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Biomedical subjects

T Cabrera

Publications and source records attributed to T Cabrera.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of a gastric tumor cell line defective in MHC class I inducibility by both alpha- and gamma-interferon.

Alpha/beta and gamma type interferons (IFN), act through distinct cell surface receptors and induce transcription of an overlapping sets of genes. MHC class I genes are inducible by both type of interferons. We have analyzed a gastric tumor cell line, AGS, which was completely defective in MHC class I response to interferon-alpha and gamma. Northern blot analysis demonstrated that the lack of IFN response was related with the absence of up-regulation of specific HLA class I mRNA. Electrophoretic mobility shift assays in various tumor cell lines after IFN-alpha and IFN-gamma treatment showed differential binding of the transcriptional factors to MHC class I regulatory elements. Comparison of kappa-B binding activity showed that IFN-alpha and IFN-gamma induced opposite changes in NF-kappa B binding activity in AGS cells, indicating that the absence of MHC class I response in AGS appears to be independent of kappa-B activity. In contrast, there were remarkable differences in the level of transcriptional factor binding to an interferon-responsive sequence element (IRSE), between AGS and other interferon-responsive tumor cell lines. This result suggests that the low level of transcriptional factor binding to IRSE in AGS cells was responsible of the lack of induction of MHC class I antigens. In this context, overlapping factors in the signal transduction pathway of both type I and II interferons may be involved in the non-responsiveness of this gastric carcinoma tumor cell line.

Adenocarcinoma↗
PubMed1996

[The value of symptoms in the diagnosis of peptic ulcer: an approximation to the primary care medium].

GOAL: To evaluate which clinical data are useful to select those patients with peptic ulcers in primary care most likely to benefit from complementary studies. METHODS: This is a prospective study done on 101 patients evaluated in a period of a year in a Primary Care Center. In all patients an endoscopy was done when a peptic ulcer was considered a possibility. In all cases a standardized questionnaire was completed before endoscopy and the patient evaluated by his primary care physician. The final diagnosis was defined according to endoscopy, done by expert endoscopists within seven days of the clinical evaluation. Statistical analysis was undertaken with SPSS software. RESULTS: An active peptic ulcer was found in 45 (44.5%) cases. A high-grade MALT lymphoma was diagnosed in one case. Male sex, smoking status, number of cigarettes, smoking-index, and a previous history of ulcer complications were significantly associated with the diagnosis, as well as severe diurnal or nocturnal pain. Mean age was lower in ulcer patients. However no clinical data in individual or combined form did show any predictive value. CONCLUSIONS: Clinical data do not permit to obviate endoscopy as the key initial procedure to diagnosis, even in primary care.

Adult↗
PubMed1995

Biological implications of HLA-DR expression in tumours.

HLA-DR antigens show restricted tissue distribution in comparison with the more extensive expression of HLA class I molecules. This constitutive expression is genetically controlled by well-defined mechanisms. In addition, DR antigen expression can be induced by a variety of cytokines through different molecular genetic events that convert DR-negative epithelia into positive cells. In this review we analyse the two major pathological situations in which abnormal DR expression occurs: autoimmune diseases and tumour development. We hypothesize that conversion to DR-positivity may produce two opposite effects in both clinical situations: (1) a useful one in tumours associated with a good prognosis; and (2) a harmful one in autoimmune diseases with increased tissue damage.

Autoimmune Diseases↗
PubMed1995

Separation distress call in the human neonate in the absence of maternal body contact.

Few studies have used the baby's cry as a means of evaluating the quality of neonatal care. In this randomized trial the newborn's cry was registered during the first 90 min after birth when infants were cared for either: (a) skin-to-skin with the mother; (b) in a cot; or (c) in a cot for the first 45 min of the 90-min observation period and then skin-to-skin with the mother. The results suggested that human infants recognize physical separation from their mothers and start to cry in pulses. Crying stops at reunion. The observed postnatal cry may be a human counterpart to the "separation distress call" which is a general phenomenon among several mammalian species, and serves to restore proximity to the mother. Our results suggest that in human newborns this cry is not dependent on earlier social experience and may be a genetically encoded reaction to separation. The findings are compatible with the opinion that the most appropriate position of the healthy full-term newborn baby after birth is in close body contact with the mother.

Crying↗
PubMed1995

Different patterns of HLA-DR antigen expression in normal epithelium, hyperplastic and neoplastic malignant lesions of the breast.

