctive histologic features. Recently, some authors have proposed that the two conditions are variants of one entity originating in the pilosebaceous duct, while others suggest that SM and EVHC are two distinct entities, on the basis of the different expression of keratins. Milia are small round cysts, commonly involving the face. In 1994, Menni and Piccinno reported the first association, in a family, between persistent infantile milia in a 9-month-old girl and SM in the father. The authors hypothesized a relationship between these two conditions. OBJECTIVE: We describe a family in which the mother showed cystic lesions and milia and her 4-year-old son and her 18-month-old daughter presented persistent infantile milia. METHODS: In addition to the clinical and genetic documentation, a biopsy was performed in the son and two biopsies in the mother. RESULTS: The histologic examination of one of the son's milium-like papules showed in the superficial dermis a small cyst typical of a milium. In serial sections it was possible to see a connection with a vellus hair follicle by an epithelial pedicle. The histologic examination of one of the mother's papules on the forehead showed a large round cystic structure with histologic features of EVHC. Close to the cyst wall, serial sections showed flattened sebaceous gland lobules. The histologic findings of the second biopsy taken from the chest showed the typical features of a steatocystoma. CONCLUSIONS: The relationship between milia, SM and EVHC is discussed; the three disease should be considered as subtypes of multiple pilosebaceous cysts that may all present overlapping histologic features. The different level of the pilosebaceous duct where the cyst originates should explain the different clinical manifestations.

Child, Preschool↗

Immunolabeling of type IV collagen, laminin, and alpha-smooth muscle actin cells in the intima of normal and varicose saphenous veins.

Smooth muscle cells (SMC) of normal and varicose human saphenous intima were studied on cryostat sections by immunohistochemistry with alpha-smooth muscle actin (ASMA), type IV collagen, and laminin antibodies and also by transmission electron microscopy. The findings suggest two structurally distinct subtypes of smooth muscle cells with thin and thicker external lamina. Thin external lamina SMC were characterized by laminin, type IV collagen, weaker external lamina reactivity, and intense cytoplasmic alpha-smooth muscle actin immunoreactivity. Ultrastructurally, they exhibited abundant cytoplasmic microfilaments and thin external lamina. These cells were found isolated or, more frequently, clustered in fascicles close to the subendothelium in focal or zonal cushions, or in diffuse enlargement of the intima. In contrast, thicker external lamina smooth muscle cells were intensely immunolabeled for laminin and collagen IV, showing irregular cytoplasmic ASMA reaction. Single or clustered thicker external lamina SMC were seen predominantly in zonal cushions and in intima diffuse enlargement. It is very likely that these cells secrete these matrices in a nonpolarized fashion. The thicker external lamina of these SMCs showed a fine granular amorphous aspect sometimes intermingled with microfibrils. These external lamina were interposed between neighboring cells and exposed to collagen fibrils and elastic fibers. The cells also exhibited rarefaction of the cytoplasmic filaments. Intermediary cells exhibiting both features were rarely seen. Thicker external lamina SMC should be discussed in the context of an adaptive/proliferative response leading to dysfunction of the fibroelastic properties of the vein wall.

Actin Cytoskeleton↗