Search PubMed⌕ Search

Biomedical subjects

A Molina

Publications and source records attributed to A Molina.

At least 91 records · Page 5Linked to original sources
PubMed1998

Interaction of wheat alpha-thionin with large unilamellar vesicles.

The interaction of the wheat antibacterial peptide alpha-thionin with large unilamellar vesicles has been investigated by means of fluorescence spectroscopy. Binding of the peptide to the vesicles is followed by the release of vesicle contents, vesicle aggregation, and lipid mixing. Vesicle fusion, i.e., mixing of the aqueous contents, was not observed. Peptide binding is governed by electrostatic interactions and shows no cooperativity. The amphipatic nature of wheat alpha-thionin seems to destabilize the membrane bilayer and trigger the aggregation of the vesicles and lipid mixing. The presence of distearoylphosphatidylethanolamine-poly(ethylene glycol 2000) (PEG-PE) within the membrane provides a steric barrier that inhibits vesicle aggregation and lipid mixing but does not prevent leakage. Vesicle leakage through discrete membrane channels is unlikely, because the release of encapsulated large fluorescent dextrans is very similar to that of 8-aminonaphthalene-1,3,6,trisulfonic acid (ANTS). A minimum number of 700 peptide molecules must bind to each vesicle to produce complete leakage, which suggests a mechanism in which the overall destabilization of the membrane is due to the formation of transient pores rather than discrete channels.

Antimicrobial Cationic Peptides↗
PubMed1998

Aortico-right ventricular tunnel.

A successful operation on an infant with a tunnel through which the aorta communicated with the right ventricle is reported. The diagnosis was suspected preoperatively on the basis of two-dimensional Doppler color echocardiography and confirmed by cardiac catheterization. The aortico-right ventricular tunnel originated independently from the left coronary ostium and above the sinus of Valsalva. Patch closure from inside the tunnel under deep hypothermia was successfully performed. Follow-up is satisfactory 5 years later.

Aorta↗
PubMed1998

Extracorporeal photochemotherapy for treatment of drug-resistant graft-vs.-host disease.

Extracorporeal photochemotherapy (EP) is a therapeutic approach to the treatment of drug-resistant graft-vs.-host disease (GVHD) that uses the known immunosuppressive and immunomodulatory effects of ultraviolet light. In 1990, we initiated a pilot study to evaluate the efficacy and safety of EP in patients with refractory GVHD. Between 1991 and 1996, six patients with acute grade IV liver GVHD, 12 patients with chronic following acute GVHD, and six patients with de novo chronic GVHD were treated with EP. All patients had failed to respond to conventional GVHD immunosuppressive drug therapy of cyclosporine and prednisone. The six patients with acute liver GVHD had also received antithymocyte globulin (ATG); therapy for chronic GVHD included thalidomide in eight patients, psoralen plus ultraviolet A in five patients, and ATG in two patients. All patients with acute liver GVHD had progressive liver failure with short survival despite frequent EP. The response rate with EP treatment was 3 of 6 for patients with de novo chronic GVHD and 3 of 12 for patients with chronic following acute GVHD. Three patients with bronchiolitis obliterans had either no response or no documented disease progression while undergoing EP. Side effects of EP were minor and included gastrointestinal upset frequently, catheter-related sepsis in four patients, increased red blood cell and platelet transfusion requirements in one patient, and leukopenia in two patients. EP was discontinued in three patients because of side effects, including GI upset in one patient and bone marrow suppression in two patients. Side effects were reversible with the discontinuation of EP. We were unable to correlate response to EP with the level of methoxypsoralen, number of lymphocytes treated, or pattern of pre- and posttreatment CD4/CD8 ratio. We concluded that EP has some efficacy in the treatment of drug-resistant chronic GVHD, with minor overall toxicity.

Adolescent↗
PubMed1998

Repercussions of acidosis on postnatal erythrocyte deformability in term and preterm newborns.