Fifteen samples of non-tumoural breast tissue, 24 cases of benign lesions, four biopsies of inflammatory carcinomas and 94 tumour samples of primitive mammary carcinomas were analysed for HLA class II expression. We found, first, that HLA class II antigens were detectable in all cases of non-neoplastic breast tissue. Secondly, HLA class II antigen expression was notably increased in benign neoplasms and hyperplastic lesions. In contrast, only 32 out of 94 carcinomas showed expression of HLA-DR antigens, 17 tumours had HLA-DP antigens and 11 carcinomas were positive for the presence of DQ molecules. The expression of class II antigen was associated with the degree of histological differentiation (P < 0.05) but was independent of stromal leucocytic infiltration. Thirdly, HLA-DR was very strongly expressed in intravascular tumoural thrombi, especially in the 'inflammatory carcinomas'. The immunophenotype of inflammatory infiltrate was analysed in benign and malignant lesions. In malignant lesions the mean number of inflammatory cells was significantly higher than in benign lesions. Interestingly, we found no differences in the amount and composition of inflammatory infiltrate between HLA-DR positive and negative tumours.

Adenocarcinoma↗
PubMed1995

[Epithelioid hemangioendothelioma: a rare hepatic tumor].

We present a case of epithelioid hemangioendothelioma of the liver (EHL). The imaging techniques did not permit the diagnosis. A liver biopsy was done under laparoscopy. One year later, the patient remains without symptoms in spite of the presence of lung metastases and the therapeutic abstention. The most outstanding aspects of this rare hepatic tumor are discussed.

Adult↗
PubMed1994

[The endoscopic management of postoperative biliary fistulae].

We report a series of 15 patients with a postoperative biliary fistula treated by endoscopic sphincterotomy. The exact location of the bile leak was revealed by ERCP in 13 cases (87%): cystic duct remnant in 6 (39%), intrahepatic biliary tree in 4 (26%), and main bile duct in 3 (20%). In all cases a distal obstacle (ie: retained stones, hydatid material) to bile flow was also found in ERCP. Treatment consisted of endoscopic sphincterotomy and subsequent removal of the distal obstacle, and could be completed in 13 (87%) cases. In our experience the treatment of postoperative biliary fistula with a distal obstruction bile flow by endoscopic sphincterotomy is a safe and effective procedure, and should be recommended as the first option in those patients.

Adult↗
PubMed1993

Natural history of HLA expression during tumour development.

HLA expression is frequently altered in tumours compared to the tissue from which they originate. Given the central role of MHC products in the restriction of T-cell recognition, regulation of tumour HLA expression might be a strategy for the evasion of immune surveillance by the malignant cells. Federico Garrido, Peter Stern and colleagues present data from a variety of tumour types, suggesting that HLA class I alterations may occur at a particular step between the development of an in situ lesion and an invasive carcinoma.

Carcinoma in Situ↗
PubMed1993

HLA class I expression and HPV-16 sequences in premalignant and malignant lesions of the cervix.

A series of 10 normal cervix epithelia, 38 condylomas, 17 CIN (cervical intraepithelial neoplasm) I/II (low-grade CIN), 10 CIN III (high-grade CIN), 27 squamous cell carcinomas and 7 adenocarcinomas of the cervix were studied in paraffin-embedded sections for the expression of MHC class I antigens, using antibodies against HLA antigens and the immunoperoxidase technique. A PCR technique was also used to evaluate the presence of HPV-16 DNA. All samples from normal tissue, benign, premalignant and CIN III lesions expressed HLA class I antigens. However, 15% of the invasive carcinomas completely lacked HLA-B and HLA-C antigen expression, 20% presented a heterogeneous pattern and 2 cases lacked HLA-B and HLA-C heavy chain but retained beta 2-microglobulin. MHC class I antigen expression on tumors was compared with clinical-pathological parameters. The absence of expression of HLA class I molecules was significantly associated with the Glanz histoprognostic index of malignancy. HPV-16 sequences were detected in 60% of the condylomas, 88% of the CIN I/II, 80% of the CIN III and 82% of the cervical carcinomas. Eight-six per cent of the tumors expressing HLA class I antigen presented HPV-16, whereas only 40% of the nonexpressing tumors did. Our results lead us to the following conclusions: a) HLA class I losses occurred when the tumor became invasive, and in tumors of a more aggressive histological type; b) The presence of HPV-16 was associated with tumors expressing HLA class I antigens.

