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Biomedical subjects

A Palma

Publications and source records attributed to A Palma.

At least 37 records · Page 2Linked to original sources
PubMed2002

Protective role of the complement regulatory protein human CD-55 in cardiac xenograft: a descriptive study and a revision of the literature.

The limited and inadequate availability of organs from human donors has resulted in the utilisation of xenografts as an alternative tool. Nevertheless, hyperacute rejection (HAR) following xenograft determines the loss of the transplanted organ. The "primum movens" is the activation of the complement pathway mediated by the binding of natural xenogenic antibodies to the endothelium of the graft, followed by the lysis of the endothelial cells with subsequent oedema, thrombosis and necrosis of the transplanted organ. In this work we describe morphological and biomolecular observations of isolated human-decay accelerating factor (h-DAF, CD55) transgenic pig hearts, after perfusion for four hours with human blood. H-DAF is a membrane glycoprotein inhibiting the complement activation in humans. We describe considerably reduced damages in transgenic hearts, compared to controls. The cardiac function resulted preserved. Our data are in agreement with what was already shown by other groups using different experimental models. In conclusion, we encourage the use of new sources of transgenic animals, pointing out the importance of morphological analysis in evaluation of xenograft.

Animals↗
PubMed2002

Defective apoptosis and tumorigenesis: role of p53 mutation and Fas/FasL system dysregulation.

The transcription factor p53 and the cytokine receptor FasL are two of the most famous regulators of cell life, and their alterations can cause a large number of pathologies, including cancer. In this review, we focused on how they can determine defective apoptosis, one of the causes of tumorigenesis and tumor progression. The importance of this knowledge lies in the new perspectives that gene therapy can offer to cure cancer.

Animals↗
PubMed2002

[Prognostic significance of programmed dialysis in patients who initiate renal substitutive treatment. Multicenter study in Spain].

BACKGROUND: The aim of our study was to analyse patient characteristics, mortality and costs, all of them in relation to whether starting dialysis was planned or unplanned. METHODS: A total of 362 patients (227 male and 135 female) from five hospitals of the National Health System, who were started on chronic renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who were started on RRT after acute renal failure were excluded. We carried out a retrospective analysis of the demographic characteristics, patients' conditions at the time of initiating dialysis and outcome and costs at six and thirty-six months of treatment. Patients were classified as planned (PL-D) or unplanned dialysis (UNPL-D), depending on whether or not the patient had a vascular or peritoneal access ready to use for initiating RRT. RESULTS: One hundred and eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176 (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis without previous nephrological follow-up. UNPL-D was associated with older age (p < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p = 0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main primary renal diseases were glomerular and polycystic disease, whereas interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005). Multivariate analysis showed that previous non nephrological follow-up, uraemic symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D was also associated with increased number of days of hospitalization at the initiation of dialysis, and during the first 6 months (p < 0.001), increase of hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%) (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006, log rank test). The costs of UNPL-D were fivefold that of the PL-D group. CONCLUSION: UNPL-D has been associated with worse overall clinical conditions at the initiation of chronic replacement therapy, choosing haemodialysis as first RRT, increased morbi-mortality and subsequent increase of costs.

Adolescent↗
PubMed2001

Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation.

Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14-mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.

Animals↗
PubMed2001

Poorly differentiated synovial sarcoma: a case report.

Poorly differentiated synovial sarcoma is a rare soft tissue tumor. We studied a case arising in the pleural cavity of a young subject, characterised by the presence of spindle cell, small cell, and large epithelioid cell areas. We performed stains for mucosubstances and analysed the expression of cytokeratins 5/6, 7, 8, 18, 19, CEA, CD34, Ber-Ep4 and calretinin to characterize the phenotype of this neoplasm. We furthermore assessed immunohistochemically the presence of p53, Bcl-2, Bax and caspase 3, four apoptotic markers, to evaluate a relationship between apoptotic activity and the behaviour of this tumor. Our findings showed a strong presence of calretinin, p53 and Bcl-2 in all three areas. The possibility that poorly differentiated synovial sarcoma could be calretinin-positive was a new data, to our knowledge, and it could be of some importance in diagnostic pathology. Moreover, the negligible positivity for Bax and caspase 3 suggested that the minor role of programmed cell death could be one of the causes of the aggressive behaviour of this tumor. These data also suggest that the reduction of apoptotic phenomena in poorly differentiated synovial sarcoma could be considered one of the major mechanisms of tumoral growth.

Adult↗
PubMed2001

Study of axillary lymph node asymmetry in a female population.

