Biomedical subjects

M Vasquez

Publications and source records attributed to M Vasquez.

At least 19 recordsLinked to original sources

PubMed2000

The effects of continuous blood gas monitoring during cardiopulmonary bypass: a prospective, randomized study--Part I.

The use of continuous in-line blood gas management (CILBGM) is steeped in controversy concerning its potential utility and impact on patient outcomes. The purpose of this study was to determine whether the use of CILBGM results in improved quality of patient care. Fifty-nine patients were enrolled in a Institutional Review Board-approved, prospective, randomized study. An in-line blood gas monitor (CDI 500) was placed into the arterial and venous lines for all patients. Blood gas monitoring in the control group was managed by intermittent sampling (every 20-30 min), while the treatment group was managed with continuous monitoring. There were no differences between groups in preoperative, surgical, anesthetic, or perfusion variables. The accuracy of the in-line monitor was comparable to laboratory analysis for arterial blood gas parameters (N = 160; pH bias = 0.00; PaCO2 bias = -1.1 mmHg; and PaO2 bias = 0.7 mmHg). There was less deviation from target values (pH = 7.40, PaCO2 = 40 mmHg, PaO2 = 150-200 mmHg) when in-line monitoring was used versus intermittent sampling (N = 784; pH deviation = 0.05 +/- 0.03 vs. 0.03 +/- 0.01, p < 0.0001; PaCO2 deviation = 4.0 +/- 2.9 mmHg vs. 2.0 +/- 0.9 mmHg, p < 0.0001; and PaO2 deviation = 22.7 +/- 16.9 mmHg vs. 11.7 +/- 8.3 mmHg, p < 0.0001). In conclusion, the results of part I of this study demonstrate that the use of CILBGM results in more accurate blood gas management during CPB.

Analysis of Variance↗

PubMed2000

The effects of continuous blood gas monitoring during cardiopulmonary bypass: a prospective, randomized study--Part II.

The impact of blood gas management during cardiopulmonary bypass (CPB) on patient care has not been examined and remains controversial. The purpose of this study was to determine whether precise blood gas management during CPB influences patient outcome. Fifty-nine patients were enrolled in an Institutional Review Board-approved, prospective, randomized study. An in-line blood gas monitor (CDI 500) was placed into the arterial and venous lines for all patients. Blood gas monitoring in the control group was managed by intermittent sampling (every 20-30 min), while the treatment group was managed with continuous monitoring. Blood gas control and measured parameters were as follows: pH 7.40 +/- 0.05, PaCO2 40 +/- 5 mmHg, PaO2 200 +/- 50 mmHg. The treatment group had the CDI 500 guide clinical decisions. Compared to the control group, the treatment group consisted of significantly more diabetic (7% vs. 47%, p < or = 0.001), renal failure (3% vs. 13%, p < or = 0.01), and chronic obstructive pulmonary disease patients (7% vs. 20%, p < or = 0.01). Internal thoracic artery utilization was higher in treatment patients than control patients (67% vs. 95%, p < or = 0.02). No other differences existed in demographic, pharmacological, surgical, or anesthetic parameters. In the perioperative period, the control group required antiarrythmic support more frequently than the treatment group (10% vs. 0%, p < or = 0.05). Compared to the control group, the treatment group required antiarrythmic (18% vs. 10%, p < or = 0.05) and cardiac glycoside therapy (11% vs. 0%, p < or = 0.05) less frequently in the postoperative period. Although treatment patients required less intraoperative pacing and cardioversion and spent less time on mechanical ventilation, in the intensive care unit (ICU), and in the hospital than control patients, statistical significance was not achieved. In conclusion, the use of continuous, in-line blood gas monitoring resulted in improvement in a number of postoperative outcome variables, although ICU and hospital stay was not effected.

Aged↗

PubMed1999

HuM291, a humanized anti-CD3 antibody, is immunosuppressive to T cells while exhibiting reduced mitogenicity in vitro.

