Search PubMed⌕ Search

Biomedical subjects

J Molina

Publications and source records attributed to J Molina.

At least 37 records · Page 2Linked to original sources

Intestinal metaplasia in patients with columnar lined esophagus is associated with high levels of duodenogastroesophageal reflux.

OBJECTIVE: To evaluate the rate of duodenogastroesophageal reflux in patients with columnar lined esophagus compared with patients with gastroesophageal reflux disease without columnar lined esophagus, and to analyze whether it is related to the presence of specialized columnar epithelium in the metaplastic segment. SUMMARY BACKGROUND DATA: The carcinomatous degeneration of columnar lined esophagus originates from a specialized columnar epithelium. The appearance of this metaplastic phenomenon is clearly related to severe prolonged gastroesophageal reflux, but only some of these patients finally develop columnar lined esophagus. For this reason other factors have been suggested, particularly the role played by the reflux of duodenal contents into the esophagus. METHODS: The authors studied 15 healthy volunteers (control group), 10 patients with reflux symptoms but without endoscopic lesions, 20 patients with reflux esophagitis without columnar lined esophagus, and 35 patients with columnar lined esophagus (complicated with ulcers or stenosis in 8 cases), of whom 22 had intestinal metaplasia. To assess the reflux of duodenal contents into the esophagus, all the patients underwent Bilitec 2000 and 24-hour esophageal pH monitoring. RESULTS: The presence of bilirubin in the material refluxed into the esophagus was greater in the patients with columnar lined esophagus than in the rest of the groups. Likewise, duodenogastroesophageal reflux was greater in the columnar lined esophagus patients who had intestinal metaplasia. CONCLUSIONS: Duodenogastroesophageal reflux may play a major role in the development of columnar lined esophagus, especially in patients with intestinal metaplasia.

Adult↗

Construction of a 1.2-Mb contig including the citrus tristeza virus resistance gene locus using a bacterial artificial chromosome library of Poncirus trifoliata (L.) Raf.

The citrus tristeza virus resistance gene (Ctv) is a single dominant gene in Poncirus trifoliata, a sexually compatible relative of citrus. To clone this gene, a bacterial artificial chromosome (BAC) library has been constructed from an individual plant that was homozygous for Ctv. This library contains 45,696 clones with an average insert size of 80 kb, corresponding to 9.6 genome equivalents. Screening of the BAC library with five chloroplast DNA probes indicated that 0.58% of the BAC clones contained chloroplast-derived inserts. The chromosome walk across the Ctv locus was initiated using three closely linked genetic markers: C19, AD8, and Z16. The walk has been completed and a contig of ca. 1.2 Mb was constructed. Based on new data, the genetic map in the Ctv region was revised, with Ctv being located between AD8-Z16 and C19 at distances of 1.2 and 0.6 cM, respectively. Utilizing DNA fragments isolated from the contig as RFLP markers, the Ctv locus was further mapped to a region of ca. 300 kb. This contig contains several putative disease-resistance genes similar to the rice Xa21 gene, the tomato Cf-2 gene, and the Arabidopsis thaliana RPS2 gene. This library will therefore allow cloning of Ctv and other putative disease-resistance genes.

Amino Acid Sequence↗

Regioselective enzymatic acylations of polyhydroxylated eudesmanes: semisynthesis, theoretical calculations, and biotransformation of cyclic sulfites.