Erythrocyte deformability in newborns, a determining factor in neonatal blood hyperviscosity, is also often responsible for decreased blood flow in the microcirculation of several organs, such as the brain, kidneys, and digestive tract. In 70 neonates classified by gestational age and by the presence or absence of acidosis, we analyzed the filterability of erythrocytes in suspension through 5 polycarbonate membranes and its relation with gasometric determinations, Anion-GAP, plasma viscosity, plasma osmolality, erythrocyte volumes, and plasma lipids. Using a logistic regression analysis, controlling gestational age (p = 0.17), mean corpuscular volume (MCV) (p = 0.63), and mean corpuscular hemoglobin concentration (MCHC) (p = 0.21), the presence of acidosis (p = 0.0049, odds ratio: 3.60) is a risk factor for an increased rigidity index in newborns. Metabolic and respiratory acidosis were significantly related with lower erythrocyte deformability in the early neonatal period (below 5 days of age). Decreased plasma bicarbonate and increased Anion-GAP (even in compensated metabolic acidosis), as well as increased pCO2 in respiratory acidosis, were significantly related with decreased erythrocyte filterability. In newborns under 32 weeks of gestational age the increase in erythrocyte rigidity index is more related to the low gestational age and increased MCV than to the presence of acidosis. These factors can produce changes in the microcirculation of these patients.

Acidosis↗
PubMed1998

Effect of seasonal acclimatization on the expression of the carp transcription factor Pit-1.

We isolated a clone comprising four exons of the carp Pit-1 gene. Using synthetic oligonucleotide probes derived from the carp Pit-1 sequence Pit-1 expression was assessed by in situ hybridization in pituitary sections from summer- and winter-acclimatized carp. Semiquantitative analyses of the hybridization signals revealed a significant higher Pit-1 expression in the proximal pars distalis (PPD) and pars intermedia (PI) of the pituitary glands from summer-acclimatized carp, compared to the winter-acclimatized fish. In both adaptive states, relative to the PPD and PI, only a basal Pit-1 expression was detected in the rostral pars distalis. Thus, during seasonal acclimatization of an eurythermal fish, Pit-1 seems to be involved in the mechanisms that underlie the compensatory response.

Acclimatization↗
PubMed1998

Impaired fungicide activity in plants blocked in disease resistance signal transduction.

Fungicide action is generally assumed to be dependent on an antibiotic effect on a target pathogen, although a role for plant defense mechanisms as mediators of fungicide action has not been excluded. Here, we demonstrate that in Arabidopsis, the innate plant defense mechanism contributes to the effectiveness of fungicides. In NahG and nim1 (for noninducible immunity) Arabidopsis plants, which normally exhibit increased susceptibility to pathogens, the fungicides metalaxyl, fosetyl, and Cu(OH)2 are much less active and fail to control Peronospora parasitica. In contrast, the effectiveness of these fungicides is not altered in Arabidopsis mutants defective in the ethylene or jasmonic acid signal transduction pathways. Application of the systemic acquired resistance activator benzothiadiazole (BTH) in combination with these fungicides results in a synergistic effect on pathogen resistance in wild-type plants and an additive effect in NahG and BTH-unresponsive nim1 plants. Interestingly, BTH treatment normally induces long-lasting pathogen protection; however, in NahG plants, the protection is transient. These observations suggest that BTH treatment can compensate only partially for an impaired signal transduction pathway and support the idea that pathogen defense mechanisms are under positive feedback control. These observations are strikingly reminiscent of the reduced efficacy of antifungal agents in immunocompromised animals.

Animals↗
PubMed1998

Differential effects of antibodies to vascular cell adhesion molecule-1 and distinct epitopes of the alpha4 integrin in HgCl2-induced nephritis in Brown Norway rats.

Four distinct epitopes (A, B1, B2, and C) have been functionally defined on the human alpha4 integrin. In this study, two cross-reactive antihuman alpha4 monoclonal antibodies (mAb) (HP2/1 and HP2/4 specific for epitopes B1 and B2, respectively) were used to functionally characterize the rat VLA-4 subunit and to define similar functional epitopes in this rodent species. It was found that B1 and B2 anti-alpha4 mAb completely block adhesion to fibronectin, but the inhibition of adhesion to vascular cell adhesion molecule-1 (VCAM-1) with HP2/1 mAb was lower than with HP2/4 mAb. It was also observed that epitope B2 HP2/4 mAb induced homotypic aggregation in rat lymphocytes, whereas epitope B1 HP2/1 mAb did not. Using the HgCl2 model of nephritis, this study shows the protective effect of both anti-alpha4 mAb against infiltration of the renal interstitium by leukocytes. Nevertheless, HP2/1 mAb, but not HP2/4 mAb, virtually abolished the anti-glomerular basement membrane antibody synthesis and glomerular deposits. These findings indicate the dual but independent role played by alpha4 integrins in both extravasation of leukocytes and in the production of antibodies. Finally, this study demonstrates that anti-rat VCAM-1 mAb showed a positive reactivity of the renal vascular endothelium and, most importantly, that administration of anti-VCAM-1 antibodies completely abrogated the interstitial cell infiltrates without affecting anti-glomerular basement membrane antibody production. These results confirm the important role played by VLA-4/VCAM-1 pathway in leukocyte infiltration, and further support the dual and independent role of alpha4 integrins in both renal infiltration and autoantibody synthesis in this model of renal disease.

