Is bcl-2 a key molecule in the abnormal immune response of hemodialysis patients?
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Apoptosis↗
Biomedical subjects
R Ramirez
Publications and source records attributed to R Ramirez.
Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group.
Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.
Adolescent↗
Ab initio study of cubyl chains and networks.
The spatial arrangements and physical properties of one- and two-dimensional structures, based on the amazing cubane (C(8)H(8)) molecule, are investigated in detail. In particular, we compute the electronic structure, both by first principle calculations and by semiempirical methods. The elastic and vibrational properties are evaluated as well. All these results are compared with those of the single cubane molecule, in order to elucidate the influence of dimensionality.
Journal Article↗
Fluocinolone acetonide topical oil for scalp psoriasis.
Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.
Administration, Topical↗
New features of rubella in Spain: the evidence of an outbreak.
In most of western Europe the rubella vaccine coverage is high. However, prior to the introduction of the vaccine in Latin America, rubella susceptibility in women of childbearing age was 10-25%. Forty one (93%) countries in Latin America have adopted the rubella vaccine since 2002. The adult immigrant population in Spain constitutes a group of susceptibles. In February 2003, the Madrid Community Measles Elimination Plan detected an increase in rubella notifications in women who had been born in Latin America. A descriptive study was undertaken to characterise the outbreak. A confirmed case was a person with fever or rash and a positive IgM serology, and living in Madrid, between 1 December 2002 and 31 March 2003. The secondary attack rate (SAR) per household was calculated. A total of 19 cases of rubella were identified, 15 were confirmed and 4 were probable cases. Fourteen (73.7%) cases were women at childbearing age. The mean age was 25.1 years. One pregnancy was diagnosed with a voluntary termination. Eleven (57.9%) cases were from Ecuador. The mean time of residence in Spain was 41 months. None of the cases or the 54 (78.3%) household contacts had been vaccinated against rubella. The SAR was 9.1%. This study showed the spread of rubella in the susceptible Latin American Community that is resident in Madrid. The interventions proposed were a vaccination programme towards immigrants, a health education campaign to prevent congenital rubella, and a health professional training programme case management.
Adolescent↗
BALB/C mice injected with LSTRA leukemic cell line are cured by in vivo treatment with IL-2 + GM-CSF.
We studied the effects of the in vivo administration of interleukin-2 (IL-2) (at low doses) + GM-CSF in BALB/C mice injected intraperitoneally with LSTRA murine leukemic cell line in order to test the possible role of this immunotherapeutic approach in the eradication of leukemia. Mice were injected intraperitoneally on day -1 with different concentrations of LSTRA cells. On day 0, mice received a lethal dose of TBI of 700 cGy from a Cs(137) source, followed by a single high dose of recombinant human-granulocyte-colony stimulating factor (rh-G-CSF) (1 microg/g) intraperitoneally 2h after TBI. This procedure rescued 80% of mice but only mice injected with the lower concentration of LSTRA cells (10(3)) could be cured. The lethal dose (LD 100/60) of LSTRA in normal mice was 10(4). The subcutaneous administration of rh-IL-2 (4.000 IU/mouse per day, from day +1 to +28) + rm-GM-CSF (1 microg/kg per day) from day +7 to +28 cured mice injected with 10(4) LSTRA cells and 40% of mice injected with 10(5) cells. Mice injected with 10(6) cells died from leukemia. We observed an increase in LAK activity on days +21 and +28 without an increase in NK activity. We show that BALB/C mice injected with LSTRA cell line can be cured by in vivo activation with IL-2 + GM-CSF depending on the cell dose injected. The curability of leukemia was confirmed at the molecular level with a PCR method.
Animals↗
Neuropsychiatric thalamocortical dysrhythmia: surgical implications.
Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.
Adult↗
Antithrombin III prevents early pulmonary dysfunction after lung transplantation in the dog.
