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Biomedical subjects

A Garcia

Publications and source records attributed to A Garcia.

At least 145 records · Page 8Linked to original sources
PubMed1997

Effect of oral supplementation of ornithine-alpha-ketoglutarate on the intestinal barrier after orthotopic small bowel transplantation.

The aim of this study was to analyze the possible protective effects of a glutamine and arginine precursor (ornithine-alpha-ketoglutarate [OKG]) on the mucosa of a transplanted intestine when administered with either a defined formula oral diet (DFD) or a standard chow. Isogenic male Lewis rats (250 g) were submitted to a laparotomy (groups 1 and 2) or to an orthotopic small bowel transplantation (SBT; groups 3-6). Groups 1, 3, and 5 received a DFD 14 days after surgery. Groups 2, 4, and 6 received standard chow. In addition, groups 5 and 6 received a daily oral supplementation of 1.4 g/kg of OKG. Weight changes and food intake were recorded daily. At the end of the study, bacterial translocation (BT) was measured in mesenteric lymph nodes, liver, and spleen. The protein/DNA index was also determined in intestinal mucosa. SBT induced BT in all transplanted groups, especially in those fed DFD. Addition of OKG (groups 5 and 6) significantly reduced BT in comparison with groups 3 and 4 and improved the protein/DNA index as well as weight gain. It is concluded that OKG supplementation protects the intestinal barrier after SBT, and that this effect is more marked when it is added to a standard chow.

Animals↗
PubMed1997

Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer.

We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. Three levels of response were considered: good - when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial - when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response - if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.

Aged↗
PubMed1997

Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation.

Tumor necrosis factor (TNF)-alpha controls T-cell activation and is a major inducer of human immunodeficiency virus (HIV)-1 replication in chronically infected cells. Therefore, we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha. Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation. Addition of neutralizing anti-TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection. Anti-TNF-alpha also prevented nuclear factor-kappa B (NF-kappa B) activation, and a good correlation between this inhibition and inhibition of HIV replication was observed. Moreover, supplementing the cultures with high doses of IL-2 reverted anti-TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures. Moreover, anti-TNF-alpha inhibited HIV-1 long terminal repeat (LTR)-driven transcription of a reporter gene in primary T cells in response to activation, either in the presence or the absence of HIV-1 Tat. Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells.

Cells, Cultured↗
PubMed1997

Activity of selected beta-lactams, ciprofloxacin, and amikacin against different Acinetobacter baumannii biotypes from Chilean hospitals.

The activity of some third generation cephalosporins, aztreonam, imipenem, ciprofloxacin, and amikacin against isolates of Acinetobacter baumannii of various biotypes has been studied. The isolates, independently of the biotype, exhibited a broad multiresistance against cephalosporins. Ceftazidime was the most active and cefoperazone the least active compound. Aztreonam also showed low activity and no imipenem-resistant strains were found. Ciprofloxacin and amikacin were somewhat more active than cephalosporins, but resistant isolates were also frequent. Isolates of Biotypes 9 and 8 exhibited broader multiresistance than those of Biotype 6 and "other."

Acinetobacter↗
PubMed1997

Expression of HIV-1 nef decreases basal phosphatidyl-inositol 3-kinase activity.

CEM lymphoid cells expressing high levels of HIV-1 nef protein displayed a significant decrease in basal phosphatidyl-inositol 3-kinase (P13-kinase) activity associated with immunoprecipitates with anti-p85 regulatory subunit. In contrast, chronically infected U937 monocytic cells displayed a significant increase in basal P13-kinase activity in cells infected with HIV-1 nef compared to those infected with isogenic HIV-1 nef+. These findings suggest that HIV-1-nef expression is accompanied by a decrease in basal intracellular phosphatidyl-inositol 3-kinase activity and suggest that P13-kinase could be important for HIV-1 replication. Moreover, wortmannin, a potent in-vitro phosphatidyl-inositol 3-kinase inhibitor, can inhibit HIV-1 replication in U937 chronically infected cells. Together these results suggest a correlation between P13-kinase activity and HIV-1 replication.

