Search PubMed⌕ Search

Biomedical subjects

M J Rodriguez

Publications and source records attributed to M J Rodriguez.

At least 19 recordsLinked to original sources
PubMed2001

The synthesis of pseudomycin C' via a novel acid promoted side-chain deacylation of pseudomycin A.

The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported.

Acylation↗
PubMed2001

Spatial and temporal evolution of trihalomethanes in three water distribution systems.

Spatial and seasonal changes in trihalomethane (THM) concentrations were investigated in three distribution systems of Quebec (Canada) which are supplied by different surface waters and which use a variety of physicochemical treatment strategies. The investigation was based on an intensive 25-week sampling programme, undertaken at a time of year when the temperature of southern Quebec surface waters exceeds 4 degrees C (April-November). THMs and other water quality and operational parameters were monitored at points along the distribution system--between the treatment plant and the system extremities--which represented variable residence times of water. Results showed that THM concentrations vary significantly (from 1.5 to 2 times, depending on the utility) between finished waters as they leave the plant and water at the system extremities. When water temperature exceeds 15 degrees C, spatial THM variations are particularly high (from 2 to 4 times, depending on the utility). The development of multivariate regression models showed that water temperature was a better predictor of THM seasonal variability than chlorine dose, surrogates of natural organic matter and pH. Also, initial THM formation (in finished waters leaving the plant) was a good predictor of THM levels at distribution system extremities.

Halogens↗
PubMed2001

Recurrent portopulmonary hypertension after liver transplantation: management with epoprostenol and resolution after retransplantation.

We report a case of portopulmonary hypertension in which the pulmonary hypertension resolved after initial orthotopic liver transplantation. Portopulmonary hypertension recurred when the transplanted liver failed and again resolved after a second liver transplantation. Intravenous epoprostenol was administered perioperatively to control the pulmonary hypertension in both instances.

Antihypertensive Agents↗
PubMed2001

Sequence of centromere separation: effect of 5-azacytidine-induced epigenetic alteration.

The factors which control the sequential separation of the various chromosomes in a genome at the meta-anaphase junction are not well understood. In genomes in which separation is correlated with the quantity of pericentric heterochromatin one factor appears to be the epigenetic nature, namely condensation, of pericentric heterochromatin. When we induced decondensation of pericentric heterochromatin in mouse cells with 10(-6), 4x 10(-6) and 6x10(-6) M 5-azacytidine (5-AC) for 8 h, it resulted in alteration of the sequence of centromere separation. The centromeres which lacked pericentric heterochromatin appeared not to have been affected because there could not be an epigenetic alteration induced by 5-AC. The major effect was on chromosomes with the largest quantity of pericentric heterochromatin. These chromosomes separated at significantly higher frequency than in the untreated population. We also treated human cells, in which separation does not depend upon the quantity of heterochromatin, with 2x10(-5) and 6x10(-6) M 5-AC for 5 and 8 h. Compared with the control, 5-AC treatment resulted in an increased frequency of separated centromeres of acrocentric chromosomes in relation to those of non-acrocentric chromosomes. In the control the acrocentric chromosomes are the last to separate; in the treated population there was almost random separation of the two types of chromosomes. This epigenetic alteration might be another factor which results in genesis of aneuploidy.

Animals↗
PubMed1999

The synthesis of water soluble prodrugs analogs of echinocandin B.

A facile synthesis of phosphonate and phosphate ester prodrugs on the phenolic hydroxy of two echinocandin semisynthetic derivatives is reported. The water solubility and stability profiles of the ECB compounds varied with the choice of alkyl group used. In some cases, the ester prodrugs with small aliphatic side chains retained antifungal activity while enhancing water solubility.

Anti-Bacterial Agents↗
PubMed1999

The first case report of the use of a zoom videoendoscope for the evaluation of small bowel graft mucosa in a human after intestinal transplantation.

BACKGROUND: Control of allograft rejection remains the most difficult dilemma in intestinal transplantation. Standard endoscopic surveillance to date has not been always accurate in the diagnosis of rejection. We describe the first application of a zoom video endoscope in monitoring graft mucosa in humans after intestinal transplantation. METHOD: A zoom video endoscope, which can magnify the image up to 100-fold, was used in this study. The patient was a 31-year-old man who received an isolated intestinal transplant. Surveillance endoscopy with the zoom video endoscope was performed through the ileostomy. Endoscopic biopsies were done at the same time. RESULTS: The zoom video endoscope showed the microscopic architecture of the graft mucosa such as villi and crypts with outstanding quality. We found that an enlargement of the crypt areas appeared to correlate with morphologic changes of early rejection. This finding was reversed with the treatment of rejection. CONCLUSIONS: The zoom video endoscope successfully showed the detailed information of intestinal mucosa. The ability to visualize a more representative view of the graft mucosa could lead to better detection of early rejection. A greater experience with this unique method will provide more accurate assessment of the intestinal allograft.

