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Biomedical subjects

G Gonzalez

Publications and source records attributed to G Gonzalez.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)].

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.

Adult↗
PubMed1994

Heme-based sensors, exemplified by the kinase FixL, are a new class of heme protein with distinctive ligand binding and autoxidation.

FixL's are chimeric heme protein kinases from symbiotic nitrogen-fixing Rhizobia. We have overexpressed three FixL variants in Escherichia coli. Bradyrhizobium japonicum FixL, a soluble dimeric protein, is the first full-length FixL to be purified. The other two proteins are soluble truncations of Rhizobium meliloti FixL, which is a membrane protein. One contains both heme and kinase domains and is dimeric; the other has only the heme domain and is monomeric. We find that all the FixL's bind oxygen and carbon monoxide non-cooperatively, with very low affinities due entirely to slow association rates. FixL P50's for oxygen are 17-76 mmHg. FixL's may sense nitric oxide and carbon monoxide in addition to oxygen, especially at the low oxygen pressures encountered in vivo. Autoxidation rates are about 50 times faster than that of sperm whale myoglobin. The carbon monoxide affinity of FixL's is about 300 times lower than that of myoglobin, resulting in the unusually low values of 7.5-17 for the partition constant, M = P50(O2)/P50(CO), between carbon monoxide and oxygen. Met-FixL's have their Soret absorption maximum at 395 nm instead of the typical 408 nm and a steep hydroxymet transition at pH > or = 9.3; these properties indicate a pentacoordinated high-spin ferric heme and suggest a sterically hindered hydrophobic heme pocket lacking a distal (E7) histidine. FixL is the first member of a new class of heme proteins, the heme-based sensors, distinct from the oxygen carriers and electron transporters. We expect that some of the novel properties of FixL will be characteristic of the class.

Bacterial Proteins↗
PubMed1994

Production and characterization of monoclonal antibodies against the major cysteine proteinase of Trypanosoma cruzi.

In the present study we describe the production and characterization of a panel of monoclonal antibodies (MoAbs) directed against cruzipain (Crz), the major cysteine proteinase from Trypanosoma cruzi. The five MoAbs, BD6, BF2, CG2, CH8, and DC10 were analysed with respect to affinity and specificity. None of the MoAbs cross-reacted with papain, which has regions of high homology with Crz. Treatment of the antigen with periodate did not affect the binding of the MoAbs, suggesting that they bind to the polypeptide moiety of Crz. CH8 recognized a continuous epitope located at the C-terminal extension of the proteinase that appeared to be highly immunogenic. Although the rest of the MoAbs recognized epitopes located in the catalytic domain, the enzymatic activity of Crz was not impaired by the binding of the MoAbs. Characterization of the antibody-binding sites revealed the presence of at least four separate epitopes.

Animals↗
PubMed1993

Regulation of the kinase activity of heme protein FixL from the two-component system FixL/FixJ of Rhizobium meliloti.

The Rhizobium meliloti two-component system FixL/FixJ regulates nitrogen fixation in response to oxygen during symbiosis. FixJ is a transcriptional activator of critical nif and fix promoters; its in vivo activity is enhanced by FixL in diminished oxygen (David, M., Daveran, M.-L., Batut, J., Dedieu, A., Domergue, O., Ghai, J., Hertig, C., Boistard, P., and Kahn, D. (1988) Cell 54, 671-683; Virts, E. L., Stanfield, S. W., Helinski, D. R., and Ditta, G. S. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 3062-3065). FixL* is a soluble truncated version of FixL that contains heme; it catalyzes its autophosphorylation and the phosphorylation of FixJ (Gilles-Gonzalez, M.A., Ditta, G. S., and Helinski, D. R. (1991) Nature 350, 170-172). We examine the kinetics of phosphoryl transfer in this system. First, there is a slow autophosphorylation of FixL* in ATP that is accelerated in the absence of oxygen and in the presence of Mn2+. This reaction is reversible, i.e. phospho-FixL* reacts with ADP to generate ATP. Since the reverse reaction is faster, most FixL* is not phosphorylated at equilibrium. Next, there is a rapid phosphoryl transfer directly from phospho-FixL* to FixJ that is unaffected by oxygen. Finally, phospho-FixJ is hydrolyzed; this reaction is very fast and not controlled by oxygen. We propose that in addition to the oxygen signal previously noted in vivo, energy charge and manganese concentration are also indicators of symbiosis that impact on the induction of nitrogen fixation genes.

