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Biomedical subjects

A Jaramillo

Publications and source records attributed to A Jaramillo.

At least 19 recordsLinked to original sources
PubMed2006

Polycystic ovaries after precocious pubarche: relation to prenatal growth.

BACKGROUND: In 1998, we revealed a sequence departing from prenatal growth restraint in girls and evolving, through precocious pubarche (PP) in mid-childhood, towards anovulatory and hyperinsulinaemic hyperandrogenism. The latter condition fulfilled the criteria for the diagnosis of polycystic ovary syndrome (PCOS), which was then defined independently of the presence of polycystic ovaries (PCOs). Since 2003, the diagnosis of PCOS has been extended by adding PCO as an alternative criterion. We verified longitudinally over 28 +or- 2 years the prevalence of PCO and its potential relationship to growth before birth in a group of post-PP women (n=14, mean age=28 years; body mass index=24.3 kg/m2) belonging to the original cohort of 35 girls in whom the PP-PCOS sequence was described. METHODS: Endocrine-metabolic variables, body composition (by dual-energy X-ray absorptiometry), carotid intima-media thickness (IMT) and ovarian morphology by transvaginal ultrasonography were assessed in all women. RESULTS: Post-PP women with a birthweight (BW) in the lowest quartile, when compared with post-PP women with a higher BW, had smaller ovaries (mean volume=4.0 versus 9.0 ml; P=0.004) and a much lower prevalence of PCO (0 versus 67%; P=0.006). The remaining variables were similar between BW subgroups. CONCLUSIONS: The presence of a PCO morphology in women with a PP history was found to relate to prenatal growth. It would be of interest to verify whether a similar relationship exists in anovulatory and/or hyperandrogenic women without PP history.

Adolescent↗
PubMed2006

Predictors for malignant middle cerebral artery infarctions: a postmortem analysis.

BACKGROUND: Early detection of malignant infarction of the middle cerebral artery (MI-MCA) is important because of possible treatment by hemicraniectomy. OBJECTIVE: To investigate the anatomic and vascular predictors of MI-MCA. METHOD: The authors evaluated 192 consecutive autopsies of patients with nonlacunar cerebral infarction affecting the MCA territory. MI-MCA was defined by an infarct with temporal or central brain herniation and brain swelling. The autopsy protocol included a systematic analysis of intracranial arteries (including the bony segments of carotid and vertebral arteries and the circle of Willis), extracranial arteries, the aortic arch, and the heart. RESULTS: A total of 45 patients with MI-MCA were identified. Their median (range) survival time was 6 (0 to 20) days as compared with 18 (0 to 2,040) days for non-MI-MCA patients. Compared with non-MI-MCA, MI-MCA cases more frequently involved the superficial and deep MCA territory and were more frequently associated with anterior cerebral and anterior choroidal artery territory infarcts. Hemorrhagic transformation, Duret hemorrhages, carotid occlusion, and ipsilateral abnormalities of the circle of Willis were also more frequent (p < 0.05). Multivariable analysis showed that younger age, female sex, absence of stroke history, higher heart weight, carotid artery occlusion, and abnormal circle of Willis ipsilaterally were all independently associated with MI-MCA (p < 0.03). CONCLUSIONS: Typical pathologic pattern for development of malignant infarction of the middle cerebral artery is a carotid occlusion with abnormal ipsilateral circle of Willis in a young patient who had a first-ever large hemispheric stroke including the superficial territory with possibly a slight predominance of female sex.

Aged↗
PubMed2006

Periodontitis is associated with preeclampsia in pregnant women.