BACKGROUND: OKT3, a mouse monoclonal antibody (Ab) specific for the human CD3 complex on T cells, is a potent immunosuppressive agent used for the treatment of acute allograft rejection. The utility of the drug has been limited by a neutralizing anti-mouse Ab response and adverse side effects resulting from T cell activation and systemic cytokine release. T cell activation is caused by OKT3-mediated cross-linking of T cells and Fc receptor-bearing cells. Studies in the mouse model have shown that global T cell activation is not necessary for immunosuppression, as Fc receptor-nonbinding anti-CD3 Abs can suppress graft rejection in the absence of the activation effects seen with Fc receptor-binding Abs. Thus, a humanized anti-CD3 antibody with a low affinity for Fc receptors might improve immunosuppressive therapy by reducing the side effects associated with OKT3. METHODS: We developed a mouse monoclonal Ab, M291, which competes with OKT3 for binding to T cells. Humanized, complementary-determining region-grafted versions of M291 featuring various Fc were engineered, including a previously described IgG2 mutant deficient in Fc receptor binding (HuM291). RESULTS: Compared with OKT3 and HuM291-IgG1, HuM291 was significantly less mitogenic to T cells in vitro and induced the release of much lower levels of the cytokines tumor necrosis factor-alpha, interferon-gamma, and interleukin-10. Despite this reduction in T cell activation, HuM291 retained the ability to modulate the CD3 complex and inhibit the mixed lymphocyte reaction. CONCLUSIONS: When evaluated in vivo, HuM291 may be an immunosuppressive agent associated with less of the acute toxicity and immunogenicity seen with OKT3 therapy.

Amino Acid Sequence↗

PubMed1999

Properties and pharmacokinetics of two humanized antibodies specific for L-selectin.

BACKGROUND: The participation of L-selectin in leukocyte recruitment during inflammation has suggested the use of L-selectin inhibitors as potential anti-inflammatory therapeutics. Blocking monoclonal antibodies could serve as such therapeutic agents, particularly if humanized to reduce their immunogenicity and improve their serum half-life. OBJECTIVES: For this purpose, two mouse monoclonal antibodies, DREG-55 and DREG-200, that block human L-selectin were humanized and characterized. STUDY DESIGN: The resulting humanized antibodies, HuDREG-55 and HuDREG-200, constructed with human IgG4 constant regions, were evaluated for their specificity, affinity and ability to block L-selectin-dependent adhesion in in vitro assays. Their pharmacokinetic behavior in rhesus monkeys was also studied. RESULTS: HuDREG-55 and HuDREG-200 were found to retain the specificity and affinity, within 2-fold, of the parent murine antibodies. HuDREG-55 and HuDREG-200 block L-selectin-dependent adhesion of human lymphocytes to high endothelial venules in frozen sections of lymph nodes. In addition, HuDREG-55 and HuDREG-200 are inhibitory in a novel L-selectin-dependent adhesion assay. This assay utilizes flow cytometry to measure binding of polymerized liposomes containing an analog of sialyl Lewis X, sialyl Lewis X glycoliposomes, to peripheral blood neutrophils and lymphocytes. Studying the pharmacokinetics of HuDREG-55 and HuDREG-200 in rhesus monkeys showed terminal elimination half-lives at 12.0 and 20.3 days, respectively. CONCLUSION: The shorter terminal elimination half-life of HuDREG-55 in rhesus monkeys may be due to the ability of HuDREG-55 but not HuDREG-200 to bind rhesus monkey L-selectin.

Amino Acid Sequence↗

PubMed1998

Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin.

E- and P-selectin (CD62E and CD62P) are cell adhesion molecules that mediate leukocyte-endothelial cell and leukocyte-platelet interactions and are involved in leukocyte recruitment during inflammation. We previously developed a murine mAb, EP-5C7 (or mEP-5C7), that binds and blocks both E- and P-selectin. When used in humans, murine mAbs have short circulating half-lives and generally induce potent human anti-mouse Ab responses. We therefore engineered a humanized, complementarity determining region-grafted version of mEP-5C7 incorporating human gamma4 heavy and kappa light chain constant regions (HuEP5C7.g4). HuEP5C7.g4 retains the specificity and avidity of mEP-5C7, binding to human E- and P-selectin but not to human L-selectin, and blocking E- and P-selectin-mediated adhesion. Surprisingly, when administered to rhesus monkeys, HuEP5C7.g4 was eliminated from the circulation very rapidly, even faster than the original murine Ab. To isolate the cause of the short serum half-life of HuEP5C7.g4, several Ab variants were constructed. A chimeric IgG4 Ab was made by replacing the humanized V regions with murine V regions. A humanized IgG2 Ab, HuEP5C7.g2, was also made by replacing the human gamma4 with a gamma2 constant region. Results from pharmacokinetic studies in rhesus monkeys demonstrated that the chimeric IgG4 is also rapidly eliminated rapidly from serum, similar to the humanized IgG4 Ab, while the humanized IgG2 Ab displays a long circulation half-life, typical of human Abs.

