Search PubMed⌕ Search

Biomedical subjects

J Luna

Publications and source records attributed to J Luna.

At least 37 records · Page 2Linked to original sources

Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model.

Integrin alpha v beta 3 is differentially expressed in angiogenic blood vessels in skin granulation tissue, and alpha v beta 3 antagonists inhibit angiogenesis in chick chorioallantoic membranes. In this study, we investigated the role of alpha v beta 3 in retinal neovascularization. There was no detectable signal for alpha v beta 3 by immunohistochemistry in normal human retina, but neovascular tissue removed from the surface of the retina of patients with diabetic retinopathy showed intense staining for alpha v beta 3 within the endothelial cells of new blood vessels. In a murine model of oxygen-induced ischemic retinopathy, there was intense staining for alpha v beta 3 in endothelial cells participating in neovascularization but no detectable staining in normal retinal blood vessels of adult mice. Synthetic peptides that bind alpha v beta 3 and perturb alpha v beta 3-mediated adhesion in vitro inhibited retinal neovascularization in the murine model when given by intraperitoneal or periocular injections. These data suggest that alpha v beta 3 antagonists may provide a useful adjunct for the treatment of retinal neovascularization.

Animals↗

Molecular cloning of the human homolog of a striatum-enriched phosphatase (STEP) gene and chromosomal mapping of the human and murine loci.

A gene for a protein tyrosine phosphatase (PTPase) was isolated from a human fetal brain cDNA library by PCR amplification. Sequence analysis revealed that the PTPase has a single phosphatase catalytic domain located at the C-terminus that includes the highly conserved amino acid domain [I/V]HCXAGXXR[S/T]GX[F/Y] found in all tyrosine phosphatases. Two proline-rich regions located at the N-terminus may contain putative Src homology domain 3 (SH3) binding motifs. Comparison of the PTPase with a previously cloned striatum enriched phosphatase (STEP) from rat and from mouse exhibited a high degree of identity (approximately 85-90%) at both the nucleotide and the amino acid levels, indicating that the human PTPase is the homolog of the rat and murine STEP gene. By using a combination of somatic cell hybrid analysis and fluorescence in situ hybridization, we have mapped the human STEP locus to chromosome 11p15.2-p15.1 and the murine STEP gene to chromosome 7B3-B5. These are two regions of known conserved synteny, providing further evidence that the human STEP is a true homolog of the murine STEP gene. Candidate disease genes in the vicinity include Usher syndrome type 1C in human and a mouse mutant locus, twister (twt).

Animals↗

Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp.

The nuclear factor of activated T cells (NFAT) is a transcription factor complex involved in the activation of cytokines and cell surface molecules associated with coordinating the actions of different cells required for an immune response. Two different genes have recently been cloned that encode proteins capable of functioning as the pre-existing (p) and cytosolic (c) component of the NFAT transcription complex, NFATc of human and NFATp of murine origin (Northrop et al., 1994; McCaffrey et al., 1993b). We report here the partial cDNA cloning of the murine homolog of NFATc and the human homolog of NFATp, and the chromosomal localization of both genes in both species to conserved syntenic regions. Through the use of mapping panels of human x Chinese hamster and mouse x rodent cells hybrids, the NFATc genes were mapped to human and mouse chromosomes 18. By analyzing a chromosome 18 radiation hybrid panel, the human NFATc gene was localized to the q terminus, closely linked to STS marker D18S497. The murine Nfatc gene was sublocalized to chromosome band 18E4 by FISH. The NFATp genes were mapped by somatic cell hybrid analysis to human chromosome 20 and mouse chromosome 2. Human NFATp was assigned to chromosome region 20q13.2-->q13.3 by FISH. Based on the conserved syntenic region on human chromosome 20 and mouse chromosome 2, murine Nfatp is predicted to reside in the vicinity of a mutant locus wasted. Homozygous wst/wst mice display a phenotype reminiscent of severe combined immune deficiency or ataxia telangiectasia, disorders that could therefore be considered candidates for NFATp mutations.

Amino Acid Sequence↗

cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12.

Lactate and pyruvate are transported across cell membranes by monocarboxylate transporters (MCTs). Here, we use the recently cloned cDNA for hamster MCT1 to isolate cDNA and genomic clones for human MCT1. Comparison of the human and hamster amino acid sequences revealed that the proteins are 86% identical. The gene for human MCT1 (gene symbol, SLC16A1) was localized to human chromosome bands 1p13.2-p12 by PCR analysis of panels of human x rodent cell hybrid lines and by fluorescence chromosomal in situ hybridization.

