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Biomedical subjects

A Molina

Publications and source records attributed to A Molina.

At least 127 records · Page 7Linked to original sources

Relationship of blood rheology to lipoprotein profile during normal pregnancies and those with intrauterine growth retardation.

AIMS: The effects on fetal growth of hyperlipidaemia in pregnancy are not well understood at present. In this study the different lipid fractions in normal pregnancies and pregnancies complicated by intrauterine growth retardation (IUGR) were determined and related to changes in plasma and serum viscosity. METHODS: Two groups of pregnant women were studied. Group 1 consisted of 35 healthy pregnant women aged between 21 and 38 years with no previous pathology and a normal pregnancy to term. Group 1 patients were studied at four periods defined at the start of the study: (1) < or = 17 weeks; (2) 18-24 weeks; (3) 25-32 weeks, (4) > or = 33 weeks. Group 2 consisted of 24 pregnant women aged between 16 and 34 years with ultrasound diagnosed IUGR confirmed after birth. Plasma lipids and plasma and serum viscosity were measured. RESULTS: Plasma triglycerides, low density lipoprotein cholesterol, and total cholesterol increased progressively throughout pregnancy, with significantly higher values after week 25. Apolipoprotein A (ApoA) and triglyceride concentrations were significantly lower in the IUGR group than in the normal group. The HDL/ApoA ratio was greater in the IUGR group than in the control group, as was the ApoB/ApoA ratio. There were no differences in the other lipids. Plasma and serum viscosity was higher in the IUGR group than in the normal group. CONCLUSIONS: Haemorheological modifications in the IUGR group are partly secondary to changes in high density lipoprotein metabolism and the competitive inhibition of fibrinolysis by ApoB, which is increased in pregnancies with IUGR. Changes in ApoA, and more specifically in the ApoB/ApoA ratio, could be good markers for the early detection of IUGR.

Adolescent↗

Biomechanical effects of different surgical procedures on the extensor mechanism of the patellofemoral joint.

Loadbearing stresses in the patellofemoral joint were studied at different degrees of flexion before and after various surgical techniques recommended to treat knee disorders. Surgical procedures intended to reduce the intensity of stress were analyzed experimentally. The study was done using different experimental methods on whole knee specimens from fresh human cadavers that were not treated with formaldehyde. The results indicate that the most predictable procedure for increasing surface area and decreasing patellar stress is a combined procedure of anterior displacement of the anterior tibial tubercle by 1 cm while displacing it 0.5 to 1 cm medially.

Biomechanical Phenomena↗

Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin.

HgCl2 induces the synthesis of anti-GBM Abs with the development of glomerular and interstitial nephritis, as well as proteinuria, in the Brown Norway rat. The development of this autoimmune disease is a consequence of the appearance of an autoreactive T cell subset-inducing activation of B cells. The administration to mercury-treated rats of the mouse anti-human VLA alpha 4 HP2/1 mAb, which cross-reacts with the rat homologue integrin, completely abrogated the interstitial cell infiltrates. As demonstrated by peripheral blood analysis, this effect is not a result of the depletion of circulating leukocytes or leukocyte subsets. Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria. Our results confirm that in vivo alpha 4 functions in adhesive interaction of circulating leukocytes and vascular endothelium, and is centrally important in the extravasation and migration of T lymphocytes to sites of tissue injury. We also found a complete absence of interstitial cell infiltrates, together with a positive glomerular IgG lineal deposition pattern, when anti-GBM Abs were passively transferred to rats pretreated with anti-alpha 4 mAb, thus indicating an independent role of alpha 4 integrin in both extravasation of immune cells and production of autoantibodies. Furthermore, these in vivo findings provide preliminary evidence for the participation of the VLA-4 integrin in mediating the intercellular interaction of leukocytes regulating the production of Abs, most likely through the existence of additional yet unknown ligand(s).

Animals↗

Prolactin gene expression and changes of prolactin pituitary level during the seasonal acclimatization of the carp.

