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Biomedical subjects

I Garcia

Publications and source records attributed to I Garcia.

At least 145 records · Page 8Linked to original sources

Phorbol ester-induced protein kinase C translocation and lysosomal enzyme release in normal and cystic fibrosis fibroblasts.

The ability of the tumor-promoting phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) to induce protein kinase C (PKC) translocation and lysosomal enzyme release was examined in skin fibroblasts from normal subjects and from patients with cystic fibrosis (CF). As compared to normal fibroblasts, those CF exhibited: (i) an increased sensitivity to the effect of PMA on the disappearance of PKC from cytosolic fractions as well as a greater and earlier recovery, in the membrane fraction, of the PKC activity lost in the cytosolic fraction; (ii) an earlier response to PMA for its effect on beta-N-acetylglucosaminidase release. In contrast, the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) proved ineffective in inducing PKC translocation and beta-N-acetylglucosaminidase release in both normal and CF fibroblasts. The data suggest a defect in the regulation of PKC activity in CF fibroblasts, which may lead to altered secretion.

Acetylglucosaminidase↗

Treatment and outcome of undifferentiated carcinoma of the nasopharynx in childhood: a 13-year experience.

Between 1970 and 1983, 22 pediatric patients diagnosed as having undifferentiated nasopharyngeal carcinoma (UNC) were treated at the National Children's Hospital of Costa Rica; primary tumor with local extension (T3-T4) was present in 45% of the patients, and metastasis of the cervical nodes (N1-N3) in 82%. Patients were divided into groups A and B according to the type of treatment received. A description of both groups is as follows. Ten patients were treated with 5,000 to 6,000 rads tumor dose to the primary and a 5,125-rad dose was administered to the lower neck between 1970 and 1977 (group A). Six patients received postradiation therapy with cyclophosphamide and vincristine and two patients also received 5-fluorouracil. The outcome in group A was as follows: four (40%) failed to respond, six (60%) achieved full remission initially with two subsequent relapses, and the remaining four are still alive and free of relapse after 90 to 160 months (average 130) (two were treated with Co60 alone and two with chemotherapy. Twelve patients were treated with chemotherapy pre- and postradiation with CPM and adriamycin for a total of 12 months (group B) between 1978 and 1984. All (100%) achieved complete initial remission; two patients relapsed and died. Ten patients have remained in relapse-free survival for 18-67 months (median 32). Though this is not a controlled study, our experience indicates that pre- and postradiation chemotherapy is effective in prolonging the disease-free survival in UNC and may allow a decrease of the radiation tumor dose.

Adolescent↗

Intracellular ATP in a glucosephosphate isomerase mutant of Saccharomyces cerevisiae.

The degree of ATP depletion caused by glucose in a glucosephosphate isomerase-deficient strain of Saccharomyces cerevisiae was determined. Even in the presence of a sugar normally fermentable by the mutant, the addition of glucose can decrease the intracellular ATP, depending on the competition of the sugars for transport and subsequent phosphorylation. For both parent and mutant cells, a correlation exists between the calculated velocity of ATP formation or ATP consumption during the utilization of different concentrations of sugars and the experimental intracellular ATP level. For initially resting yeast cells, a rate increase of 35 mumol per min per g ATP was calculated to increase the intracellular level of this nucleotide by 1 mumol per g cell mass.

Adenosine Triphosphate↗

On fast algorithms for interval selection in event related potentials.

In this paper a computational algorithm is proposed which allows one to detect event related potentials (ERP) components and the way these components modify their amplitude with electrode location and with the variation in experimental conditions. The results of applying this algorithm to the ERPs obtained in two experimental situations (which require different modes of cognitive processing of a same visual information) are also exposed.

Algorithms↗

Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine.