We analysed a large series of axillary lymph nodes, with and without metastases following radical mastectomy for breast cancer. We found left/right asymmetry in numbers of lymph nodes, and also asymmetry of lymph node dimensions, which could have been the caused by tumoral antigenic stimulation. The distribution of hyperplastic node patterns differed significantly.

Adult↗
PubMed2001

Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocytic enzymatic disorder in Italy and is characterized by wide clinical, biochemical and molecular variability. We studied the clinical and hematologic data from 54 G6PD-deficient, unrelated males from the Apulia region. DESIGN AND METHODS: Analyses for enzymatic activity, G6PD electrophoresis and molecular typing were performed on all subjects. Thirty-nine subjects (72.2%) showed a severe G6PD deficiency (<10% residual enzymatic activity) and 15 subjects (27.8%) a moderate deficiency (10--60% residual activity). RESULTS: The Mediterranean variant was found in 48.2% of cases, the Seattle variant in 33.3%, the A- variant in 7.45% and the Montalbano variant in 3.7%; the variant was not identified in four subjects. Thirty-two patients (59.2%) were asymptomatic; of these, 37.04% demonstrated acute hemolytic crises induced mainly by ingestion of fava beans and 3.7% had had neonatal jaundice. Acute hemolytic anemia was found in 53.8% of subjects with the Mediterranean variant, in 5.5% with the Seattle variant, in 100% with the A-variant and 0% with the Montalbano variant. INTERPRETATION AND CONCLUSIONS: Enzymatic activity was shown to be a poor predictive parameter of acute hemolytic crises and was not correlated with clinical features. Subjects with Mediterranean or A- variants had a more severe clinical phenotype which was not related to enzymatic activity. The Seattle, and probably the Montalbano, variant appears to have a milder clinical expression.

DNA Mutational Analysis↗
PubMed2001

Expression of CD94 and NKG2 molecules on human CD4(+) T cells in response to CD3-mediated stimulation.

We investigated the ability of human peripheral CD4(+) cells to express CD94 and NKG2 molecules as a consequence of CD3-mediated activation. Using highly purified peripheral CD4(+) T cells, we found expression of both CD94 and NKG2A 15 days after CD3-mediated stimulation of cells. We also determined by reverse transcriptase-PCR that all gene members of NKG2 family-namely, NKG2A, -C, -D, and -E-are sequentially expressed on CD4(+) cells. We found that this expression is tightly regulated by cytokines, and we identified transforming growth factor-beta1 and interleukin-10 as the main factors that, on CD3-dependent stimulation, positively contribute to the expression of CD94 and NKG2A on CD4(+) cells. We also investigated the functional role of NKG2A and found that coligation of CD3 and NKG2A by specific monoclonal antibodies results in significant inhibition of interferon gamma and tumor necrosis factor alpha production by stimulated CD4(+) cells. The presence and function of these receptors on CD4(+) lymphocytes support a more general role for NKG2 molecules, whose functions were originally thought to be confined to cytotoxic cells, in the immune system.

Antigens, CD↗
PubMed2000

Inhibitors of the fungal cell wall. Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on beta(1-3) glucan and chitin synthases.

As part of our project devoted to the search for antifungal agents, which act via a selective mode of action, we synthesized a series of new 4-aryl- or 4-alkyl-N-arylamine-1-butenes and transformed some of them into 2-substituted 4-methyl-tetrahydroquinolines and quinolines by using a novel three-step synthesis. Results obtained in agar dilution assays have shown that 4-aryl homoallylamines not possessing halogen in their structures, tetrahydroquinolines and quinolines, display a range of antifungal properties in particular against Epidermophyton floccosum and Microsporum canis. Regarding the mode of action, all active compounds showed in vitro inhibitory activities against beta(1-3) glucan-synthase and mainly against chitin-synthase. These enzymes catalyze the synthesis of beta(1-3) glucan and chitin, respectively, major polymers of the fungal cell wall. Since fungal but not mammalian cells are encased in a cell wall, its inhibition may represent a useful mode of action for these antifungal compounds.

Allylamine↗
PubMed2000

Different patterns of renal osteodystrophy in Iberoamerica.

The various forms of renal osteodystrophy are predominant hyperparathyroid bone disease, mixed uremic osteodystrophy, low turnover osteomalacia, and adynamic bone disease. The present study analyses a total number of 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain). Low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. In all centers, independent of the aluminum staining technique used, the extent of aluminum deposited in bone was greater in patients presenting with low bone turnover, whether from low turnover osteomalacia or adynamic bone disease, than in the predominant hyperparathyroid bone disease. In summary, even though recent reports have indicated that, over the last decade, the incidence of aluminum-induced toxicity was reduced, aluminum still seems to be implicated in a great percentage of symptomatic low bone remodelling lesions in Iberoamerica.

