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F Bosch

Publications and source records attributed to F Bosch.

At least 109 records · Page 6Linked to original sources
PubMed1994

PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas.

PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.

Adult↗
PubMed1994

Prognostic significance of the loss of heterozygosity of Nm23-H1 and p53 genes in human colorectal carcinomas.

BACKGROUND: Nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. Nm23 is localized on chromosome 17q21.3-22, whereas the p53 suppressor gene is on 17p13. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients. METHODS: Allelic deletions of Nm23 and p53 genes were studied in 56 colorectal carcinomas using different restriction fragment length polymorphisms. DNA ploidy and proliferative activity of the tumors were studied by flow cytometry. Actuarial disease free and overall survival were analyzed by the Kaplan--Meier method, and the curves were compared with the log rank test. RESULTS: Thirty-eight patients were heterozygous for Nm23 gene (68%), and 9 of them (24%) exhibited a loss of heterozygosity in the tumor sample. One of the homozygous patients showed a loss of both Nm23 alleles. Allelic deletions of 17p13 were found in 63% of the 41 informative patients. All patients' tumors that had loss of heterozygosity of the Nm23-H1 locus also had allelic losses on the short arm of chromosome 17 (17p13) and in other loci on 17q. No relationship was found between localization, invasion, lymph node metastasis, or proliferative index of the tumors and the allelic deletions of the Nm23-H1 or 17p13 locus. Nm23-H1 deletions were relatively more frequent in poorly differentiated adenocarcinomas (P = 0.03). A significant association between 17p13 deletions and DNA aneuploidy was found (P = 0.016). A similar tendency was observed with Nm23-H1 deletions (P = 0.051). Loss of Nm23-H1, but not of 17p13, was significantly associated with a shorter disease free (P = 0.025) and overall (P = 0.04) patient survival. CONCLUSIONS: Allelic deletions of Nm23-H1 are significantly associated with a more aggressive behavior of colorectal carcinomas. The loss of this gene seems to be part of extensive deletions of chromosome 17, and it is also associated with DNA aneuploidy. More studies are needed to determine whether Nm23-H1 or a gene linked to this locus is the specific target of the progression of these tumors.

Adenocarcinoma↗
PubMed1994

Glucokinase expression in rat hepatoma cells induces glucose uptake and is rate limiting in glucose utilization.

In contrast to hepatocytes, hepatoma cells lack glucokinase activity and show increased aerobic glycolysis. FTO-2B and H4IIE rat hepatoma cell lines were obtained in which the rat glucokinase gene was expressed (FTOGK and H4GK). These lines were generated by infection of the hepatoma cells with a retroviral vector carrying the phosphoenolpyruvate carboxykinase (PEPCK)-glucokinase chimeric gene. Both the FTOGK and H4GK cells expressed the chimeric gene in a regulated manner, like the endogenous PEPCK gene. Glucokinase activity was detected in both FTOGK and H4GK. These cells lines showed a marked increase in glucose uptake with 18.5 mM glucose in the incubation medium. FTOGK and H4GK showed an increase in the content of glucose 6-phosphate, and were able to accumulate high levels of glycogen, in contrast to FTO-2B cells, which were unable to store the polysaccharide. In addition, cells expressing glucokinase showed high concentration of fructose 2,6-bisphosphate and substantial lactate production, which was related to the glucose concentration in the medium and the time of incubation. These results suggest that glucose phosphorylation is rate limiting for glucose uptake and utilization in FTO-2B and H4IIE cells.

Animals↗
PubMed1994

[Diagnosis of paroxysmal nocturnal hemoglobinuria with cytofluorometric of molecules bound to the membrane by glycosylphosphatidylinositol groups].