After administration of furafylline, a, 1,3,8-trisubstituted xanthine, to beagle dogs at 0.5 and 10 mg kg-1 an elimination half-life 2-10 times longer than that of theophylline was observed. The kinetics were dose-dependent but no phase I metabolites were detected. When the compound was given orally to humans at a dose of 1.3-1.9 mg kg-1 a mean beta elimination half-life of 48.1 +/- 10.8 h was obtained after an initial distribution phase. Evidence of non-linear kinetics for plasma levels below 0.6 microgram ml-1 was also obtained. Other 1,3,8-trisubstituted xanthines, may also have a lower elimination rate than theophylline.

Adult↗

Establishment of two rabbit mammary epithelial cell lines with distinct oncogenic potential and differentiated phenotype after microinjection of transforming genes.

The goal of this work was to establish an assay for transformation of epithelial cells. Two epithelial cell lines were obtained after microinjecting transforming genes into primary rabbit mammary secretory cells. The cell lines were analyzed for their oncogenic potential and for the maintenance of a differentiated phenotype. A fully transformed cell line, which retained epithelial cell organization, was obtained by coinjecting simian virus 40 DNA and the activated human c-Ha-ras gene. The proliferation rate of these cells was high, with a doubling time of 16 h. Their growth was anchorage independent, and they had lost contact inhibition. The cells were tumorigenic in nude mice, but had no metastatic potential. Both microinjected DNAs were efficiently transcribed and translated, in contrast to the casein genes, which were expressed in primary cells but not in the transformed cell line. An immortalized cell line established after injection with simian virus 40 DNA alone was characterized by a moderate rate of proliferation with a doubling time of approximately 30 h. The growth of these cells was contact inhibited and anchorage dependent. The cells were not tumorigenic in nude mice. The viral DNA was expressed during early passages, as shown by the presence of the large T antigen in cell nuclei, but not at later passages. A high number of lactogenic hormone receptors were found associated with the cell surface. Despite the presence of these receptors, no induction of genes coding for milk proteins was observed after addition of prolactin. These data demonstrate that this assay system can be used to assess the immortalizing and transforming potential of candidate oncogenes in epithelial cells.

Animals↗

Production of the angiotensin converting enzyme (ACE) in cultures of rat peritoneal macrophages.

Some authors attributed an increase in ACE activity in sarcoidosis to high production of this enzyme by alveolar macrophages. In order to study the production of ACE by peritoneal rat macrophages, we measured the ACE activity, by a modified version of Friedland and Silverstein's technique, in cultures of rat peritoneal macrophages, with dexamethasone, with Complete Freund Adjuvent (C.F.A.) or sarcoidosis node extract (Kveim Antigen). ACE activity was not detected in cultures. Our results were discussed.

Animals↗

Biochemical studies in Niemann-Pick disease. III. In vitro and in vivo assays of sphingomyelin degradation in cultured skin fibroblasts and amniotic fluid cells for the diagnosis of the various forms of the disease.

Sphingomyelinase activities were assayed in vitro in cultured skin fibroblasts of 61 patients with Niemann-Pick disease (NPD). Residual activities found in type A and B were 1% and 4%, respectively, of the mean control values, i.e. significantly higher in type B. In 27 cases with NPD type C, the mean activity was 42% of that in controls, with residual activities ranging from 15% up to normal. Fifteen pregnancies at risk for NPD type A and B were monitored; 4 affected foetuses were found. The uptake of exogenously added radiolabelled sphingomyelin by cultured cells and metabolism of the choline moiety of this lipid were studied in 35 patients with NPD and 14 controls. No difference of uptake between normal and mutant cells was observed. Normally, 77 +/- 5% of the radioactivity taken up was converted to phosphatidylcholine after 18 h incubation, compared to 5 +/- 2% (n = 7) in NPD type A. A substantially greater hydrolysis (31 +/- 12%; n = 8) occurred in NPD type B, and the test allowed complete discrimination between these two types. In NPD type C, 16 patients showed an abnormally low rate of intracellular sphingomyelin degradation (48 +/- 5%) while 4 others were not distinguishable from controls. There was a correlation (r = 0.76) between the results of the in vitro and in vivo assays, but also between the severity of the clinical symptoms and the impairment in sphingomyelin degradation. For the diagnosis of NPD type C, the in vivo test gave more reproducible and more clearcut results than the in vitro assay.

