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Biomedical subjects

A Cano

Publications and source records attributed to A Cano.

At least 19 recordsLinked to original sources
PubMed1992

Role of protein kinase C and transcription factor AP-1 in the acid-induced increase in Na/H antiporter activity.

Chronic incubation of cultured renal tubular epithelial cells in acid medium causes an increase in Na/H antiporter activity that persists after removal from acid, is dependent on protein synthesis, and is associated with an increase in Na/H antiporter mRNA. Chronic activation of protein kinase C has similar effects in these cells. The present studies examined the role of protein kinase C in the effect of acid incubation. Incubation of MCT cells in acid for 24 h caused a 50% increase in Na/H antiporter activity. This was prevented by inhibition of protein kinase C, either with sphingosine or by protein kinase C downregulation. Pertussis toxin pretreatment did not prevent the increase in antiporter activity. Acid incubation caused an increase in transcription factor AP-1 activity, as shown by an increase in expression from a reporter gene containing six tandem AP-1 binding sites. This was associated with transient increases in c-fos and c-jun mRNAs. This response is typical of that for gene activation by protein kinase C. These studies demonstrate that acid activation of the Na/H antiporter requires protein kinase C and is associated with c-fos and c-jun expression and increased AP-1 activity.

Animals↗
PubMed1992

Expression of simple epithelial cytokeratins in mouse epidermal keratinocytes harboring Harvey ras gene alterations.

Activation of a Harvey ras (H-ras) protooncogene is a frequent event associated with mouse epidermal carcinogenesis. We report that the transfection of a human H-ras oncogene into an immortalized mouse epidermal cell line (MCA3D) induces the anomalous expression of cytokeratins (CKs) 8 and 18 characteristic of simple epithelia. The comparison of various transfectant cell clones indicated a direct correlation between the levels of CK8 expression and the mutated H-ras p21s. The expression of simple epithelial CKs is also described in cell lines derived from mouse skin carcinomas (HaCa4, CarC) and in keratinocytes transformed in vitro by a chemical carcinogen (PDV, PDVC57), all of which contain altered H-ras genes. The induction of CK8 and CK18 occurs at the mRNA level and, although both CK8 and CK18 mRNAs are expressed, CK18 protein does not accumulate whereas CK8 is incorporated into intermediate filaments. Immunofluorescence studies show that the pattern of CK8 protein expression is heterogeneous; some cells express very low amounts of CK8, whereas others synthesize relatively high levels of this protein. However, selection of strongly CK8-positive cells was found in one case where a more malignant population of cells (PDVC57) was derived by tumor transplantation of PDV. Our results suggest that activation of a H-ras gene can alter the normal differentiation program of epidermal cells and that the ability to synthesize CK8 and CK18 could be related to tumor progression.

Animals↗
PubMed1992

Expression of alpha 6 beta 4 integrin increases during malignant conversion of mouse epidermal keratinocytes: association of beta 4 subunit to the cytokeratin fraction.

The expression of alpha 6 beta 4 integrin has been analyzed in several keratinocyte cell lines representative of various stages of mouse epidermal carcinogenesis. The immunological analyses carried out show that alpha 6 beta 4 is expressed at the cell surface of the cell lines which exhibit an epithelial or epithelioid morphology. The relative levels of alpha 6 beta 4 expressed at the cell surface increase noticeably from premalignant to malignant cells, as detected by fluorescence flow cytometry. This increase also correlates with the abundance of soluble beta 4 subunit detected by Western immunoblotting in the different cell lines. However, complete absence of alpha 6 beta 4 has been found in spindle carcinoma cells showing a fibroblast-like phenotype in culture. The integrin remains associated to detergent- and high salt-insoluble cytoskeletal components, organized in stable anchoring contacts, as in human keratinocytes (Carter et al., J. Cell Biol., 111, 3141, 1990). In addition, a significant fraction of the beta 4 subunit is detected associated to highly purified cytokeratin fractions. These results, together with those regarding the organization of both cellular components in drug-treated cells, support the existence of a close association between alpha 6 beta 4 and the intermediate filaments of the cytoskeleton.

Animals↗
PubMed1992

Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta.

Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3',5'-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 mumol/l final concentration in all cases), and were stimulated with terbutaline, a beta-adrenergic agonist, (0.1 mmol/l) or angiotensin II (1 mumol/l). The cAMP content was measured by a competitive protein binding assay, and the generation of labelled inositol phosphates formation in explants prelabelled with 3H-myo-inositol was measured by anion exchange chromatography. Progesterone increased significantly basal cAMP concentrations in comparison with control or estradiol-treated tissues (169 +/- 13, 72 +/- 8, and 69 +/- 2 pmol/g wet wt tissue, mean +/- SEM, respectively). However, following terbutaline stimulation cAMP levels (mean +/- SEM) increased to similar values under all conditions (182 +/- 33, 197 +/- 36, and 237 +/- 17 pmol/g wet wt tissue for control, estradiol-, and progesterone-treated tissues, respectively). Angiotensin II stimulated inositol phosphates generation in placental explants by an average of fivefold, but this increase was significantly reduced in the presence of progesterone (5.2 +/- 0.7, 3.7 +/- 0.4, and 2.2 +/- 0.3 fold increase vs non-angiotensin-stimulated tissues, for control, estradiol-, and progesterone-treated placenta, mean- +/- SEM, respectively). These data suggest that progesterone modulates the formation of second messengers in human placenta at term.

Angiotensin II↗
PubMed1992

[Prevalence of hepatitis C virus antibody in chronic HBsAg-negative non alcoholic hepatopathy].

The presence of antibody to hepatitis C virus was determined in 316 HBsAg-negative patients with non-alcoholic chronic hepatitis who did not receive any blood transfusion once the diagnosis was made. A titre of antinuclear antibodies of 1/40 or lower was found in 18 patients. Persistent chronic hepatitis was present in 21 patients, active chronic hepatitis in 145, hepatic cirrhosis in 128, and hepatocarcinoma in 22 patients. One hundred and three patients had previously received blood transfusion, 76 had undergone previous surgery without transfusion, a clinical episode of hepatitis could be traced in 14, 13 patients were drug addicts (all of them HIV negative), 1 patient had received multiples injections, another had been treated with acupuncture, and 108 patients were free of any of the above. Anti-HCV was present in 76.6% of patients; a significantly higher proportion (87.4%) was found among patients who had received blood transfusion than in patients with previous surgery (72.4%) (p = 0.012), clinical hepatitis (57.1%), or without previous hepatic disease (70.3%) (p = 0.003). The incidence of anti-HCV was lower among cirrhotics (70.3%) than in patients with active chronic hepatitis (84.1%) (p = 0.006); in contrast, previous blood transfusion was significantly higher (p = 0.001) among the latter (40.7%) than in cirrhotics (21.9%). The incidence of anti-HCV was similar among patients with (78.6%) and without (75.8%) type B infection. Our results suggest that infection with virus C may account for a high proportion of non-alcoholic non-B chronic hepatitis.

Adolescent↗
PubMed1992

Expression of syndecan in transformed mouse keratinocytes.

BACKGROUND: Malignant transformation is frequently associated with altered behavior of cells, a phenomenon that also suggests changes in cell-matrix interactions. We have studied expression of syndecan, a cell surface proteoglycan that binds extracellular matrix components and growth factors, in various chemically transformed mouse keratinocyte cell lines that differ in their morphology and tumorigenicity. EXPERIMENTAL DESIGN: A monoclonal antibody, specific for mouse syndecan, and a cDNA clone for mouse syndecan, were used to detect syndecan in seven different keratinocyte cell lines. The glycosaminoglycan composition of syndecan was studied using differential digestions of heparan sulfate and chondroitin sulfate chains. RESULTS: In general, the tumorigenic cells were found to express lower amounts of syndecan, both at protein and mRNA levels, than the nontumorigenic cells. The most tumorigenic cell line CarC revealed barely detectable syndecan expression. Also, molecular polymorphism of syndecan was observed, as three forms of syndecan with different molecular weights appeared on the surfaces of different keratinocytes. The highly tumorigenic cells, that expressed low amounts of syndecan, expressed syndecan with the largest molecular weight. The different molecular weights were shown to reflect an increased amount of both heparan and chondroitin sulfate chains attached to the core protein. An increased shedding of syndecan ectodomain from the membrane-associated domain was observed in cells that express high amounts of mutated Ha-ras p21. CONCLUSIONS: The results suggest, that transformed epithelial cells can modulate the appearance of syndecan on the cell-surface by at least two ways: (a) by altering its glycosylation or (b) by increasing its shedding from the cell surface. These modulations, together with overall suppression of syndecan expression, could be associated with malignant transformation of keratinocytes.

Animals↗
PubMed1991

[Enterococcus faecalis bacteremia].