Adult↗
PubMed1998

Identification of a common antigenic site in the nucleocapsid protein of European and North American isolates of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N) protein has been identified as the most immunodominant viral protein. The N protein genes from two PRRSV isolates Olot/91 (European) and Quebec 807/94 (North American) were cloned and expressed in Escherichia coli using the pET3x system. The antigenic structure of the PRRSV N protein was dissected using seven monoclonal antibodies (MAbs) and overlapping fragments of the protein expressed in E.coli. Three antigenic sites were found. Four MAbs recognized two discontinuous epitopes that were present in the partially folded protein or at least a large fragment comprising the first 78 residues, respectively. The other three MAbs revealed the presence of a common antigenic site localized in the central region of the protein (amino acids 50 to 66). This hydrophillic region is well conserved among different isolates of European and North American origin. However, since this epitope is not recognized by many pig sera, it is not adequate for diagnostic purposes. Moreover, none of the N protein fragments were able to mimic the antigenicity of the entire N protein.

Animals↗
PubMed1998

Novel glycopeptide antibiotics: N-alkylated derivatives active against vancomycin-resistant enterococci.

LY264826 (A82846B) is a naturally-occurring glycopeptide antibiotic, differing from vancomycin in the stereochemistry of the amino-sugar of the disaccharide function, and the presence of a third sugar attached at the benzylic position of amino acid residue 6. Despite these seemingly subtle differences, LY264826 is approximately 10 times more active than vancomycin against the enterococci. In the pursuit of new antibiotics active against multiresistant Gram-positive organisms, an extensive side chain SAR was developed focusing on the reductive alkylation of LY264826 at the amino function of the disaccharide moiety. A new series of derivatives having varying degrees of structural diversity in the side chain (e.g. varying lengths and degrees of rigidity) was found to have potent activity against vancomycin-resistant enterococci (MIC's < 1.0 microgram/ml) as well as activity against staphylococci and streptococci as good or better than vancomycin.

Alkylation↗
PubMed1997

Epitope mapping of the nucleocapsid protein of European and North American isolates of porcine reproductive and respiratory syndrome virus.

Two major genotypes of porcine reproductive and respiratory syndrome virus (PRRSV) have been described, which correspond to the European and North American isolates. PRRSV nucleocapsid (N) protein has been identified as the most immunodominant viral protein. The N genes from two PRRSV isolates, Olot/91 (European) and Québec 807/94 (North American), were cloned and expressed in: (i) baculovirus under the control of the polyhedrin promoter and (ii) Escherichia coli using the pET3x system. The N protein from both isolates was expressed much more efficiently in E. coli as a fusion protein than in baculovirus. The antigenicity of the protein was similar in both systems and it was recognized by a collection of 48 PRRSV-positive pig sera. The antigenic structure of the PRRSV N protein was investigated using seven monoclonal antibodies (MAbs) and overlapping fragments of the protein expressed in E. coli. Four MAbs recognized two discontinuous epitopes that were present in the partially folded protein, or at least a large fragment comprising the first 78 residues. The other three MAbs revealed the presence of a common antigenic site localized in the central region of the protein (amino acids 50-66). This region is well conserved among different isolates of European and North American origin and is the most hydrophilic region of the protein. However, this epitope, although recognized by the MAbs and many pig sera, is not useful for diagnostic purposes. Moreover, none of the N protein fragments were able to mimic the antigenicity of the entire protein.

Amino Acid Sequence↗
PubMed1997

The synthesis and antifungal activity of N-alkylated analogs of echinocandin B.

The synthesis and biological activity of a series of N-alkylated derivatives of echinocandin B are described and compared with the N-acylated analogs. The linear, rigid geometry of the side chain that was essential to improve the antifungal potency of the N-acylated series gave similar in vitro results with the N-alkylated derivatives. However the slight structural variation forfeited all in vivo activity.

Animals↗
PubMed1996

Oral immunization of rabbits with VP60 particles confers protection against rabbit hemorrhagic disease.

Rabbit hemorrhagic disease virus (RHDV) causes more than 90% mortality in adult rabbits. In this study, the cDNA of the VP60 coding sequence of RHDV was cloned under the control of the polyhedrin and p10 promoters of baculovirus to be expressed in insect cells. The expression of RHDV VP60 under the control of the p10 promoter was 5-10 times higher than using the polyhedrin promoter. The p10-derived VP60 was able to assemble into virus-like particles (VLPs). RHDV VLPs were successfully used to protect rabbits against the disease even at doses as low as 0.5 micrograms when injected intramuscularly or subcutaneously. The ability to elicit an immune response was independent of the adjuvant or the route of immunization. Remarkably, oral administration of RHDV VLPs efficiently induced protecting antibodies to RHD at doses as low as 3 micrograms. The use of binary ethylenimine for the stabilization of the VLPs was decisive for eliciting a good oral immunity. This report demonstrates the potential use of these procapsids in obtaining RHD oral vaccines and opens the door to the use of these capsids for the prevention of the disease in wild animals. Therefore, a new, and potentially important application of recombinant VLPs in the induction of protective immunity by the oral route is foreseen.