Aluminum↗
PubMed1999

Antimicrobial susceptibility of anaerobic and aerobic bacteria isolated from patients with mixed infections in Nicaragua.

The agar dilution method was used to test the activity of ampicillin, benzylpenicillin, cefoxitin, imipenem, clindamycin, metronidazole, chloramphenicol, gentamicin, methicillin and vancomycin against 241 anaerobic and 227 aerobic bacteria isolated from 136 patients with intraabdominal infections and 49 with nonintraabdominal infections. Beta-lactamase production was tested in all strains. Overall, imipenem, metronidazole and chloramphenicol were the most active antimicrobial agents against anaerobic bacteria followed by clindamycin. Only the Bacteroides fragilis group was shown to be less susceptible to clindamycin (MIC90 8 mg/l). Ampicillin and cefoxitin were the least active beta-lactam antibiotics against the most common isolated B. fragilis group strains (MIC(90) >1024 and 64 mg/l, respectively) and against Escherichia coli strains (MIC(90) >1024 and >1024 mg/l, respectively). Chloramphenicol showed low activity against the Gram-negative aerobic bacteria, while gentamicin had good activity against the aerobic bacteria tested, except for E. coli and Pseudomonas. Among the Gram-positive aerobic and anaerobic bacteria tested, Staphylococcus aureus was shown to be less susceptible to beta-lactam antibiotics (29% were methicillin resistant). No vancomycin-resistant S. aureus strains were found. A good correlation between beta-lactamase production and beta-lactam resistance was observed.

Bacteria, Aerobic↗
PubMed1999

Antimicrobial susceptibility of anaerobicand aerobic bacteria isolated from patientswith mixed infections in Nicaragua.

The agar dilution method was used to test the activity of ampicillin, benzylpenicillin, cefoxitin, imipenem, clindamycin, metronidazole, chloramphenicol, gentamicin, methicillin and vancomycin against 241 anaerobic and 227 aerobic bacteria isolated from 136 patients with intraabdominal infections and 49 with nonintraabdominal infections. Beta-lactamase production was tested in all strains. Overall, imipenem, metronidazole and chloramphenicol were the most active antimicrobial agents against anaerobic bacteria followed by clindamycin. Only the Bacteroides fragilis group was shown to be less susceptible to clindamycin (MIC90 8 mg/l). Ampicillin and cefoxitin were the least active beta-lactam antibiotics against the most common isolated B. fragilis group strains (MIC(90) >1024 and 64 mg/l, respectively) and against Escherichia coli strains (MIC(90) >1024 and >1024 mg/l, respectively). Chloramphenicol showed low activity against the Gram-negative aerobic bacteria, while gentamicin had good activity against the aerobic bacteria tested, except for E. coli and Pseudomonas. Among the Gram-positive aerobic and anaerobic bacteria tested, Staphylococcus aureus was shown to be less susceptible to beta-lactam antibiotics (29% were methicillin resistant). No vancomycin-resistant S. aureus strains were found. A good correlation between beta-lactamase production and beta-lactam resistance was observed.

Journal Article↗
PubMed1998

Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas.

We describe the first potent and selective blocker of the class E Ca2+channel. SNX-482, a novel 41 amino acid peptide present in the venom of the African tarantula, Hysterocrates gigas, was identified through its ability to inhibit human class E Ca2+ channels stably expressed in a mammalian cell line. An IC50 of 15-30 nM was obtained for block of the class E Ca2+ channel, using either patch clamp electrophysiology or K+-evoked Ca2+ flux. At low nanomolar concentrations, SNX-482 also blocked a native resistant or R-type Ca2+ current in rat neurohypophyseal nerve terminals, but concentrations of 200-500 nM had no effect on R-type Ca2+ currents in several types of rat central neurons. The peptide has the sequence GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH and is homologous to the spider peptides grammatoxin S1A and hanatoxin, both peptides with very different ion channel blocking selectivities. No effect of SNX-482 was observed on the following ion channel activities: Na+ or K+ currents in several cultured cell types (up to 500 nM); K+ current through cloned potassium channels Kv1.1 and Kv1. 4 expressed in Xenopus oocytes (up to 140 nM); Ca2+ flux through L- and T-type Ca2+ channels in an anterior pituitary cell line (GH3, up to 500 nM); and Ba2+ current through class A Ca2+ channels expressed in Xenopus oocytes (up to 280 nM). A weak effect was noted on Ca2+ current through cloned and stably expressed class B Ca2+ channels (IC50 > 500 nM). The unique selectivity of SNX-482 suggests its usefulness in studying the diversity, function, and pharmacology of class E and/or R-type Ca2+ channels.