BACKGROUND: Recent investigations have demonstrated a positive association between periodontitis and pregnancy complications. The purpose of this study was to determine the effect of periodontitis and the subgingival microbial composition on preeclampsia. METHODS: A case-control study was carried out in Cali, Colombia that included 130 preeclamptic and 243 non-preeclamptic women between 26 to 36 weeks of pregnancy. Sociodemographic data, obstetric risk factors, periodontal status, and subgingival microbial composition were determined in both groups. Preeclampsia was defined as blood pressure>or=140/90 mm Hg, and >or=2+ proteinuria, confirmed by 0.3 g proteinuria/24 hours of urine specimens. Controls were healthy pregnant women. Odds ratios (ORs) for periodontitis and subgingival microbiota compositions were calculated. RESULTS: A total of 83 out of 130 preeclamptic women (63.8%) and 89 out of 243 controls (36.6%) had chronic periodontitis (OR: 3.0; 95% confidence interval (CI): 1.91 to 4.87; P<0.001). Clinical attachment loss increased in the case group (4.0+/-0.10 mm) compared to the control group (3.0+/-0.08 mm) (P<0.001). The average newborn birth weight from preeclamptic mothers was 2.453 g, whereas in controls was 2.981 g (P<0.001). Two red complex microorganisms, Porphyromonas gingivalis and Tannerella forsythensis, and the green complex microorganism Eikenella corrodens were more prevalent in the preeclamptic group than in controls (P<0.01). CONCLUSIONS: Chronic periodontal disease and the presence of P. gingivalis, T. forsythensis, and E. corrodens were significantly associated with preeclampsia in pregnant women. Further research is needed to establish pathogenic mechanisms of active periodontal disease and subgingival periodontopathogens related to preeclampsia development.

Adolescent↗
PubMed2001

Prevention of obliterative airway disease in HLA-A2-transgenic tracheal allografts by neutralization of tumor necrosis factor.

BACKGROUND: Inflammatory cytokines play an important role in the development of experimental obliterative airway disease (OAD) after transplantation. To further determine the immunologic mechanisms associated with OAD development, we used a murine tracheal transplant model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4+ T cells and then determined whether neutralization of several inflammatory cytokines affected the development of OAD. METHODS: Tracheas from HLA-A2+ C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Recipients were treated with neutralizing antibodies against tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), or interleukin-1 (IL-1). Allograft histology as well as anti-HLA-A2 antibody development and T cell proliferative responses were determined at days +5, +15, +28, and +60. RESULTS: Allografts in untreated and anti-IFN-gamma-treated recipients demonstrated full development of OAD by day +28. Allografts in anti-TNF-treated recipients showed no evidence of OAD, even at day +60. Allografts in anti-IL-1-treated recipients showed airway epithelium changes by day +28 but minimal evidence of OAD by day +60. Spleen cells from untreated and anti-IFN-gamma-treated recipients showed significantly higher proliferative responses to HLA-A2+ cells, compared with syngeneic recipients (negative controls). In contrast, anti-TNF and anti-IL-1-treated recipients showed significantly lower proliferative responses to HLA-A2+ cells, compared with untreated recipients. Development of anti-HLA-A2 antibodies was detected in all recipients by day +15, with the exception of those treated with anti-TNF. CONCLUSION: Among the inflammatory cytokines, TNF seems to play a crucial role in the immunopathology of OAD developed after transplantation.

Airway Obstruction↗
PubMed2001

CD4+ T cell recognition of a single discordant HLA-A2-transgenic molecule through the indirect antigen presentation pathway induces acute rejection of murine cardiac allografts.

To further define the role of indirect allorecognition, cardiac allografts from HLA-A2-transgenic (HLA-A2+) C57BL/6 mice were heterotopically transplanted into normal C57BL/6, CD4 T cell-knockout (KO) C57BL/6 mice, CD8 T cell-KO C57BL/6 mice, fully MHC-discordant BALB/c mice (allogeneic control), and HLA-A2+ C57BL/6 mice (syngeneic control). HLA-A2+ grafts were acutely rejected when transplanted into BALB/c mice (mean survival time: 10+/-0.8 days), normal C57BL/6 mice (mean survival time: 16.5+/-2.1 days) as well as CD8-KO mice (mean survival time: 12.8+/-1.3 days). Histopathological analysis revealed classical acute cellular rejection with moderate to severe diffuse interstitial CD4+ and CD8+ cellular infiltrates and significant intra-graft deposition of IgG and complement. In contrast, HLA-A2+ grafts were not rejected when transplanted into CD4-KO mice or HLA-A2+ mice. CD8-KO recipients treated with an anti-CD4 monoclonal antibody, but not with an anti-NK monoclonal antibody, failed to reject their allografts with prolonged administration of antibody (30 days). Spleen cells from mice rejecting HLA-A2+ allografts failed to lyse HLA-A2+ target cells indicating a lack of involvement of CD8+ T cells in the rejection process. In contrast, spleen cells from rejecting animals proliferated significantly to both HLA-A2+ cells and to a peptide derived from the HLA-A2 molecule. Development of anti-HLA-A2 antibodies was observed in all animals rejecting HLA-A2+ allografts. These results suggest that indirect allorecognition of donor MHC class I molecules leads to rejection of cardiac allografts and development of alloantibodies in this unique transplant model in which there is a single MHC discordance between donor and recipient.