The effect of seasonal acclimatization on the extent of prolactin (PRL) gene expression and on the content of this was studied in summer- and winter-carp (Cyprinus carpio) hormone pituitary glands. PRL content in the rostral pars distalis (RPD) was evaluated by immunocytochemistry using antibodies against a cross-linked synthetic peptide comprising the sequence of 15 amino acids which conform to the primary structure of carp PRL. To assess the level of PRL gene transcription, a 24-mer synthetic oligonucleotide probe whose sequence included nucleotides 2041-2064 located in exon V of the carp PRL gene, was used. Employing in situ hybridization assays, a high expression of PRL mRNA was observed in the RPD of summer-acclimatized carp. A negligible level of transcription was observed in tissue sections of pituitary glands from winter-acclimatized carp. Concurrently, immunodetection of the PRL-producing cells in the RPD revealed that the pituitary hormone level was significantly higher in the warm season-adapted carp.

Acclimatization↗

High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells.

PURPOSE: To evaluate (1) the effect of granulocyte colony-stimulating factor (G-CSF) on peripheral-blood stem-cell (PBSC) mobilization; (2) the rate of hematopoietic recovery after G-CSF-mobilized PBSC transplantation; and (3) the outcome of high-dose myeloablative therapy and PBSC transplantation in patients with relapsed or refractory lymphoma. PATIENTS AND METHODS: Ninety-five patients with lymphoma underwent high-dose therapy followed by PBSC transplant in three sequentially treated cohorts of patients in a nonrandomized study. The first 30 patients received nonmobilized PBSCs (unprimed) without G-CSF after transplant, the next 26 patients received PBSC that were mobilized with G-CSF 5 micrograms/kg/d (primed-5) plus G-CSF after transplant, and the last 39 patients received PBSC mobilized by G-CSF 10 micrograms/kg/d (primed-10) plus G-CSF after transplant. The conditioning regimen consisted of fractionated total-body irradiation (FTBI) 12 Gy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg. Patients with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. RESULTS: The use of G-CSF-mobilized PBSCs in combination with G-CSF posttransplant resulted in a significantly accelerated time to recovery of both granulocyte and platelet when compared with the unprimed group. The median number of days to an absolute granulocyte count (ANC) of greater than 0.5 x 10(9)/L was 10 days for G-CSF primed versus 20 days for the unprimed (P = .0001). The median days to platelet transfusion independence was 16 and 31 days (P = .0001) for the G-CSF primed and unprimed, respectively. There were also significant reductions in the number of platelet (P = .02) and RBC transfusions (P = .006) for the G-CSF primed. Multivariate analysis of prognostic factors identified CD34+ cell dose as the only additional factor predicting engraftment. Sixty-nine patients are alive at a median follow-up of 15.9 months (range, 7.4 to 63.7). The cumulative probability of 2-year disease-free survival is 59% (95% confidence interval [CI], 36% to 79%) and 39% (95% CI 25% to 55%) for patients with Hodgkin's disease and non-Hodgkin's lymphoma, respectively. CONCLUSION: The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free survival over 2 years can be achieved in some patients with relapsed lymphoma after high-dose therapy and PBSC transplantation. However, longer follow-up is required to confirm the curability of this approach.

Adolescent↗

In vitro modulation of interleukin-1 beta secretion by cultured rat doxorubicin-stimulated whole glomeruli and dissociated mesangial glomerular cells.

Doxorubicin-stimulated whole rat glomeruli and dissociated mesangial and resident glomerular macrophage cells produced the release of interleukin (IL)-1 beta cytokine. This activity increased after the addition of lipopolysaccharide (LPS) or LPS plus indomethacin to the cultures. In the presence of WEB2086 [platelet-activating factor (PAF)-acether antagonist], this activity showed a drastic reduction, without modification after sodium furegrelate (thromboxane synthetase inhibitor) was added to the cultures. Our results also demonstrate that this IL-1 beta activity is mainly produced by glomerular-resident macrophage cells. These findings support the important role by both IL-1 beta and PAF-acether mediator factors, at the cellular level, in the rat model of doxorubicin-induced nephrosis.

Animals↗

Lipid transfer proteins (nsLTPs) from barley and maize leaves are potent inhibitors of bacterial and fungal plant pathogens.