Amino Acid Sequence↗

Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin.

It has been previously reported that inhibition of human erythroid colony-forming units (CFU-E) in vitro by interleukin-1 (IL-1) is an indirect effect, occurring through the production of interferon gamma (IFN gamma). IFN gamma, in turn, inhibits CFU-E colony formation directly, and its inhibitory effect can be overcome by exposure to high concentrations of erythropoietin (EPO). To develop an in vitro animal model for investigating inhibition of erythropoiesis by IFN gamma, the effects of recombinant murine (rm) IFN gamma on highly purified CFU-E from the spleens of mice infected with the anemia strain of the Friend virus (FVA) were studied. rmIFN gamma inhibited CFU-E colony formation in a dose-dependent manner. This inhibition occurred with large (> or = 8 cell) colonies only; smaller colonies were not affected. The inhibitory effect was corrected to 72% of control by high EPO concentrations of 64 U/mL. Murine CFU-E were then cultured with rmIFN gamma in the presence of a soluble murine IFN gamma receptor fused to the hinge and Fc domains of the human IgG1 heavy chain (mIFN gamma R-IgG). Inhibition of CFU-E colony formation by rmIFN gamma (100 U/mL) was corrected by mIFN gamma R-IgG in a dose-dependent manner, with an approximate IC50 of 0.05 nmol/L, and complete or near complete correction at 0.5 nmol/L. Similarly, a human IFN gamma R-IgG greatly reduced the inhibitory effect of recombinant human IFN gamma on human CFU-E. These experiments provide an in vitro animal model for studying the inhibitory effects of IFN gamma on erythropoiesis and indicate that IFN gamma R-IgG may be a useful agent for reducing the toxicity of IFN gamma in vivo.

Animals↗

Characterization of gap junctions between pairs of Leydig cells from mouse testis.

Leydig cells are coupled in vivo by numerous gap junctions. In vivo and in vitro cells were immunolabeled by connexin 43 (Cx43) but not by Cx26 or Cx32 antibodies; immunoblotting confirmed specificity of Cx43 labeling. Pairs of Leydig cells dissociated from mouse testis were studied by dual whole cell voltage clamp, and a high incidence of dye (n = 20) and electrical coupling (n = 60; > 90%) was found. Coupling coefficients were near 1 and junctional conductance (gj) averaged 7.2 +/- 1.2 nS (SE, n = 40). Large transjunctional voltage (Vj) decreased gj; currents decayed exponentially with time constants of seconds that decreased at greater Vj. The residual conductance at large Vj was at least approximately 40% of the initial conductance. Exposure of cell pairs to saline solutions saturated with CO2 (n = 15) or containing 2 mM halothane (n = 15) or 3.5 mM heptanol (n = 15) rapidly and reversibly reduced gj. In eight cell pairs, gating of single junctional channels was observed during halothane-induced reduction in gj. Most gating events at Vj < 40 mV were fit by a Gaussian distribution with a mean of approximately 100 pS. With Vj > 40 mV, smaller transitions of approximately 30 pS were also recorded, and the frequency and duration of the approximately 100-pS transitions decreased. Also, approximately 70-pS transitions between 30- and 100-pS conductances were observed in the absence of 70-pS transitions to or from the baseline, indicating that the 30-pS conductance was a substate induced by large Vj.

Alcohols↗

Regional localization of 56 new human chromosome 18-specific yeast artificial chromosomes.

Fifty-six chromosome 18-specific yeast artificial chromosomes (YAC) were isolated from a human monochromosomal somatic cell hybrid DNA library. Fluorescence in situ hybridization revealed that the clones were evenly distributed throughout the chromosome. The clones, with an average insert size of 250 kb, cover about 18% of the euchromatic part of chromosome 18. Of 90 STS markers tested, 17 were represented in this YAC collection. Together with our previously reported set of unique chromosome 18-specific YACs, we now have available 111 regionally mapped, essentially nonchimeric, clones that provide more than 30% coverage and form a framework for the complete physical map.

Animals↗

A radiation hybrid map of human chromosome 18.