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (NPH) is a clonal disease in which a deficit in the expression of molecules bound to the cell membrane by glycosyl-phosphatidylinositol (MUGFI) groups has been demonstrated. The MUGFI are widely distributed and among them proteins regulating the action of complement may be found. The development of monoclonal antibodies (MoAb) against MUGFI may allow the introduction of a new diagnostic method in this disease and increase the sensitivity, particularly in transfused individuals. METHODS: The erythrocytic and leukocytic phenotype of 14 patients with NPH clonality demonstrated by the classic tests of sensitivity to the complement was analyzed by immunofluorescence techniques and flow cytometry with the use of MoAb which recognize MUGFI (CD55, CD59, CD14, CD16 and CD24). RESULTS: Cells with a decrease or absence of MUGFI were observed in all the patients. The defect was demonstrated in the red cells, monocytes and neutrophils of all the patients, while it was only observed in the lymphocytes of three patients. The percentage of cells with a decrease in MUGFI was variable (2-100%) as well the pattern of deficiency against the different MoAb used. The MoAb with greatest sensitivity for the detection of clonal population were the CD59 in erythrocytes, the CD14 in monocytes and the CD24 in neutrophils. The CD16 was normal in one patient and the CD55 in two. The transfusion of packed red cells did not influence the abnormal leukocyte pattern, with abnormalities even being observed in the erythrocytary CD59. The Ham test was negative in those cases in which the percentage of negative CD59 erythrocytes was lower than 5% of the total erythrocytic population. CONCLUSIONS: The study of glucosylphosphatidylinositol by flow cytometry and monoclonal antibodies is a useful technique for the detection and quantification of the nocturnal paroxistic hemoglobinuria clone even in transfused patients.

Adult↗
PubMed1994

[International diffusion of clinical trials carried out in Spain. An analysis based on their publication in scientific journals].

BACKGROUND: Few studies have evaluated the clinical trials carried out in Spain and published in international journals. The present study has analyzed this situation over the period from 1981 to 1990. METHODS: Spanish studies including "clinical trial" as a key word present in Excerpta Medica CD (Drugs and Pharmacology) or MEDLINE in the CD-ROM version were evaluated. RESULTS: Two hundred forty-one original articles were obtained. The number of clinical trials was relatively stable from 1981 to 1986 (n = 8.15) increasing to a maximum from 1986 to 1988 (n = 64) with a posterior decrease. The languages of publication were English (51%) and Spanish (49%). A significant increase was observed in the number of articles published in English (p < 0.01) in the last five years. Phase III and IV clinical trials were the most frequent (89%) followed by those of phase II (9%) and phase I (2%). The open design predominated in the phase III-IV trials (58%) over the double blind trials (37%) and the single blind trials (5%). Among the former 70% were comparative and 57% followed randomized treatments. The clinical trials were published in 112 journals, Medicina Clínica (n = 32) and Current Therapeutic Research Clinical and Experimental (n = 6) were the most frequently used in Spanish and English, respectively. Two hundred sixty-three drugs were studied in the clinical trials, cisplatin was the most frequently studied (n = 10). The most commonly studied pharmacologic groups were antiinfectious (n = 40) and cytostatic (n = 35). The number of randomized clinical trials increased significantly after 1986 (p < 0.01). CONCLUSIONS: An increase in the number of clinical trials published in international journals was observed with preference for publication in English. The growing presence of randomized double blind clinical trials suggests an improvement in the quality of the clinical trials performed in Spain, particularly after 1986.

Clinical Trials as Topic↗
PubMed1994

Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations.

Transgenic mice expressing the P-enolpyruvate carboxykinase (PEPCK)/human insulin chimeric gene have been obtained as a model to study the feasibility of gene therapy for diabetes. These transgenic animals were healthy and normoglycemic and expressed human insulin in a physiologically regulated manner, mainly in the liver. Streptozotocin-treated transgenic mice had high levels of human insulin immunoreactivity in serum and showed a significant decrease (up to 40%) in glycemia compared with streptozotocin-treated control mice. The expression of genes involved in liver glucose metabolism, such as glucokinase, pyruvate kinase, and PEPCK, which is markedly altered by diabetes, was significantly recovered in transgenic mice treated with streptozotocin. In addition, the activity of both glucokinase and glycogen synthase, and the content of glucose 6-phosphate and glycogen, were normal in the liver, even when transgenic animals were treated with diabetogenic doses of streptozotocin. These results constitute an indication in vivo that diabetes gene therapy is possible, by means of the production of insulin in extrapancreatic tissues.

