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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 109 records · Page 6Linked to original sources

Intestinal alphabeta T cells of symptomatic celiac disease patients show oligoclonal TCRBV repertoire but polyclonal rearrangement patterns.

Celiac disease is an immunological disease provoked by some cereal proteins in HLA-DQ-mediated susceptible individuals. The role of intestine infiltrating alphabeta T cells in the pathogenesis of the disease has been functionally established. In the present report, we have studied the repertoire of TCRBV genes, spectratype distribution, and CDR3 sequences of intestinal T cell populations isolated from three CD patients at diagnosis and two normal control biopsies. Oligoclonal TCRBV usage was observed both in CD and control samples. However, a much more restricted TCRBV usage was evident in normal mucosa. The use of BV gene families was linked to no dominant rearrangements in CD, while apparent oligoclonal patterns were found in normal biopsies. Only 3 out of 73 sequenced transcripts derived from preponderant TCRBV genes in the three celiac samples were obtained twice. In contrast, only 13 different rearrangements were found out of 32 analyzed in control samples. In spite of the polyclonal behavior of T cells in CD mucosa, some conserved motifs in the CDR3 region were noticed among rearrangements derived from different TCRBV genes and patients. The lack of expanded T cell clones in the damaged tissue could be explained in terms of antigen diversity or by non-specific immunological responses in the symptomatic phase of the disease.

Celiac Disease↗

Successful cadaveric renal transplantation of patients highly sensitized to HLA Class I antigens.

The purpose of our investigation was to evaluate long-term graft survival and the role of histocompatibility in patients who were highly sensitized to human leukocyte antigen (HLA) Class I antigens and received a cadaveric renal transplant. Our multi-institutional study evaluated 7-yr graft outcomes and the histocompatibility requirements of 61 (6.1%) highly sensitized (anti-human globulin panel reactive antibody [AHG PRA], > or = 80%) cadaveric renal transplantation patients, transplanted between 1988 and 1997, among 999 consecutive cadaveric renal transplants. One- and 7-yr graft survival in the high PRA group (n = 61) was 76 and 59%, and was not significantly different from that in the low PRA group (n = 938), 86 and 59% (Wilcoxon = 0.11; log-rank = 0.45) (died with a functioning graft [DWFG] not censored). When those data were divided into primary and regrafts, 1- and 7-yr graft outcomes for high and low PRA groups were not significantly different [(primary, 1- and 7-yr survival: high PRA = 83 and 74%, n = 30, and low PRA = 87 and 61%, n = 825; log-rank = 0.37 for DWFG not censored) (regrafts, 1- and 7-yr survival: high PRA = 70 and 42%, n = 31, and low PRA = 80 and 43%, n = 113; log-rank = 0.36 for DWFG not censored)]. We did observe a subgroup of the high PRA patient group that had inferior graft outcomes. Graft outcome at 1 and 6 yr in the high PRA group for patients who had one to two DR mismatches (65 and 50%, n = 41) was significantly worse than for high PRA patients who had zero DR mismatches with their donors (100 and 78%, n = 20) (log-rank = 0.01 for DWFG not censored). Furthermore, the mean number of HLA-A and -B mismatches was significantly greater in the high PRA/DR-mismatched group (1.7 +/- 1.2, n = 41) compared with the high PRA/zero DR-mismatched group (0.5 +/- 1.1, n = 19) (p < 0.001). Overall, these data suggest that the patient who is highly sensitized to HLA Class I antigens has a long-term graft outcome that is equivalent to less sensitized patients, but that HLA-DR mismatching and a higher degree of Class I mismatching may be poor prognostic indicators in such patients.

Adult↗

Severe polyhydramnios in twin reversed arterial perfusion sequence: successful management with intrafetal alcohol ablation of acardiac twin and amniodrainage.

We present two cases of twin reversed arterial perfusion (TRAP) sequence complicated by severe polyhydramnios during the second trimester. Both cases were successfully managed at 27 and 26 weeks with ultrasound-guided intrafetal alcohol ablation of the acardiac twin and amniodrainage. The pump twins were delivered at 35 and 37 weeks, respectively, and both had uneventful postnatal courses. These cases suggest that, in the setting of severe polyhydramnios, prenatal intervention in TRAP sequence could certainly improve the otherwise poor prognosis of the pump twin. Targeting the main intra-abdominal vessel of the acardiac twin rather than its umbilical cord seems to be a good alternative in the prenatal treatment of these cases. The option of percutaneous intrafetal alcohol injection is widely available and less invasive, simpler and easier to perform than recently advocated endoscopic techniques.

