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Biomedical subjects

J Moreno

Publications and source records attributed to J Moreno.

At least 109 records · Page 6Linked to original sources

Anti-neutrophil cytoplasmic autoantibodies in leprosy.

The objective was to evaluate the frequency of cytoplasmic and peripheral antineutrophil cytoplasmic antibodies (ANCA) in patients with leprosy, and to correlate the presence of ANCA with type and disease activity. Consecutive patients with leprosy were assessed clinically, and IgG ANCA were measured by indirect immunofluorescence. The presence of three of the following was used to assess disease activity: reactional state, fever, new cutaneous lesions, erythrocyte sedimentation rate and C-reactive protein. Sixty-four patients were studied and divided according to the Ridley-Jopling classification: of 38 patients with lepromatous leprosy, eight (21%) had perinuclear (p) ANCA and two (6%) had cytoplasmic ANCA. ANCA titres ranged from 1:20 to 1:320. Of six borderline leprosy patients, one (16%) had p-ANCA. All 20 tuberculoid leprosy patients and 65 healthy control subjects had negative ANCA. There was no correlation between ANCA titres and disease activity in positive patients. ANCA, mainly those with a perinuclear pattern, may be present in leprosy, especially in the lepromatous pole. This disease should be added to the spectrum of diseases with ANCA positivity.

Adult↗

Role of prolactin in the recovered T-cell development of early partially decapitated chicken embryo.

Although different experimental approaches have suggested certain regulation of the mammalian immune system by the neuroendocrine system, the precise factors involved in the process are largely unknown. In previous reports, we demonstrated important changes in the thymic development of chickens deprived of the major neuroendocrine centers by the removal of embryonic prosencephalon at 33-38 hr of incubation (DCx embryos) (Herradón et al., 1991; Moreno et al., 1995). In these embryos, there was a stopping of T-cell maturation that resulted in an accumulation of the most immature T-cell subsets (CD4-CD8- cells and CD4-CD8lo cells) and, accordingly, in decreased numbers of DP (CD4+CD8+) thymocytes and mature CD3+TcRalphabeta+ cells, but not CD3+TcRgammadelta lymphocytes. In the present work, we restore the thymic histology as well as the percentage of distinct T-cell subsets of DCx embryos by supplying recombinant chicken prolactin, grafting of embryonic pituitary gland, or making cephalic chick-quail chimeras. The recovery was not, however, whole and the percentage of CD3+TcRalphabeta+ thymocytes did not reach the normal values observed in 17-day-old control Sham-DCx embryos. The results are discussed on the basis of a key role for prolactin in chicken T-cell maturation. This hormone could regulate the transition of DN (CD4 CD8 ) thymocytes to the DP (CD4+CD8+) cell compartment through its capacity for inducing IL-2 receptor expression on the former.

Animals↗

Localization of the centromere protein CENP-B using scleroderma sera and evidence for a role in centromere survival.

OBJECTIVE: To determine whether centromeric CENP A, B and C proteins play a role in centromere survival. METHODS: Sixteen anti-centromere sera from scleroderma patients were used. The most common reactivity demonstrated by Western blot was anti-CENP-A, followed by anti-CENP-B and -C, in that order. The reactivity of these sera with HEp-2 cells was studied using an indirect immunofluorescence assay with and without prior digestion by a DNase, Aspergillus nuclease and the restriction endonucleases Bam HI, Hind III, and Eco RI. CENP-B was purified using affinity chromatography and anti-CENP-B antibody. The interaction between CENP-B and the CENP-B box was evaluated using immunoprecipitation. Precipitates containing alphaDNA were amplified using a PCR method with specific primers for the CENP-B box. RESULTS: None of the nucleases altered the fluorescence pattern. PCR amplification showed that CENP-B adsorbed on a Sepharose-4B/anti-CENP-B antibody column retained alphaDNA satellites. No retention was seen in the absence of CENP-B. CONCLUSIONS: CENP-B protects alphaDNA from digestion by nucleases and prevents DNase or restriction enzyme digestion from affecting the morphology and location of centromeres. CENP-B may promote and maintain joining of DNA satellites in the centromere.

Antibodies, Antinuclear↗

Clonal population structure of Colombian sylvatic Trypanosoma cruzi.

Isoenzyme variability and evidence of genetic exchange were evaluated in 75 wild stocks of Trypanosoma cruzi obtained from different hosts from 5 geographical regions within the endemic area in Colombia. Cluster analysis of genetic variability was attempted. Thirty-three multilocus enzyme genotypes (clonets) were identified from 75 stocks, 27 of which clustered with zymodeme Z1 and 6 with zymodeme Z3. Two stocks isolated from human infections showed the potential risk to rural communities in Colombia. The stocks exhibited departures from Hardy-Weinberg expectations, including both fixed heterozygote and fixed homozygote demes, where both segregation and recombination were absent. To inspect for population subdivision that might falsely imply clonality in these stocks, Wright's F statistics were calculated. Theta values (Fst) were significantly different from 0 when 33 clonets, 27 Z1-like clonets, and 5 geographical subpopulations were compared; thus, a significant amount of divergence has occurred between and within them. In addition, linkage disequilibrium was detected for most possible pairwise comparisons of loci. In conclusion, the above results all support a scenario of long-term clonal evolution in Colombian sylvatic T. cruzi populations.