BACKGROUND: This study was prompted by the increasing role of E. faecalis in hospital acquired infections, their morbidity and mortality and the development of resistances. The aim of the study was to define the epidemiological features, the predictive factors of bacteremia and the mortality prognosis in a group of patients with E. faecalis bacteremia. METHODS: The clinical and epidemiological features on admission, after 3 days and one week of therapy and one month after therapy were evaluated in 57 cases of true E. faecalis bacteremia. The effectiveness of therapy was assessed by the rate of clinical and microbiological cures, deaths and survivals. RESULTS: The incidence of E. faecalis bacteremia was 5.9%. 78% of them were hospital acquired, with unknown source in 31%. Generally, they developed in surgical services and usually the patients had received antibiotic treatment or instrumentation. 63% of bacteremias were monomicrobial. Male sex, hospitalization (particularly in surgical or intensive care services), underlying disease of rapidly fatal prognosis, the previous use of third generation cephalosporins and/or ciprofloxacin, and previous instrumentation or surgery were found to be predictive factors of bacteremia. On the other hand, underlying disease with rapidly fatal prognosis, with initial poor or critical clinical condition, the previous use of wide spectrum antibiotics, polymicrobial bacteremia, and the presence of leukocytosis or complications were significantly associated with a higher mortality. The resistance rates ranged between 42% to kanamycin and 1% to amikacin. CONCLUSIONS: In view of the results, a better knowledge of the predictive and prognostic factors of E. faecalis bacteremia is required for prevention and treatment.

Enterococcus faecalis↗
PubMed1991

Effect of continuous oestradiol-medroxyprogesterone administration on plasma lipids and lipoproteins.

Plasma lipids and lipoproteins were measured in 21 post-menopausal women after 4 and 8 months of continuous treatment with an orally administered combination of oestradiol and medroxyprogesterone acetate. The mean concentrations of cholesterol and low-density-lipoprotein (LDL) cholesterol were reduced by 12% (P less than 0.001) and 11% (P less than 0.01), respectively, after 4 months of treatment and by 9% (P less than 0.05) and 12% (P less than 0.05) after 8 months. The mean level of high-density-lipoprotein (HDL) cholesterol showed an initial fall of 5% (P less than 0.05) after 4 months and then increased by 13% (P less than 0.05) after 8 months of treatment. The plasma triglycerides level oscillated around the baseline value, but the changes were not statistically significant. Indexes such as the HDL-cholesterol/LDL-cholesterol and cholesterol/HDL-cholesterol ratios, which are considered to be good indicators of atherogenic risk, showed changes towards patterns considered to be beneficial. Although the clinical significance of these changes remains uncertain at present, it seems clear that an oestradiol and medroxyprogesterone combination administered continuously produces biochemical changes which are regarded as protective against cardiovascular disease. Additionally, the endometrial inertness attributed to the continuous oestrogen-progestogen therapy would warrant its use as a good alternative in post-menopausal replacement therapy.

Adult↗
PubMed1991

A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis.

The expression of the cell-cell adhesion molecules E- and P-cadherin has been analyzed in seven mouse epidermal keratinocyte cell lines representative of different stages of epidermal carcinogenesis. An inverse correlation between the amount of E-cadherin protein and tumorigenicity of the cell lines has been found, together with a complete absence of E-cadherin protein and mRNA expression in three carcinoma cell lines (the epithelioid HaCa4 and the fibroblastoid CarB and CarC cells). A similar result has been detected in tumors induced in nude mice by the cell lines, where induction of E-cadherin expression takes place in moderately differentiated squamous cell carcinomas induced by HaCa4 cells, although at much lower levels than in well-differentiated tumors induced by the epithelial PDV or PDVC57 cell lines. Complete absence of E-cadherin expression has been observed in spindle cell carcinomas induced by CarB or CarC cells. P-cadherin protein was detected in all cell lines that exhibit an epithelial (MCA3D, AT5, PDV, and PDVC57) or epithelioid (HaCa4) morphology, as well as in nude mouse tumors, independent of their tumorigenic capabilities. However, complete absence of P-cadherin was observed in the fibroblast-like cells (CarB and CarC) and in spindle cell carcinomas. The introduction of an exogenous E-cadherin cDNA into HaCa4 cells, or reactivation of the endogenous E-cadherin gene, leads to a partial suppression of the tumorigenicity of this highly malignant cell line. These results suggest a role for E-cadherin in the progression to malignancy of mouse epidermal carcinogenesis. They also suggest that the loss of both E- and P-cadherin could be associated to the final stage of carcinogenesis, the development of spindle cell carcinomas.