Adenosine Diphosphate↗
PubMed1993

L-leucine intestinal transport at different ages in chicken: effect of anticoccidial drugs.

1. L-Leucine transport by everted slices of duodenum, jejunum ileum and cecum of 1-, 2- and 3-week-old chickens has been determined. 2. The effects of the administration with the diet of three anticoccidial drugs: monensin, maduromicin ammonium and nicarbazine have been studied. 3. In the control animals, there is a reduction on intestinal transport with age, except in the duodenum which is not age-dependent. 4. Momensine induces an increase on leucine transport in the duodenum and cecum at all ages studied and only in the 3-week-old animals in the jejunum and ileum. 5. Nicarbazine reduces jejunal absorption of leucine and does not affect the function of the other segments. 6. Maduromicin ammonium has almost no effect on the absorptive process.

Aging↗
PubMed1993

Activity of imipenem, third-generation cephalosporins, aztreonam and ciprofloxacin against multi-resistant gram-negative bacilli isolated from Chilean hospitals.

The activity of imipenem against nosocomial strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-resistant Staphylococcus aureus resistant to some third-generation cephalosporins, aztreonam, or ciprofloxacin was assessed. These strains represent the most prevalent multi-resistant nosocomial microorganisms in Chile since they were isolated from clinical specimens in 11 Chilean hospitals. A high proportion of the strains were resistant to several beta-lactams, yet all strains of K. pneumoniae and Acinetobacter spp. were susceptible to imipenem; resistance was exhibited by only one strain of P. aeruginosa and 16 strains of S. aureus. Synergy between cefotaxime and clavulanic acid was found in almost all strains of K. pneumoniae, suggesting the presence of plasmid-coded beta-lactamases, probably with extended-spectrum activity. Killing A. baumannii by imipenem was rapid, but slower for P. aeruginosa. Killing of K. pneumoniae was also somewhat slower despite the lower MIC of imipenem for this strain. Bactericidal activity was even slower against one strain of methicillin-resistant S. aureus. These results suggest that imipenem would be an adequate alternative to other broad-spectrum agents in the treatment of infections due to nosocomial multi-resistant Gram-negative bacilli.

Anti-Bacterial Agents↗
PubMed1993

Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass?

OBJECTIVE: To evaluate the effect of selective digestive decontamination on endotoxemia and cytokine activation during the ischemic phase of cardiopulmonary bypass surgery. DESIGN: Prospective, open, randomized, controlled trial. SETTING: Two multidisciplinary intensive care units in tertiary care hospitals. PATIENTS: Eighty consecutive patients randomly allocated to two groups: selective digestive decontamination (group 1, n = 40) and controls (group 2, n = 40). INTERVENTIONS: Preoperative administration of oral antibiotics (polymyxin E, tobramycin, and amphotericin B) vs. untreated controls. MEASUREMENTS AND MAIN RESULTS: Assessment of decontamination by bacteriologic evaluation of rectal swabs (colony-forming units [cfu]/mL) were made in each group, along with circulating endotoxin, tumor necrosis factor and interleukin-6 (IL-6) determinations before surgery, during ischemic and reperfusion phases of bypass, and at 4 hrs and at 24 hrs after surgery. Group 1 patients showed that rectal bacteria decreased ten-fold after treatment for 24 hrs, thousand-fold after 48 hrs, and registered 0 cfu/mL after digestive decontamination was administered for > 72 hrs. Endotoxin and IL-6 assays showed significantly lower values in this latter group vs. those circulating concentrations of control patients. On the other hand, both endotoxin and IL-6 concentrations correlated positively with the duration of surgical ischemia. CONCLUSIONS: Selective digestive decontamination reduces the gut content of enterobacteria, with complete elimination after 3 days of treatment. This fact could explain the lower endotoxin and cytokine concentrations found in the blood samples of patients who had been fully decontaminated. Duration of aortic cross-clamping is an important factor in generating endotoxemia and in the activation of cytokines.

Adult↗
PubMed1992

The LIM family transcription factor Isl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells.

Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.

Base Sequence↗
PubMed1992

Cloning of cDNAs encoding human caldesmons.