Androstadienes↗
PubMed1997

Wortmannin inhibits IGF-dependent differentiation in the mouse myogenic cell line C2.

Evidence has accumulated that suggests that insulin-like growth factors (IGFs) exert a positive influence on myoblast differentiation. We have undertaken to study the signalling events required for differentiation resulting from type-1 IGF receptor stimulation in C2 myoblasts, where autocrine production of IGF-II was abolished by means of antisense RNA. Exposure of the cells to IGFs leads to a rapid and sustained activation of phosphatidyl-inositol 3-kinase followed by the expression of Myod, myogenin and differentiation. The fungal metabolite, wortmannin, inhibits both PI 3-kinase and muscle differentiation with an IC 50 in the nanomolar range. IGFs are also known to cause a rapid activation of MAP kinase. However, the synthetic inhibitor of MEK, PD098059, which prevents MAP kinase activation, does not affect myoblast differentiation. These results provide evidence that PI 3-kinase, but not MAP kinase, is required for insulin-like growth factor receptor-dependent differentiation of muscle cells.

Androstadienes↗
PubMed1997

Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma.

OBJECTIVE: To study the presence of germline mutations in the von Hippel-Lindau gene (vhl) in a kindred with a predominance of familial phaeochromocytoma in order to confirm the diagnosis of von Hippel-Lindau disease (VHLD) as well as to identify asymptomatic members. DESIGN: DNA extracted from peripheral blood was amplified by the polymerase chain reaction using oligonucleotide primers corresponding to exon 3 of the vhl gene. Specific mutations in codon 238 were screened by restriction endonuclease digestion of PCR products with Msp I. The results were confirmed by DNA sequence analysis. PATIENTS: Two generations of a family consisting of 15 individuals were studied. RESULTS: A germline missense point mutation at codon 238 of the vhl gene (CGG-->TGG; Arg-->Trp) was detected in all patients with phaeochromocytoma and in only one of the asymptomatic family members. CONCLUSION: Mutational analysis of the vhl gene in patients with familial phaeochromocytoma may permit specific diagnosis of von Hippel-Lindau disease, and is a good method for the identification of asymptomatic individuals at risk of von Hippel-Lindau disease.

Adolescent↗
PubMed1997

Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility.

We describe here a case-control study to identify associations between polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) and cytochrome P-450 1A1 (CYP1A1) genes and susceptibility to endometrial cancer. Accordingly, genotype frequencies in 80 endometrial carcinoma patients were compared with frequencies in 60 controls. DNA analysis suggest a significantly increased endometrial cancer risk with an alanine to valine substitution at nucleotide 677 of MTHFR gene with an odds ratio of 2.8 (95% confidence interval: 1.36-6.14, P = 0.002). Moreover, the tumors from patients with the valine allele were more undifferentiated (P = 0.03). On the other hand, a recently described mutation in exon 7 of CYP1A1 gene (threonine exchanged to asparagine in codon 461) showed a strong association with endometrial cancer risk with an odds ratio of 6.36 (95% confidence interval: 1.99-26.5, P = 0.0004). Thus, this study suggests that polymorphisms at MTHFR and a novel CYP1A1 variant could influence susceptibility to endometrial cancer, although larger sample sizes would be required to corroborate these findings.

Carcinoma↗
PubMed1997

Modelling the annual risk of tuberculosis infection.

BACKGROUND: Tuberculosis has been declining in developed countries for a long time, as a result of the intrinsic epidemiological characteristics of this disease, combined with improvement in the standard of living and more recently the use of antibiotics. In these low prevalence countries, decisions concerning the objectives of tuberculosis programmes have to be taken and the consequences of short term changes in the sanitary situation have to be assessed. METHODS: A deterministic model, without age structure, of the dynamics of pulmonary tuberculosis is proposed. The model extends that of Waaler and is intended to be more suitable for application to developed countries. The flows between seven subgroups of population, based on the natural history of the disease, are modelled and vaccination is taken into account. Values of model parameters and initial prevalences were deduced from published data. RESULTS: As a first step, qualitative comparisons are performed between the model-predicted decline in the annual risk of infection (ARI) and data from the Netherlands tuberculosis survey. Using parameter values suited to France, our model shows that the predicted decline is slower in France than in the Netherlands; a result which tallies with epidemiological observations. Uses of the model as a decision tool are illustrated in two cases, that of ending systematic BCG vaccination and that of a sudden increase in the number of infectious cases.