Amino Acid Sequence↗
PubMed1998

[Duodenogastric reflux: validation study of its endoscopic visualization].

BACKGROUND: Duodenogastric reflux is a normal event that can be deleterious to the esophagic or gastric mucosa, depending on its magnitude, persistence, composition and gastric pH. There is not a definitive method to measure this phenomenon. AIM: To compare the endoscopic visualization of duodenogastric reflux with the quantitation of total bile acids in fasting gastric content (QTBA). PATIENTS AND METHODS: The presence of duodenogastric reflux, defined as the staining of gastric walls with bile during upper gastrointestinal endoscopy, was assessed in 62 patients (26 male), aged 21 to 73 years old. During the week after the endoscopy a sample of fasting gastric content was obtained to measure QTBA, using an enzymatic method. RESULTS: Median QTBA was 0.205 mumol/gastric residue. Fourteen of 31 patients with QTBA values over the median had endoscopically visible duodenogastric reflux, whereas 1 of 31 with values below the median had visible reflux (p < 0.001). CONCLUSIONS: Endoscopic visualization of duodenogastric reflux is statistically associated to the quantitation of total bile acids in fasting gastric residue.

Adult↗
PubMed1996

Bone alkaline phosphatase isoenzyme in renal osteodystrophy.

Serum total alkaline phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but alkaline phosphatase originates from different organs and sometimes lacks specificity. Bone isoenzyme measurement is considered superior to total alkaline phosphatase for the assessment of bone metabolism. We have studied the value of bone isoenzyme, determined by a new. IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total alkaline phosphatase and bone alkaline phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone alkaline phosphatase and PTH (r = 0.79, P < 0.001) and between bone and total alkaline phosphatase (r = 0.84, P < 0.001) in all patients. The patients who underwent a bone biopsy showed osteitis fibrosa in 17, mixed lesion in one, adynamic bone disease in one and normal bone in one. Bone alkaline phosphatase showed a significant correlation with static and dynamic histomorphometric indices similar to that obtained with PTH and better than those of total alkaline phosphatase and osteocalcin. It is concluded that bone alkaline phosphatase (ostase) seems to be a useful non-invasive marker of bone metabolism in patients on haemodialysis with high turnover bone disease. More studies are necessary to know its value in low turnover bone disease.

Adult↗
PubMed1995

SNX-325, a novel calcium antagonist from the spider Segestria florentina.

A novel selective calcium channel antagonist peptide, SNX-325, has been isolated from the venom of the spider Segestria florentina. The peptide was isolated using as bioassays the displacement of radioiodinated omega-conopeptide SNX-230 (MVIIC) from rat brain synaptosomal membranes, as well as the inhibition of the barium current through cloned expressed calcium channels in oocytes. The primary sequence of SNX-325 is GSCIESGKSCTHSRSMKNGLCCPKSRCNCRQIQHRHDYLGKRKYSCRCS, which is a novel amino acid sequence. Solid-phase synthesis resulted in a peptide that is chromatographically identical with the native peptide and which has the same configuration of cysteine residues as the spider venom peptide omega-Aga-IVa [Mintz, I. M., et al., (1992) Nature 355, 827-829]. At micromolar concentrations, SNX-325 is an inhibitor of most calcium, but not sodium or potassium, currents. At nanomolar concentrations, SNX-325 is a selective blocker of the cloned expressed class B (N-type), but not class C (cardiac L), A, or E, calcium channels. SNX-325 is approximately equipotent with the N-channel selective omega-conopeptides (GVIA and MVIIA as well as closely related synthetic derivatives) in blocking the potassium induced release of tritiated norepinephrine from hippocampal slices (IC50s, 0.1-0.5 nM) and in blocking the barium current through cloned expressed N-channels in oocytes (IC50s 3-30 nM). By contrast, SNX-325 is 4-5 orders of magnitude less potent than is SNX-111 (synthetic MVIIA) at displacing radioiodinated SNX-111 from rat brain synaptosomal membranes. SNX-325 will be a useful comparative tool in further defining the function and pharmacology of the N- and possibly other types of high-voltage activated calcium channels.

Amino Acid Sequence↗