Four homogeneous proteins (Cw18, Cw20, Cw21, Cw22) were isolated from etiolated barley leaves by extraction of the insoluble pellet from a Tris-HCl (pH 7.5) homogenate with 1.5 M LiCl and fractionation by reverse-phase high-performance liquid chromatography. All 4 proteins inhibited growth of the pathogen Clavibacter michiganensis subsp. sepedonicus (EC50s = 1-3 x 10(-7) M) and had closely related N-terminal amino acid sequences. The complete amino acid sequences of proteins Cw18 and Cw21 were determined and found to be homologous to previously described, non-specific lipid transfer proteins from plants (32-62% identical positions). The proteins also inhibited growth of the bacterial pathogen Pseudomonas solanacearum (EC50s = 3-6 x 10(-7) M) and the fungus Fusarium solani (EC50s = 3-20 x 10(-6) M). A homologous protein from maize leaves (Cw41) was purified in a similar manner and also found to have inhibitory properties. A synergistic effect against the fungus was observed when protein Cw21 was combined with thionins. A defense role for non-specific lipid transfer proteins from plants is proposed.

Amino Acid Sequence↗

Developmental and pathogen-induced expression of three barley genes encoding lipid transfer proteins.

Clones for three barley non-specific lipid transfer proteins (LTP2, LTP3, and LTP4; formerly Cw18, Cw20 and Cw21, respectively) which had been previously shown to inhibit growth of plant pathogens, were selected and characterized from a cDNA library derived from young etiolated leaves. Genes Ltp2 and Ltp4 were located in chromosome 3H and gene Ltp3 was assigned to chromosome 7H by Southern blot analysis of wheat-barley disomic addition lines, using gene-specific probes (3'-ends of cDNAs). These assignments were confirmed by the polymerase chain reaction, using specific primers. The three genes were expressed in stem, shoot apex, leaves and roots (at low levels) throughout development. Genes Ltp3 and Ltp4 were expressed at high levels, and Lpt2 at low levels, in the spike (rachis, lemma plus palea and grain coats). Neither of the mRNAs was detected in endosperm. The proteins were localized by tissue-printing with polyclonal antibodies in the outer cell layer of the exposed surfaces of the plant, throughout the embryo, and in vascular tissues. Expression levels in leaves were moderately increased by 0.34 M NaCl and by 0.1 mM abscisic acid and were not affected by cold, drought, salicylate, 2,6-dichloro-isonicotinic acid, ethylene or ethephon. Methyl Jasmonate (10 microM) switched off all three genes. Inoculation with Av6 or vir6 isolates of the fungal pathogen Erysiphe graminis increased the three mRNAs, especially that of LTP4, which reached a maximum nine-fold increase 12-16 h after infection.

Amino Acid Sequence↗

Expression of adhesion molecules in allograft renal dysfunction. A distinct diagnostic pattern in rejection and cyclosporine nephrotoxicity.

We have studied in thirty renal biopsies (from 30 cadaver allograft patients) the expression of both LFA-1 and VLA-4 leukocyte adhesion receptors and their respective ICAM-1 and VCAM-1 endothelial cell ligands, during early allograft dysfunction (24 +/- 5 days after transplantation), reversed either by antirejection therapy (n = 14) or by reduction in CsA dose (n = 16). We have found that the levels of expression of the integrin VLA-4 and the activation signal AIM/CD69 (activation inducer molecule) on interstitial cells were significantly (P < 0.001) higher in rejection than in nephrotoxicity. A main differential expression pattern was observed for VCAM-1, the endothelial cell ligand of VLA-4. Interestingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody in rejection, as compared with a weak reactivity in endothelium and discrete staining pattern on tubules in nephrotoxicity. On the other hand, we found that the mean percentage of infiltrating cells bearing LFA-1 molecules and the intensity of ICAM-1 (a LFA-1 ligand) expression on endothelium were closely similar in both rejection and CsA nephrotoxicity. Nevertheless, a discrete significant (P < 0.05) "de novo" expression of ICAM-1 was present on tubular cells during rejection. Our results strongly suggest that in rejection the interstitial cell infiltrate seems to be facilitated by the contribution of both LFA-1/ICAM-1 and VLA-4/VCAM-1 cell adhesion mechanisms, and also that VLA-4/VCAM-1 leukocyte interaction does not play a role in cases with CsA nephrotoxicity. Furthermore, the differential expression patterns of VLA-4 and VCAM-1 molecules found between rejection and CsA nephrotoxicity could provide valuable immunohistochemical criteria in the diagnosis of allograft dysfunction.

Adult↗

Expression of the alpha-thionin gene from barley in tobacco confers enhanced resistance to bacterial pathogens.