Epidemiologic Methods↗
PubMed1997

Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.

PURPOSE: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study. PATIENTS AND METHODS: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks. RESULTS: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur. CONCLUSION: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.

Aged↗
PubMed1997

The glucocorticoid receptor and AP-1 are involved in a positive regulation of the muscle regulatory gene myf5 in cultured myoblasts.

The muscle regulatory factor, myf5, is involved in the establishment of skeletal muscle precursor cells. Little is known, however, about the control of the expression of the gene encoding this basic helix-loop-helix (bHLH) factor. We have addressed this question in the mouse myogenic cell line, C2, and in a derivative of this cell line where the myf5 gene is the only muscle-specific bHLH factor to be expressed at the myoblast stage. We present evidence that the synthetic glucocorticoid dexamethasone, and the pharmacological agent anisomycin, act synergistically to rapidly up-regulate the levels of myf5 transcript and protein. The glucocorticoid antagonist RU 486 abolishes this synergy, demonstrating the involvement of the glucocorticoid receptor. The expression of a dominant negative mutant of c-jun which interferes with the transactivating properties of all AP-1 family members also blocks the induction of myf5 by anisomycin and dexamethasone. An activator of protein kinase C (PKCs), 12-O-tetradecanoyl phorbol 13-acetate (TPA), abolishes the up-regulation of myf5 gene expression by dexamethasone and anisomycin, and its effect is counteracted by an inhibitor of PKCs, GF 109203X. These results point to the possible involvement of PKCs in the negative control of myf5. Evidence that both positive and negative regulation of myf5 transcripts, described here, does not require the fresh synthesis of transcription factors suggests that myf5 may behave like an immediate early gene.

Animals↗
PubMed1997

Effect of imipenem and sulbactam on sessile cells of Acinetobacter baumannii growing in biofilm.

The effect of the age of biofilms formed by Acinetobacter baumannii on the activity of sulbactam and imipenem on sessile cells was investigated. Against cells of young biofilms both antibiotics were rapidly bactericidal. As the biofilm aged, sulbactam lost most of its activity, but imipenem continued to be bactericidal to some extent. This fact probably reflects the ability of imipenem to exert bactericidal activity on slow-growing bacteria.

Acinetobacter↗
PubMed1996

Estrus synchronization in cattle using estradiol, melengestrol acetate and PGF.

In Experiment 1, all cattle were fed MGA (0.5 mg/head/d) for 7 d (designated Days 0 to 6) and given PGF on Day 6. One-half were administered estradiol valerate (EV; 5 mg, im) on Day 0. At Location 1, a higher proportion (P < 0.005) of EV-treated heifers were detected in estrus and bred by AI between Days 7 and 13 than control heifers not receiving EV (27 of 33 versus 15 of 32), but the number of pregnancies (12 vs 10) was not significantly different. Eighty-three of 104 EV-treated and 89 of 106 control cows were inseminated, resulting in 50 and 45 pregnancies, respectively (not significant). At Location 2, cattle were similarly treated and exposed to bulls on Days 7 to 49. Fall pregnancy rate was higher (P < 0.015) for EV-treated than control heifers (44 of 48 vs 33 of 46), but was not significantly different for cows (22 of 26 vs 19 of 23). In Experiment 2, estradiol 17beta (E17beta; 5 mg, im) and progesterone (100 mg, im) were administered on Day 0 (instead of EV). In a third group (designated the PGF group), cattle were bred on Days 0 to 6, and PGF was administered on Day 6 to those not yet bred. For 213 cows, the percentage pregnant to a synchronized estrus was greater in the PGF group (72%) than in either the control group treated with MGA (49%; P = 0.005) or the group receiving MGA and E17beta (54%; P < 0.025). Fall pregnancy rates were 91, 89, and 96% for the 213 cows (not significant) and 89, 93, and 98% for 131 heifers (not significant) in the PGF, MGA and E17beta groups, respectively. In cattle without a functional CL, the average diameter of the largest follicle at Day 6 was 1 to 2 mm smaller in the E17beta + MGA group than in the MGA group (difference significant only in cows at Location 1). Combined for both locations, the synchronized pregnancy rate in heifers without a functional CL on Day 6 was higher (P < 0.05) in the E17beta + MGA group than in the MGA group (11 of 21, 52% versus 4 of 20, 20%). Estrogen treatment caused regression of ovarian follicles with emergence of a new follicular wave. Including estrogen in an estrus synchronization program utilizing MGA and PGF significantly increased fall pregnancy rate in heifers (at 1 location) and the synchronized pregnancy rate of heifers without a functional CL at the time of PGF treatment (combined for both locations).

