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Biomedical subjects

J Sancho

Publications and source records attributed to J Sancho.

At least 127 records · Page 7Linked to original sources
PubMed1989

Preparation and properties of a cross-linked complex between ferredoxin--NADP+ reductase and flavodoxin.

The electrostatically stabilized complex between Anabaena variabilis ferredoxin--NADP+ reductase and Azotobacter vinelandii flavodoxin has been covalently cross-linked by treatment with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The covalent complex exhibits a molecular mass and FMN/FAD content consistent with that expected for a 1:1 stoichiometry of the two flavoproteins. Immunochemical cross-reactivity is exhibited by the covalent complex with rabbit antisera prepared separately against each protein. The complex retains NADPH-ferricyanide diaphorase activity although the Km for ferricyanide is increased twofold and the turnover number is decreased by a factor of two when compared to native reductase. NADPH-cytochrome-c reductase activity of the complex is observed at a level that is quite similar to that determined at saturating concentrations of flavodoxin, while it is only 1-2% of that exhibited by the reductase in the presence of ferredoxin. No stimulation of cytochrome-c reductase activity is observed on adding ferredoxin to the cross-linked complex. Stopped-flow data show that covalent cross-linking of the flavodoxin to the reductase reduces the rate of electron transfer from its semiquinone form to cytochrome c by a factor of 60. Anaerobic titrations of the reduced complex with NADP+ show the semiquinone/quinol couple of the flavodoxin is increased 100 mV relative to the free form and the quinone/quinol couple of complexed ferredoxin-NADP+ reductase is increased by only 25 mV, relative to the free protein. Addition of NADPH to the cross-linked complex reduces the FAD of the reductase as well as the FMN moiety of flavodoxin to a mixture of semiquinone and quinol forms.

Azotobacter↗
PubMed1989

Mechanism of mononuclear cell activation by an anti-CD43 (sialophorin) agonistic antibody.

CD43 (sialophorin, gpL115) is a sialoglycoprotein expressed on a wide variety of blood cells including lymphocytes, monocytes, neutrophils, and platelets. L10, an anti-CD43 mAb, has been shown to induce monocyte-dependent activation and proliferation of human T lymphocytes. We have studied the signaling mechanism involved in this activation process. Treatment of PBMC and purified populations of T cells and monocytes with L10 induced the hydrolysis of phosphoinositides with the resultant generation of the phosphoinositide-derived second messengers diacylglycerol and inositol phosphates. This was associated with the translocation of protein kinase C from cytosol to membrane fractions and an increase in free intracellular Ca2+ in treated cells. In human leukemic T cell lines, the magnitude of signaling via CD43 did not correlate with the density of the TCR/CD3 surface expression nor with the intensity of signaling via the TCR/CD3. Moreover, a mutant derived from the leukemic T cell line HPB-ALL that was severely defective in TCR/CD3 surface expression and signaling nevertheless had normal CD43 surface expression and signaling compared with the parent cell line. It is concluded that CD43 is functionally coupled to the phospholipase C/phosphoinositides signaling pathway. In human T cells, signaling via CD43 proceeds independently of TCR/CD3. The widespread expression of CD43 suggests a potentially important role for this molecule in orchestrating the activation of multiple cell types.

Adult↗
PubMed1989

Introduction of T cell receptor (TCR)-alpha cDNA has differential effects on TCR-gamma delta/CD3 expression by PEER and Lyon-1 cells.