Analysis of Variance↗
PubMed1998

[Giant fusiform aneurysm of the middle cerebral artery. Surgical treatment with multiple clipping: a case report].

INTRODUCTION: Giant cerebral aneurysms (GCA) are defined by sizes above 2.5 cm. GCA clinically appear by the mass effect exerted on adjacent structures, and in other cases, by embolismal action of the mural thrombo or as a post rupture subarachnoid hemorrhage. THERAPEUTICAL OPTIONS INCLUDE: inducting mural thrombosis, inserting an intraneurysmatic balloon, setting a bypass and surgical clipping. The major characteristics of giant fusiform aneurysm (GFA), the lack of neck and the inclusion of main vessels, give surgical treatment a great complexity. CLINICAL CASE: 25 year old woman diagnosed of GFA of the middle cerebral artery, treated with direct surgical access with clipping and reconstruction of the vascular wall with fenestrated clips arranged in tandem. CONCLUSIONS: The lack of an accessible neck for clipping and exclusion of giant and fusiform intracranial aneurysms, forced practising bypass as a compulsory surgical alternative. Multiple clipping was a viable choice because of its simplicity and less surgical risk. This technique is not applicable to giant serpentine aneurysms as it is only feasible in cases of fusiform aneurysms with no intraluminal thrombosis. A satisfactory evolution of this case, keeping asintomatic after 18 months of the intervention guarantees its application in young patients with giant thrombosed aneurysms of low clinical repercussion.

Adult↗
PubMed1997

Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group.

We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor-risk aggressive lymphoma. There were 42 patients with intermediate-grade or immunoblastic lymphoma who were considered to be high (60%) and high-intermediate risk (40%) groups at diagnosis based on the age-adjusted International Prognostic Index (IPI) and 10 patients with high-grade, SNCCL (small non-cleaved cell, Burkitt's, and non-Burkitt's), who at presentation had poor-risk features defined as elevated serum lactate dehydrogenase level, stage IV, and bulky mass >/=10 cm. The median age was 34 years (range, 16 to 56 years). Thirty-nine were transplanted in first complete remission and 13 in first partial remission after conventional therapy. Conditioning regimens consisted of total body irradiation (TBI) administered as a single fraction 750 cGy in 3 patients and in fractionated doses for a total of 1,200 cGy in 44 patients, in combination with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide. Five patients with prior radiotherapy received 450 mg/m2 carmustine instead of TBI. Stem cell sources were either bone marrow and/or peripheral blood. No in vitro purging was used. All patients engrafted. Two SNCCL patients died of venoocclusive disease at 25 days and acute leukemia at 27 months posttransplantation. There were six relapses at 1.5 to 12.8 months posttransplantation. At a median follow-up of 44 months (range, 1 to 113 months), the estimated 3-year overall survival (OS) and disease-free survival (DFS) for all patients was 84% (95% confidence interval [CI], 70% to 92%) and 82% (95% CI, 68% to 91%), respectively. In the subset of patients with intermediate-grade and immunoblastic lymphoma, the 3-year DFS was 89% (95% CI, 74% to 96%) for all patients, 87% (95% CI, 67% to 96%) for high-risk patients, and 92% (95 CI, 61% to 99%) for high-intermediate risk patients. The 3-year OS and DFS for SNCCL patients were identical at 60% (95% CI, 30% to 84%). These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma. A prospective randomized study comparing high-dose therapy and ASCT with conventional chemotherapy in IPI high-risk patients with aggressive non-Hodgkin's lymphoma should be undertaken.

Adolescent↗
PubMed1997

Differential effects of five types of antipathogenic plant peptides on model membranes.

The effects of five antipathogenic plant peptides, wheat alpha-thionin, potato PTH1 defensin, barley LTP2 lipid transfer protein, and potato tuber DL1 and DL2 defensins, have been tested against phospholipid vesicles (liposomes). Wheat thionin very actively induces aggregation and leakage of negatively charged vesicles. LTP2 displays the same activities, although to a limited extent. Under certain conditions PTH1 and DL2 induce vesicle aggregation, but not leakage. Potato defensin DL1 failed to show any effect on liposomes. The same peptides have been assayed against a plant pathogenic bacterium, both the membrane-active and -inactive compounds having efficient antibacterial action.