Animals↗
PubMed1991

P29, an oestrogen receptor-associated protein, is down-regulated by mifepristone in first trimester human placenta and decidua.

P29 is an oestrogen receptor-associated protein which acts as a marker of oestrogen action in several systems. The concentration of P29 was measured in placenta and decidua from women following medical termination of pregnancy with the antiprogesterone steroid mifepristone (RU 38,486) and a prostaglandin E1 analogue, and compared with the concentration of P29 found in matched controls undergoing surgical aspiration of pregnancy. Oestrogen receptors were also measured in the same samples. Placental and decidual P29 concentrations (IU/mg protein) in patients treated with mifepristone were 9.6 (4.6-54) and 4.8 (1.3-13.3) (median and range), respectively. These values were significantly lower than the corresponding values, 39.5 (27-69) and 22.0 (2-107) in the surgical group. In contrast, the levels of oestrogen receptors did not change significantly in either decidua or placenta. These data show that mifepristone causes down-regulation of P29 in placenta and decidua, and therefore its action may disrupt oestrogen function in uterine tissues.

Abortion, Legal↗
PubMed1991

Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts.

Increased Na/H antiporter activity has been demonstrated after in vivo chronic metabolic acidosis as well as in vitro acid preincubation of cultured rabbit renal tubule cells. To study the underlying molecular mechanisms of this adaptive increase in Na/H antiporter activity, the present studies examined the effect of low pH media on Na/H antiporter activity and mRNA abundance in cultured renal tubule cells. Na/H antiporter activity was increased by 60% in a mouse renal cortical tubule cell line (MCT), and by 90% in an opossum kidney cell line (OKP) after 24 h of preincubation in acid (low [HCO3]) media. The ethylisopropylamiloride sensitivity of the Na/H antiporters were different in these two cell lines (MCT IC50 = 65 nM; OKP IC50 = 4.5 microM). In MCT cells, Na/H antiporter mRNA abundance measured by RNA blots increased by two- to fivefold after 24 h in low [HCO3] media. Na/H antiporter mRNA abundance was also increased in MCT cells with high CO2 preincubation as well as in rat renal cortex with in vivo chronic acid feeding. In contrast to renal epithelia, acid preincubation of NIH 3T3 fibroblasts led to suppression of Na/H antiporter activity. RNA blots of 3T3 fibroblasts revealed the same size Na/H antiporter transcript as in MCT cells. However, Na/H antiporter mRNA levels were suppressed by acid preincubation. These studies demonstrate differential regulation of Na/H antiporter activity and mRNA abundance in renal epithelial cells and fibroblasts in response to an acidotic environment.

Acidosis↗
PubMed1991

[The spontaneous regression of a rhabdomyoma of the right ventricle].

Rhabdomyoma is the most common intracardiac tumor in the newborn. The diagnosis is made by the clinical history and the physical examination, the electrocardiogram, chest X-ray, and the echocardiographic data. It has a poor prognosis, 80% dying in the first year of life because congestive heart failure or sudden death. Rarely, spontaneous regression has been described. We present the case of a newborn diagnosed of tuberous sclerosis, with an echocardiographic image of a rhabdomyoma in the right ventricle with a spontaneous total regression of the tumor 2 years later.

Echocardiography↗
PubMed1990

Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause.

Estrogen receptors (ERs), progesterone receptors (PRs), and P29, an ER-associated protein, were studied immunohistochemically in human cervix with use of specific monoclonal antibodies. In ectocervical epithelium, homogeneous staining was found for P29 throughout the menstrual cycle and after menopause. Weak or moderate staining was found for ER in the basal and, occasionally, the parabasal layers of ectocervix during the proliferative phase. In contrast, staining decreased in secretory phase and postmenopausal epithelia. Staining was negative for PR in all the exocervical epithelia. Heterogeneous staining, more pronounced for P29, was found for the three antigens of the study in endocervical epithelium. Staining did not change with the hormonal status of patients, except for ER, where staining decreased during the secretory phase. Stromal cells were negative or weakly positive, whereas muscular fibers were positive. This study suggests that the capacity of response of the steroid apparatus of cervical cells to fluctuations of circulating estrogens and progestins is limited compared with some of the cell functions, such as mucus secretion, or with other target tissues, such as endometrium. Additionally, the differences found in the pattern of expression of the three antigens studied suggest that the steroid-dependent growth and differentiation in ectocervix is regulated differently to endocervix.

Biomarkers, Tumor↗