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Biomedical subjects

M Santos

Publications and source records attributed to M Santos.

At least 199 records · Page 11Linked to original sources
PubMed1989

Solubilization of SV40 plasma-membrane-associated large tumor antigen using single-phase concentrations of 1-butanol.

The nature of the interaction of the simian virus 40 (SV40) transforming protein, large tumor antigen (T-ag), with the plasma membrane of transformed cells is not well understood. We report here that SV40 plasma-membrane-associated large tumor antigen (pmT-ag) can be solubilized by using single-phase concentrations of 1-butanol. Purified plasma membranes from SV40-transformed mouse cells yielded T-ag when treated with 2.5% butanol; solubilization of T-ag from the purified membranes in butanol was temperature dependent, with approximately 10-fold more T-ag extracted at 37 degrees C than at 22 degrees C; and application of 2.5% butanol to mKSA cells after cellular surface proteins had been radiolabeled with 125I resulted in the release of iodinated T-ag. Butanol-extracted pmT-ag coprecipitated with p53 and several cellular proteins ranging in size from 35 to 60 kDa. One cellular component migrated at a mobility similar to that of tubulin (56 kDa), and a monoclonal antibody against the alpha subunit of tubulin coprecipitated T-ag. Immunoblotting of proteins immunoprecipitated with monoclonal antibodies against T-ag or p53 from butanol extracts with a monoclonal antibody against the beta subunit of tubulin revealed specific coprecipitation of tubulin with T-ag and p53. This suggests that complexes composed of tubulin, T-ag, and p53 exist in butanol extracts. Control experiments eliminated the possibility of an artifactual association of tubulin with T-ag and p53 induced by butanol. Two-dimensional gel analyses revealed that 2.5% butanol at 37 degrees C extracted a subset of membrane-associated proteins and some cytosolic proteins, as well as a number of proteins that were not soluble in either high salt or detergent. Thus, the butanol extraction conditions employed in this study recovered a species of pmT-ag that appears to complex with tubulin. As butanol reportedly is less deleterious to native protein structures than other agents, including high salts and detergents, this extraction procedure may be useful for studying the structure and function of other membrane-associated proteins.

1-Butanol↗
PubMed1989

Postoperative radical radiotherapy with concurrent weekly intra-arterial cis-platinum for treatment of malignant glioma: a pilot study.

Twelve patients with histologically proven malignant glioma have been treated with a combination of intra-arterial (IA) cis-platinum (CDDP) and radical radiation therapy (RT). Chemotherapy consisted of intracarotid (IC) CDDP, 40-60 mg/m2, weekly, repeated for 3-5 treatments. Radiation therapy consisted of whole-brain irradiation 5000 cGy in 5 weeks, plus a cone-down boost (1000 cGy in one week) to the primary tumour lesion. Ocular toxicity derived from IC chemotherapy was observed in 3 out of 41 procedures analyzed (7%). Results in tumour response assessed by computed tomography (CT) showed 5 complete remissions, 6 partial remissions and one patient was not evaluable. The median survival time for the entire group was 10 months. Median survival time in patients with complete response is 17 months, and 10 months in patients with partial response. Four patients are still alive with a follow-up ranging from 6+ to 27+ months.

Adult↗
PubMed1989

Intraoperative radiotherapy for recurrent and/or residual colorectal cancer.

Intraoperative radiotherapy (IORT) is an attractive boosting modality in the combined treatment of recurrent and/or residual colorectal cancer. Twenty seven patients treated with IORT are analysed. Residual disease following resection of the primary tumor was treated in 11 cases (group I). Localized recurrent disease without previous radiotherapy was treated in 11 cases (group II). IORT was used in five additional patients with local recurrences in previously irradiated areas (group III). The treatment program consisted of maximal tumor resection, IORT (10-30 Gy) to the area of residual disease and external beam radiotherapy (46-50 Gy). The median follow-up time for the entire series of patients is 11 months. Local tumor control rates are 90% in group I, 63% in group II and 60% in group III. Toxicity and complications related to IORT observed in this initial experience have been pelvic pain (29%) and lower extremity neuropathy (3%). These early clinical results suggest that the IORT combined with surgery and external beam radiotherapy is feasible in primary and recurrent disease. Local control rates obtained in patients not suitable for curative surgery are encouraging.

Adenocarcinoma↗
PubMed1989

Intraoperative and external beam radiotherapy in advanced resectable gastric cancer: technical description and preliminary results.