BACKGROUND: Ischemia-reperfusion injury with the resulting inflammatory response is a devastating complication of lung transplantation; much of the tissue damage could be diminished by control of the inflammatory response. Recent studies have show that antithrombin III (AT III) has an anti-inflammatory effect in addition to its established role in the regulation of blood coagulation. Thus, we hypothesized that the administration of AT III might help to prevent ischemia-reperfusion injury after lung transplantation. METHODS AND RESULTS: The study was performed in a dog model of orthotopic lung transplantation. Dogs were randomly assigned to receive either vehicle (controls) or AT III. We observed that in control dogs, during the 180-minute period after lung transplantation, the arterial O(2) partial pressure decreased and both the alveolar-arterial O(2) difference and the pulmonary vascular resistance increased. By contrast, these parameters remained unchanged in the group of dogs receiving AT III. Dogs with transplants receiving AT III did not show an increase in cell adhesion molecules, and histological examination revealed almost an absence of inflammatory response. The administration of AT III produced a marked increase in serum prostacyclin (PGI(2)) levels, whereas in control dogs, the PGI(2) levels did not change. The beneficial effect of AT III was not observed when dogs received indomethacin to prevent the stimulation of PGI(2) release by AT III. CONCLUSIONS: Our results demonstrate that AT III prevents ischemia-reperfusion injury in a dog model of lung transplantation and that this effect is conditioned by an increase in PGI(2) production.
6-Ketoprostaglandin F1 alpha↗
Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population.
We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.
Alleles↗
Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model.
The mechanism of antidepressant action, at the cellular level, is not clearly understood. It has been reported that chronic antidepressant treatment leads to an up-regulation of brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampus, and that physical activity (voluntary running) enhances this effect. We wished to investigate whether BDNF expression brought about by these interventions may overcome deficits caused by acute stress, and might impact behavior in an animal model. In this report, we have tested the hypothesis that the combination of the antidepressant, tranylcypromine, and physical exercise could lead to decreased neurotrophin deficits and enhanced swimming time in animals that have been forced to swim in an inescapable water tank. Rats were either treated with tranylcypromine, engaged in voluntary running, or both for one week. After these treatments, the animals underwent a two-day forced swimming procedure. BDNF mRNA levels were significantly depressed in untreated animals subjected to forced swimming. Animals that either underwent prior activity or received antidepressant showed BDNF mRNA levels restored to baseline. Animals receiving the combined intervention showed an increase in hippocampal BDNF mRNA well above baseline. Swimming time during a five-minute test was significantly enhanced in animals receiving the combined intervention over untreated animals. Swimming time was not significantly enhanced over that of animals receiving antidepressant alone, however. Enhanced swimming time correlated with increased levels of BDNF mRNA in one hippocampal sub-region (CA4-hilus). These results suggest that the combination of exercise and antidepressant treatment may have significant neurochemical, and possibly behavioral, effects. In addition, these results support the possibility that the enhancement of BDNF expression may be an important element in the clinical response to antidepressant treatment. The induction of BDNF expression by activity/pharmacological treatment combinations could represent an important intervention for further study, to potentially improve depression treatment and management.
Animals↗
Genome screening for linkage disequilibrium in a Costa Rican sample of patients with bipolar-I disorder: a follow-up study on chromosome 18.
Linkage disequilibrium (LD) methods offer great promise for mapping complex traits, but have thus far been applied sparingly. In this paper we describe an LD mapping study of severe bipolar disorder (BP-I) in the genetically isolated population of the Central Valley of Costa Rica. This study provides the first complete screen of a chromosome for a complex trait using LD mapping and presents the first application of a new LD mapping statistic (ancestral haplotype reconstruction (AHR)) that evaluates haplotype sharing among affected individuals. The results of this chromosome-wide analysis are instructive for genome-wide LD mapping in isolated populations. Furthermore, the analysis continues to support a possible BP-I locus on 18pter, suggested by previous analyses in this population. Evidence for a possible BP-I locus on 18q12.2 is also described.
Bipolar Disorder↗
Prevalence and correlates of antisocial behaviors among three ethnic groups.