Different lipase enzymes have been tested in order to perform regioselective acetylations on the eudesmane tetrol from vulgarin. High yields (95%) of 1,12-diacetoxy derivative (4) were achieved in 1 h with Candida antarctica lipase (CAL). However, only the 12-acetyl derivative (6) was obtained in similar yield with Mucor miehei (MML) or Candida cylindracea (CCL) lipases. The enzymatic protection at C-1 and C-12 has been used to form eudesmane cyclic-sulfites between C-6 and C-4 atoms. The R/S-sulfur configuration has been assigned by means of the experimental and theoretical (13)C and (1)H NMR chemical shifts. The theoretical shifts were calculated using the GIAO method, with a MM+ geometry optimization followed by a single-point calculation at the B3LYP/6-31G(*) level (B3LYP/6-31G(*)//MM+). Moreover, B3LYP/6-31G(*) geometry optimizations were carried out to test the B3LYP/6-31G(*)//MM+ results, for the deacetylated sulfites (12 and 15). In addition to the delta(C) and delta(H) shifts, the (3)J(HH) coupling constants were also calculated and compared with the experimental values when available. Finally, different reactivities have been checked in both sulfites by biotransformation with Rhizopus nigricans. While the R-sulfite gave 2 alpha- and 11 beta-hydroxylated metabolites, the S-sulfite yielded only regioselective deacetylations. Furthermore, both sulfites showed different reactivities in redox processes.

Acylation↗

Sugarcane yellow leaf virus: an emerging virus that has evolved by recombination between luteoviral and poleroviral ancestors.

We have derived the genomic nucleotide sequence of an emerging virus, the Sugarcane yellow leaf virus (ScYLV), and shown that it produces one to two subgenomic RNAs. The family Luteoviridae currently includes the Luteovirus, Polerovirus, and Enamovirus genera. With the new ScYLV nucleotide sequence and existing Luteoviridae sequence information, we have utilized new phylogenetic and evolutionary methodologies to identify homologous regions of Luteoviridae genomes, which have statistically significant altered nucleotide substitution ratios and have produced a reconstructed phylogeny of the Luteoviridae. The data indicate that Pea enation mosaic virus-1 (PEMV-1), Soybean dwarf virus (SbDV), and ScYLV exhibit spatial phylogenetic variation (SPV) consistent with recombination events that have occurred between poleroviral and luteoviral ancestors, after the divergence of these two progenitor groups. The reconstructed phylogeny confirms a contention that a continuum in the derived sequence evolution of the Luteoviridae has been established by intrafamilial as well as extrafamilial RNA recombination and expands the database of recombinant Luteoviridae genomes that are currently needed to resolve better defined means for generic discrimination in the Luteoviridae (D'Arcy, C. J. and Mayo, M. 1997. Arch. Virol. 142, 1285-1287). The analyses of the nucleotide substitution ratios from a nucleotide alignment of Luteoviridae genomes substantiates the hypothesis that hot spots for RNA recombination in this virus family are associated with the known sites for the transcription of subgenomic RNAs (Miller et al. 1995. Crit. Rev. Plant Sci. 14, 179-211), and provides new information that might be utilized to better design more effective means to generate transgene-mediated host resistance.

Amino Acid Sequence↗

PAIR as percutaneous treatment of hydatid liver cysts.

Hydatid disease of the liver remains an important and challenging problem in rural areas; although, surgery is considered the treatment of choice, percutaneous treatment of hydatid cysts is relatively new, and the data related to it are limited. The purpose of the study was to present the results of percutaneous treatment of liver hydatid cysts. Thirty-four patients (13 male and 21 female), ranging in age between 14 and 80 years, with 55 liver hydatid cysts underwent percutaneous treatment with albendazole prophylaxis. Cysts were treated with a one-stage procedure that consisted of puncture of the cysts under guidance with computed tomography, aspiration of fluid, injection of hypertonic saline solution as scolicidal agent and reaspiration. Follow-up examinations showed progressive reduction and solidification of the cysts. The mean reduction in volume was 72%. No mortality, abdominal dissemination, or tract seeding occurred. Minor complications were urticaria with pruritus in two patients. One patient had a subcapusular hematoma without problem. Hospitalization courses varied from ambulatory procedures to 15 days of in-patient, mean hospital stay was 1.82 days. The results of percutaneous liver hydatid cyst treatment, indicating that the procedure is efficient and safe and offers complete cure in selected patients with a short hospitalization and that this technique should be considered an alternative to surgery.

Adolescent↗

Results of the cooperative protocol (N-III-95) for metastatic relapses and refractory neuroblastoma.