Twenty-two patients with resectable gastric cancer treated with intraoperative radiotherapy and external beam irradiation, in a Phase I-II oriented study, were analyzed. Tumor Stages were III & IV in 18 cases (82%). Tumor histology was described as diffuse undifferentiated type in 14 cases (63%). Following surgical resection of the primary tumor, IORT 15 Gy was delivered in the celiac axis area, using high energy electron beams ranging from 9 to 20 MeV. External beam irradiation fields covered the draining nodal areas of the upper abdomen and the gastric bed. There were no postoperative deaths. Reversible postoperative complications were recorded in 14 patients (63%). Long term complications observed were vertebral collapse and liver hemangiomas. First sites of recurrence have been: hepatic hilum (three cases), peritoneum combined with central axis nodes (two cases), liver metastasis (one case), and lung metastasis (one case). Survival data shows a follow-up period ranging from 1+ to 33+ months, with a median survival time for the entire group of 13+ months. At the time of this report, 16 patients (72%) are still alive and six have died (four from progressive malignant disease and two from intercurrent disease). From this preliminary data, it can be concluded that a combined approach with surgical resection, intraoperative radiotherapy, and external beam irradiation is feasible in advanced gastric carcinoma, and is not limited by toxicity or any complications observed. Despite this intense loco-regional therapeutic approach, the upper abdominal failure rate has been demonstrated in 22% of the cases.

Adult↗
PubMed1989

Intrahepatic bile duct changes in human hepatosplenic schistosomiasis mansoni.

Wedge liver biopsies of 132 patients with hepatosplenic mansonian schistosomiasis were studied and divided in two groups according to the presence (Group I - 69 cases) or absence (Group II - 63 cases) of markers of the actual presence of the parasite in the liver tissue. Histological variables indicating bile duct injury were analysed in each case: periductal fibrosis, hyperplasia of the bile duct epithelium, bile duct degeneration, and marginal ductular proliferation. The presence of one or more of these variables defined two sub-groups: A - bile duct lesions present (73 cases), and B - bile duct lesions absent (59 cases). The variables "bile duct degeneration" and "ductular proliferation" were related to the actual presence of the parasite in the host. In 55.3% of all cases of human mansonian schistosomiasis a spectrum of injuries to the bile ducts was present. Epithelial hyperplasia alone or associated with patterns of mucopolysaccharide production was observed in 87.6% cases of the Sub-group A. The bile ducts changes in mansonian schistosomiasis are close to those described in liver fluke infestations such as clonorchiasis, fascioliasis and opistorchiasis. Statistical analysis revealed that high mucopolysaccharide production was associated with epithelial hyperplasia. The pathogenesis of the bile duct changes in human mansonian schistosomiasis and its relation to the parasitic infestations and their antigens is discussed.

Bile Ducts, Intrahepatic↗
PubMed1989

Comparative study of aztreonam in gram-negative pneumonia versus a therapeutic regimen that includes an aminoglycoside. Spanish Study Group.

Gram-negative pneumonia is a frequent complication in hospitalized patients, particularly in those with diminished defenses. The severity of the infections makes it necessary to start immediately an empirical antimicrobial therapy that usually combines a broad-spectrum beta-lactam antibiotic with an aminoglycoside (AMG), despite the potential toxicity of this regimen. We have compared the efficacy of a new beta-lactam antibiotic, aztreonam, which shows both a specific spectrum of activity against gram-negative bacteria and a very good diffusion into pulmonary tissue, with that of another antibiotic regimen including an AMG. Of a total of 69 patients, 43 were treated with aztreonam and the remaining patients with an AMG. Both groups were comparable with respect to the severity of infection and underlying pathology. Clinical efficacy was similar in the two regimens (81% aztreonam, 62% AMG). However, antimicrobial efficacy was superior in the aztreonam group (88% aztreonam, 65% AMG), although differences disappeared in patients treated with the combination amikacin + cefotaxime or ticarcillin in the AMG group. Colonization/superinfection was also similar in both groups, although the selection of gram-negative bacteria occurred more frequently in the AMG group. Our results suggest that aztreonam, in monotherapy, may be a useful alternative for the treatment of gram-negative pneumonia.

Adult↗
PubMed1989

Changes in nuclear distribution of large tumor antigen correlate with the proliferative activity of simian virus 40-transformed cells.