Amino Acid Sequence↗

PubMed1998

Is splenectomy necessary in devascularization procedures for treatment of bleeding portal hypertension?

OBJECTIVE: To investigate whether splenectomy as a part of devascularization procedures is necessary. DESIGN: Prospective, controlled, randomized trial. SETTING: University hospital, referral center. PATIENTS: A total of 55 patients (Child-Pugh class A and B) with a history of bleeding portal hypertension were treated by means of a modified Sugiura-Futagawa procedure. Twenty-three patients underwent splenectomy and 22 did not. METHODS: Postoperative outcome was recorded and comparison of the 2 groups was done with the Fisher exact test. Kaplan-Meier survival curves were constructed. Main outcome and postoperative differences between the patients who underwent splenectomy and those who did not were investigated. RESULTS: Both groups were comparable in the postoperative period. Significant differences were observed in transfusion requirements and postoperative portal vein thrombosis, both favoring the group without splenectomy. No differences in rebleeding, encephalopathy rate, operative time, or postoperative complications were observed. CONCLUSION: Splenectomy is not routinely necessary in devascularization procedures for bleeding portal hypertension.

Adolescent↗

PubMed1998

Comparative study of 2 variants of a modified esophageal transection in the Sugiura-Futagawa operation.

OBJECTIVE: To compare 2 techniques of esophageal transection in our modification of the Sugiura-Futagawa procedure for the treatment of bleeding portal hypertension in low-risk patients who cannot undergo surgery to have shunts placed. DESIGN: A prospective controlled trial comparing 2 variants of transection (classic, complete section of the anterior muscularis externa and whole mucosa; modified, placement of a circumferential running suture without opening the mucosa). SETTING: Academic university hospital. PATIENTS: Eighty-three low-risk patients (Child-Pugh score A and B) with a history of bleeding portal hypertension were operated on (35 classic, 48 modified transections) between 1989 and 1996. Both groups were comparable. MAIN OUTCOME MEASURES: Postoperative dehiscence of the transection was evaluated as well as fistulization, postoperative stenosis, rebleeding, postoperative endoscopic findings, survival, and mortality. RESULTS: Fistulization was observed in 1 (2%) of the patients in the modified group, and dehiscence in 1 patient (2%). In the classic group, 3 (8%) of the patients had dehiscence (relative risk, 2.6) and 1 (2%) of the patients, fistulization. No differences were observed regarding rebleeding (6 patients [6%] vs 5 patients [7%]), postoperative stenosis (4 patients [8%] vs 5 patients [10%]), postoperative endoscopic findings, survival, and mortality (early and late). CONCLUSION: The modified variant of the transection has a lower frequency of postoperative dehiscence, with the same long-term results.

Esophageal and Gastric Varices↗

PubMed1998

Measurement of micronucleated erythrocytes and DNA damage during chronic ingestion of phenolphthalein in transgenic female mice heterozygous for the p53 gene.