BACKGROUND: Prognosis of relapsed and refractory neuroblastoma is uniformly fatal; new therapeutic approaches are needed. PROCEDURE: Relapsed and refractory neuroblastoma patients were treated with continuous infusion chemotherapy combined with MIBG. RESULTS: Over 4 years, 35 heavily pretreated patients were registered, 29 with bone or/and bone marrow metastases. Grade 3 or 4 hematologic toxicity was frequent, without toxic deaths. Sixteen patients responded. The probability of 5-year overall survival was 0.19. CONCLUSIONS: This approach is feasible and toxicity manageable; it rescued some patients and prolonged their survival. It merits assay in newly diagnosed high-risk neuroblastoma patients.

3-Iodobenzylguanidine↗

DNA ploidy status and proliferative activity as markers of malignant potential in Barrett's esophagus: flow cytometric study using routinely paraffin-embedded tissue.

Regular endoscopic surveillance is recommended for patients with Barrett's esophagus to detect dysplasia and to diagnose carcinoma while it is in an early and possibly treatable stage. However, there are numerous unknown aspects regarding the natural history of dysplasia in this disease, and there is still a need for more accurate markers of risk of a malignant change. The aim of this study was to investigate the usefulness of DNA flow cytometry in Barrett's esophagus to define subgroups of patients showing similar histologic findings but with a different malignancy potential. Routinely formalin-fixed and paraffin-embedded tissues of 43 patients with Barrett's esophagus were processed for flow cytometric measurements (ploidy, proliferative index) and the results were compared with the histologic evolution observed in these patients. Only in the group of patients with "indefinite" dysplasia did we find statistically significant differences between the samples from patients with and without progression to more severe lesions (mean proliferative index of stable patients: 5.2% versus 8.3% in patients with progression, p = 0.001, Student's t-test). The presence in the flow cytometric analysis of a DNA aneuploid cell line is closely related to the presence of severe histologic alterations (i.e., high-grade dysplasia: p < 0.001, Fisher's exact test). Our results suggest that this procedure is at least capable of distinguishing between a real, although incipient, neoplastic process and morphologic changes of a reactive or reparative type. The increment in the tissue proliferative index could be an indicator of an early genomic instability which, with time, will develop into lesions with a more altered DNA content: aneuploidy.

Adenocarcinoma↗

Use of concurrent G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells in children with malignant disease.

There is limited experience in the mobilization of peripheral blood progenitor cells (PBPC) in children and the optimal method for PBPC mobilization is unknown. The present study was conducted to ascertain whether mobilization with G-CSF + GM-CSF (group I) provides some advantage over G-CSF alone (group II) in terms of collected CD34+ cells and hematopoietic recovery following myeloablative conditioning in children with malignancies. An economic analysis was also performed. Each group comprised 21 consecutive patients. The mean number of aphereses was 1.5+/-0.5 in group I and 1.2+/-0.46 in group II (NS). The mean number of CD34+ cells was 3.8 x 106+/-4.03/kg in group I and 4.2+/-5.4 in group II (NS). The mean number of total blood volumes (TBV) processed was 4.4+/-1.5 in group I and 4.3+/-1.5 in group II (NS). The mean duration of the procedure was 276+/-74.1 min in group I and 286.7+/-75.9 min in group II (NS), and the inlet flow was 45.1+/-12 ml/min in group I and 39.5+/-15.1 ml/min in group II (NS). No significant differences in the neutrophil and platelet engraftment probability were observed between the two groups. The mean overall cost of group II was not statistically significant from that of group I (US$ 9521+/-330 vs US$ 10201+/-1028, P = NS). The cost of mobilization was significantly higher in group I than in group II, conditioning regimen costs were similar in both groups and the costs related to the post-transplant period were similar in both groups. We conclude that PBPC mobilization with G-CSF + GM-CSF in children does not enhance hematological recovery in comparison with mobilization using G-CSF alone. However, the combination of G-CSF + GM-CSF does not significantly increase the overall cost of transplantation.