Amniotic Fluid↗

The importance of corticoids added to continued treatment with Factor VIII concentrates in the suppression of inhibitors in haemophilia A.

A protocol is presented to suppress inhibitors in haemophilia A using continued treatment with f. VIII (50 U/kg b.w./day) and fluprednisolone (0.5 mg/kg b.w., for 21 days) until reaching correct in vivo recovery after therapeutic administration. 5 high responder patients were treated whose inhibitors were detected at least 2 years before beginning the treatment. The inhibitors were eradicated in 4 patients using continued treatment for between 4 and 24 months. Patient 1 was treated exclusively with factor and the others also with corticoids when the level was 0 B.U. (or 20 B.U., patient 4). The patients began tri-weekly prophylactic treatment and rehabilitation exercises after recovery test normalization. After progressive reduction of the prophylactic treatment they started on demand treatment. After more than 5 months of this treatment no anamnestic response has been detected in any patient, in spite of several factor VIII administrations.

Adolescent↗

Nucleotide sequence of a cDNA encoding the constant region of a rabbit immunoglobulin light chain of the lambda type.

A cDNA library has been constructed in the plasmid pBR322 using as template 12 S poly(A)-RNA isolated from spleen cells of a hyperimmunized Basilea rabbit. One of these cDNA-containing clones was used to determine the nucleotide sequence coding for the lambda light chain constant (C) region. The deduced amino acid sequence of this cDNA was found in good agreement with a Basilea rabbit C lambda region amino acid sequence previously determined. The nucleotide sequence of the rabbit C lambda-coding region was compared with man, mouse and chicken C lambda sequences and showed 78%, 72% and 66% homology, respectively. Southern blot hybridization analyses of liver DNA from various rabbits were carried out. The comparison of the restriction patterns suggests that a few C lambda-related genes occur in the rabbit genome. In addition, discrete differences in the restriction patterns may exist between rabbits of different genetic backgrounds.

Animals↗

Bacillus cereus meningitis and bacteremia associated with an Ommaya reservoir in a patient with lymphoma.

After placement of an Ommaya reservoir, meningitis and bacteremia due to Bacillus cereus occurred in a patient with stage IV lymphoblastic lymphoma and meningeal involvement. Bacillus species have been implicated as meningeal pathogens after lumbar punctures. These organisms have become an important cause of severe infection, especially in immunologically compromised patients.

Adult↗

In vitro activity of WIN 49375 compared with those of other antibiotics in isolates from cancer patients.

The activity of WIN 49375 [6-fluoro-1, 4-dihydro-1-(methylamino)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid], a new synthetic quinolone, was tested in vitro against 587 clinical isolates. The MICs for 90% of isolates of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were 0.20, 1.56, and 0.39 microgram/ml, respectively. The MICs for 90% of isolates of Pseudomonas aeruginosa and Serratia marcescens were both 3.12 micrograms/ml. WIN 49375 was minimally active against gram-positive cocci. Its in vitro activity suggests that it may be useful for the treatment of gram-negative bacillary infections.

Anti-Bacterial Agents↗

Nonbacterial thrombotic endocarditis in a male homosexual with Kaposi's sarcoma.

Nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, was found at autopsy in a young male homosexual with Kaposi's sarcoma. Vegetations were seen in the mitral and aortic valves. Embolic phenomena and cytomegalovirus infection were noted in the brain, spleen, liver, lung, gastrointestinal tract, and bone marrow. To our knowledge, this is the first reported case of NBTE in a young immunosuppressed homosexual man with Kaposi's sarcoma.

Adult↗

Effect of broad-spectrum cephalosporins on the microbial flora of recipients.

