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Biomedical subjects

L Vargas

Publications and source records attributed to L Vargas.

At least 19 recordsLinked to original sources
PubMed2001

Diabetogenic transferrin damages podocytes in early human diabetic nephropathy.

The exact mechanisms by which growth hormone (GH) damages the kidney inducing diabetic nephropathy has not yet been elucidated. Recently, it has been shown that transferrin has the same diabetogenic effects of GH, being its mediator. Transferrin was studied using immunohistochemistry and immunoelectron microscopy in cases of early diabetic nephropathy, and in controls. Transferrin was only found in diabetic cases in podocytes and Bowman's capsule cells, but also in the tubular cells of both diabetic and non-diabetic controls. Immuno-electron microscopy for the presence of transferrin showed positive signals in the cytoplasm of diabetic podocytes, but not in pedicels. This selective deposition was associated with signs of organelle and cytoskeleton damage. On the basis of previous evidence and present glomerular findings, these results suggest an indirect diabetogenic effect on the kidney by GH mediated through transferrin.

Adult↗
PubMed2001

[Endoscopic ligation plus sclerotherapy in esophageal varices treatment. Experience in active bleeding and in the elective treatment].

BACKGROUND: Endoscopic ligation is the treatment of choice for bleeding esophageal varices. The usefulness of additional sclerotherapy is not clear. AIM: To assess the effectiveness of ligation followed by sclerotherapy in the treatment of variceal bleeding. PATIENTS AND METHODS: Forty eight patients with variceal bleeding admitted for emergency treatment and 73 patients admitted for elective treatment were studied. Varices were ligated until a significant reduction in size was achieved. Eradication was completed with the injection of 1% polidocanol. RESULTS: In 34 of 48 patients admitted for emergency treatment, the site of variceal rupture was identified. In all these subjects, and in 13 of 14 patients in whom the rupture site was not identified, hemorrhage was stopped with the procedure. Varices were eradicated in 108 of the 121 patients. Hemorrhage recidivated in 12.5% of patients admitted for emergency treatment, in a period of 14 months of follow up and in 9.6% of those admitted for elective treatment, in a period of 16 months follow up. Mortality was 14, 18 and 57% among patients classified as Child Pugh A, B or C, respectively. CONCLUSIONS: Endoscopic ligation is effective in the treatment of variceal bleeding. Adding sclerotherapy, variceal eradication is achieved in a high percentage of patients. Survival depends on hepatic function.

Adolescent↗
PubMed2000

Nucleocytoplasmic shuttling of Bruton's tyrosine kinase.

Bruton's tyrosine kinase (Btk), a nonreceptor cytoplasmic tyrosine kinase belonging to the Tec family of kinases, has been shown to be critical for B cell proliferation, differentiation, and signaling. Loss-of-function mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA), a primary immunodeficiency in humans, and the less severe condition xid in mice. Although Btk is mainly localized in the cytoplasm under steady state conditions, it translocates to the plasma membrane upon growth factor stimulation and cross-linking of the B cell receptor. Nevertheless, in ectopically as well as endogenously Btk-expressing cells, it can also translocate to the nucleus. Deletion of the pleckstrin homology (PH) domain (DeltaPH1) leads, however, to an even redistribution of Btk within the nucleus and cytoplasm in the majority of transfected cells. In contrast, an SH3-deleted (DeltaSH3) mutant of Btk has been found to be predominantly nuclear. We also demonstrate that the nuclear accumulation of DeltaPH1 is dependent on Src expression. This nucleocytoplasmic shuttling is sensitive to the exportin 1/CRM1-inactivating drug, leptomycin B, indicating that Btk utilizes functional nuclear export signals. In addition, while the DeltaPH1 mutant of Btk was found to be active and tyrosine-phosphorylated in vivo, DeltaSH3 displayed decreased autokinase activity and was not phosphorylated. Our findings indicate that the nucleocytoplasmic shuttling of Btk has implications regarding potential targets inside the nucleus, which may be critical in gene regulation during B cell development and differentiation.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases.

