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Biomedical subjects

M Serrano

Publications and source records attributed to M Serrano.

At least 37 records · Page 2Linked to original sources
PubMed1994

[The combined treatment of anaplastic thyroid carcinoma].

Five patients with anaplastic thyroid carcinoma (ATC) were treated with chemotherapy (adriamycin 60 mg/m2 and cisplatin 90 mg/m2) followed by surgery and postoperative radiotherapy. The average survival in this series was 11.2 months. Partial response of the cervical tumoration was observed in 4 patients and of the distant metastasis, in 1 of 3 cases. One patient with mixed thyroid carcinoma (follicular and anaplastic) had complete remission of the disease. Four patients died: two due to metastatic disease and two due to local tumor growth. We conclude that this type of combined therapy is affective in patients with anaplastic thyroid carcinoma in terms of local control of the disease, avoiding mortality due to local invasion in some of these patients.

Aged↗
PubMed1993

A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.

The division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase. CDK4 exists, in part, as a multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen and a protein, p21 (refs 7-9). CDK4 associates separately with a protein of M(r) 16K, particularly in cells lacking a functional retinoblastoma protein. Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes. p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein.

Amino Acid Sequence↗
PubMed1993

Superhelical path of the DNA in the nucleoprotein complex that activates the initiation of phage phi 29 DNA replication.

Initiation of bacteriophage phi 29 DNA replication is activated by protein p6, a viral double-stranded DNA-binding protein that forms a nucleoprotein complex at the viral replication origins. This complex consists of a DNA right-handed superhelix wrapped around a multimeric protein p6 core with protein p6 dimers regularly bound every 24 base-pairs (bp). In this paper, we have constructed a concatemer formed by direct repeats of a 24 bp sequence previously proposed to act as a signal for protein p6 binding at a phi 29 replication origin. DNase I footprinting shows that protein p6 binds to the concatemer in a similar way to the phi 29 DNA replication origins but with higher affinity, indicating that the 24 bp sequence is a recognition signal for protein p6. Furthermore, the concatemer was cloned in a plasmid and, by electron microscopy, it was shown to be the highest-affinity protein p6 binding region present in the plasmid. Based on these observations, the linking number change restrained by protein p6 has been measured in a series of plasmids containing concatemers with different numbers of 24 bp repeats; from the values obtained the linking number change restrained by a single protein p6 dimer has been estimated (delta Lkd = 0.1). In addition, when protein p6-DNA complexes fixed with glutaraldehyde were analysed by electron microscopy, it was observed that protein p6 compacts 4.2-fold the length of naked DNA. These data, together with the previously known value of the surface-related DNA helical repeat in the complex (12 bp), completely define the superhelical path of the DNA in the complex: one superhelical turn approximately involves 63 bp and 2.6 protein p6 dimers, and the DNA superhelix has a diameter of 6.6 nm and a slope of 14 degrees. The data obtained also indicate that the DNA in the protein p6-DNA complex is undertwisted (11.5 bp/turn) and strongly bent (66 degrees/12 bp). These DNA conformational changes might contribute to the activation of phi 29 DNA initiation of replication by protein p6.

Bacillus Phages↗
PubMed1993

[Yield of laboratory tests in the detection of excessive drinkers in the work place].

BACKGROUND: The identification of personnel consuming excess quantities of alcoholic beverages in the work place is necessary due to the economic, health, and laboral problems caused by alcohol. The objectivity of laboratory tests provides great credibility and these tests have replaced other methods as the anamnesis. METHODS: A transversal study was carried out of the employees of a Barcelona enterprise. During the periodic medical check ups the consumption of alcoholic beverages and laboratory blood tests were obtained from the employees seven days previously. RESULTS: All the laboratory tests presented a weak positive correlation with the consumption of alcohol. The calculation of diagnostic efficacy for weekly consumption equal to or grater than 280 g of pure alcohol in a male shows that the greatest sensitivity corresponds to mean corpuscle volume (33%) followed by gammaglutamyltranspeptidase (GGT) (16%) with high specificity being observed in both (85% and 93%, respectively). The results are better in employee consuming more than or equal to 420 g of alcohol weekly. CONCLUSIONS: The diagnostic efficacy of laboratory tests in identifying subjects with elevated consumption of alcohol in the work place has low clinical performance and the use of anamnesis on the consumption of alcoholic beverages should first be evaluated.