Phenolphthalein, a common ingredient in nonprescription laxatives and a multisex, multispecies rodent carcinogen, was evaluated under chronic exposure conditions for genotoxicity in transgenic female mice heterozygous for the p53 gene (heterozygous TSG-p53 mice). Phenolphthalein was administered in the diet at 200, 375, 750, 3,000, and 12,000 ppm (corresponding to a time-weighted average of 37, 71, 146, 569, and 2,074 mg/kg/day, respectively) for 6 months (183 days). On days 39, 92, 137, and 183 of treatment, peripheral blood samples were collected and evaluated for the frequency of micronucleated polychromatic and normochromatic erythrocytes (MN-PCE and MN-NCE, respectively), the percentage of PCE (%PCE) among total erythrocytes, and the extent of DNA damage (single strand breaks, alkali labile sites, DNA crosslinking) in leukocytes. In addition, the extent of DNA damage was evaluated in liver parenchymal cells sampled from mice at the end of the 6-month treatment period. DNA damage was evaluated using the alkaline (pH > 13) Single Cell Gel (SCG) assay. In addition, using a modified SCG technique, the frequencies of leukocytes and liver parenchymal cells with extremely low molecular weight DNA (indicative of apoptosis and/or necrosis) were determined. At each sample time, phenolphthalein induced a highly significant, dose-dependent increase in the frequency of MN-PCE and MN-NCE and in %PCE. Maximal induction of MN-PCE and %PCE decreased with increasing treatment duration, most likely due to a treatment duration-dependent decrease in the relative amount of ingested phenolphthalein. A comparative analysis of the kinetochore status of MN in erythrocytes sampled from control mice and mice ingesting phenolphthalein at 12,000 ppm for 183 days indicates that the induced MN resulted predominantly but not exclusively from numerical chromosomal damage. The analysis for increased levels of DNA damage in blood leukocytes was inconclusive, with a small but statistically significant increase in DNA migration on days 39 and 137 but not on days 92 and 183. The extent of DNA migration in liver parenchymal cells sampled from mice at the end of treatment was not altered significantly. The frequencies of apoptotic and/or necrotic leukocytes and liver parenchymal cells were not increased among mice ingesting phenolphthalein. The lowest effective dose at which a significant genotoxic response (i.e., the induction of MN-NCE) was detected was 200 ppm, the lowest dose tested in this study. This dose in mice is comparable to doses (on a mg/m2 basis) experienced by humans.

Administration, Oral↗

PubMed1996

Humanized anti-Lewis Y antibodies: in vitro properties and pharmacokinetics in rhesus monkeys.

ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two Phase I/II trials in relapsed small cell lung cancer and metastatic breast cancer. To improve the effector functions of the antibody, increase its half-life in circulation, and avoid the human antimouse antibody response, two chimeric and several humanized antibodies were constructed for evaluation. The chimeric IgG1 is more potent than the murine IgG3 in tumor cell lysis via activation of human peripheral mononuclear cells (10-fold), but somewhat less effective in complement-dependent lysis (2-3 fold). The chimeric IgG3 is slightly less potent than the IgG1. A humanized IgG1 was constructed by combining the complementarity-determining regions of the ABL 364 antibody with human framework and constant regions. Several additional variants were subsequently constructed to improve the binding affinity and increase expression of the antibody. Two of the variants, designated I and K, differ by a single amino acid at position 75 of the heavy chain. Both variants have affinity within 2-fold of the chimeric IgG1 antibody and retain the cytolytic activities toward tumor cell lines. However, it was possible to express variant K at a significantly higher level (5- 10-fold) than variant I. Pharmacokinetics of the humanized ABL 364 antibody variant K was compared with that of the parent murine antibody in rhesus monkeys. It was shown that the terminal half-life of the humanized antibody in rhesus monkeys is 14-20 days, with a mean of 16.3 days, while that of the parent murine antibody is only 1.9 days.

Amino Acid Sequence↗

PubMed1996

A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137).

Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with > or = 400/mm3 CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 microgram) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated.

AIDS Vaccines↗

PubMed1995

Nutritive value evaluated on rats of new cultivars of common beans (Phaseolus vulgaris) released in Chile.

Five new cultivars of common beans (Phaseolus vulgaris) recently released were analyzed for their proximate chemical composition and protein biological quality. The crude protein content in these cultivars ranged from 21.9 percent in cultivar Arroz 3 to 26.9 percent in cultivar Tórtola Diana (dry matter basis). Rats fed cultivar Tórtola INIA gained more weight, had a higher protein intake and registered higher PER and NPR than Tórtola corriente. On the other hand, rats consuming cultivars Arroz 3 and Fleetwood had lower weight gain, lower protein intake and lower PER and NPR than cultivar Coscorrón corriente. However, all these cultivars have a relatively good protein value as compared to other plant protein sources.

Analysis of Variance↗

PubMed1995

Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation.

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.

Age Factors↗

PubMed1994

A humanized antibody specific for the platelet integrin gpIIb/IIIa.

C4G1, a murine mAb reactive with the platelet gpIIb/IIIa integrin, was humanized for potential treatment of thrombosis-related disorders. The variable regions of light- and heavy-chain cDNAs from the C4G1 hybridoma were first cloned and sequenced. Humanized C4G1 Ab of the IgG1 isotype was constructed by combining the complementarity-determining regions of C4G1 with human framework and constant regions. The human framework was chosen to maximize homology with the C4G1 variable region sequence, and a computer model of C4G1 was used to aid design of the final framework sequence. Genetic constructs were also developed to produce Fab and F(ab')2 fragments of the humanized C4G1 Ab. The humanized IgG1 Ab as well as the Fab and F(ab')2 fragments showed equivalent binding affinities to their murine counterparts, indicating no loss in binding affinity during the humanization process. The humanized Ab and its fragments were also shown to inhibit platelet aggregation and to inhibit binding of fibrinogen to gpIIb/IIIa in vitro.

