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Biomedical subjects

G Santos

Publications and source records attributed to G Santos.

36 records · Page 2Linked to original sources
PubMed1989

Effects of c-myc overexpression on the growth characteristics of MCF-7 human breast cancer cells.

Amplification and overexpression of the c-myc protooncogene have been observed in 22 to 32% of primary human breast cancers, yet the exact role of this gene in mammary tumor progression is unclear. We sought to elucidate this role by overexpressing cloned myc genes in the human breast carcinoma cell line MCF-7. We found that augmented myc RNA levels were associated with slower in vitro growth rates, but that estrogen receptor levels, the requirement for estrogen for in vivo growth in castrated athymic nude mice, and sensitivity to the antiestrogen, tamoxifen were not altered. Furthermore, chemosensitivity to the cytotoxic agent, Adriamycin, was not affected. Lastly, overexpression of a transfected myc gene did not suppress endogenous myc levels unlike the findings in lymphoma cells. Thus our data suggest that the effect of augmented myc expression in human breast cancer cells is complex and may not induce more malignant patterns of growth as has been suggested for other human cancers.

Animals↗
PubMed1988

Hypertension and renal dysfunction in bone marrow transplant recipients.

The incidence of acute renal failure, hypertension and electrolyte disorders in 64 bone marrow transplant recipients randomized to receive either cyclosporin or cyclophosphamide was investigated. Sixty-four per cent of patients developed acute renal failure, 75 per cent hypertension, and 88 per cent significant hypomagnesemia. The incidence of diastolic hypertension and hypomagnesemia was greater in the patents treated with cyclosporin. Hypomagnesemia was due to magnesium wasting by the kidney. Both groups received similar cumulative doses of aminoglycoside antibiotics. Significant proteinuria developed in all but one patient and nephrotic-range proteinuria was noted in 21 per cent. The cause of the proteinuria is unclear; no obvious morphologic changes were seen at autopsy in patients who exhibited nephrotic-range proteinuria. The abnormalities of renal function were shown to be transient in patients who were observed for periods ranging from one to three years. It is concluded that hypertension, renal failure and hypomagnesemia are common in the setting of bone marrow transplantation. Whereas cyclosporin probably aggravates the severity of these disorders, it is likely that other factors (e.g., aminoglycoside antibiotics) play a major role as shown by the high incidence of renal and electrolyte disorders in patients treated with cyclophosphamide alone.

Acute Kidney Injury↗
PubMed1986

Hemorrhagic cystitis associated with adenovirus infection in bone marrow transplantation.

A retrospective study of bone marrow transplant recipients shedding adenovirus type 11 in the urine was carried out to determine the association between viral shedding and hemorrhagic cystitis in this population. Weekly urine virology surveillance cultures were obtained during the first 100 days following transplantation. Adenovirus type 11 was cultured from five of 502 bone marrow transplant recipients from 1977 through 1984. In four of these five patients there was associated hemorrhagic cystitis. This contrasts with an overall incidence of hemorrhagic cystitis of 20% in this bone marrow transplant population. A case of hemorrhagic cystitis occurred in a patient following bone marrow transplantation. Recognition of a viral origin of hemorrhagic cystitis may explain the occurrence of late hemorrhagic cystitis in patients despite interventions designed to prevent cyclophosphamide-induced hemorrhagic cystitis. Hemorrhagic cystitis may be the presenting sign of a lethal adenoviral infection.

Adenoviridae Infections↗
PubMed1984

Mechanisms for the renal secretion of cisplatin.

Cisplatin (cisDDP) inhibits the active uptake of tetraethylammonium and p-aminohippurate by mouse kidney slices. The shapes of the dose-response curves for inhibition of the organic cation and organic anion transport are different, and the inhibition is competitive in each case. Thus, the inhibition by cisDDP may be due to interaction of cisDDP or its aquated products with the specific transport sites rather than to nonspecific metabolic poisoning of the slices by cisDDP. In mice, cimetidine inhibits the renal secretion of tetraethylammonium but fails to inhibit the secretion of p-amminohippurate. The renal clearance of total platinum in mice treated with cisDDP did not exceed that of inulin; however, the clearance of platinum was reduced by cimetidine. These results suggest that the organic cation secretory system plays a role in the renal handling of cisDDP or its products.

Animals↗
PubMed1983

Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.

We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.

Androgens↗
PubMed1983

Tamoxifen and 5-fluorouracil in breast cancer: modulation of cellular RNA.

Biochemical studies were undertaken with the human breast carcinoma cell line, 47-DN, to explore the mechanisms underlying cytotoxic synergy between tamoxifen (TAM) and the fluoropyrimidines, 5-fluorouracil (FUra) and 5-fluorouridine (FUrd). The influence of TAM pretreatment was measured on intracellular FUra accumulation, FUra nucleotide formation, and incorporation of fluoropyrimidines into cellular RNA. Unlike other modulators of FUra metabolism and toxicity. TAM decreased intracellular FUra accumulation and total RNA incorporation by 20 to 60%. Cells treated with TAM contained 10 to 20% less cellular RNA and showed reduced transcription and altered RNA turnover, independent of fluoropyrimidine treatment. Newly synthesized RNA from control and TAM-treated cells was fractionated by sucrose gradient centrifugation. The specific incorporation of FUrd (2 hr) was compared to that of FUra (6 hr) and labeled uridine incorporation into controls. Compared to its effect on uridine incorporation, TAM produced nearly twice as much FUra incorporation and 3 times as much FUra incorporation into 32 to 45S RNA. Since accumulation of this high-molecular-weight RNA has been associated with fluoropyrimidine toxicity and impaired ribosomal RNA processing, it is believed that TAM enriched the RNA-mediated toxicity of FUra and FUrd in this breast carcinoma cell line.