A human x Chinese hamster (CH) somatic cell hybrid subclone deficient in HPRT and containing only human chromosome 18 was irradiated with 7000 rad and fused to a thymidine kinase deficient CH cell line. Radiation-rescued hybrid cell lines, selected in HAT medium, were analyzed for human DNA with human interspersed-repeat sequence primers. Size and number of human chromosome fragments retained in a subset of hybrids were determined by FISH. A panel of 98 radiation hybrids (RH) was selected and analyzed for 90 chromosome 18-specific STSs by PCR, and for the D18Z1 centromeric marker by Southern blotting. STSs were developed from previously mapped RFLP loci and from published sequences. In addition, 32 novel STSs were generated from an 18-specific lambda library and from 18-specific YACs previously localized to chromosome bands by FISH. Marker retention frequency varied from 8-65% with an average of 24%. In selected RH the STS typing data were correlated with the chromosome 18 regions retained using 'reverse FISH' of IRS-PCR products from the RH to normal metaphase chromosomes. The order and intermarker distances of loci were determined using two-point and multipoint maximum likelihood methods. The resulting RH map covers most of chromosome 18 with four groups of tightly linked markers and three regions of loosely linked markers, one around the centromere and two on the long arm. More than a third of the markers are polymorphic and allow integration with the linkage map. This RH map provides a framework for establishing a clone contig of the entire chromosome 18.

Animals↗

[Differential aspects of drug prescriptions in elderly people living in the northeast area of Granada: study of 366 individuals].

BACKGROUND: The geriatric population consumes greater numbers of medicines than other age groups. We compared drug prescription and consumption in elderly persons residing in a nursing home or living in their own home. METHODS: We studied 366 elderly men and women (older than 65 years) who lived either in nursing homes or in their own home. The variables recorded were the most frequent diseases, number and types of drugs prescribed per person, and adverse reactions of the most frequently prescribed drugs. RESULTS: The most common diseases recorded among subjects living at home were arterial hypertension and rheumatic diseases; among those in nursing homes, the most common ailment was dementia. Subjects in nursing homes were prescribed more different drugs (2.8 +/- 1/person) than individuals living on their own (1.8 +/- 1/person). The percentage of adverse reactions was highest in ambulatory patients (64%) and in patients taking benzodiazepines (56%). A large proportion of all prescriptions (74.5%) were for solid galenic forms. CONCLUSIONS: We draw attention to the greater consumption of drugs by elderly persons residing in nursing homes, as well as the prescription of benzodiazepines and analgesic-antiinflammatory drugs within old age.

Aged↗

Generation of a human chromosome 18-specific YAC clone collection and mapping of 55 unique YACs by FISH and fingerprinting.

A yeast artificial chromosome (YAC) library was constructed from a somatic cell hybrid line in which the human chromosome content had been reduced by repeated subcloning to one or two copies of chromosome 18. Screening of 4700 primary yeast transformants generated 74 clones containing a YAC with a human DNA insert averaging 190 kb in size. The human YACs were localized to subregions of chromosome 18 by in situ hybridization of biotin-labeled Alu-PCR products obtained using total yeast DNA as a template. Comparisons of interspersed repetitive sequence-PCR and restriction fragment fingerprint patterns identified five sets of identical and three sets of overlapping YACs. Dual-label fluorescence in situ hybridization interphase mapping was used to determine the order of some nonoverlapping YACs. STS (sequence-tagged site) content mapping was carried out with PCR primers for 56 chromosome 18-specific markers. The identification of YACs containing four known genes--encoding the pituitary adenylate cyclase activating polypeptide (PA-CAP), the myelin basic protein (MBP), ferrochelatase (FECH), and SSAV1, an endogenous retroviral element related to the SSAV virus--provides a precise cytological map position for the respective loci. Our final collection of 55 randomly isolated, unique, and regionally localized YACs (D18S107-D18S161) is distributed over the entire chromosome and collectively covers approximately 12 Mb, i.e., 16% of the estimated 77 Mb of DNA in euchromatin of chromosome 18. These YACs provide reagents for the isolation of genes in these regions and represent nucleation points for the generation of STS to increase coverage of the chromosome by YAC contigs.

Adenylyl Cyclases↗

Pulmonary function after laparoscopic cholecystectomy.

BACKGROUND: The purpose of this study was to prospectively compare the effect of laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) on postoperative pulmonary function. METHODS: Forty consecutive patients (20 in each group) who were evenly matched in terms of pulmonary risk factors were assigned to either elective LC or OC. Pulmonary function studies, oxygen saturation, and chest radiography were performed on both groups before and after the operation until baseline levels were reached. Narcotic requirements and pulmonary complications were compared. The t test, ANOVA, and chi-squared analysis were used. RESULTS: Compared to the patients who underwent OC, patients who underwent LC had a significant reduction in postoperative pulmonary impairment (30% to 38%) in all areas studied including forced vital capacity; forced expiratory volume in 1 second; forced expiratory flow, mid-expiratory phase; maximum forced expiratory flow; maximum voluntary ventilation; total lung capacity; and oxygen saturation. Pulmonary function returned to baseline levels 4 to 10 days sooner after LC. Pulmonary complications including atelectasis and hypoxia were less frequent after LC. An eight-fold decrease was noted in postoperative pain medication requirement in the LC group. CONCLUSIONS: Compared to OC, laparoscopic cholecystectomy results in a significantly reduced compromise in pulmonary function and narcotic requirement leading to fewer postoperative pulmonary complications. Laparoscopic cholecystectomy should be considered the procedure of choice for elective cholecystectomy.