Thionins are cysteine-rich, 5 kDa polypeptides which are toxic to plant pathogens in vitro. Expression of the gene encoding alpha-thionin from barley endosperm, under the 35S promoter from cauliflower mosaic virus, conferred to transgenic tobacco enhanced resistance to the bacterial plant pathogens Pseudomonas syringae pv. tabaci 153 and P. syringae pv. syringae. The barley alpha-thionin gene, which has two introns, was correctly spliced in tobacco. The alpha-thionin in transgenic plants had the expected mobility in the gradient, when separated by high-performance liquid chromatography, reacted with monospecific antibodies and showed the expected antibiotic properties in vitro.

Antimicrobial Cationic Peptides↗

Detection of Epstein-Barr genome in the lymph nodes of Hodgkin's disease.

We have used the enzymatic in situ hybridization method to investigate the presence of Epstein-Barr virus (EBV) genome in lymph node tissues from patients with Hodgkin's disease. Also, 11 patients with persistent human immuno-deficiency virus-associated generalized lymphadenopathy as well as seven autopsy cases with no Hodgkin's disease, formed part of these studies. EBV DNA-positive reaction was demonstrated in Reed-Sternberg cells and variants in seven of 16 cases and in the small accompanying lymphocyte cell population in 14 of the 16 cases. It was also found in eight of the 11 cases with persistent generalized lymphadenopathy but in none of the lymph nodes from negative selective autopsy cases. Our results indicate that the colorimetric in situ hybridization technique is useful in EBV nucleic acid detection and cell-type localization in Hodgkin's disease. Additionally, the detection of EBV genome, not only in the diagnostic cells but in the small lymphocyte cell components, could provide new insights into the potential role of this agent in the pathogenesis of Hodgkin's disease.

AIDS-Related Complex↗

Reprogramming of nucleolar gene expression during the acclimatization of the carp.

During seasonal acclimatization of eurythermal fish, the nucleolus of the hepatocyte undergoes ultrastructural reprogramming. In winter acclimatized carp, the nucleolar components are segregated, a condition that suggests a decreased transcription of rRNA. The same nucleolar reorganization was observed when pituitary cells from winter- and summer-acclimatized carp were examined. In situ analyses of nucleolar RNA revealed a marked lowering of RNA content in the segregated nucleoli. Accordingly, in vitro synthesis of RNA was shown to be significantly lower in pituitary tissue from cold-acclimatized fish where precursor accumulated. Conversely, in pituitary tissue from summer-adapted fish the rate and extent of synthesis and of rRNA processing was notably higher. The involvement of pre-rRNA processing events during seasonal acclimatization was corroborated by the strong differences of U3 RNA content detected by in situ hybridization in pituitary cells from summer- and winter-fish. When RNA polymerase I activity from both acclimatized states were assayed, no differences were detected. Thus, it appears that in fish RNA polymerase I itself does not play an important role in the control of nucleolar gene expression and the nucleolar gene expression reprogramming that the seasonal rearrangement represents might involve, among the many nucleolar-specific proteins, transcription factors.

Acclimatization↗

IL-1-like production in adriamycin-induced nephrotic syndrome in the rat.

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.

Animals↗

Effect of anti-interleukin-1 administration to rats with adriamycin-induced nephrosis.

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and histologic lesions similar to those found in minimal change nephrotic syndrome in humans. We found that whole isolated glomeruli from rats injected with adriamycin secreted an IL-1-like cytokine which closely resembled macrophage IL-1. Maximal IL-1-like activity was detected on day 14 of the experiment when rats were heavily proteinuric. Administration of anti-IL-1 antiserum to rats with adriamycin-induced nephrosis provoked a transient but marked reduction in the urinary protein excretion. Our results indicate that IL-1-could be an important mediator implicated in the development of proteinuria in this experimental nephropathy.

Animals↗

In situ demonstration of Epstein-Barr virus in intravenous drug abusers with generalized lymphadenopathy.

We have studied by the in situ hybridization method the presence of Epstein-Barr virus (EBV) DNA genome in lymph node tissues from 11 patients with persistent generalized lymphadenopathy. Using a biotinylated EBV DNA probe, we demonstrated EBV nucleic acid in scattered germinal centre cells in eight of the 11 cases. Our results suggest that EBV is not a determinant factor in the pathogenesis of this lymphadenopathy, but support its possible implication in B cell malignant transformation in cases of AIDS-associated lymphoma.

AIDS-Related Complex↗