Animals↗
PubMed1994

Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) is a key enzyme in the ketone body pathway. To determine its role in the regulation of liver ketogenesis, transgenic mice expressing a P-enolpyruvate carboxykinase/HMG-CoA synthase chimeric gene have been obtained. An increase in the concentration of mitochondrial HMG-CoA synthase mRNA was detected in these mice, which was associated with a 3-fold increase in HMG-CoA synthase activity in liver mitochondrial extracts. Transgenic mice were normoglycemic and had normal levels of plasma triglycerides and lower free fatty acids. However, the plasma concentration of ketone bodies was about three times higher in transgenic mice than in control animals. Hepatocytes in primary culture from transgenic mice expressed the chimeric gene in a regulated manner and showed a 3-fold increase in beta-hydroxybutyrate and acetoacetate concentrations in the medium. This animal model thus shows that the overexpression of mitochondrial HMG-CoA synthase causes ketone body overproduction, suggesting that this enzyme may be a regulatory step in liver ketogenesis.

3-Hydroxybutyric Acid↗
PubMed1994

Expression of the neomycin-resistance (neo) gene induces alterations in gene expression and metabolism.

The amino 3'-glycosyl phosphotransferase (neo) gene is the selectable marker most widely used in stable transfection or infection protocols. Because the neo gene product has phosphotransferase activity, it might modify the phosphorylation state when introduced in mammalian cells. NIH-3T3 fibroblast cells expressing the neo gene, after either infection with retroviral vectors or transfection with plasmids, showed a 50% reduction in both fructose 2,6-bisphosphate (Fru 2,6-P2) concentration and lactate production compared with control NIH-3T3 cells, indicating that these neo-expressing cells are less glycolytic. In addition, a marked decrease in the levels of mRNA for the procollagen 1 alpha and fibronectin genes was also observed in neo-expressing NIH-3T3 cells. This decrease was concomitant with an increase in the mRNA concentration of the endogenous c-myc gene. FTO-2B rat hepatoma cells also showed modifications in gene expression when the neo gene was introduced by stable transfection or infection. In these cells an increase in both P-enolpyruvate carboxykinase (PEPCK) and tyrosine aminotransferase (TAT) mRNA was observed. These results suggest that neo gene expression may induce changes in the cells, which should be considered when neo-selected cells are used to deliver specific genes in different therapy approaches and in embryo manipulation.

3T3 Cells↗
PubMed1994

Impact of response to treatment on survival in multiple myeloma: results in a series of 243 patients.

Two hundred and forty-three patients diagnosed with multiple myeloma (MM) in a single institution over a 22-year period and treated with standard chemotherapy were analysed in an attempt to determine the impact of response to therapy on survival. The overall response rate in 229 evaluable patients was 50.1% (34.9% objective response plus 15.2% partial response). Median survivals of patients with objective and partial response were 43.4 and 42.8 months, respectively, versus 19 months for nonresponders. Median survival of 14 patients who achieved a complete remission was 42 months, whereas in 21 rapid responders (< or = 2 months) median survival was 43.3 months. A significant correlation between response and survival was observed with the landmark (P = 0.0169), the Mantel & Byar (P = 0.0001) and the Cox regression model (P < 0.0001) methods. These results indicate that, in responding patients, neither the degree of response nor the response kinetics has a significant influence on survival. However, the response to therapy is associated with a significantly longer survival in MM patients.