Acute Disease↗
PubMed2001

Activation of human airway epithelial cells by non-HLA antibodies developed after lung transplantation: a potential etiological factor for bronchiolitis obliterans syndrome.

BACKGROUND: The main cause of morbidity and mortality after lung transplantation (LT) is bronchiolitis obliterans syndrome (BOS). Anti-HLA antibodies development after LT has been shown to play an important role in BOS pathogenesis. However, the nature of non-HLA antibodies developed after LT and their role in BOS pathogenesis have not been determined. METHODS: Sera from 16 BOS+ patients and 11 BOS- patients were collected at 12, 24, 36, and 48 months after LT. Anti-HLA class I and class II antibodies were absorbed with pooled human platelets and pooled human lymphoblastoid cell lines, respectively. Then, the presence of non-HLA antibodies against several cell lines from different origin was determined by flow cytometric analysis. Antibody-positive samples were tested for induction of proliferation and growth factor production in two selected airway epithelial cell (AEC) lines. RESULTS: Five of 16 BOS+ patients (31.2%) and 0 of 11 BOS- patients (0%) developed anti-AEC antibodies after LT (P=0.05). No reactivity against endothelial cells, lymphocytes, monocytes, or granulocytes was detected. Further analysis of two selected sera demonstrated the development of reactivity against a 60-kDa antigen expressed by 60% of AEC lines and only 12% of cell lines from other tissues. Antibody binding to this antigen induced intracellular Ca++ influx, tyrosine phosphorylation, proliferation, and up-regulation of transforming growth factor-beta and heparin-binding epidermal growth factor mRNA transcription in AECs. CONCLUSIONS: These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.

Antibodies↗
PubMed2001

Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome.

A correlation between indirect allorecognition of mismatched donor HLA class I peptides and development of bronchiolitis obliterans syndrome (BOS) after lung transplantation has been previously observed. The aim of this study was to determine whether there was a correlation between indirect allorecognition of mismatched donor HLA class II peptides and development of BOS after lung transplantation. Peripheral blood mononuclear cells from nine BOS+ and nine BOS-lung transplant recipients were cultured with synthetic peptides corresponding to the beta-chain hypervariable region of a mismatched donor HLA-DR molecule. Then, proliferative alloreactivity as well as frequency of alloreactive T cells were determined. In addition, the immunodominant epitopes from the donor HLA-DR molecules were identified in selected patients. T cells from BOS+ patients showed a dose-dependent proliferative alloreactivity against donor HLA-DR peptides that was significantly higher than that observed in BOS- patients (p=0.001). Similarly, the frequency of HLA-DR alloreactive T cells was significantly higher in BOS+ patients than in BOS- patients (p=0.001). This T-cell alloreactivity was directed against a single immunodominant HLA-DR peptide. These results suggest that indirect alloreactivity to donor HLA class II molecules may play a role in the pathogenesis of BOS after lung transplantation.

Amino Acid Sequence↗
PubMed2001

Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration.

PURPOSE: Evidence suggests that both humoral and cellular autoimmune processes directed toward heat shock proteins (hsp) contribute to the pathogenesis of atherosclerosis. We characterized a human hsp distinct from those previously characterized in atherosclerotic lesions, termed HDJ-2. METHODS: To determine the role of HDJ-2 in atherosclerosis, we compared the level of HDJ-2 mRNA expression with the level of hsp60 and hsp70 mRNA expression in 26 carotid endarterectomy specimens and 17 normal arteries. The level of expression of HDJ-2 mRNA was also correlated to the presence of plaque ulceration and the degree of luminal stenosis associated with the lesion. RESULTS: The expression of HDJ-2 and hsp70 was significantly higher in carotid artery plaques as compared with normal arteries: HDJ-2, 6.7 +/- 1.6 vs 0.1 +/- 0.04, (P =.001); hsp70, 9.5 +/- 0.9 vs 3.7 +/- 0.8, (P =.002). There was no significant difference in hsp60 expression between carotid artery plaques and normal arteries (21.0 +/- 0.9 vs 20.6 +/- 0.8, P =.65). Increased HDJ-2 expression in carotid artery plaques was independent of hsp70 (Pearson correlation, r = 0.11; Bartlett chi(2) analysis, P =.71). Within the ulcerated plaque group, there was a correlation between degree of stenosis and high HDJ-2 mRNA expression (r = 0.896, P =.016). However, there was no correlation between degree of stenosis and high HDJ-2 mRNA expression within the nonulcerated plaque group (r = 0.530, P =.076) or within the entire group of patients (r = 0.0085, P =.97). CONCLUSION: These results demonstrate that expression of HDJ-2 is significantly increased in atherosclerotic carotid artery plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in ulcerated atherosclerotic carotid artery plaques.