A correlation between intranuclear distribution of large tumor antigen (T-ag) and proliferative activity in Simian virus 40 (SV40)-transformed cells has been established. Nuclear T-ag was cytochemically detected by the immunoperoxidase reaction. Cell populations with a high growth rate displayed a heterogeneous pattern with patches of positive reaction surrounded by large and irregular negative areas. By contrast, cell populations with a low growth rate presented a rather homogeneous distribution of nuclear T-ag with a finely granular positive reaction all over the nucleus, excluding nucleolus-like areas. The latter pattern was also observed in cells that had been inhibited from traversing S phase. In this case, the heterogeneous distribution of T-ag within the nucleus was recovered once the cells were allowed to proceed again through S phase, or through G2 phase. Highly condensed chromatin in mitotic chromosomes appeared to exclude T-ag fully as early as in prophase. Then, nuclear distribution of T-ag changes throughout the cell cycle, thus suggesting it might be a cell cycle-dependent event. Interestingly, thymidine-labeled cells from cultures with a high growth rate presented a heterogeneous distribution of autoradiographic grains. Regardless of their mechanism(s) of origin, T-ag-enriched areas might correspond to nuclear sites where a specific function, such as DNA synthesis, is being carried out.

Animals↗
PubMed1989

Intraoperative radiotherapy in the multidisciplinary treatment of pediatric tumors. A preliminary report on initial results.

From September 1984 to July 1987, 33 children received intraoperative radiotherapy as part of a multidisciplinary tumor treatment. Their age ranged from 2 to 17 years. Tumors types: Ewing's sarcoma (n = 11), osteosarcoma (n = 8), soft tissue sarcomas (n = 5), Wilms' tumor (n = 3), neuroblastoma (n = 3), malignant pheochromocytoma (n = 1), Hodgkin's disease (n = 1), and optic nerve glioma (n = 1). In 25 patients the disease was localized while 8 had distant metastases. Intraoperative radiotherapy was used in 26 previously untreated patients as part of a radical treatment program and in 7 cases as an effort to rescue local failures (5 in previously irradiated areas). The intraoperative radiation field included the surgically exposed tumor or tumor bed, and the single doses ranged from 10 to 20 Gy, with 6-20 MeV electrons. Patients with osteosarcoma and recurrent tumor in a previously irradiated area did not receive postoperative external beam radiotherapy. With a median follow-up time of 10 months (1 to 31 + months) 24 out of 33 patients are alive without local recurrence and 9 have died from tumor (5 with local disease progression). Intraoperative radiotherapy seems to be a feasible treatment which might promote local control in pediatric tumors.

Adolescent↗
PubMed1989

[The 4th complement factor (C4) and t haplotypes in wild mice].

Five different lines of tailless mice bearing different t recessive haplotypes (tAn, tMo, tRa, tLa and tQu) have been established in our laboratory and maintained in combination with the brachury chromosome (T). These t haplotypes were derived from widely separated Chilean wild mouse populations. The immunoelectrophoretic typing for Ss and Slp isotypic variants of C4 showed that all lines had the Ss-High. Slp-negative phenotype suggesting that the t haplotypes might be associated with similar S regions of the major histocompatibility system of the mouse.

Animals↗
PubMed1989

The effect of glucose-6-phosphate isomerase genotype on in vitro specific activity and in vivo flux in Mytilus edulis.

Four samples of the mussel Mytilus edulis were taken between 1984 and 1987 from Stony Brook, New York, and used to study the glucose-6-phosphate isomerase (GPI) polymorphism in this species. In vitro specific activity and in vivo flux measured in the same animals were found to be significantly correlated. A significant effect of GPI genotype on flux was observed in one of the samples; overall, significant evidence of effect of genotype on enzyme activity was also obtained. GPI activities of common genotypes tend to deviate less from the population mean than those of rare (frequency less than 5%) genotypes. This suggests the possibility that rare GPI genotypes are rare as a consequence of having biochemical properties that deviate from an optimum level and, therefore, having a lower fitness. In support of this hypothesis, we found in one of our samples that shell length is a concave function of GPI activity with an intermediate optimum activity level.

Analysis of Variance↗
PubMed1989

[Changes in radiation lesions using platinum derivatives. Biological bases and clinical experience].

The biological basis of radiation damage modulation with platinum derivatives are reviewed. Cisplatin and Carboplatin are cytostatic agents used increasingly in the treatment of different human tumours. In vitro and in vivo studies have established the interest of the simultaneous combination of platinum compounds and radiation in tumor cells and neoplastic tissue, describing potentiation, sensitization, and inhibition of sublethal damage repair effects from radiation. Clinical trials have been recently activated in order to explore a possible benefit from the biological modulation with platinum compounds of radiotherapy. In the frame of developmental therapeutic protocols in modern oncology, this approach might explore a positive effect on the therapeutic index of radiotherapy for malignant tumors. The initial clinical results reported indicate that the available platinum derivatives used in human oncology behave as radiopotentiating and radiosensitizing agents.

Animals↗
PubMed1988

Zellweger syndrome amniocytes: morphological appearance and a simple sedimentation method for prenatal diagnosis.