Adult↗
PubMed1994

Cloning of a gene involved in rRNA precursor processing and 23S rRNA cleavage in Rhodobacter capsulatus.

In Rhodobacter capsulatus wild-type strains, the 23S rRNA is cleaved into [16S] and [14S] rRNA molecules. Our data show that a region predicted to form a hairpin-loop structure is removed from the 23S rRNA during this processing step. We have analyzed the processing of rRNA in the wild type and in the mutant strain Fm65, which does not cleave the 23S rRNA. In addition to the lack of 23S rRNA processing, strain Fm65 shows impeded processing of a larger 5.6-kb rRNA precursor and slow maturation of 23S and 16S rRNAs from pre-23S and pre-16S rRNA species. Similar effects have also been described previously for Escherichia coli RNase III mutants. Processing of the 5.6-kb precursor was independent of protein synthesis, while the cleavage of 23S rRNA to generate 16S and 14S rRNA required protein synthesis. We identified a DNA fragment of the wild-type R. capsulatus chromosome that conferred normal processing of 5.6-kb rRNA and 23S rRNA when it was expressed in strain Fm65.

Bacteriochlorophylls↗
PubMed1994

Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.

PURPOSE: Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS: One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS: After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P < .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P < .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P < .0001) and International Index (P < .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION: In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.

Actuarial Analysis↗
PubMed1994

Low-grade lymphoma: clinical and prognostic studies in a series of 143 patients from a single institution.

Clinical and prognostic studies were carried out in a series of 143 patients with low-grade (small-lymphocytic, follicular small cleaved cell, follicular mixed small- and large-cell) lymphoma. After treatment with alkylating agents (21.5% cases), combination chemotherapy (73.3%) or other therapies (5.2%), complete response (CR) was obtained in 40.7% of cases and partial response (PR) in 43.7%. The stage of the disease was the most important factor for response. With a median follow-up of 6.5 years, 48.0% (95% Cl: 37.5-58.5) of patients were alive 10 years after diagnosis. Among the initial parameters, advanced stage. B-symptoms, poor performance status, nodal involvement > 3 sites, extranodal involvement > or = 2 sites, WBC count > or = 10 x 10(9)/L, leukemic expression, high serum LDH levels, and bone marrow infiltration were all related to survival; treatment modality, however, had no influence on survival. In the multivariate analysis, stage (p = 0.008) and age (p = 0.053) were the most important prognostic factors. When considering response to therapy, both CR (p < 0.001) and PR (p = 0.003) emerged as the most important predictive variables, with only the absence of B-symptoms retaining its prognostic significance (p = 0.014) among the other parameters. In addition, in CR patients the duration of the response (< or = 1 year vs. > 1 year) was the most significant parameter for survival (p < 0.001). Finally, the initial stage (p = 0.011) and the histologic subtype (those patients with follicular mixed lymphoma relapsing less frequently than the others) (p = 0.052) were the only significant factors for relapse.

Adult↗
PubMed1993

Calcium-mobilizing effectors inhibit P-enolpyruvate carboxykinase gene expression in cultured rat hepatocytes.

Incubation of primary cultures of hepatocytes from fed and fasted rats with calcium ionophore strongly decreased glucose production from pyruvate. Like insulin, calcium ionophore A23187, phenylephrine, vasopressin, and prostaglandins E2 and F2 alpha caused a significant reduction (50-60%) in basal concentrations of mRNA for P-enolpyruvate carboxykinase (PEPCK), the main regulatory enzyme of gluconeogenesis. Phenylephrine, prostaglandin E2 and calcium ionophore A23187 were also able to counteract the induction of PEPCK gene expression by Bt2cAMP. These effects were similar to those exerted by both vanadate and phorbol ester TPA. The decrease in extracellular calcium by the addition of the calcium-chelating agent EGTA to the incubation medium caused an increase in PEPCK mRNA levels. This effect was additive to that of Bt2cAMP and was counteracted by vanadate.

Animals↗