Arteriosclerosis↗
PubMed2001

Automatic procedures for protein design.

This review describes computational procedures for deriving the amino acid sequences that are compatible with a given protein backbone structure. Such procedures can be used to gain insight into the constraints imposed by the 3D structure of the protein sequence, or to design proteins that are likely to adopt a given backbone conformation. We start by presenting a short overview of the various types of approaches to protein design developed over more than a decade. This is followed by a more detailed presentation of a recently developed sequence selection procedure DESIGNER. This latter presentation illustrates the basic principles underlying this type of procedures, described what they may teach us when applied to small proteins, and highlights issues that need to be addressed in order to go forward.

Amino Acid Sequence↗
PubMed2000

Indirect recognition of porcine swine leukocyte Ag class I molecules expressed on islets by human CD4+ T lymphocytes.

Xenotransplantation of porcine islets is considered a viable alternative treatment for type 1 diabetes mellitus. Therefore, we characterized human PBL responding to porcine islets both in vitro by coculture and in vivo using SCID mice reconstituted with human PBLs (HuPBL-SCID) and transplanted with porcine islets. T cell lines generated in vitro and graft-infiltrating T cells obtained from HuPBL-SCID mice were CD4+-proliferated specifically to porcine islets cultured with autologous APC. This proliferation was abrogated by an anti-human class II Ab. These T cell lines also proliferated to purified swine leukocyte Ag (SLA) class I molecules in the presence of self-APC, indicating that the primary xenoantigens recognized are peptides derived from SLA. This CD4+ T cell line lysed porcine islets but not splenocytes. CD4+ T cell clones with Th0, Th1, and Th2 cytokine profiles were isolated. The Th0 and Th1 clones lysed porcine islets, whereas the Th2 clone that secreted a large amount of IL-4 was not lytic. These results demonstrate that human T cells responding to porcine islets are primarily CD4+ and recognize porcine xenoantigens by the indirect Ag pathway presentation. These activated T cells produce cytokines that lyse islets. Furthermore, we demonstrate that the major porcine xenoantigens recognized are SLA class I molecules.

Animals↗
PubMed2000

Anti-HLA antibody binding to hla class I molecules induces proliferation of airway epithelial cells: a potential mechanism for bronchiolitis obliterans syndrome.

OBJECTIVE: Development of anti-HLA antibodies is associated with development of bronchiolitis obliterans syndrome after lung transplantation. We sought to determine the mechanism by which anti-HLA antibodies affect the development of bronchiolitis obliterans syndrome. We postulated that anti-HLA antibodies bind to the donor lung epithelium and stimulate phosphorylation and proliferation. METHODS: The A549 lung epithelial carcinoma cell line was cultured in serum-deficient medium to produce static growth. Then the cells were treated with anti-HLA sera from lung transplant recipients, pooled anti-HLA serum from highly sensitized patients, or normal human serum. The cells were also treated with the W6/32 mouse anti-HLA class I monoclonal antibody or control mouse IgG. Tritiated thymidine uptake was determined at 24, 48, and 72 hours. In parallel experiments the cells were treated as described above, and the levels of tyrosine phosphorylation were determined by Western blot analysis. RESULTS: Cells treated with anti-HLA serum or the W6/32 monoclonal antibody exhibited significantly greater proliferation and tyrosine phosphorylation of proteins of approximately 170, 130, 110, and 70 kd compared with cells treated with normal human serum or mouse IgG, respectively. CONCLUSIONS: These data indicate that anti-HLA antibodies have the ability to stimulate airway epithelial cell proliferation and that they may play an important role in the development of bronchiolitis obliterans syndrome. Prevention of HLA sensitization and immunosuppression with agents capable of blocking indirect antigen presentation and the humoral immune response against the allograft may be pivotal in preventing the development of bronchiolitis obliterans syndrome after lung transplantation.