Adolescent↗

[Primary mental health care for the victims of the disaster in Armero, Colombia].

Seven to eight months after the disastrous volcanic mudslide that destroyed the town of Armero, Colombia, 200 victims were screened up by means of the Self-Reporting Questionnaire (SRQ) for emotional disorders identification. In order to assess disorders' specific nature, a 104-victim subsample was interviewed by psychiatrists. The most frequent diagnosis ranged among (a) Post-traumatic stress syndrome, (b) Depressión, and (c) Generalized anxiety disorder. Our findings help us to point out that (1) In a developing country a higher prevalence of well-defined emotional disorders among victims of any first-magnitude disaster is to be detected at such a level it can safely be said a real epidemic is to be tackled with, (2) Basically, the identified symptomatology confines itself to anxiety-depression disorders, (3) SRQ is indeed an apt instrument for disasters victims screening, and (4) Mental health specialized resources proved to be insufficient for an adequate coverage of the needs of the affected communities to be performed. As far as mental health is concerned, if the necessary services are to be offered so that all aspects involved are taken care of, it is imperative that victims be attended to by primary care workers. So far, mental health primary care area is still lacking a systematical research within a disaster situation framework. We understand that our paper may serve as an initial orientation for this care strategy being duly implemented and furthered up.

Adolescent↗

[Experimental esophageal transsection. Application to the treatment of hemorrhage in portal hypertension].

Nineteen of twenty dogs undergoing experimental esophageal transection with mechanical suturing were followed up over 1 to 120 days by means of light and electron microscopy examinations to evaluate changes in suture line. Histology showed few reactions to the metallic clips, the absence of new vessel formation with early healing from the 4th day, development of collagen fascicles after 1 week and consolidation after 2 weeks with reparation by the end of 1st month. Stability of healing process was apparent between 3 and 4 months, without evidence of stenosis due to scar tissue.

Animals↗

Identification of the receptor for erythropoietin by cross-linking to Friend virus-infected erythroid cells.

Erythropoietin (Epo) is a glycoprotein hormone that regulates erythroid development and interacts with surface receptors on developing erythroid cells. In this laboratory, a cell system with a relatively pure population of erythroid cells that respond to Epo has been developed. Immature erythroid cells are obtained from the spleens of mice infected with the anemia strain of Friend virus. The binding of 125I-labeled Epo (125I-Epo) to plasma membranes from these cells was studied in this investigation. 125I-Epo binding reached equilibrium within 20 min at 37 degrees C. Twenty percent of the receptors bound 125I-Epo with a Kd of 0.08 X 10(-9) M, while the remaining receptors bound the hormone with a Kd of 0.6 X 10(-9) M. In this study, a receptor for Epo was identified by cross-linking 125I-Epo to the receptor in intact cells and plasma membrane preparations using disuccinimidyl suberate. Polyacrylamide gel electrophoresis revealed two labeled bands of 100 and 85 kDa. The 85-kDa band was more heavily labeled (65%) than the 100-kDa band. Both bands were equally decreased when increasing amounts of unlabeled Epo were included in the binding mixture, indicating a specific interaction of 125I-Epo with the receptor.

Animals↗

Screening for the psychological consequences of a major disaster in a developing country: Armero, Colombia.

Seven months following the volcanic eruption that destroyed the small town of Armero, 200 victims were screened for emotional problems with the Self-Reporting Questionnaire, a simple and reliable instrument. Fifty-five percent of the victims were found to be emotionally distressed. Variables associated with the presence of emotional distress included living alone, having lost previous job, feeling not being helped, not knowing date for leaving temporary shelter, being dissatisfied with living arrangements, complaining of non-specific physical symptoms or epigastric pain, and presenting several physical problems. The high prevalence of emotional distress supports the need to deliver mental care to disaster victims in developing countries through the primary level of care. Our findings provide guidelines for early detection of individuals at risk for developing emotional problems.

Adolescent↗