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Biomedical subjects

M Serrano

Publications and source records attributed to M Serrano.

At least 73 records · Page 4Linked to original sources
PubMed1998

Increased Na,K,Cl cotransporter and Na, K-ATPase activity of vascular tissue in two-kidney Goldblatt hypertension.

The properties of the Na/K pump and Na,K,Cl cotransporter were studied in vascular tissue of two-kidney Goldblatt hypertensive rats. These transport systems were measured as ouabain-sensitive and bumetanide-sensitive 86Rb/K uptake in aortic rings, left ventricular muscle and soleus skeletal muscle fibers of control and hypertensive Sprague-Dawley rats. A dramatic increment in Na/K pump activity was observed in intact aortic rings from the hypertensive group. The same was true for the Na,K,Cl cotransporter. The transport parameters related to the left ventricular muscle and soleus skeletal muscle were not significantly altered in the hypertensive rats. Measurements of the catalytic isoforms of the Na+, K(+)-ATPase in the aortic rings indicated that both isoforms (alpha 1 and alpha 2) were elevated in the same proportion in the hypertensive rats. The results also indicate that the endothelium plays an important role in both transport systems: in the absence of endothelium, a much lower 86Rb/K uptake was observed than in intact aortic rings, either from control or hypertensive vascular tissue. Nevertheless, when the 86Rb/K transport activity was measured in denuded aortic rings, a significantly higher ouabain and bumetanide sensitive 86Rb/K uptake was also observed in the hypertensive rats. These data also show no alteration in the endothelium of the hypertensive rats as compared to control animals. The presence of endothelium had a more striking effect on the alpha 2 catalytic isoform activity than on the alpha 1 isoform. We conclude that there is a significant increment in the Na/K pump and Na,K,Cl cotransporter in two kidney-Goldblatt hypertension, that is specific for vascular smooth muscle.

Animals↗
PubMed1997

The tumor suppressor protein p16INK4a.

The tumor suppressor protein p16INK4a (inhibitor of CDK4) is one of the most direct links between cell-cycle control and cancer. The p16INK4a gene is frequently inactivated in human tumors, and inheritance of mutant alleles results in susceptibility to several types of cancer. p16INK4a is part of a cell-cycle regulatory pathway that converges in the tumor suppressor protein Rb. The mechanisms that regulate p16INK4a are starting to be characterized.

Alleles↗
PubMed1997

17Beta-oestradiol reduces cardiac leukocyte accumulation in myocardial ischaemia reperfusion injury in rat.

We investigated whether oestrogens modulate the phenomenon of leukocyte accumulation during ischaemia and reperfusion of the myocardium. Anaesthetized rats were subjected to total occlusion (1 h) of the left main coronary artery followed by 1 h reperfusion. Sham myocardial ischaemia-reperfusion rats (Sham) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity, serum creatinine phosphokinase activity, serum and macrophages tumour necrosis factor (TNF-alpha) and the myocardial staining of intercellular adhesion molecule-1 (ICAM-1) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum creatinine phosphokinase activity (348 +/- 38 U/ml) and cardiac myeloperoxidase activity, a marker of polymorphonuclear leukocyte accumulation, both in the area at risk and in the necrotic area (MPO 9 +/- 1.1 mU/g tissue and 8.2 +/- 1 mU/g tissue, respectively), and induced a marked increase in the macrophage (156 +/- 14 U/ml at the end of reperfusion) and serum (344 +/- 12 U/ml, at the end of reperfusion) levels of TNF-alpha. Finally, myocardial ischaemia-reperfusion injury increased ICAM-1 staining in the myocardium. Administration of 17beta-oestradiol (5, 10 and 20 microg/kg, i.m. 5 min after induction of myocardial ischaemia-reperfusion injury), lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in the necrotic area, reduced serum and macrophages TNF-alpha (20 +/- 3 U/ml and 9 +/- 3 U/ml, respectively) and decreased serum creatinine phosphokinase activity (67 +/- 3 U/ml). Oestrogen treatment also blunted the increased staining of ICAM-1 in the injured myocardium. Finally, 17beta-oestradiol added in vitro to peritoneal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury, significantly reduced TNF-alpha production. Our results suggest that 17beta-oestradiol, by inhibiting TNF-alpha production, limits the deleterious ICAM-1-mediated binding of leukocytes to injured myocardium and protects against myocardial ischaemia-reperfusion injury.