Antibodies, Monoclonal↗
PubMed2000

Airway epithelial cell damage mediated by antigen-specific T cells: implications in lung allograft rejection.

The aim of this study is to assess the mechanisms associated with airway epithelial cell (AEC) injury, which may have implications in lung allograft rejection. Three AEC lines, KDI-650, Beas-2B and A549 were analyzed. Effect of cytokines on the expression of Fas, HLA class I, and HLA class II were assessed by flow cytometry. AEC-specific T cells were generated in vitro and assessed for lysis by (51)Cr release assay. HLA class I and Fas were expressed on all AEC lines. Beas-2B and A549 expressed low levels of class II compared with KDI-650, which lack this expression. Expression of HLA class II was augmented on KDI-650 and Beas-2B by IFN-gamma treatment. AEC-specific T cells generated in vitro were predominantly CD8(+) and lysed relevant AEC targets. Anti-HLA class I monoclonal antibodies inhibited the lysis of AEC by specific T cells while anti-Fas and anti-HLA class II monoclonal antibodies did not have any effect on the T cell induced lysis of AECs. AECs cultured with supernatant derived from T-cell cultures induced the expression of Fas, HLA class I, as well as HLA class II. These results suggest AEC damage is mediated by AEC-specific T cells primarily by the conventional HLA class I/peptide complex and TCR interaction. Further, the factors released by these T cells also induce the expression of Fas, as well as HLA class I and class II, which may have implications on the outcome of the immune response against AECs.

Antibodies, Monoclonal↗
PubMed1999

Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.

BACKGROUND: Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients. METHODS: Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets. RESULTS: When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules. CONCLUSIONS: Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

Antibodies↗
PubMed1999

A dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals.

Slob is a novel protein that binds to the carboxy-terminal domain of the Drosophila Slowpoke (dSlo) calcium-dependent potassium (K(Ca)) channel. A yeast two-hybrid screen with Slob as bait identifies the zeta isoform of 14-3-3 as a Slob-binding protein. Coimmunoprecipitation experiments from Drosophila heads and transfected cells confirm that 14-3-3 interacts with dSlo via Slob. All three proteins are colocalized presynaptically at Drosophila neuromuscular junctions. Two serine residues in Slob are required for 14-3-3 binding, and the binding is dynamically regulated in Drosophila by calcium/calmodulin-dependent kinase II (CaMKII) phosphorylation. 14-3-3 coexpression dramatically alters dSlo channel properties when wild-type Slob is present but not when a double serine mutant Slob that is incapable of binding 14-3-3 is present. The results provide evidence for a dSlo/Slob/14-3-3 regulatory protein complex.

14-3-3 Proteins↗
PubMed1998

Possibilities and limitations in miniaturized sensor design for uric acid.

Uric acid (UA) has been under intensive investigation by electrochemists owing to its important role as a metabolite in biological fluids. One of the major problems in biological determinations of uric acid comes from electrochemical interferences such as ascorbic acid (AA), which has a similar oxidation potential, E1/2 approximately 200 mV versus SCE, at graphite electrodes, and is present at high concentrations in biological systems. UA undergoes a 2 H+, 2 e- oxidation in aqueous buffers. The oxidation product, a diimine, is an unstable intermediate with a half-life of less than 22 ms. A follow-up hydration reaction converts the diimine to an imine alcohol. Results of previous work show that UA weakly adsorbs and undergoes a fast electron transfer reaction, ks = 54 s-1, at carbon fiber electrodes. These characteristics make UA an excellent candidate for fast scan voltammetric (FSV) determinations. This paper presents the results of FSV at bare carbon fiber electrodes. The results show good selectivity and sensitivity in the determination of low concentrations of UA in the presence of high concentrations of AA. By increasing the scan rate above 500 V s-1, voltammograms of UA in the presence of AA can be resolved because of the kinetic differences in the response of the two anions, without the need for a permselective film on the electrode. Results are also presented that demonstrate an effective way to reach a stable background current at bare carbon fiber electrodes, which is required in FSV because the signal from the analyte is smaller than the electrochemical signal from the background current. Signal-to-noise ratios at bare carbon fiber electrodes in FSV are improved, because the high temporal resolution in fast scan methods allows the acquisition of a large number of scans that can be signal averaged in a short period of time. In addition, large signals can be measured because the voltammetric peak current increases with increase in scan rate.

Electrochemistry↗