Using data from the MECA Study, this report examines the prevalence of Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), and various levels of antisocial behavior and their correlates among three ethnic groups: Hispanics, subdivided into Island Puerto Ricans and Mainland Hispanics; African Americans; and Mainland Non-Hispanic, Non-African Americans. Correlates considered include stressful life events, birth defects, low birth weight, learning difficulties, teen mothers, family environment, marital adjustment, social competence, parental monitoring, and family relationships. Logistic regression was used to determine the association of outcomes with individual correlates and of interaction terms with ethnicity. Differences between adjusted rates and observed rates of disorders and levels of antisocial behaviors are compared to estimate the extent to which each correlate explains the group differences in rates. Island Puerto Ricans had a lower prevalence of CD, ODD, and various levels of antisocial behavior than mainland Hispanics, African Americans, and non-Hispanic Whites. The lower prevalence appears to be associated with differences in the extent to which a number of these correlates are found on the island, the most salient being better family relations between the target children and their parents and siblings.
Adolescent↗
Uptake of D-mannoheptulose by normal and tumoral pancreatic islet cells.
D-mannoheptulose was recently proposed as a possible tool to label preferentially insulin-producing cells in the pancreatic gland. In the present study, D-[3H]-mannoheptulose uptake by rat pancreatic islets or dispersed islet cells was found to represent a time-related and temperature-sensitive process inhibited by cytochalasin B. This mould metabolite also inhibited the efflux of D-[3H]-mannoheptulose from prelabelled islets. After 60 min incubation at 37 degrees C, the apparent intracellular distribution space of the tritiated heptose was close to or somewhat higher than that of D-[5-3H]glucose and close to 50% of the intracellular 3HOH space. It was further enhanced by D-glucose and a high concentration of 10 mM of D-mannoheptulose. The uptake of D-[3H]mannoheptulose was much lower however than that of D-[3H]mannoheptulose hexaacetate. As judged from the fate of D-mannoheptulose hexa[2-14C]acetate, the latter ester was efficiently hydrolyzed in the islet cells. The internalization of D-[3H]mannoheptulose (or its ester) coincided with the generation of tritiated acidic metabolites, reflecting phosphorylation of the heptose. The situation found in normal islet cells sharply differed from that found in tumoral islet cells of either the RINm5F or INS-1 line, in which the apparent distribution space of D-[3H]mannoheptulose represented only about 3 and 9%, respectively, of the intracellular 3HOH space. These results indicate that the entry of D-mannoheptulose into islet cells represents a carrier-mediated process, possibly mediated at the intervention of GLUT2 and, hence, provide further support to the possible use of a suitable D-mannoheptulose analog as a tool for the preferential labelling of insulin-producing cells in the pancreatic gland.
Animals↗
Uptake of D-mannoheptulose by rat erythrocytes, hepatocytes and parotid cells.
D-[3H]mannoheptulose (or D-[1-14C] mannoheptulose) net uptake was measured in rat erythrocytes, parotid cells and hepatocytes. In the erythrocytes and parotid cells, the intracellular distribution space of the heptose (0.1 mM) represented only about 1 and 13%, respectively, of the intracellular 3HOH space. In hepatocytes, however, it amounted to approximately 45% of the intracellular 3HOH space. In all cases, the apparent distribution space of D-[3H]mannoheptulose hexaacetate largely exceeded that of unesterified D-[3H]mannoheptulose. Relative to the intracellular water space, the generation of acidic metabolites (expressed as an apparent distribution space) from radioactive D-mannoheptulose was one order of magnitude lower in parotid cells (< or = 3%) than in hepatocytes (> or = 20%). These findings are compatible with the hypothesis that D-mannoheptulose is transported into cells mainly, if not exclusively, at the intervention of GLUT2.
Animals↗
Thermal convection in fluidized granular systems
Thermal convection is observed in molecular dynamic simulations of a fluidized granular system of nearly elastic hard disks moving under gravity, inside a square box. Boundaries introduce no shearing or time dependence, but the energy injection comes from a slip (shear-free) thermalizing base. The top wall is perfectly elastic and lateral boundaries are either elastic or periodic. The spontaneous temperature gradient appearing in the system due to the inelastic collisions, combined with gravity, produces a buoyancy force that, when dissipation is large enough, triggers convection.