Anti-Infective Agents↗
PubMed1997

Identification and functional characterization of a K+ channel alpha-subunit with regulatory properties specific to brain.

The physiological diversity of K+ channels mainly depends on the expression of several genes encoding different alpha-subunits. We have cloned a new K+ channel alpha-subunit (Kv2.3r) that is unable to form functional channels on its own but that has a major regulatory function. Kv2.3r can coassemble selectively with other alpha-subunits to form functional heteromultimeric K+ channels with kinetic properties that differ from those of the parent channels. Kv2.3r is expressed exclusively in the brain, being concentrated particularly in neocortical neurons. The functional expression of this regulatory alpha-subunit represents a novel mechanism without precedents in voltage-gated channels, which might contribute to further increase the functional diversity of K+ channels necessary to specify the intrinsic electrical properties of individual neurons.

Amino Acid Sequence↗
PubMed1997

Pore mutations in Shaker K+ channels distinguish between the sites of tetraethylammonium blockade and C-type inactivation.

1. We have studied the effect of external K+ and tetraethylammonium (TEA) on several mutants of Shaker B K+ channels with amino acid substitutions in the pore which alter TEA affinity and the rate of C-type inactivation. In all channels studied high external K+ makes C-type inactivation slower. 2. In the wild-type channel, TEA blockade is voltage dependent and produces slowing of the inactivation time course. However, in the double mutant channel (T449Y, D447E) TEA blockade, although of higher affinity, is voltage independent and does not affect the rate of C-type inactivation. 3. Mutants with a charged amino acid at position 449 (T449K and T449E) are resistant to TEA block. In these channels, C-type inactivation is also unaffected by TEA. 4. These results indicate that the sites where TEA blocks and competes with C-type inactivation can be segregated. To modulate inactivation, TEA must enter deeply into the channel mouth. These results suggest that C-type inactivation is not due to a large molecular rearrangement in the outer channel vestibule, but it is essentially produced by a conformational change restricted to a local site in the pore.

Animals↗
PubMed1997

Effect of CD34+ selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer.

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (> or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to > or = 500/microL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P < or = .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier "sacrificial" reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.

Adult↗
PubMed1997

Spinal intraosseous arteriovenous malformation as a cause of juvenile scoliosis. A case report.

STUDY DESIGN: A case report. OBJECTIVES: To report and discuss an unusual case of scoliosis resulting from an arterial malformation of the spine. SUMMARY OF BACKGROUND DATA: This is a report of clinical manifestation, physical findings, computed tomography scan, magnetic resonance imaging, bone scan, and results after surgery in an 8-year-old boy with a painful scoliosis resulting from an intraosseous arteriovenous malformation of the spine. METHODS: Radiographs, computed tomography scan, magnetic resonance imaging, and bone scans were studied and oriented us to the diagnosis of scoliotic attitude secondary to a benign-appearing tumor in the right lamina of L4. Surgery was performed through a posterior midline approach to remove the lesion en bloc. Postoperative treatment was performed with a Boston orthosis. RESULTS: Final pathology reports diagnosed an intraosseous arteriovenous malformation. After 32 months, the boy had no pain, and scoliotic attitude diminished despite radiographs still showing a single 10 degrees right lumbar curve. CONCLUSIONS: Primary intraosseous arteriovenous malformations are rare. This case shows the scarce specificity of clinical findings, radiology, and bone scan in the diagnosis of these lesions when they are localized in vertebral territory. Surgical excision of the lesion relieves pain but does not completely correct the scoliotic attitude.

Arteriovenous Malformations↗
PubMed1997

Differential expression of pathogen-responsive genes encoding two types of glycine-rich proteins in barley.

Gene-specific probes (3' ends of cDNAs) were obtained from barley cDNAs encoding two types of glycine-rich proteins: HvGRP2, characterized by a cytokeratin-like and a cysteine-rich domain, and HvGRP3, whose main feature was an RNA-binding domain. Expression of genes Hvgrp2 and Hvgrp3, which are present at one (or two) copies per haploid genome, was ubiquitous and gene Hvgrp3 was under light/darkness modulation. Cold treatment increased Hvgrp2 and Hvgrp3 mRNA levels. Methyl jasmonate (10 microM) switched off the two genes. Expression of Hvgrp2, but not that of Hvgrp3, was induced by ethylene treatment (100 ppm). Fungal pathogens Erysiphe graminis and Rhynchosporium secalis increased the mRNAs levels of the two genes, both in compatible and in incompatible interactions, while bacterial pathogens did not.

Amino Acid Sequence↗