Bruton's tyrosine kinase (Btk) is a member of the Tec family of protein tyrosine kinases (PTK) characterized by an N-terminal pleckstrin homology domain (PH) thought to directly interact with phosphoinositides. We report here that wild-type (wt) and also a gain-of-function mutant of Btk are redistributed following a wide range of receptor-mediated stimuli through phosphatidylinositol 3-kinase (PI 3-K) activation. Employing chimeric Btk with green fluorescent protein in transient transfections resulted in Btk translocation to the cytoplasmic membrane of live cells through various forms of upstream PI 3-K activation. The redistribution was blocked by pharmacological and biological inhibitors of PI 3-K. A gain-of-function mutant of Btk was found to be a potent inducer of lamellipodia and/or membrane ruffle formation. In the presence of constitutively active forms of Rac1 and Cdc42, Btk is co-localized with actin in these regions. Formation of the membrane structures was blocked by the dominant negative form of N17-Rac1. Therefore, Btk forms a link between a vast number of cell surface receptors activating PI 3-K and certain members of the Rho-family of small GTPases. In the chicken B cell line, DT40, cells lacking Btk differed from wt cells in the actin pattern and showed decreased capacity to form aggregates, further suggesting that cytoskeletal regulation mediated by Btk may be of physiological relevance.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

The search for natural bioactive compounds through a multidisciplinary approach in Bolivia. Part II. Antimalarial activity of some plants used by Mosetene indians.

Forty-six different species collected in the Mosetene ethnia, dwelling in the Andean Piedmont of Bolivia, were screened for antimalarial properties. Thirty-three extracts were screened for antimalarial activity in vitro on Plasmodium falciparum chloroquine resistant strain (Indo), and forty-seven extracts were evaluated in vivo on the rodent malaria P. vinckei petteri 279BY. Only two plants are specifically used in combination by the Mosetene against malaria attack (Hymenachne donacifolia and Tesseria integrifolia), but they did not display any activity in vivo at 1000 mg/kg. The in vivo most active extracts were Swietenia macrophylla bark, Trema micrantha bark and Triplaris americana bark, not all of them were used for antimalarial purposes by the Mosetene. The following extracts were moderately active: Jacaratia digitata inner bark and Momordica charantia aerial part (both traditionally used as febrifuge), Kalanchoe pinnate aerial part (used in inflammatory processes), Lunania parviflora twigs and leaves, Phyllanthus acuminatus (used as piscicide), Tynanthus schumannianus fruit (used against diarrhoea), Triumfetta semitrilobata (used as febrifuge, to alleviate kidney and gynecological pain) and finally Solanum mammosum fruit (used against scabies). We present here the results of this screening, emphazing on the in vivo antimalarial activity of the selected plants. The antimalarial in vivo activity of the selected species, in relation with their traditional Mosetene use is then discussed.

Animals↗
PubMed2000

Taenia solium disease in humans and pigs: an ancient parasitosis disease rooted in developing countries and emerging as a major health problem of global dimensions.

This article reviews current knowledge on human and porcine cysticercosis caused by Taenia solium. It highlights the conditions favorable for its prevalence and transmission, as well as current trends in research on its natural history, epidemiology, immunopathology, diagnosis, treatment and prevention. Our opinions on the most urgent needs for further research are also presented.

Animals↗
PubMed1999

Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.

Adolescent↗
PubMed1999

Increase in granulocyte-macrophage-colony-stimulating factor secretion and the respiratory burst with decreased L-selectin expression in hyper-IgE syndrome patients.

BACKGROUND: The hyper-IgE syndrome is a primary immunodeficiency characterized by severe recurrent abscesses, pneumonia with pneumatocele formation, and elevated serum IgE. Eosinophilia, neutrophil chemotactic defects, and marked tissue damage are frequently present in this syndrome. OBJECTIVE: To study whether functional changes in cytokines, adhesion molecules, and neutrophils might help explain these clinical observations. METHODS: The following functions were analyzed in patients with the hyper-IgE syndrome and in controls: (1) production of granulocyte-macrophage-colony-stimulating factor by peripheral blood mononuclear cells by ELISA; (2) respiratory burst and reactive oxygen intermediates production by peripheral neutrophils using the luminol-enhanced chemiluminescense technique; and (3) expression of L-selectin on granulocytes and lymphocytes by flow cytometry. RESULTS: Patients with hyper-IgE syndrome had significantly increased production of granulocyte-macrophage-colony-stimulating factor by resting or stimulated mononuclear cells, increased generation of reactive oxygen intermediates by neutrophils treated with opsonized zymosan, and reduced L-selectin expression on quiescent and activated granulocytes and lymphocytes. CONCLUSIONS: Our results suggest that an important feature of the hyper-IgE syndrome is the increased production of granulocyte-macrophage-colony-stimulating factor, which may explain the reduced L-selectin expression, decreased chemotaxis, and increased oxygen radical production and tissue damage in this disease.

Adolescent↗
PubMed1999

[Esophagogastric varix hemorrhage. Experience with cyanpoacrylate and polidocanol in 68 patients with active hemorrhage].