Alanine Transaminase↗
PubMed1993

Multimeric complexes formed by DNA-binding proteins of low sequence specificity.

Some proteins bind to double-stranded DNA with low sequence specificity, forming regular multimeric complexes that extend over large regions of DNA, strongly distorting its conformation. Formation of these complexes at particular DNA sites usually depends on the structural ability of the DNA to follow the path imposed by the protein array. These complexes are found in both prokaryotic and eukaryotic organisms and participate in processes such as DNA replication, transcription and packaging.

DNA↗
PubMed1993

[Chronic renal insufficiency and secondary hyperparathyroidism in rats. Biochemical and histological evaluation].

Chronic renal failure (CRF) in rats (surgical nephrectomy, 5/6) as well as its derived bone lesions have been studied. Eighty-five male Wistar rats were used, to which chronic renal failure was induced in 1 or 2 surgical times, the parameters of renal function in basal conditions and at different times after surgery being determined. With the method used chronic renal failure is induced with values of creatinine clearance 2/3 times lower than the initial ones (p < 0.05), which stabilize at the 7th week. On the other hand the parathyroid hormone levels (PTH) in serum triple (from 125 +/- 49 to 395 +/- 191, p < 0.05), and a decrease in the tubular phosphate reabsorption is produced (p < 0.001). In bone histology an increase in resorption and bone formation is observed as well as paratrabecular fibrosis, all of which is compatible with the histological diagnosis of hyperparathyroidism. The model of surgical renal insufficiency with ablation of 5/6 of the renal mass, reduces renal function to 1/3 of the initial values after 7 weeks, this procedure having a 20% global mortality without differences being observed between the carrying out of nephrectomies in 1 or 2 surgical times. This degree of CRF was accompanied by secondary hyperparathyroidism both at the biochemical and histological levels, findings which are of great usefulness for future experimental studies.

Animals↗
PubMed1992

DNA conformational change induced by the bacteriophage phi 29 connector.

Translocation of viral DNA inwards and outwards of the capsid of double-stranded DNA bacteriophages occurs through the connector, a key viral structure that is known to interact with DNA. It is shown here that phage phi 29 connector binds both linear and circular double-stranded DNA. However, DNA-mediated protection of phi 29 connectors against Staphylococcus aureus endoprotease V8 digestion suggests that binding to linear DNA is more stable than to circular DNA. Endoprotease V8-protection assays also suggest that the length of the linear DNA required to produce a stable phi 29 connector-DNA interaction is, at least, twice longer than the phi 29 connector channel. This result is confirmed by experiments of phi 29 connector-protection of DNA against DNase I digestion. Furthermore, DNA circularization assays indicate that phi 29 connectors restrain negative supercoiling when bound to linear DNA. This DNA conformational change is not observed upon binding to circular DNA and it could reflect the existence of some left-handed DNA coiling or DNA untwisting inside of the phi 29 connector channel.

Bacillus Phages↗
PubMed1992

[Detection of hepatitis B virus DNA in serum by gene amplification in patients with chronic hepatitis B and in patients chronic hepatitis C].

BACKGROUND: The polymerase chain reaction (PCR) constitutes important methodological progress for detecting the presence of viral nucleic acids when these are found in small quantities in serum or tissues. The aim of this study was the use of PCR to detect DNA of the hepatitis B virus (HBV) in patients with chronic HBsAg positive hepatitis (HC-B) and in patients with chronic non A non B hepatitis with antibodies against the virus of hepatitis C (anti-HCV) positive (HC-C). METHODS: The DNA of the HBV was determined with PCR in the serum of 40 patients with HC-B and in 15 with HC-C. Moreover, the presence of anti-HCV was studied in the patients with HC-B. RESULTS: The presence of DNA of the HBV was detected by PCR in 69% of the HC-B patients presenting HBeAg positive and DNA of the HBV negative by simple hybridization as well as in 50% of the patients with HBeAg negative, anti-HBe positive and DNA of HBV negative by simple hybridization. In addition, DNA of HBV was detected by PCR in 27% (4/15) of the subjects with HC-C, three of whom had anti-HBc antibodies. On the other hand, 20% of the patients with HC-B had anti-HCV. Anti-HCV positivity was associated to a greater hypertransaminasemia in patients with HC-B in a non replicative phase. CONCLUSIONS: PCR is a sensitive method for detecting viral replication. Its use permits the detection of low DNA concentrations of the HBV in a low but appreciable percentage of chronic negative HBsAg hepatitis. Coinfection by the B and C viruses of hepatitis is not exceptional and explains hypertransaminasemia in some HC-B in a non replicative phase.