Caldesmon (CDM) is a potential actomyosin regulatory protein found in smooth muscle and nonmuscle cells. Domain mapping and physical studies suggest that CDM is an elongated molecule with an N-terminal myosin/calmodulin-binding domain and a C-terminal tropomyosin/actin/calmodulin-binding domain separated by a 40-nm-long central helix. An 1100-nucleotide (nt) cDNA probe encoding the C terminus of avian caldesmon (aCDM) was used to screen a human aorta library and clone smooth-muscle and non-muscle CDM-encoding cDNAs (CDM). The human (h) smooth-muscle hCDM is 3050-3630 nt long, having variation in length in the 3'-untranslated region. The predicted hCDM protein has a high degree of identity, greater than 90%, to aCDM in the N- and C-terminal-binding domains. The central helical domain is more variable, but retains characteristic repeated peptides and an 'i, i + 4' acidic/basic amino acid (aa) motif found in aCDM which can form intra-helical salt bridges to stabilize the central helix. The predicted smooth-muscle protein is 793 aa long (93,262 Da) with a calculated pI of 5.75. As is the case for the chicken, nonmuscle hCDM is missing the central helical domain, 256 aa overall. Our nonmuscle clone is not full length, but the C-terminal end is identical to the smooth-muscle form. If the N-terminal domain is identical, as it is in the chicken, the predicted protein is 537 aa (62,558 Da). Examination of the 'junctions' at either end of the deleted central domain gives a clear indication of the splice sites and suggests that the nonmuscle form is generated by exon skipping.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Research note: age-dependent changes in 3-oxy-methyl-D-glucose and leucine intestinal absorption in chickens.

Intestinal absorption of 3-oxy-methyl-D-glucose (3-OMG) and leucine were studied in intestinal slices from fasted 1-, 2-, and 3-wk-old chickens. The intestinal segments studied were the duodenum, jejunum, ileum, and cecum, with the latter divided into proximal and medial regions. There was a decrease in the intestinal absorption of 3-OMG and leucine in the duodenal, jejunal, and proximal cecal segments with increasing age of the chicken. The medial cecum did not show age-dependent differences in the uptake of substrates. In the ileum, there was a decrease in intestinal absorption of 3-OMG and leucine between Weeks 1 and 2, but thereafter the uptake was similar to that of the 2nd wk.

3-O-Methylglucose↗
PubMed1992

Induction chemotherapy with carboplatin and ftorafur in advanced head and neck cancer. A randomized study.

From 1987 to 1989, 42 patients with locally advanced squamous cell carcinoma of the head and neck (Stages III-IV, Mo) were randomized to receive radiotherapy (Group A) or three courses of induction chemotherapy followed by radiotherapy (Group B). There were 36 evaluable patients, 17 in Group A and 19 in Group B. The radiotherapy regimen was the same for both groups, 66-74 Gy total tumor doses with standard fractionation scheme of 2 Gy/day. The chemotherapy regimen was a combination of carboplatin 400 mg/m2 by intravenous bolus injection on day 1, and Ftorafur 1,000 mg/m2 orally once a day for 14 days. Cycles were given every 4 weeks. The complete response rate in Group A was 65%; in group B it was 31.5% after induction chemotherapy and 84% after radiotherapy. The 42-month actuarial overall survival rates were 34% for Group A and 47% for Group B (P = NS). Patients from both groups with a complete response had a significantly longer survival time than those with a partial response (P less than 0.001). No significant differences in disease-free survival were found between the two treated groups. The chemotherapy regimen was well tolerated, with moderate hematologic and gastrointestinal toxicity. Increased in radiation toxicity by chemotherapy was not observed.

Adult↗
PubMed1991

A prospective study on the treatment of retinoblastoma in 72 patients.

Seventy-two patients with retinoblastoma (RTB) (unilateral [47 patients] and bilateral [25 patients]) were studied for a period of 6 years. Treatment consisted of enucleation of those eyes that had severe involvement and was followed by radiation therapy and/or chemotherapy (systemic or intrathecal) according to clinical pathologic staging. All patients who underwent nonsurgical treatment received systemic chemotherapy. Intrathecal chemotherapy was administered when there was involvement of the central nervous system. Nonsurgical treatment consisted of radiation therapy and/or light coagulation, followed by enucleation if there was no response. The overall survival rates were 79% for unilateral disease (median follow-up time, 63 months) and 72% for bilateral disease (median follow-up time, 81 months). Vision was regained in 14 of 21 conserved eyes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Respiratory manifestations of hemorrhagic rectocolitis].