Animals↗
PubMed1997

Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de novo methylation with independence of p16INK4a alterations in murine primary T-cell lymphomas.

A wide panel of murine induced T-cell lymphomas have been analysed for p16INK4a or p15INK4b alterations. Only one gamma-radiation-induced lymphoma showed p16INK4a homozygous deletion and no other intragenic mutations were found in these INK4 genes. However, de novo methylation of the 5' CpG islands of the murine p15INK4b and p16INK4a genes was found to be highly frequent. While p16INK4a hypermethylation was found in 36% of the neutron-radiation-induced lymphomas and 15% of the gamma-radiation-induced lymphomas, de novo methylation of p15INK4b occurs in 88% and 42% of these tumors respectively, correlating with deficient expression of the corresponding mRNA and allelic losses in the p15INK4b and p16INK4a chromosome location. These data represent, to our knowledge, the first report on the significant involvement of hypermethylation of these INK4 genes in murine primary tumors. Moreover, they show the importance of allelic losses and CpG island methylation of p15INK4b gene inactivation and support a tumor suppressor role for p15INK4b in T-cell lymphomas independent of p16INK4a.

Animals↗
PubMed1997

Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.

Oncogenic ras can transform most immortal rodent cells to a tumorigenic state. However, transformation of primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest. The arrest induced by ras is accompanied by accumulation of p53 and p16, and is phenotypically indistinguishable from cellular senescence. Inactivation of either p53 or p16 prevents ras-induced arrest in rodent cells, and E1A achieves a similar effect in human cells. These observations suggest that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an oncogenic stimulus. Negation of ras-induced senescence may be relevant during multistep tumorigenesis.

Animals↗
PubMed1997

Gliomatosis cerebri mimicking a metastatic breast cancer: fatal outcome.

Gliomatosis cerebri (GC) is defined by the World Health Organization as a neoplasm of the glial cells. It is extremely rare, and there exists only 160 documented cases since 1897. There is no known treatment and the median survival rate is one year. The association of extracranial and CNS tumors is unusual, only three cases of breast cancer have been associated with gliomas and meningiomas but none with GC. Below we describe a case of breast cancer associated with GC and review the anatomoclinical and radiological manifestations of Gliomatosis Cerebri.

Aged↗
PubMed1997

Prognostic value from DNA quantification by static cytometry in breast cancer.

OBJECTIVE: To determine if DNA quantification on fine needle aspiration (FNA) has predictive value in breast cancer. STUDY DESIGN: Forty-nine patients with breast cancer were selected for this study because of their common characteristics. The smears were studied using image cytometry. RESULTS: With the type of histogram and value of entropy, two large groups, with high and low degrees of malignancy, were obtained. Survival was utilized as a variable of interest. Kaplan-Meier survival curves for both groups were formulated, and the results were supported with statistical data. CONCLUSION: The survival differences between both groups were statistically significant (P < .001), thus demonstrating the predictive value of DNA quantification.

Biopsy, Needle↗
PubMed1997

[Age as source of variation in various parameters of 'delta sleep'].

INTRODUCTION: The clinic usefulness of a diagnostic test is in relationship to the precision with which measures the studied phenomenon. The lack of precision involve the reliability upon causing confounded results of the normal and diseased populations. OBJECTIVE: Since the sleep varies in function of the age, to find sleep parameters that fit better to the changes that the aging produces in the sleep. MATERIAL AND METHODS: Spectral analysis through the Fast Fourier Transformation of the ambulatory EEG of 28 healthy subjects. RESULTS: Maximum value of power (maximum depth) in a frequency of ended in a point of the sleep goes losing in a way specifies and systematical with the age. CONCLUSIONS: The variance accounted by this parameter is of the 87%, what, being tried to a phenomenon so variable as the sleep, supposes a interesting starting point to be applied to some pathologies in those which is presumed that the slow sleep (to which is attributed a paper in the cerebral restoration) is decreased.