Administration, Oral↗
PubMed1996

Corticosterone, prolactin and thyroid hormones as hormonal mediators of the stimulated phagocytic capacity of peritoneal macrophages after high-intensity exercise.

The aim of this study was to evaluate the effect of high-intensity physical activity (swimming until exhaustion) with or without previous training on the phagocytosis and destruction of inert particle capacities of macrophages, and the role of corticosterone, prolactin and thyroid hormones as possible hormonal mediators. The results indicated that high-intensity exercise provokes a stimulation of both phagocytosis and destruction of inert particles when performed in absence of previous training. However, swimming until exhaustion after a one month training program (25 min/day) induced an increase in phagocytosis but not in the destruction of latex beads. Corticosterone, prolactin and thyroid hormones can be considered as hormonal mediators of the exercise-induced stimulation of phagocytosis, since these hormones increased plasma concentration, and the in vitro incubation of macrophages with the same higher physiological plasma concentrations of each hormone, as after exercise, also induced phagocytic stimulation of these cells.

Animals↗
PubMed1996

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci.

Certain derivatives of the glycopeptide antibiotic LY264826 with N-alkyl-linked substitutions on the epivancosamine sugar are active against glycopeptide-resistant enterococci. Six compounds representing our most active series were evaluated for activity against antibiotic-resistant, gram-positive pathogens. For Enterococcus faecium and E. faecalis resistant to both vancomycin and teicoplanin, the MICs of the six semisynthetic compounds for 90% of the strains tested were 1 to 4 micrograms/ml, compared with 2,048 micrograms/ml for vancomycin and 256 micrograms/ml for LY264826. For E. faecium and E. faecalis resistant to vancomycin but not teicoplanin, the MICs were 0.016 to 1 micrograms/ml, compared with 64 to 1,024 micrograms/ml for vancomycin. The compounds were highly active against vancomycin-susceptible enterococci and against E. gallinarum and E. casseliflavus and showed some activity against isolates of highly vancomycin-resistant leuconostocs and pediococci. The MICs for 90% of the strains of methicillin-resistant Staphylococcus aureus tested were typically 0.25 to 1 micrograms/ml, compared with 1 microgram/ml for vancomycin. Against methicillin-resistant S. epidermidis MICs ranged from 0.25 to 2 micrograms/ml, compared with 1 to 4 micrograms/ml for vancomycin and 4 to 16 micrograms/ml for teicoplanin. The spectrum of these new compounds included activity against teicoplanin-resistant, coagulase-negative staphylococci. The compounds exhibited exceptional potency against pathogenic streptococci, with MICs of < or = 0.008 microgram/ml against Streptococcus pneumoniae, including penicillin-resistant isolates. In in vivo studies with a mouse infection model, the median effective doses against a challenge by S. aureus, S. pneumoniae, or S. pyogenes were typically 4 to 20 times lower than those of vancomycin. Overall, these new glycopeptides, such as LY307599 and LY333328, show promise for use as agents against resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant pneumococci.

Animals↗
PubMed1996

Relationship between structure and biological activity of novel R106 analogs.

The retro-aldol reaction at residue 8 of R106-1 produced a chemical handle, in the form of a sarcosine residue, that was amenable to classical aldol alkylation conditions. In vitro assay of several new hydroxylated analogs have shown that L isomers exhibit more potent antifungal activity than D isomers. However, all analogs exhibited a significant decrease in activity against Cryptococcus neoformans. By contrast, structural modifications of R 106 were tolerated by some Candida spp., but the potency of activity was diminished as compared to that of the natural product R106-1. The full structure-activity relationship of the new R106 analogs has provided important information about the steric and electronic requirements of binding to target receptors. Furthermore, comparison of the structural differences between R106-1 and other derivatives, suggested that the potential for hydrogen bonding (at residue 8) was a key structural feature that was required to maintain activity against Cryptococcus neoformans.

Anti-Bacterial Agents↗
PubMed1996

Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity.

Reductive alkylation of the A82846 family of glycopeptide antibiotics has the potential of producing seven products. N-Alkylation of the disaccharide amino function can be accomplished selectively, and offers the greatest increase in antibacterial activity. Products resulting from N-alkylation of LY264826 (A82846B) provide the most potent derivatives as compared to other members of this class of antibiotics. Two of these derivatives, LY307599 and LY333328 are approximately 500 times more active than vancomycin against vancomycin-resistant enterococci.

Alkylation↗