DNA, Viral↗
PubMed1992

[Value of fine needle aspiration cytology in the diagnosis and treatment of tumors].

UNLABELLED: We report the cytologic results of 186 fine needle aspirations on accessible lymph nodes and tumoral masses as well as deep masses under radiologic control. We assessed the ratios of diagnostic accuracy and the utility of this procedure for staging solid tumors and taking therapeutic decisions. RESULTS: sensitivity, 89.6%; specificity, 100%; positive predictive value, 100%; negative predictive value, 57% and accuracy index, 89.2%. Using this technique we detected a metastatic disease in 62% of neoplastic patients. We took a therapeutic decision (active treatment or analgesia) in accordance with the results of the cytology in 63% of patients with solid tumors. Two patients, after a transthoracic aspiration, developed pneumothorax as a complication. Cytology by fine needle aspiration is a fast and simple method for diagnosing, staging and taking a therapeutic decision on patients with solid tumors.

Adult↗
PubMed1991

[The treatment of large-cell non-Hodgkin's lymphomas with the MACOP-B protocol].

BACKGROUND: To investigate the results of the treatment of large-cell non-Hodgkin's lymphomas (LCNHL) with the MACOP-B chemotherapy protocol. METHODS: 20 patients with the following inclusion criteria were treated: LCNHL with a definite majority of large lymphoid cells and absence of previous therapy, HIV infection or severe underlying diseases. RESULTS: Three patients died during therapy and 15 (75%) achieved a complete remission. Actuarial survival after 36 months (0.66) was significantly better (p = 0.05) than that of a comparable historical series of LCNHL treated with CHOP (0.28). Age, stages III-IV, B symptoms, large lymphatic mass (LLM) and bone marrow infiltration did not negatively affect survival. The toxicity of the MACOP-B protocol was high: mucositis (65%), cytopenia (55%), neuropathy (40%), complications of steroid therapy (15%), and mortality directly related with therapy in 15%. Residual masses were found after therapy in 7% (70%) with BD, which were localized in lymphoid areas or in parenchyma (spleen and kidney). Surgical exploration showed that the residual masses were not tumoral in three cases, and in another three magnetic resonance suggested inactive disease. CONCLUSIONS: The MACOP-B protocol is highly effective for the treatment of LCNHL. The essential prognostic factor for survival in these NHL appears to be the cell composition with a great majority of large cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Transcription activation at a distance by phage phi 29 protein p4. Effect of bent and non-bent intervening DNA sequences.

Protein p4 of the Bacillus subtilis phage phi 29 switches on the transcription of the viral late genes by binding to the viral late promoter at a region close to the RNA polymerase binding site. Gel retardation and DNase I footprinting assays show that the presence of protein p4 is required for RNA polymerase recognition of the late promoter. The protein p4 and RNA polymerase DNA binding sites have been separated by the insertion of bent and non-bent DNA sequences of different lengths. These mutant promoters were used to study in vitro their protein p4-dependent transcriptional activity and their interaction with both protein p4 and RNA polymerase. The results indicate that protein p4 is able to function at longer DNA distances from the RNA polymerase binding site than in the natural promoter. The extent of protein p4 activity depended on the length and conformation of the inserted DNA. Activation of transcription and RNA polymerase binding was favoured when the relative orientation of protein p4 and RNA polymerase was conserved and when the intervening DNA had a bent conformation. These data, together with the DNase I footprints, suggest that activation at distance by protein p4 involves a DNA loop held by the interaction of protein p4 and RNA polymerase.

Bacillus subtilis↗
PubMed1991

Contamination and radiation exposure from 201Tl in patients undergoing dialysis after a nuclear medicine study.

Our institution is a major kidney research and transplant center. Hemodialysis patients that are scheduled for renal transplant are given a 201Tl stress test. Possible radiation exposure and contamination are of concern to attending personnel. We investigated this situation and found measurable activity in the effluent of patients receiving dialysis but no significant contamination of equipment. We determined that dialysis personnel received minimal radiation exposure.

Equipment Contamination↗