BACKGROUND: Sclerosis, injection of cianoacrylate and rubber band ligation are the most commonly used endoscopic techniques for the treatment of bleeding esophageal varices. AIM: To assess the effectiveness of cianoacrylate and polidocanol in the treatment of bleeding esophageal varices. PATIENTS AND METHODS: Sixty eight patients with active variceal bleeding were studied. Bleeding varices were classified as thin, thick or gastric. Bleeding from thin varices was treated with polidocanol. Bleeding from thick or gastric varices was treated with cianoacrylate. Variceal eradication was done with polidocanol. RESULTS: Bleeding came from thin esophageal varices in 23% of patients and endoscopic treatment stopped bleeding in 95% of them, from thick esophageal varices in 62% and endoscopic treatment was successful in 94% of these, and from gastric varices in 12% and treatment stopped bleeding in 87% of these (in 3% bleeding was considered subcardial). Twenty-five percent of patients bled again during variceal eradication, 12% died due to uncontrollable bleeding and 20% died due to liver failure. During variceal eradication 59% of patients classified as Child Pugh C, died. CONCLUSIONS: Treatment of bleeding esophageal varices with cianoacrylate or polidocanol is effective. Patients classified as Child Pugh C have a had prognosis.

Adolescent↗
PubMed1998

A study of granulocyte respiratory burst in patients with allergic bronchial asthma.

The respiratory burst of phagocytes plays an important role in the tissue damage that accompanies the inflammatory response. One of these conditions is allergic bronchial asthma, therefore, to evaluate the activation state of peripheral granulocytes the generation of reactive oxygen metabolites was evaluated using Luminol-enhanced chemiluminescence (LCL) and reduction of cytochrome C by superoxide. The resting granulocytes of the asthmatic patients under crisis showed a higher LCL compared to the noncrisis patients and control subjects. The granulocytes stimulated with PMA presented a significant increase in the respiratory burst in both groups of asthmatics. The granulocytes of noncrisis asthmatics challenged with Ops-Zym and with fMLP + Ops-Zym showed a higher metabolic activity, whereas the asthmatics under crisis presented no difference between reactive oxygen generation and that of the control group. The quantitative analysis of superoxide generation by granulocytes of the same patients did not show differences among the groups. Our findings suggest that the granulocytes of crisis and noncrisis asthmatics seem to be in a hyperreactive state and with a higher metabolic response when compared to the control group. However, the patients present a different behavior depending on stimulus used to activate cells. This could indicate that in peripheral blood exist different granulocyte populations depending on the inflammatory response taking place in the respiratory tract.

Adult↗
PubMed1998

Insulin antagonism: a novel role for human serum transferrin.

We have purified alpha2-glycoprotein (alpha2-GP), an insulin antagonist from human plasma which is induced by growth hormone (GH), and shown that pure alpha2-GP is a potent antagonist of severe insulin-induced hypoglycemia, producing acute hyperglycemia in intact rats and ketonuria in diabetic rats. The N-terminal amino acid sequence of alpha2-GP and the reactivity of alpha2-GP with an antitransferrin monoclonal antibody show that alpha2-GP is identical to human serum transferrin. Furthermore, pure human serum transferrin and non-glycosylated recombinant human transferrin reproduce the insulin antagonist effects of alpha2-GP in rats, whereas ovotransferrin shows no such effect. The neutralization of the insulin antagonism of human serum transferrin by an anti-transferrin monoclonal antibody shows that transferrin has a new function as a potent insulin antagonist. This novel role for human serum transferrin in the regulation of glucose metabolism provides a reasonable mechanism for the diabetogenic effect of GH, and has important implications for the etiology and progression of diabetes.

Amino Acid Sequence↗
PubMed1997

Incidence of non-fatal workplace assault injuries determined from employer's reports in California.

Although fatal work-related assault assault injury rates are routinely reported in the United States, reports of non-fatal injuries are not routinely examined. Non-fatal workplace assault injuries can be reported through many agencies. One of the most common reporting mechanisms in California is the Employer's Report of Occupational Illness and Injury. Employer's Reports filed from October 1, 1994 through January 31, 1995 in the state of California were the source of workplace assault information for this study. All reports indicating an assault-related injury were identified and characterized by gender and occupation of the victim, type of assault and weapon used, and industry. Annual rates were determined based on the number of estimated annual reports and the civilian working population. The estimated annual rate of workplace assault injuries for California based on Employer's Reports is 72.9 per 100,000 workers, which is approximately 50 times the fatal rate. Rates differed by industry, with retail, hospital, transportation and police workers exhibiting the highest rates. Assaults were predominantly Type I, which involve criminal activity, and Type II, which involve an assault by a client, patient, or inmate. The rates of non-fatal work-related assault injury are much greater and have different characteristics than fatal injuries. These non-fatal injury patterns need to be considered when estimating the burden of assault injuries on businesses, and can help identify the most effective prevention strategies.

Absenteeism↗