A TCR heterodimer composed of a TCR gamma-chain and a TCR delta-chain was found to be expressed in association with CD3 by a small population of human peripheral blood T cells, thymocytes, and certain leukemic T cell lines. The leukemic T cell lines PEER and Lyon-1 express such a TCR-gamma delta/CD3 complex at the cell surface. In addition, PEER and Lyon-1 cells transcribe a productively rearranged TCR-beta gene. Introduction of TCR alpha-chain cDNA of human or murine origin resulted in cell surface expression of a TCR-alpha beta/CD3 complex on PEER and Lyon-1 cells. The expression of the TCR-gamma delta/CD3 complex on PEER cells was not affected by introduction of TCR-alpha cDNA. In contrast, introduction of a TCR-alpha cDNA and expression of the TCR-alpha beta/CD3 complex in Lyon-1 cells resulted in the disappearance of the TCR-gamma delta/CD3 complex. These data were confirmed by indirect immunofluorescence, at the protein level and by gene expression analysis. Triggering of the TCR-alpha beta/CD3 complexes by anti-CD3 mAb or anti-TCR mAb resulted in increased internal Ca2+ levels, indicating that these receptors were functional in signal transduction. These results indicate that, besides TCR gene rearrangements, membrane expression of TCR-alpha beta heterodimers may be important in regulating TCR-gamma delta cell surface expression.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

[Lumbosacral plexopathy caused by aneurysms of the abdominal aorta].

We report three patients who presented pain in the sciatic-crural region as presenting feature of an aneurysm of the abdominal aorta. The first patient developed a fullblown plexopathy with bad condition due to a large aneurysm of common iliac artery. The remaining two patients had abdominal aneurysms each that manifested as femoral neuropathy in one case and as L5-S1 radiculopathy in the other patient. The mechanism of neural involvement is discussed and those clinical and radiologic findings which may prompt us to think of such etiology in front of painful clinical pictures in this region are emphasized.

Aneurysm↗
PubMed1989

Treatment of 27 postoperative enterocutaneous fistulas with the long half-life somatostatin analogue SMS 201-995.

Twenty-seven patients with postoperative enterocutaneous fistulas were treated with parenteral nutrition and SMS 201-995 (100 micrograms/8 hours, subcutaneously), a long half-life somatostatin analogue. At the time SMS 201-995 was started, 11 patients had low output fistulas (less than 1000 ml/48 hours), 11 patients had high output fistulas (above 1000 ml/48 hours), and 5 patients had fistulas sitting in large abdominal wall defects. Within 24 hours of treatment, a mean reduction of 55% of the fistula output was observed. Fistula site or output before treatment had no influence on the magnitude of output reduction. Spontaneous closure was achieved in 77% of the patients after a mean of 5.8 +/- 2.7 days of treatment with this drug. Two patients died (7.4%). Pain at the injection site was referred by 15% of the patients but no other side effects were observed. Glucose intolerance was not observed. SMS 201-995 has been shown to be very useful in the conservative treatment of enterocutaneous fistulas because of its ability to rapidly reduce fistula output and accelerate spontaneous closure.

Adult↗
PubMed1989

Diuretic and natriuretic properties of fenoldopam in chronic renal failure.

The effect of intravenously administered fenoldopam on diuresis and natriuresis was investigated in a group of 10 patients with advanced chronic renal failure. After an initial basal period of 1 h, a fenoldopam infusion was started and maintained for 12 h at rates varying between 0.025 and 0.1 microgram/kg per min. During the study, blood pressure was measured every 10 min and urine volume, natriuresis and creatinine clearance were measured hourly. Fenoldopam induced a significant increase in urine volume, natriuresis and creatinine clearance (P less than 0.05-0.001) accompanied by a small but significant drop in blood pressure (P less than 0.05-0.01). These results show that for advanced chronic renal failure, fenoldopam has diuretic and natriuretic properties that could be of clinical relevance.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

[Neurophysiologic study in patients with human immunodeficiency virus infection].

Peripheral nervous system (PNS) involvement in the form of different neuropathies in human immunodeficiency virus (HIV) infection is increasingly more common. We present a series of 20 HIV + patients subjected to neurophysiological study. The most commonly observed neurological disorder was a slight axonal-type sensitivo-distal polyneuropathy that predominantly affected the lower limbs during the early stages of infection. As HIV infection evolves, the polyneuropathy worsens and becomes a sensitivo-motor polyneuropathy with a more important axonal component. Secondary demyelinization is observed, with additional involvement of the upper limbs in the final stages of infection. The most frequent neurophysiological finding was a decrease in somatosensory evoked potential (SEP) and conduction velocity (CV) of the sural nerve.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Leptomeningeal carcinomatosis as the primary manifestation of a carcinoma of probable renal origin].