Animals↗

Neuroprotection by the novel calcium antagonist PCA50938, nimodipine and flunarizine, in gerbil global brain ischemia.

Calcium is involved in the physiopathology of cerebral ischemia. Calcium antagonists might prevent the calcium overload and death of cells from ischemically compromised tissue. We compare the neuroprotective effect of various doses (0.2, 0.5 and 1 mg/kg) of two dihydropyridines, nimodipine and the novel 1,4-dihydropyridine derivative PCA50938, and flunarizine in the gerbil model of global ischemia. Improvements in morbidity were observed 2 h after the end of carotid occlusion (McGraw's scale) with 0.5 mg/kg of flunarizine, all doses of PCA50938 and 0.2 mg/kg nimodipine. Neuronal loss in the CA1 sector of the hippocampus was examined. The animals treated with 0.5 mg/kg flunarizine and those treated with 1 mg/kg PCA50938 showed a significant reduction in the percentage of damaged neurons in the hippocampal CA1 area, 72 h after transient ischemia. None of the animals treated with 0.5 mg/kg flunarizine had more than 80% of the evaluated neurons altered. We conclude that PCA50938 and flunarizine may act as neuroprotective drugs with different patterns of dose-response and neuroprotective-morbidity-mortality relationships, in the model of global cerebral ischemia in the gerbil. Flunarizine has a narrow therapeutic range.

Animals↗

Interleukin-7 treatment promotes the differentiation pathway of T-cell-receptor-alpha beta cells selectively to the CD8+ cell lineage.

In this report we have studied the influence of interleukin-7 (IL-7) on thymocyte differentiation by evaluating the effects of IL-7 on the generation of T-cell receptor-alpha beta (TCR-alpha beta) and TCR-gamma delta thymocyte subpopulations in rat fetal thymus organ culture. IL-7 enhanced the differentiation pathway of TCR alpha beta thymocytes, first increasing the numbers of immature CD8+ cells, and later those of both CD4+ CD8+ and mature thymocytes. The kinetics of thymocyte migration out of thymic lobes was also accelerated, and the average number of mature TCR-alpha beta phi emigrants per day was increased in the presence of IL-7. Moreover, mature CD4- CD8+ thymocytes were preferentially generated after IL-7 administration. This TCR-alpha beta hi cell population was not actively dividing, indicating that IL-7-promoted thymocyte differentiation was selective to the CD8 cell lineage. Distribution of some TCR-V alpha and TCR-V beta segments among mature thymocytes was also modified in IL-7-treated thymic lobes. On the contrary, the maturation of TCR-gamma delta was not affected by IL-7 addition during the first days of culture, but their numbers sharply increased by day 6 of culture. These results were confirmed with IL-7-treated cultures for 24 hr, showing that IL-7 responsiveness was acquired by TCR-gamma delta cells late in thymus ontogeny. The present results thus indicate a key role for IL-7 in the maturation of TCR-alpha beta thymocytes and the expansion of thymic TCR-gamma delta cells.

Animals↗

Urodynamically based modification of Mitrofanoff procedure.

This paper reviews our experience with the Mitrofanoff principle as applied in eight patients. Of four patients with post-traumatic urethral stricture, three required the appendix as continent catheterizable conduit, with a modified appendicovesical anastomosis technique-that is, without a submucosal tunnel- and in one patient, the remnant ureter of a previous simple nephrectomy was used. Of the four remaining patients, one with a hypotonic bladder and three with urethral stricture, a complete laparoscopic approach was used to perform the same modified Mitrofanoff procedure with the appendix. With a mean follow-up of 19.5 months, all patients were completely dry. Only three patients had persistently positive urine cultures, but without evidence of renal function impairment. The modified direct appendicovesical anastomosis technique reduces the operative time, has a lower complication rate, and allows us to use a laparoscopic approach with the resulting benefits of a minimally invasive surgical procedure. As shown in urodynamic tests, urinary continence is preserved.

Adolescent↗

SAMe restores the changes in the proliferation and in the synthesis of fibronectin and proteoglycans induced by tumour necrosis factor alpha on cultured rabbit synovial cells.