Journal Article↗
Tyrosine kinase expression is increased in papillary thyroid carcinoma of children and young adults.
Tyrosine kinases (TKs) are important candidate genes for malignant transformation and at least 21 different TKs have been identified in the thyroid gland. We hypothesized that the collective activity of these TKs might be increased in thyroid carcinoma and have association with the clinical behavior of individual tumors. To test this, we determined TK expression by immunohistochemistry in 74 archival thyroid tissue blocks (48 papillary thyroid carcinoma, PTC; 9 follicular thyroid carcinoma, FTC; 17 benign thyroid diseases) from children and young adults. Mean TK expression was greater for PTC (2.1 +/- 0.11) than benign lesions (1.6 +/- 0.2, p = 0.027), and also tended to be greater in FTC (2.1 +/- 0.25, p = 0.12). Recurrence risk was three-fold greater for PTC with intense TK expression (4/15, 27%) than for PTC with minimal - moderate TK expression (3/33, 9.0%). However, this was not statistically significant (p = 0.10). In PTC, TK expression correlated with expression of the receptor for hepatocyte growth factor / scatter factor (cMET, r = 0.31, p = 0.044). In FTC, TK expression did not correlate with cMET, but tended to be greater in young patients (r = -0.59, p = 0.09). We conclude that TK expression is increased in PTC and possibly associated with an increased recurrence risk.
Adolescent↗
Over-expression of hepatocyte growth factor/scatter factor (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma.
OBJECTIVE: The study determined if hepatocyte growth factor/scatter factor (HGF/SF) or the HGF/SF receptor (cMET) might be important for metastasis in thyroid cancer. DESIGN: We examined HGF/SF and cMET expression by immunohistochemistry in a retrospective group of benign and malignant thyroid lesions from children and young adults, and correlated the intensity of expression with clinical outcome. PATIENTS: Patients included 42 children and young adults with papillary thyroid carcinomas (PTC), seven with follicular thyroid carcinomas (FTC), two with medullary thyroid carcinomas (MTC), 14 with benign thyroid disorders, and two with normal thyroids. MEASUREMENTS: Expression of cMET was graded from 0 (absent) to 4 (intense); and HGF/SF expression was graded from 0 (absent-minimal) to 3 (diffuse and intense). RESULTS: cMET staining was greater in PTC (mean intensity 2.3 +/- 0.4 vs. 0.8 +/- 0.2, P < 0.005) and FTC (2.4 +/- 0.6 vs. 0.8 +/- 0.2, P = 0.04) than benign lesions (0.8 +/- 0.2) or normal thyroids (0.4 +/- 0.5). PTC with intense cMET staining had shorter disease free survival (P = 0.05) and increased HGF/SF staining (r = 0.39, P = 0.017). HGF/SF correlated with the extent of disease at diagnosis (r = 0.33, P = 0.049). Patients with PTC were stratified into quartiles based on combined cMET and HGF/SF staining. Those with intense cMET and HGF/SF staining were younger (P = 0.05), and had reduced disease free survival (P = 0.03). CONCLUSIONS: We conclude that increased cMET and HGF/SF expression is associated with a high risk for metastasis and recurrence in children and young adults with papillary thyroid carcinoma.
Adolescent↗
Activation of the coagulation system in Gulf War Illness: a potential pathophysiologic link with chronic fatigue syndrome. A laboratory approach to diagnosis.
Most symptoms of Gulf War Illness (GWI) are similar to Chronic Fatigue Syndrome (CFS) and/or Fibromyalgia (FM). We investigated whether these symptoms are associated with an activated coagulation system as has been reported in some cases of CFS/FM. The coagulation assays include activation markers of the cascade, platelet activation and hereditary risk factors. Our findings show activation of the coagulation system in GWI. This evidence of a hypercoagulable state suggests that symptoms may be due to poor blood flow and, therefore, a basis for the potential utility of anticoagulant therapy.
Adult↗