Journal Article↗
PubMed1996

High-density lipoprotein 3 receptor-dependent endocytosis pathway in a human hepatoma cell line (HepG2).

The internalization of HLD3 into HepG2 cells at 37 degrees C was precisely measured, taking advantage of the previously observed rapid dissociation of HDL3 from its two binding sites [Barbaras, R., et al. (1994) Biochemistry 33, 2335-2340]. We observed a high level of HDL3 internalization (100 ng/mg of cell protein, corresponding to 45.5% of the total HDL3 associated to the cells at 37 degrees C) reaching a plateau at 15 min. Apolipoprotein A-I (the main HDL3 apolipoprotein) associated with dimyristoylphosphatidylcholine (DMPC) complexes was also internalized by HepG2 cells, at levels comparable to those obtained with HDL3 lipid-free apolipoprotein A-I, which can bind only to the HDL3 high-affinity binding site, and displayed a weak internalization (5 ng internalized/mg of cell protein compared to 250 ng/mg for apolipoprotein A-I complexed with DMPC). Clathrin-coated vesicle purification following HDL3 or LDL internalization at 37 degrees C showed radioactivity associated with these vesicles, and further content analysis evidenced the presence of radiolabeled apoA-I and apoB, respectively. Treatment of the cells either by saccharose hypertonic shock or by potassium depletion, in order to block clathrin-coated vesicle formation, completely inhibited HDL3 internalization, as also observed with LDL. Altogether, these observations clearly demonstrate that HDL3 internalization into HepG2 cells occurs through an endocytosis pathway involving an interaction between apolipoprotein A-I and a cell surface protein, leading to the formation of clathrin-coated vesicles.

Apolipoprotein A-I↗
PubMed1996

Changes in circulating hormone concentrations, testes histology and testes ultrasonography during sexual maturation in beef bulls.

Nine groups of bull calves (n = 5 to 6 per group) were castrated every 5 wk from 5 to 45 wk of age, and the stages of spermatogenesis were identified histologically. Prior to castration, the testes of each calf were examined by ultrasonography, and the pixel intensities of the parenchyma were quantitated. Testis ultrasonograms were also recorded every 2 wk from 10 bull calves between 2 and 40 wk of age. Blood samples were collected at weekly intervals until castration. There was an early transient rise in circulating LH concentrations between 4 and 25 wk of age, while circulating FSH concentrations were high initially but decreased between 14 and 30 wk of age. Circulating testosterone concentrations increased gradually from 6 to 35 wk of age and then rapidly to 42 wk of age. There was a progressive increase in the more mature cell types during spermatogenesis as the animals aged, with the most dramatic changes occurring between 15 and 45 wk of age. Outer seminiferous tubule diameter increased between 10 and 45 wk of age, with the most rapid increase occurring from 30 wk of age. Inner tubule diameter increased between 30 and 35 wk of age. The echogenicity of the testes (as determined by ultrasonography) increased between 20 and 40 wk of age. From these data we conclude that testis echogenicity increased during the most active phase of growth of the seminiferous tubules as more mature germ cells were produced. Cessation of the early rise in gonadotrophin secretion immediately preceded this active phase of testicular development. Testosterone secretion rose markedly with the production of mature spermatozoa.

Journal Article↗