Zellweger syndrome is the prototype of a growing group of genetic diseases caused by an absence or deficiency of peroxisomes. The defect causes the enzyme catalase to remain in the cytosol instead of being packaged into peroxisomes. This mislocalization can be easily detected by sedimentation analysis. Amniocytes were homogenized and then centrifuged to pellet organelles. Catalase was found to sediment with the peroxisomes in the homogenates of normal cells, but to remain in the supernatant with Zellweger syndrome amniocyte homogenates. This striking difference is unambiguous and reproducible, and provides a simple method for prenatal diagnosis. Moreover, it allows one to differentiate diseases in which peroxisomes are deficient from other peroxisomal diseases in which the organelle is intact, but one enzyme is defective. Electron microscopic observations support the biochemical determinations. Normal amniocytes contain small peroxisomes in which a weak cytochemical reaction for catalase may be demonstrated. Zellweger amniocytes appear to lack these organelles, although some cells have rare structures that might be residual or abnormal peroxisomes.

3,3'-Diaminobenzidine↗
PubMed1987

Differential response to environmental alcohol among second-chromosome arrangements in experimental populations of Drosophila buzzatii.

Drosophila buzzatii feeds and breeds on the decaying cladodes and fruits of several species of Opuntia (prickly pear) which contain significant levels of ethanol and isopropanol. The potential influence of these two alcohols on the inversion polymorphism of the second and fourth chromosomes was investigated in ten experimental populations with different amounts of alcohol (either ethanol or isopropanol) added to the culture medium. All populations were started with the offspring of 29 wild females collected at Adeje (Tenerife, Canary Islands) and their genetic composition was monitored for about two years (more than 30 generations). Consistent changes in the frequency of most second- and fourth-chromosome arrangements occurred in all populations including those without alcohol (control). The comparison of inversion frequency through the various treatments revealed a significant influence of the alcohol on the frequency changes of the four second-chromosome arrangements. Moreover, this influence was of a different type for every one of them, sometimes with opposite effects between alcohols and/or concentrations. These results indicate genetic differentiation among second-chromosome arrangements with regard to alcohol and suggest that the alcohol heterogeneity found in the species' trophic niche may play an important role in the maintenance of this polymorphism and also in the recent historical changes in the frequency of some arrangements associated with colonization.

1-Propanol↗
PubMed1987

Study of appendicitis in children treated with four different antibiotic regimens.

This is a prospective and randomized study of 100 patients with acute appendicitis who were less than 10 years old, in which four different antibiotic regimens commonly in use against gram-negative and anaerobic bacteria were compared in terms of postoperative septic complications. The antibiotics were begun immediately preoperatively and continued for five days. Ten percent of the patients developed infection complications, with 4% requiring further surgery. The best results were obtained with cefoxitin (4% of infection), metronidazole plus amikacin and latamoxef (8%), while the regimen of clindamycin plus amikacin was associated with the greatest number of complications (20%). On analyzing the main microbiologic findings of the study, we conclude that some sort of antibiotic treatment is indicated in all types of appendicitis, due to the occult presence of bacteria in the peritoneal cavity, even without clinical evidence of gangrene or perforation. Further, we emphasize the significance of Streptococcus faecalis as being responsible, along with Escherichia coli and Bacteroides fragilis, for serious postoperative complications.

Anti-Bacterial Agents↗
PubMed1986

Atrioventricular block in acute inferior wall myocardial infarction: harbinger of associated obstruction of the left anterior descending coronary artery.

In a prospective study 51 consecutive patients who survived the acute phase of inferior wall myocardial infarction underwent coronary arteriography. Eleven patients developed some degree of atrioventricular (AV) block in the acute phase of infarction that disappeared within a few days and was considered by electrocardiographic analysis to be located in the AV node. Patients with AV block during acute myocardial infarction had a significantly higher prevalence of left anterior descending coronary artery obstruction (91 versus 55%, p less than 0.05) than did patients without AV block and the obstruction preceded the exit of the first septal perforator branch in 73% of cases with heart block and in 30% of cases without block (p less than 0.01). The sensitivity, specificity and predictive values were 31, 95 and 91%, respectively, for the existence of left anterior descending coronary artery obstruction when AV block occurred during acute inferior myocardial infarction, and 40, 90 and 73%, respectively, for the occurrence of the coronary artery obstruction before the exit of the first septal perforator branch. Patients with inferior myocardial infarction and left anterior descending coronary artery obstruction have a sixfold greater chance of developing heart block in the acute phase of infarction than do patients with inferior infarction without such obstruction (p less than 0.05). These findings also support the observations that the proximal AV conduction system usually has a dual arterial blood supply from both the right and left anterior descending coronary arteries, and may explain the transient behavior of heart block and lack of necrosis of the AV node seen in these patients.

Angiography↗