Adult↗

The effect of a venous anastomosis Tyrell vein collar on the primary patency of arteriovenous grafts in patients undergoing hemodialysis.

PURPOSE: Vein collars and patches are used at the distal anastomoses of infrainguinal prosthetic grafts to improve graft patency. We initiated a randomized, prospective study to determine whether a Tyrell vein collar at the venous anastomosis of forearm loop arteriovenous grafts (AVGs) would improve patency. METHODS: Patients who required new forearm AVGs were randomized to (1) a standard end-to-side graft-vein anastomosis (control group) or (2) a Tyrell vein collar between the graft and the vein (study group). End points were (1) graft thrombosis, (2) graft removal and ligation, or (3) inadequate graft function. Randomization of 75 subjects was planned. The study was terminated early for ethical reasons. RESULTS: Seventeen patients (eight men, nine women) with a mean age of 52.8 years (range, 31-79 years) had 17 grafts placed (control group, n = 10; study group, n = 7). Comorbidities were not different between the groups (P>.05). Six (86%) of seven study grafts failed by 9 months (mean, 4.6 months). Four (66%) failed study grafts had venous outflow tract stenosis from intimal hyperplasia. This was confirmed at surgery in three and by angiography in one. The 9-month primary patency was 80% for the control group versus 17% for the study group (P =.015). Smaller outflow vein diameter in the study group (P =. 048) did not account for this inferior graft patency. CONCLUSION: A Tyrell vein collar at the venous anastomosis of a forearm AVG resulted in premature graft failure. The use of a Tyrell vein collar may accelerate venous anastomosis intimal hyperplasia.

Adult↗

Regulation of prostaglandin E2 production by the superoxide radical and nitric oxide in mouse peritoneal macrophages.

The purpose of this study was to elucidate the role of NO and O2 on enzymatic components of cyclooxygenase (COX) pathway in peritoneal macrophages. Activation of murine peritoneal macrophages by lipopolysaccharides (LPS) resulted in time-dependent production of nitric oxide (NO) and prostaglandin E2 (PGE2). This stimulation was also accompanied by the production of other reactive oxygen species such as superoxide (O2-), and by increased expression of COX-2. Our results provide evidence that O2- may be involved in the pathways that result in arachidonate release and PGE2 formation by COX-2 in murine peritoneal macrophages stimulated by LPS. However, we were not able to demonstrate that NO participates in the regulation of PG production under our experimental conditions.

Animals↗

Resistance rather than virulence selects for the clonal spread of methicillin-resistant Staphylococcus aureus: implications for MRSA transmission.

The population structure of methicillin-resistant Staphylococcus aureus (MRSA) is predominantly clonal, which may be related to the fitness of the genetic background of the methicillin-susceptible S. aureus (MSSA) into which the mecA chromosomal resistant determinant has inserted. To test this idea, we assessed whether the genotypes of New York MRSA are present in MSSA populations by using a combination of protein A gene sequence typing (spa typing) and pulsed-field gel electrophoresis (PFGE). Although about 16% of colonizing MSSA isolated from community subjects were related to MRSA, only one of the five predominant New York MRSA clonal types was found among the MSSA isolates. Similarly, among nosocomial MSSA, only four MRSA homologues were observed, two of which may have arisen through deletion of the mec element. Thus, MRSA clonal types represent a limited spectrum of the diversity seen in community and hospital S. aureus populations. The data are best explained by antibiotic selection pressure, as opposed to increased transmissibility or virulence, being responsible for the clonal dissemination of the resistance phenotype in MRSA genetic backgrounds, an in turn, the limited spread of these strains outside of the hospital environment.

Amino Acid Sequence↗

The effect of intercourse on pregnancy rates during assisted human reproduction.

Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.

Coitus↗

Two key chiral intermediates in a new 4-hydroxyisoleucine synthesis.