The flora in the throat and the stools of 10 patients receiving chemotherapy for malignant diseases in a laminar air-flow room was studied during the prophylactic administration of ceftazidime. Ten percent of aerobic gram-negative bacilli, 41% of aerobic gram-positive organisms, 59% of anaerobes, and 70% of fungi persisted in stool specimens during ceftazidime administration. This drug had a less pronounced effect on the throat flora; 66% of organisms persisted during antibiotic administration. The throat and fecal flora of another eight patients were studied during the prophylactic administration of ceftriaxone. This antibiotic had a profound effect on the fecal flora; none of the gram-negative bacilli, only 24% of aerobic gram-positive organisms, and only 10% of anaerobes persisted during ceftriaxone administration. Like ceftazidime, ceftriaxone had a less marked effect on the throat flora; 59% of organisms persisted during antibiotic administration. The results show that new, expanded-spectrum cephalosporins can have a major suppressive effect on patients' endogenous microbial flora.

Adult↗

Multiple-dose pharmacokinetics of ceftazidime in cancer patients.

The pharmacokinetic parameters of ceftazidime were determined in 25 patients with neoplastic diseases. A group of 13 patients each received 1 g of ceftazidime over 15 min as a single intravenous dose. The mean peak drug concentration in serum was 77.4 micrograms/ml, and the serum half-life was 144 min. Urinary excretion at 12 h was 64.5%. These 13 patients also received 2 g of ceftazidime over 15 min at 8-h intervals for 7 or 8 days. The mean peak drug concentrations in serum were 103.6 micrograms/ml on day 1 and 87 micrograms/ml on day 7 or 8. A second group of 12 patients received 1 g of ceftazidime over 30 min, followed by 1 g over 2 h and every 4 h thereafter. The mean peak drug concentration in serum at 30 min was 57.5 micrograms/ml. Average peak and trough levels obtained on day 2 or 3 were 65 and 34.8 micrograms/ml, respectively, and remained in this range thereafter. The above-mentioned dose schedules produced high and adequate ceftazidime concentrations in serum.

Adolescent↗

In vitro activities of new beta-lactam antibiotics against Acinetobacter spp.

The in vitro activities of new beta-lactam antibiotics was studied and compared with those of other known agents against 51 clinical isolates of Acinetobacter calcoaceticus subsp. anitratus and 23 isolates of A. calcoaceticus subsp. lwoffi. Of the new beta-lactam antibiotics, imipemide (N-formimidoyl thienamycin), ceftazidime, ceftizoxime, ceftriaxone, and piperacillin demonstrated good activities. The minimal inhibitory concentrations for A. calcoaceticus subsp. lwoffi were lower than those obtained for A. calcoaceticus subsp. anitratus.

Acinetobacter↗

Regulation of ketonaemia in hyperthyroidism: study of the role of free fatty acids.

We have indirectly assessed the role of free fatty acids (FFA) and of hepatic ketogenesis in the regulation of ketone body levels in euthyroid and hyperthyroid subjects. All studies were performed under controlled dietary conditions (35 and 45 kcal/kg body weight/day respectively for euthyroid and hyperthyroid subjects). In the post-absorptive state hyperthyroid patients had normal, glucagon levels and, in spite of increased insulinemia (p less than 0.02), elevated concentrations of blood glucose (p less than 0.01), glycerol (p less than 0.001) and ketone bodies (p less than 0.05). In the face of this hyperketonaemia, there was no significant increase of plasma FFA, suggesting possible increased hepatic conversion of FFA to ketone bodies. However, when FFA were acutely raised to high levels, the induced rise of ketone bodies was similar in hyperthyroid and euthyroid subjects. Oral propranolol administration to hyperthyroid patients in the post-absorptive state decreased the concentrations of glycerol (p less than 0.05) and ketone bodies (p less than 0.05) without altering insulin concentrations. Ketone bodies fell without any significant decrease of FFA suggesting a possible direct effect of propranolol administration on hepatic ketogenesis. However, the ketone body response to raised FFA levels was unaffected by propranolol. We have evidence in hyperthyroid patients of increased lipolysis and ketogenesis in spite of increased daily caloric intake. These results suggest that these metabolic abnormalities are not merely due to relative starvation. We have tentative evidence for modification of the intra-hepatic conversion of FFA to ketone bodies in the post-absorptive state but no supporting evidence when FFA levels were experimentally raised.

Adult↗