Adolescent↗

Decreased sperm function of patients with myotonic muscular dystrophy.

Myotonic muscular dystrophy (MMD) is a genetic disease caused by a defective enzyme, myotoninkinase. Male patients with MMD are reported to have reduced fertility. The purpose of this work was to study sperm capacitation and acrosome reaction in the ejaculates of sterile males with MMD and of healthy males (control group). The expression of the specific D-mannose receptors was explored by microscopic examination and by flow cytometry analysis. In addition, the binding patterns of Pisum sativum (PSA) lectin to acrosome content and outer acrosomal membrane in the spermatozoa of each group were analysed. Both the capacitation and the acrosome reaction in the spermatozoa of the MMD group were deficient and these findings strongly suggest that these anomalies may account for the sterility of these patients.

Acrosome Reaction↗

In vivo activity of the bis-triazole D0870 against drug-susceptible and drug-resistant strains of the protozoan parasite Trypanosoma cruzi.

We report the in vivo activity of the bis-triazole derivative D0870 against a variety of strains of Trypanosoma cruzi, the causative agent of Chagas' disease, including nitroimidazole/nitrofuran-resistant strains. In both acute and chronic murine models of the disease, treatment with D0870 at < or = 10 mg/kg on alternate days for a total of 20 doses provided 60-100% protection against death, regardless of the drug sensitivity of the infecting strain. In the acute model we obtained 70-100% parasitological cure in seven of the nine strains tested, including one intermediate and two highly drug-resistant strains. D0870 was able to cure 30-45% of animals chronically infected with various strains, including those harbouring the Colombiana strain, among which no cures were obtained with benznidazole. We also found that the anti-T. cruzi activity of D0870 is largely retained even if the hosts are immunosuppressed.

Animals↗

Detection of microsporidia in surface water: a one-year follow-up study.

In order to estimate the rate and seasonal variation of Enterocytozoon bieneusi contamination of surface water, sequential samples of water from the River Seine in France were collected during a 1-year period. Each sample (300-600 l) was submitted to sequential filtrations, and the filters were then examined for microsporidia using light microscopy and nested polymerase chain reaction (PCR) for E. bieneusi. Amplified products were hybridized with a E. bieneusi-specific probe. Twenty-five samples of water were analyzed during 1 year. Microscopic examination of stained filters proved unreliable for the identification of spores. Using nested PCR, 16 of 25 specimens were positive (64%). Unexpectedly, E. bieneusi was identified in only one sample by specific hybridization underlining the lack of specificity of ours primers. Nevertheless, using DNA sequence analysis, unknown microsporidia species were identified in eight cases, which had highest scores of homology with Vittaforma corneae or Pleistophora sp. This study shows a low rate of water contamination by E. bieneusi suggesting that the risk of waterborne transmission to humans is limited.

Animals↗

Activities of the triazole derivative SCH 56592 (posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts.