Adenocarcinoma↗
PubMed1993

Lower body temperatures in infants delivered by caesarean section than in vaginally delivered infants.

Clinical experience suggests that infants delivered by caesarean section have difficulties maintaining normal body temperature during the first hours after birth. To test this hypothesis, body and skin temperatures were measured and compared in healthy full-term caesarean section and vaginally delivered newborn infants. The babies were studied during the first 90 min after birth. Axillary and skin temperatures were significantly higher in the vaginally delivered group than in infants delivered by caesarean section. Infants born by non-elective caesarean section were slightly warmer during the first 90 min after birth compared to infants born by elective caesarean section. There were no significant differences in temperatures between infants cared for in a cot as compared to those cared for in an incubator. An incubator creates a physical barrier between babies and parents and incubator care might cause parental anxiety. Thus the routine of putting healthy, full-term caesarean section infants in incubators can be abandoned from a thermoregulatory point of view.

Axilla↗
PubMed1992

HLA class II antigen expression in human papillomavirus-associated cervical cancer.

The observation that tumor cells of some neoplasms display major histocompatibility complex (MHC) class II molecules may be of functional significance, influencing the progression of malignancy by allowing the cancer cells to present antigen to the immune system. In the normal cervix, class II molecules are expressed by columnar but not squamous epithelium. The pattern of MHC class II expression in cervical carcinomas has been documented using immunohistochemical methods. Of 53 cervical squamous carcinomas examined for MHC class II expression, only 17% maintained a negative phenotype characteristic of the epithelium from which they were derived, while the remaining tumors exhibited either uniform (45%) or heterogeneous (38%) expression. Tumor areas which were class II positive also express class II associated invariant chain and the adhesion molecules lymphocyte function antigen 3 and intercellular adhesion molecule 1. The DR, DP, and DQ class II MHC subloci are differentially expressed, suggesting independent regulation. There is a trend for tumors with the uniform class II phenotype to predominantly express DR antigen, whereas tumors of the heterogeneous class II phenotype express with equal frequency either DR or DP antigens dominantly. There is no apparent influence of class II status on lymphocyte infiltration of the tumors. The presence of human papillomavirus 16 DNA in the cervical carcinoma specimens was analyzed by Southern blotting of restriction enzyme digested DNA and no correlation between the presence of human papilloma virus and MHC class II expression was found.

Adult↗
PubMed1992

HLA molecules in basal cell carcinoma of the skin.

Fifty basal cell carcinomas (BCC) and 8 samples of healthy skin were studied for HLA class I and class II antigen expression and for the presence of mutations in codon 12 of the K-ras and H-ras genes. All samples of healthy skin and of epithelium near the tumor showed high levels of class I molecules, whereas 38% of the tumors showed complete absence. Sixty-two percent of the tumors presented positive class I expression with heterogeneous staining. These losses were due to the simultaneous lack of heavy chain and beta 2-microglobulin. Selective losses of HLA-A or HLA-B antigens were not detected. Class II antigens were absent in most of the tumors, only two tumors showing a few weakly positive cells with anti-HLA-DR mAb. The loss of class I expression correlated significantly with the degree of histological differentiation and aggressiveness. We were unable to correlate class I expression with clinical size, depth of invasion or the extent of leukocytic infiltrate surrounding the tumor. Analysis by PCR amplification of codon 12 of the K-ras and H-ras oncogenes detected H-ras mutations in 1 out of 50 cases, and no K-ras mutations in any of the tumors studied. Thus, a positive relationship between K-ras and H-ras mutations and BCC tumorigenesis or MHC alterations seems unlikely in this neoplasia.

Antigens, Neoplasm↗
PubMed1991

Altered HLA class I expression in non-small cell lung cancer is independent of c-myc activation.

We studied the expression of major histocompatibility complex class I antigens in 59 bronchogenic carcinomas, as well as in pneumocytes and epithelial respiratory cells distant from the tumor. We observed in all cases that normal lung tissue expressed major histocompatibility complex class I antigens, while this expression was completely lost in 16 tumors (27%). The defect in HLA gene expression affected both heavy chain and beta 2-microglobulin, as demonstrated by the null reactivity with the monoclonal antibodies GRH1, W6/32, and HC10. Selective underexpression was detected in 1 tumor for HLA-A locus antigens and in 3 tumors for HLA-B locus antigens. Southern blot analyses of major histocompatibility complex class I genes were performed in 20 tumor tissue specimens and 6 cell lines. No class I gene rearrangements were detected using HLA coding and locus specific noncoding probes. We also used the Southern blot method to investigate the possible relationship between c-myc amplification and HLA class I antigens in non-small cell lung cancers and detected no apparent amplification in 20 tumor tissue specimens (5 negative for HLA class I antigens) and 6 cell lines (3 with decreased expression). Northern blot analysis revealed no relationship between c-myc mRNA levels and specific mRNA for HLA-A and HLA-B antigens in cell lines with imbalanced HLA-A or HLA-B expression.