Several respiratory complications have been described in patients with ulcerative colitis (UC), and are the subject of this review. Involvement of the bronchial tree is the most frequent of them. Chronic bronchitis (16 patients) and bilateral bronchiectasis (16 patients) are responsible for chronic disabling bronchial suppuration. Symptoms related to the bronchial disease most often develop in patients in whom the diagnosis of ulcerative colitis is already established (88% of cases). Occurrence before the diagnosis of UC is possible, but unusual. Bronchial involvement can develop in patients whose UC is in complete remission, or who have undergone coloproctectomy up to several years earlier. Impressive improvement of cough and sputum production commonly occur following inhaled steroids. This is of great diagnostic and therapeutic significance. Other complications include subacute asphyxiating tracheal obstruction due to intralumenal inflammatory overgrowth (1 patient), small airways disease and panbronchiolitis (2 patients), BOOP (4 patients), pulmonary angiitis (6 patients), desquamative interstitial pneumonitis and granulomatosis (2 and 3 patients respectively), biapical pulmonary infiltrates (2 patients) and serositis. In addition, UC patients can develop less specific pulmonary problems such as pulmonary edema, pulmonary embolism and sulfasalazopyridine-induced pneumonitis and fibrosis.

Bronchial Diseases↗
PubMed1991

Is exocrine pancreatic cancer a hormone-dependent tumor? A study of the existence of sex hormone receptors in normal and neoplastic pancreas.

The 5-year survival rate of patients with exocrine pancreatic cancer after surgery is less than 5%, in patients treated with radical surgery, with or without adjuvant therapy. It has been well documented clinically and experimentally that sex hormones influence the physiology of the exocrine pancreas. Hormone manipulation inhibits the growth of human pancreatic cancer in nude mice. Several nonrandomized studies have suggested the efficacy of antihormone therapy in the treatment of advanced pancreatic cancer. However, the existence of sex hormone receptors in exocrine pancreatic cancer has been a matter of controversy. This study was designed to investigate the presence of sex hormone receptors (estrogens, progesterone and androgens in normal pancreas and exocrine pancreatic cancer, using two different methods: immunohistochemistry and enzyme immunoassay. Twenty-eight biopsies of normal pancreas and 15 biopsies of exocrine pancreatic cancer were studied. Estrogen receptors and progesterone receptors were measured by enzyme immunoassay, using specific monoclonal antibodies. Androgen receptors were determined by radioligand assay. Sixteen biopsies of normal pancreas and 12 biopsies of exocrine pancreatic cancer were studied by immunohistochemistry. In exocrine pancreatic cancer we could not detect estrogen receptors or progesterone receptors, either by enzyme immunoassay or immunohistochemistry. Androgen receptors were always negative (less than 2 fm/mg). In the normal pancreas, 5 out of 28 cases showed increased levels of progesterone receptors (greater than 10 fm/mg) as measured by enzyme immunoassay. Immunohistochemistry revealed progesterone receptors in the pancreatic islets of 16 normal pancreases studied. Nuclear staining was observed in more than 70% of the cells. Estrogen receptors were always negative by immunohistochemistry and enzyme immunoassay in the normal pancreas.2+n

Adenocarcinoma↗
PubMed1990

Effect of lung T lymphocytes on fibroblasts in idiopathic pulmonary fibrosis and extrinsic allergic alveolitis.

Increased fibroblast replication and interstitial collagen accumulation occur commonly in the interstitial lung disease that progress to fibrosis. The processes controlling lung fibrogenesis are not completely understood, however. This study was designed to analyse the influence of T lymphocytes from lung tissue obtained at open lung biopsy from four patients with idiopathic pulmonary fibrosis and four patients with extrinsic allergic alveolitis on fibroblast proliferation and collagen synthesis in vitro. Lung T cell supernatants from patients with both diseases induced a moderate but significant inhibition of human lung fibroblast cell line growth. In contrast, there was a clear difference in the effect of T cells from the two groups of patients in relation to collagen production. Lung T lymphocytes from all four patients with idiopathic pulmonary fibrosis produced a substantial increase in collagen synthesis (from 371% to 514% of control values), whereas T cells from three of the four patients with extrinsic allergic alveolitis induced a significant decrease in collagen production (to 35%, 36%, and 43% of control values); in the fourth case there was an increase in collagen synthesis but this was lower than that seen with T cells from any of the patients with idiopathic pulmonary fibrosis. Peripheral T cells from six patients and control subjects caused a small increase in fibroblast proliferation and no change in collagen synthesis. The findings suggest that at least two types of interaction occur between lung T cells and fibroblasts in these disorders. A variable degree of inhibition of cell proliferation is observed in response to lung T cell supernatants from patients with both idiopathic pulmonary fibrosis and extrinsic allergic alveolitis; a substantial increase in collagen synthesis is triggered by lymphokines from patients with idiopathic pulmonary fibrosis.

Adult↗