We have studied the in vivo activity of the new experimental triazole derivative SCH 56592 (posaconazole) against a variety of strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, in both immunocompetent and immunosuppressed murine hosts. The T. cruzi strains used in the study were previously characterized as susceptible (CL), partially resistant (Y), or highly resistant (Colombiana, SC-28, and VL-10) to the drugs currently in clinical use, nifurtimox and benznidazole. Furthermore, all strains are completely resistant to conventional antifungal azoles, such as ketoconazole. In the first study, acute infections with the CL, Y, and Colombiana strains in both normal and cyclophosphamide-immunosuppressed mice were treated orally, starting 4 days postinfection (p.i.), for 20 consecutive daily doses. The results indicated that in immunocompetent animals SCH 56592 at 20 mg/kg of body weight/day provided protection (80 to 90%) against death caused by all strains, a level comparable or superior to that provided by the optimal dose of benznidazole (100 mg/kg/day). Evaluation of parasitological cure revealed that SCH 56592 was able to cure 90 to 100% of the surviving animals infected with the CL and Y strains and 50% of those which received the benznidazole- and nifurtimox-resistant Colombiana strain. Immunosuppression markedly reduced the mean survival time of untreated mice infected with any of the strains, but this was not observed for the groups which received SCH 56592 at 20 mg/kg/day or benznidazole at 100 mg/kg/day. However, the overall cure rates were higher for animals treated with SCH 56592 than among those treated with benznidazole. The results were confirmed in a second study, using the same model but a longer (43-dose) treatment period. Finally, a model for the chronic disease in which oral treatment was started 120 days p.i. and consisted of 20 daily consecutive doses was investigated. The results showed that SCH 56592 at 20 mg/kg/day was able to induce a statistically significant increase in survival of animals infected with all strains, while benznidazole at 100 mg/kg/day was able to increase survival only in animals infected with the Colombiana strain. Moreover, the triazole was able to induce parasitological cures in 50 to 60% of surviving animals, irrespective of the infecting strain, while no cures were obtained with benznidazole. Taken together, the results demonstrate that SCH 56592 has in vivo trypanocidal activity, even against T. cruzi strains naturally resistant to nitrofurans, nitroimidazoles, and conventional antifungal azoles, and that this activity is retained to a large extent in immunosuppressed hosts.

Acute Disease↗

24-h pH monitoring is necessary to assess acid reflux suppression in patients with Barrett's oesophagus undergoing treatment with proton pump inhibitors.

BACKGROUND: Control of acid reflux is the main objective of treatment for Barrett's oesophagus. However, as these patients have a reduced sensitivity to acid reflux, disappearance of symptoms may not correlate with efficient control of acid reflux. The aim of this study was to determine in a group of patients with Barrett's oesophagus whether treatment with proton pump inhibitors suppressed pathological acid reflux once the symptoms of reflux had been controlled and the associated inflammatory lesions cured. METHODS: Eighteen consecutive patients with Barrett's oesophagus were studied, all of whom presented with heartburn. Twenty-four-hour oesophageal pH monitoring before treatment showed pathological acid reflux in all cases: median percentage of total time with pH less than 4, 22 (range 8-52) per cent. All patients received proton pump inhibitors (dose 20-60 mg/day) until symptoms were controlled. RESULTS: While on therapy, pH was reduced (median percentage of total time with pH less than 4, 3 versus 22 per cent; P < 0.001). However, three patients had persistent pathological rates of acid reflux. CONCLUSION: Disappearance of symptoms is not a good indicator of control of pathological acid reflux in patients with Barrett's oesophagus. Twenty-four-hour pH monitoring should be performed for proper adjustment of the dose of medication.

Adolescent↗

Assessing the feasibility of linkage disequilibrium methods for mapping complex traits: an initial screen for bipolar disorder loci on chromosome 18.

Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at approximately 6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I-susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.

Bipolar Disorder↗

Differential effect of estradiol on antibody secretion of murine hybridomas.

The need for increased antibody production by hybridomas has been approached by the addition to cell cultures of different growth factors; in vitro addition of estradiol-17beta (E2) to human blood lymphocytes increases the accumulation of plasma-blasts and Ig-secreting cells. Four different murine-murine hybridomas secreting different monoclonal antibodies (MAbs) were treated with E2. Specific antibody concentration was measured by enzyme-linked immunoadsorbent assay (ELISA) in culture supernatants whereas expression of E2-receptor in the hybridoma cells was determined by polymerase chain reaction (PCR). When E2 was added as a growth supplement to alpha-estrogen receptor positive murine-murine hybridomas it enhanced MAb secretion by as much as 255%, in a dose-dependant manner. This effect lasted for as long as the alpha-estrogen receptor was detected in the hybridoma cells, was inhibited by tamoxifen and was not observed in alpha-estrogen receptor negative hybridomas. The synthetic estrogen analogue diethylstilbestrol had no effect. Estradiol-17beta should be added to the list of hybridoma-inducing growth factors.

Animals↗

Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic lupus erythematosus: comparison between Colombians and Spaniards.

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.

Abortion, Spontaneous↗