S-Adenosyl-L-methionine (SAMe) is a naturally occurring compound involved in transmethylation and trans-sulphuration reactions. The administration of SAMe to patients with osteoarthritis (OA) seems to have a protective effect, although the mechanisms of its action are largely unknown. We have studied the effect of SAMe as a protective agent against the modifications induced by tumour necrosis factor alpha (TNF alpha) on synovial cell proliferation and extracellular matrix protein synthesis, two important hallmarks of progressive articular diseases. The stimulation of cells with 100 U/ml TNF alpha for 24 h decreased the proliferative rate (58 +/- 14% with TNF alpha vs basal 100%, P < 0.05), fibronectin (FN) mRNA expression (36 +/- 14% vs basal, P < 0.05) and FN synthesis (79 +/- 20% vs basal, P > 0.05). By contrast, TNF alpha raised total protein and proteoglycan synthesis (127 +/- 12% vs basal and 239 +/- 40% vs basal, respectively, P < 0.05). The addition of increasing concentrations of SAMe (10(-10)-10(-6) M) to synoviocytes incubated with TNF alpha reversed the effects induced by the cytokine, while SAMe alone did not modify significantly the metabolic processes studied. These results indicate that, in cultured synovial cells, SAMe restores basal conditions after cell damage elicited by TNF alpha stimulation.

Animals↗

Delayed encephalopathy in fulminant hepatic failure in the pediatric population and the role of liver transplantation.

BACKGROUND: Liver transplantation is the therapeutic choice for fulminant hepatic failure in children. METHODS: All 66 cases of fulminant hepatic failure in the pediatric population seen at UCLA from May, 1985 to November, 1993 were reviewed to determine changes in survival rates since the advent of liver transplantation. We evaluated the clinical course and events leading to the exclusion of surgical management of nonsurvivors, who otherwise would have benefited from a liver transplant. We also compared the latter's clinical course with the nontransplant survivors to determine parameters for screening patients for liver transplantation. RESULTS: Fifty-one patient (77%) were put on the transplant list initially but eventually, only 38 (58%) patients underwent orthotopic liver transplantation (OLT) and of these 30 (79%) patients survived. Of the remaining 29 (42%) patients who did not undergo liver transplantation, only 10 (36%) patients survived. Nine patients died while waiting for a donor liver secondary to complications of hepatic failure. The majority of nonsurvivors in the OLT and no-OLT groups succumbed because of irreversible neurologic deterioration. In the no-OLT group, comparisons between survivors and non-survivors were made. There were no significant demographic differences. It took a mean of 8 days (+/-8) versus 22 days (+/-15), (p = 0.009), from onset of illness to first hospital admission for survivors and nonsurvivors, respectively. Time to reach stage II encephalopathy was a mean of 5 days (+/-5) for survivors versus 18 days (+/-16), (p = 0.05) for nonsurvivors. Nonsurvivors were transferred to the transplant center at a mean of 12.2 days (+/-12) after being first admitted elsewhere as compared to a mean of 1.9 days (+/-18) for survivors, (p = 0.02). Mean prothrombin time decreased by a mean of 13.4 s/day (+/-16) for survivors as against 2.25 s/day (+/-6) for nonsurvivors, (p = 0.06). Mean peak total bilirubin for nonsurvivors was 460 mumol/L (27 mg/dl) versus 220 mumol/L (13 mg/dl) for survivors, (p = 0.06). Nonsurvivors died at a mean of 30 days (+/-19) from onset and survivors' liver tests started to improve at a mean of 11 days (+/-9) from onset. CONCLUSIONS: From these studies, we conclude that liver transplantation remains the therapeutic choice for fulminant hepatic failure in children. Early referral and closer follow-up is necessary for timely admission to liver transplant centers to enable screening and proper preparation of these patients for liver transplantation.

Adolescent↗

Structure-absorption relationships of a series of 6-fluoroquinolones.

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally.

Animals↗

Leishmania and human immunodeficiency virus coinfection: the first 10 years.

Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses.

Animals↗

Resource utilization among neonatologists in a university children's hospital.

OBJECTIVE: We studied factors affecting length of hospital stay and resulting hospital charges among patients managed by two separate groups of neonatologists in the same academic health science center. DESIGN: Retrospective analysis of clinical and financial data base information. METHODS: Neonatal intensive care was provided in the same acute care nursery in a large university children's hospital by: (1) neonatologists in a full-time academic division (group A) and (2) a group associated with a private managed care organization (group B). Clinical and financial parameters of all neonates admitted in fiscal year 1994 were compared for the two provider groups. Stepwise regression analysis was used to evaluate factors influencing hospital charges and length of hospital stay (LOS) and to adjust for differences in clinical variables between the two groups. RESULTS: Group A physicians provided care for 340 infants, while 137 were treated by those of group B. Group A included older patients, more outborns, more level III patients, more sepsis, more intermittent positive pressure ventilation, and more patent ductus arteriosus. The incidence of transient tachypnea of the newborn was higher among group B patients. Hospital charges were primarily determined by LOS, which was similar for the two groups. When the data were corrected for differences in risk and patient acuity, however, a significant relationship between physician group and LOS was demonstrated, with LOS being an average of 7.8 days shorter for group A. A net reduction of $3 114 969 in hospital charges might have been realized had group A physicians provided care for all study patients. CONCLUSIONS: Hospital charges were determined by LOS. In this setting, academic neonatologists produced shorter LOS and comparable clinical outcomes, despite caring for a population at greater risk. The reduction in LOS could have resulted in more than $3.1 million in annualized savings had the academic group provided care for all of the study patients.

Analysis of Variance↗