Amino Acid Sequence↗

PubMed1994

Structure of rotavirus particle: interaction of the inner capsid protein VP6 with the core polypeptide VP3.

The structural relationship between VP6 (inner capsid polypeptide) and the viral core was studied using chemical cross-linking with dithiobis(succinimidyl propionate). Crosslinked single shelled and reconstituted rotavirus particles, suggest the existence of a complex organization of VP6 molecules in the inner capsid and a direct interaction with the core polypeptide VP3. The inhibition of the recovery of RNA polymerase activity associated with the reconstitution of the single shelled particle in the presence of antiVP6 monoclonal antibodies indicates that a VP6 domain between amino acids 56 and 58 seems to be important in viral transcription. A VP6 gene temperature-sensitive mutant (ts G) carrying a mutation affecting assembly of single shelled particles was used in reconstitution experiments. The mutant was able to recover RNA polymerase activity at restrictive temperature. Wild type cores or VP6 were able to reconstitute the particle with both the mutant cores and VP6. These results suggest the existence of various steps for the assembly of single shelled particles, where the VP6-VP3 interaction seems to be important for recovery of RNA polymerase activity.

Antibodies, Viral↗

PubMed1993

Spontaneous development of a chromosomal translocation 5;14 in an Epstein-Barr-virus-associated B-cell lymphoma in a SCID mouse.

C.B-17 SCID mice were inoculated with human peripheral blood leukocytes (PBLs) from normal Epstein-Barr virus (EBV)-seropositive and -seronegative donors. Confirmation of a functioning human immune response was demonstrated by the detection of human antibody after inoculation with rotavirus, tetanus toxoid, or EBV. One group of animals inoculated with PBLs from an EBV-seropositive donor developed immunoblastic lymphomas approximately 9 weeks after transplantation. Confirmation of the species and sex of origin of the tumor cells was established using a spontaneous cell line prepared from the tumor. At passage I, the tumor-cell line (AGTI) showed 15% of the metaphases with a translocation involving chromosomes 5 and 14. A lymphoblastoid cell line (AGLCL) established from the same PBLs from the same donor at the time of inoculation of the mice had a normal female karyotype. The AGLCL and a clone of AGTI cells were analyzed for rearrangement of immunoglobulin heavy chain (IgH) genes; both cell lines showed rearrangement of both IgH alleles. The results outlined in this report suggest that a spontaneous chromosomal translocation involving chromosome 14 occurred in normal PBLs in the SCID mouse.

Animals↗

PubMed1993

Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody.

M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the original murine antibody. Here we show that the increase in binding affinity resulted from eliminating an N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential.

Amino Acid Sequence↗

PubMed1993

Neutralizing monoclonal antibodies that distinguish three antigenic sites on human cytomegalovirus glycoprotein H have conformationally distinct binding sites.

Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map of two nonoverlapping antigenic sites that are bridged by a third antigenic site. Neutralization assays with 15 laboratory or clinical human cytomegalovirus strains indicated that the monoclonal antibodies recognize three antigenically variable and three conserved epitopes within the three antigenic sites. The variable-domain genes encoding monoclonal antibodies representing each of the three antigenic sites were cloned and sequenced, and molecular models of their binding sites were generated. Conformational differences in the antibody-binding sites suggested a structural basis for experimentally observed differences in gH epitope recognition.

Amino Acid Sequence↗

PubMed1993

Dear Hillary.

Michael Vasquez, president of Health Care Expert Systems, Inc., attended a meeting the task force on healthcare reform. After the meeting, he sent the following letter to Hillary Rodham Clinton, to members of Iowa's Congressional delegation and to Steven Schroeder, M.D., of the Robert Wood Johnson Foundation, who moderated the discussion along with Clinton and HHS Secretary Donna Shalala. Vasquez said he was "concerned that the role of information systems was not adequately represented as part of the possible solution during the discussion."

Efficiency↗