We present the crystal and molecular structure of two key compounds of a new synthesis strategy for isomers of natural (2S,3R, 4S)-4-hydroxyisoleucines, 2,3,5,6,7, 8-hexahydro-3-(1-hydroxy-1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a-trimethyl-5H-1,4-benzoxazin-2-one, C(16)H(23)NO(4), and 2,3,5,6,7, 8-hexahydro-3-(1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a-trimethyl-5H-1,4-benzoxazin-2-one, C(16)H(23)NO(3). A new optically pure chiral oxazinone auxiliary derived from (1R,2R, 5R)-2-hydroxypinan-3-one was used.

Crystallography, X-Ray↗

A silaproline-containing dipeptide.

The silaproline-containing dipeptide N-(3, 3-dimethyl-1-pivaloyl-1-aza-3-sila-5-cyclopentylcarbonyl)-L- alanine isopropylamide, C(17)H(33)N(3)O(3)Si, has two independent molecules in the asymmetric unit and each adopts a beta-II folded conformation, where the amide on the terminal C interacts intramolecularly with the pivaloyl O atom. The five-membered silaproline ring is C(beta)-puckered, an infrequent conformation for the homologous proline ring.

Crystallography, X-Ray↗

Abortifacients: toxidromes, ancient to modern--a case series and review of the literature.

Between 1998 and 1999, four women presented to an emergency department after having attempted a nonmedical abortion. All four reported turning to pharmacologically induced abortion because their access to health care was limited by lack of insurance and resources. These cases serve as a reminder that self-induced abortion remains a significant health problem for women, a problem that emergency physicians as toxicologists should be aware of.

Abortifacient Agents↗

The third intracellular loop of the rat and mouse cholecystokinin-A receptors is responsible for different patterns of gene activation.

It has previously been reported that the cholecystokinin analog JMV-180 behaves differently on the rat and the mouse cholecystokinin-A receptor (CCK-AR). In mice this analog acts as an agonist on low- and high-affinity sites of the CCK-AR, whereas in rats this compound acts as an agonist on high-affinity sites and as an antagonist on low-affinity sites. In an attempt to understand why the same compound behaves differently on these two CCK-A receptors, we cloned the cDNA encoding the mouse CCK-AR. We then investigated a cellular model able to mimic the effect that was observed in rats and mice. HeLa cells were transiently cotransfected with plasmids leading to expression of the rat or mouse CCK-AR in the presence of pFos-Luc as reporter plasmid; such a plasmid placed the regulatory part of the human c-Fos gene upstream from the firefly luciferase structural gene (Luc). We then observed that the two CCK-A receptors behaved differently, not only in the presence of compound JMV-180 but also in the presence of cholecystokinin or even in absence of ligand; the rat CCK-AR was 2 to 3 times more potent than the mouse CCK-AR in inducing the reporter protein, whatever the ligand studied. This result was confirmed using the same kind of experiment with the reporter plasmid p(TRE)(3)-tk-Luc. Using various mutated receptors, we investigated the role of the putative third intracellular loop. We concluded that both the primary structure of the receptor and the cellular context are in part responsible for the differential behavior of these CCK-A receptors.

Animals↗

A simple, rapid method for demonstrating bacterial flagella.

We developed a simple, rapid method for demonstrating flagellation of bacteria using the fluorescent protein stain NanoOrange (Molecular Probes, Eugene, Oreg.). The NanoOrange reagent binds to hydrophobic regions of proteins, which results in substantial enhancement of fluorescence. Unbound reagent is essentially nonfluorescent. NanoOrange fluorescently stained bacterial cell bodies, as well as flagella and other appendages, which could be directly observed by epifluorescence microscopy. Detection of flagella was further improved by using a charge-coupled device camera for image capture and processing. The reliability of the method was tested by using 37 pure cultures of marine bacteria. Detection of flagella on the isolates by NanoOrange staining was compared to detection by transmission electron microscopy (TEM). For 36 of 37 cultures, the two methods yielded the same results. In one case, flagella were detected by TEM but not by NanoOrange, although the difference may be attributable to differences between the culture preparations. NanoOrange staining is rapid (10 to 15 min) and does not require fixation or dehydration, so live samples can be stained. Since NanoOrange is a general protein stain and works directly in seawater, it may also prove to be useful for staining other proteinaceous material that is of interest to aquatic microbial ecologists.

Bacteria↗