Breast Neoplasms↗
PubMed1982

Prevention of cyclophosphamide-induced hemorrhagic cystitis.

The occurrence of hemorrhagic cystitis with the use of high-dose cyclophosphamide is thought to be a toxic effect of cyclophosphamide metabolites directly on the bladder mucosa. To decrease both the concentration of metabolites in contact with the bladder mucosa and the time of such contact, a regimen of diuresis and frequent voiding or catheter drainage was instituted in patients at risk for the development of hemorrhage. Prior to institution of this regimen, 8 of 97 patients experienced massive clot-producing hemorrhage, three-quarters of whom died as a direct result of such hemorrhage. Subsequent to use of this regimen, only 1 of 198 patients experienced this degree of hemorrhage. Although this is only a phase II study, the dramatic decrease in the incidence of hemorrhage strongly suggests the efficacy of this regimen in decreasing the potential morbidity associated with cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide↗
PubMed1981

Successful engraftment of blood derived normal hemopoietic stem cells in chronic myelogenous leukemia.

The ability of blood-derived stem cells to restore hemopoietic function was investigated in a patient with chronic myelogenous leukemia with bone marrow cells containing the Philadelphia chromosome marker (Ph1+). After treatment with high dose cyclophosphamide, 26.3 X 10(9) blood mononuclear leukocytes, among them 26.2 X 10(5) granulocyte/macrophage progenitor cells (CFUC), were harvested by means of 5 successive leukaphereses when the bone marrow cells had converted to Ph1--. When the patient entered the aggressive phase (blast crisis), myeloablative treatment with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) was given, followed by transfusion of the cryopreserved blood leukocytes. Restoration of marrow and blood cellularity was completed about 20 days after this autologous blood stem cell transplantation (ABSCT). Marrow CTUC recovery was complete 2 weeks after ABSCT, and all karyotypes of the patient's marrow cells were free of the marker chromosome. The patient died of toxicity but with normal bone marrow cellularity. This report confirms the therapeutic usefulness of autologous blood-derived stem cells harvested in remission in restoring hemopoietic function after myeloablative treatment.

Adult↗
PubMed1981

Special capabilities of the sexes: differences in the molecular repertoire of mammal brain, heart and skeletal muscle.

World records for men's and women's (anaerobic) 200 meter dash are 19.67 and 21.9 seconds respectively. Here the transphosphorylation mechanisms are operative and not the glycolytic anaerobic and aerobic ones. The purpose of this paper is to try to find molecular differences during the neuro-muscular sexual differentiation in the Wistar rat. Creatine kinase (CPK: EC 2.7.3.2) as model transphosphorylase and the protein synthesis pattern, determined from the post 125,000 x g cytosol fraction of the brain, heart and masseter muscle, were chosen as molecular monitors. The CPK specific activity profiles showed differences among tissues and sexes. In rats with similar weights between 200 and 320 g, the epigenetic control of protein synthesis in the studied tissues, reflected genome differential activation depending on sex and age. The electrophoretograms differed in regard to the number and position of the protein bands of homologous tissues of different sexes. As an original finding, against the generally accepted criterion (the brain fundamentally synthesizes BB-CPK isoenzyme), MB-CPK and MM-CPK isoenzymes appeared in the brain of both sexes. The molecular sexual differences in the studied tissues determine functional and anatomical differences.

Animals↗
PubMed1976

Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality.

A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17-100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4-20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1-11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.

Androgens↗
PubMedDate not supplied

Rosette inhibition factor (s) in the sera of cardiopathic patients.

Sera from patients with active and inactive rheumatic fever, as well as with other cardiac or lung diseases, were examined for the presence of rosette inhibition factors. In addition, the levels of antistreptolysin-O and of C-reactive protein activity were also determined. Sera from patients and dog alveolar macrophages were used as the in vitro system for the formation of rosettes. Aggregated normal human gammaglobulin was used as control. Inhibitory activity was present in 50, 71, 90 and 93% of the sera tested from patients with active rheumatic fever, inactive rheumatic fever, other cardiopathies, or pulmonary diseases, respectively. Sera from healthy individuals showed only 3% inhibitory activity and this, only at a very low titre. No correlation was found between the titre of inhibitory activity and either the levels of antistreptolysin-O or the presence of C-reactive protein. It was concluded that the rosette inhibition effect seems to be a nonspecific manifestation of cardiac or pulmonary diseases and to be unrelated to either etiology or pathogenesis of the diseases.

Animals↗