Adolescent↗
PubMed1996

Activation of replication origins in phi29-related phages requires the recognition of initiation proteins to specific nucleoprotein complexes.

Protein p6 of Bacillus subtilis phage phi29 activates the initiation of viral DNA replication by forming a multimeric nucleoprotein complex at the origins of replication, located at both ends of the linear genome. This activation requires a precise positioning of the protein p6 array with respect to the initiation site. To investigate this activation mechanism, we have purified the phi29 protein p6 counterparts from the related phages Nf and GA-1 and analyzed the formation of complexes with DNA. In the homologous protein p6-DNA complexes the phi29 and Nf protein arrays showed an identical positioning, different than that of the GA-1 protein array. In contrast, in the heterologous complexes the protein showed a different arrangement except in the case of the Nf protein-phi29 DNA complex. We have also purified the proteins involved in the initiation of replication (terminal protein and DNA polymerase) from phages Nf and GA-1 and measured the ability of the different p6 proteins to activate homologous and heterologous replication origins. The results obtained indicate that the activation requires not only the formation of a specific nucleoprotein complex but also its specific recognition by the proteins involved in the initiation of DNA replication.

Bacillus Phages↗
PubMed1996

Role of the INK4a locus in tumor suppression and cell mortality.

The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor-associated alterations in the INK4a locus may also affect the overlapping gene encoding p19ARF and the adjacent gene encoding p15I1NK4b, both negative regulators of cell proliferation. We report the phenotype of mice carrying a targeted deletion of the INK4a locus that eliminates both p16INK4a and p19ARF. The mice are viable but develop spontaneous tumors at an early age and are highly sensitive to carcinogenic treatments. INK4a-deficient primary fibroblasts proliferate rapidly and have a high colony-formation efficiency. In contrast with normal cells, the introduction of activated Ha-ras into INK4a-deficient fibroblasts can result in neoplastic transformation. These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth.

Alleles↗
PubMed1996

Analysis of p16INK4a and its interaction with CDK4.

The interaction between cyclin-dependent kinase 4 (CDK4) and its inhibitor p16INK4a (p16) was studied by random mutagenesis and yeast two-hybrid system. The gene encoding p16 was mutagenized randomly and the amino acid changes that affect the binding of p16 to CDK4 were identified. Several amino acid residues were shown to be important for the binding and many of these changes occur at residues conserved in all known human p16 family proteins Most of the mutant p16 proteins that failed to bind to CDK4 contained multiple amino acid changes, and these alterations were observed throughout the entire gene with no apparent mutational patterns or hot spots. Some of the mutations that moderately reduced the binding activity severely affected the kinase-inhibitory activity of p16.

Amino Acid Sequence↗
PubMed1996

Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16INK4.

The function of p16INK4 as a putative tumor suppressor gene was examined by investigating its ability to inhibit the growth of cancer cell lines in vitro and tumor formation in vivo. A p16INK4 cDNA expression vector was transfected into five human cancer cell lines that varied in their p16INK4 and retinoblastoma (Rb) status. Suppression of colony-forming efficiency was seen in four cell lines. Of two cell lines wild type for p16INK4 but null for Rb protein expression, one (Hep 3B) showed inhibition of colony formation, whereas the other (Saos-2) did not. This observation may demonstrate involvement of p16INK4 independent of Rb. The transfected p16INK4 gene was frequently selected against and lost during continued growth in vitro. When compared to the colon carcinoma cell line (DLD-1),p16INK4-transfected DLD-1 clone 1 cells were less tumorigenic in athymic nude mice. Tumors arising from p16INK4-transfected DLD-1 clones, which were growth suppressed in vitro, either lost the integrated exogenous p16INK4 or expressed reduced amounts of p16INK4 protein. Therefore, p16INK4 was also selected against during tumor formation in vivo. These data are consistent with the hypothesis that p16INK4 is a tumor suppressor gene.