Carcinoma, Bronchogenic↗
PubMed1991

Molecular analysis of MHC-class-I alterations in human tumor cell lines.

Molecular characterization of HLA-class-I expression was investigated in human tumor cell lines at the protein and mRNA levels using locus-specific monoclonal antibodies (MAbs) and probes. Some cell lines exhibited a differential expression of HLA-A and HLA-B products and also showed differences in the inducibility of HLA-class-I genes by gamma-IFN. Thus, gamma-IFN stimulation induced predominantly HLA-B mRNA in the HeP-2 cell line, which showed imbalances in basal levels of HLA-A and HLA-B expression. This unequal inducibility of HLA genes may imply that locus-specific regulatory mechanisms are involved in the expression of individual HLA products. The specific mechanism controlling the differential expression of HLA subsets appears to be independent of c-myc activity. Northern blot analysis found no relationship between c-myc mRNA levels and specific mRNA for HLA-A and HLA-B antigens.

Antibodies, Monoclonal↗
PubMed1991

Can the HLA phenotype be used as a prognostic factor in breast carcinomas?

There is evidence indicating that change in the expression of HLA-ABC antigens can modulate the biological behavior and metastatic potential of certain neoplasms. We studied 15 samples of normal breast epithelium, 94 breast carcinomas and 24 benign and pre-malignant lesions of the mammary gland. All cases of normal breast epithelium and non-malignant lesions presented high levels of expression of class-I antigens. In contrast, 22 out of 94 carcinomas showed a reduction in the level of expression and a heterogeneous pattern. In addition, 31 tumors were considered negative for HLA-class-I expression, and 6 cases showed selective loss of HLA-ABC: 2 tumors for HLA locus A, and 4 for HLA locus B. We found a direct relationship between patient survival and HLA-negative phenotype (p less than 0.001), as well as between histological grade of malignancy and the level of expression of class-I antigens (p less than 0.0005). Moreover, the presence of class-I molecules was significantly related to tumor ploidy (p less than 0.005). Our results lead us to conclude that HLA-ABC-negative tumors have a higher metastatic potential and greater clinical aggressiveness: patients with carcinomas exhibiting low HLA expression have more lymph-node metastases (p less than 0.02) and achieve shorter survival times (p less than 0.001).

Adult↗
PubMed1991

HLA class I and II expression in rhabdomyosarcomas.

The expression of class I and II histocompatibility antigens was studied in 43 specimens of skeletal and in 36 specimens of cardiac muscle. Expression was also analyzed in the tumoral counterpart of striated muscle tissue, in 21 rhabdomyosarcomas (13 embryonic, 2 alveolar and 6 pleomorphic). Normal striated muscle showed very weak HLA class I antigen expression and no class II expression. The rhabdomyosarcomas showed increased class I expression, possibly related to malignant transformation of this type of tissue and with the degree of cellular differentiation. In our series of rhabdomyosarcomas, we observed class II neoexpression only in some HLA class I positive specimens, which was unrelated to the degree of cellular differentiation in these tumors.

Cell Differentiation↗
PubMed1991

Loss of HLA heavy chain and beta 2-microglobulin in HLA negative tumours.

Expression of HLA class I antigens on the cell surface requires the association of heavy chain, endogenous peptide and beta 2-microglobulin (beta 2m). We have studied the expression of free class I heavy chain and beta 2m in cryostatic sections of 51 HLA class I negative human tumours of different origin. Selective low expression of beta 2m was observed only on the 9 colorectal adenocarcinomas. In contrast, simultaneous under-expression of heavy chain and beta 2m was detected in the rest of the tumours studied. Our results suggest that the accumulation in the cytoplasm of HLA heavy chain in HLA negative colorectal carcinomas is a particular mechanism that cannot be applied to all HLA negative tumours.

Adenocarcinoma↗