Animals↗
PubMed1996

p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A.

We and others previously showed that cyclin G is a transcriptional target of the p53 tumor suppressor protein. However, cellular proteins which might form a complex with cyclin G have not yet been identified. To gain insight into the biological role of cyclin G, we used the yeast two-hybrid screen and isolated two mouse cDNAs encoding cyclin G-interacting proteins. Interestingly, both positive cDNAs encoded B' regulatory subunits of protein phosphatase 2A (PP2A). One clone encodes B'alpha, while the other clone codes for a new member of the B' family, B'beta. B'beta is 70% identical to other members of the B' family. B'alpha associated both in vitro and in vivo with cyclin G but not with the other mammalian cyclins. Furthermore, cyclin G formed a complex with B'alpha only after induction of p53 in p53 temperature-sensitive cell lines. These results indicate that cyclin G forms a specific complex with the B' subunit of PP2A and that complex formation is regulated by p53. Potential roles for the cyclin G-B' complex in p53-mediated pathways are discussed.

Alternative Splicing↗
PubMed1996

Evaluation of the international index in the prognosis of high grade gastric malt lymphoma.

The International Prognostic Index identifies four risk groups with different survival rates in aggressive non-Hodgkin's lymphoma. We have studied whether a slight modification of this index has prognostic significance in high grade gastric B-cell MALT lymphoma. In 53 patients with high grade gastric B-cell MALT lymphoma the following survival factors were investigated: age over or under 60 years, sex, B symptoms, more than one extranodal site of involvement other than the stomach, serum LDH levels, performance status, stage I/IIE1/IIE2 v.s. stage III/IV, treatment with surgery, chemotherapy or both modalities together and the four risk groups as defined by the Modified International Prognostic Index (MIPI). A multivariate Cox's test was used to evaluate the independent prognostic significance on survival of all the above variables. Advanced stage (III/IV) and involvement of more than one extranodal site not including stomach were the only variables influencing survival. The MIPI was not sufficient to separate groups with significant differences in survival or to stratify prognostic groups. In this series, the MIPI did not show prognostic significance in high grade gastric B-cell MALT lymphoma.

Adolescent↗
PubMed1996

[Doppler echocardiography in the postoperative assessment of the arterial switch in the repair of transposition of the great arteries and double outlet right ventricle].

OBJECTIVE: To evaluate the usefulness of Doppler-echocardiography in the follow-up of anatomical repair in transposition of great arteries and double outlet of right ventricle. PATIENTS AND METHODS: 108 Doppler-echo studies, in a follow-up protocol of the first 32 consecutive patients who successfully passed anatomical repair, were analyzed. The mean age for operation was 50 days (6-472 days) (25 patients before 21 days of age) with a mean follow-up time of 406 days (1 day-4.5 years). We studied subjective impression of left ventricular function and its quantification by systolic shortening fraction, the functioning of four heart valves; diagnosis and quantification of stenosis in arterial sutures of neoaorta and neopulmonary, the most useful windows and planes and, finally, the difficulties found during the examination. RESULTS: Thirteen patients (41%) showed a low left ventricular shortening fraction, though 85% of these patients had anomalous ventricular septal motion. Neoaortic valve insufficiency was detected in 12 patients (37%) (mild in 10 and moderate in 2) and neopulmonary valve regurgitation in 14 patients (44%) (mild in 11 and moderate in 3). Stenosis of arterial sutures was detected in: 2 (6%) patients at neopulmonary artery and 1 (3%) at neoaortic artery. The biggest technical difficulty was found in the neopulmonary artery evaluation. CONCLUSIONS: 1) Doppler echocardiography is an excellent method for anatomical and functional evaluation in these patients and is necessary in their follow-up evaluations; 2) Surgical results obtained in this series are good; 3) Left ventricle fractional shortening is misleading in the evaluation of ventricular function in these patients because of the high incidence of abnormal ventricular septal motion, and 4) The study of neopulmonary arteries is often very difficult.

Double Outlet Right Ventricle↗