Leptomeningeal carcinomatosis (LC) is commonly observed in malignant lymphoproliferative diseases (leukemias and lymphomas), and it can rarely be the presenting feature of a solid tumour. The types of tumour most commonly associated with that condition are breast, lung and gastrointestinal carcinomas and malignant melanoma. We report a patient with a carcinoma of probable renal origin who presented with meningeal carcinomatosis, without any symptom attributable to the initial tumour. We review and discuss the diagnostic criteria, the pathophysiology and the therapeutic outlook of this relatively uncommon type of metastatic disease.

Carcinoma↗
PubMed1988

Purification and properties of ferredoxin-NADP+ oxidoreductase from the nitrogen-fixing cyanobacteria Anabaena variabilis.

The isolation and characterization of ferredoxin-NADP+ -oxidoreductase from Anabaena variabilis, a nitrogen-fixing, filamentous cyanobacterium, is described. Purified enzyme was obtained in four steps with a 55% yield and 300-fold purification utilizing chromatographic separations on DEAE-cellulose and Cibacron Blue-Sepharose columns. The enzyme is quite similar but not identical to the spinach enzyme as judged by isoelectric focusing, molecular weight determination, and amino acid composition. N-terminal sequence analysis allowed identification of 28 of the first 33 residues. Alignment with the corresponding sequences from spinach and Spirulina FNR preparations was possible. A higher degree of homology was found with the Spirulina enzyme than with the spinach enzyme. Small differences with the spinach enzyme were also shown by absorption and circular dichroism spectral measurements. Oxidation-reduction potential measurements of the bound FAD coenzyme show an Em = -320 mV at pH 7 for the two-electron process. Complex formation between the reductase and ferredoxin from the same organism was observed by difference absorption spectroscopy with a Kd = 4 microM. Similar Kd and difference absorption properties were observed on complex formation with spinach ferredoxin.

Amino Acid Sequence↗
PubMed1988

Renal effects of fenoldopam in refractory hypertension.

Fenoldopam, a dopamine-1 (D1) agonist, was administered by a 6-h intravenous infusion to patients with refractory hypertension [diastolic blood pressure (DBP) greater than 115 mmHg while on triple therapy] in order to achieve a fall in DBP of 30 mmHg. The evolution of blood pressure, heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, renal excretion of sodium, potassium, chloride, calcium, uric acid, phosphate, plasma renin activity (PRA), aldosterone and prolactin were evaluated. A significant fall in blood pressure (P less than 0.01) accompanied by an increase in heart rate (P less than 0.01) was attained after 30 min. GFR and RPF increased significantly (P less than 0.01) but the filtration fraction fell. Urine volume and urinary output of sodium, potassium, chloride, calcium, uric acid and phosphate increased markedly (P less than 0.01). Meanwhile, plasma potassium fell (P less than 0.01) and the hormonal parameters showed no significant change. We concluded that in refractory hypertension fenoldopam has potent renal and systemic vasodilatory properties through which blood pressure falls. The hypotensive effect of fenoldopam is also facilitated by its marked diuretic and natriuretic properties. The absence of variations of plasma prolactin confirm the D1 selectivity of fenoldopam and the lack of increase in PRA indicates that fenoldopam blocks the renin-angiotensin-aldosterone system.

Adult↗
PubMed1988

Defective function of the mononuclear phagocytic system in rats with chronic nephritis. Evidence of a decreased degradation of IgG aggregates by Kupffer cells.

In a model of chronic nephritis induced by daily injections of ovalbumin (OVA), the fate of stable, well-defined heat-aggregated rat IgG (A-IgG) was examined by comparing it to that observed in normal rats of the same age. Following i.v. injection of traced amounts of 125I-A-IgG 0.5 hr after the administration of OVA (Group I), rats with nephritis showed delayed blood clearance (t1/2 = 4.6 +/- 2.3 min) compared to the control group (t1/2 = 2.4 +/- 0.8 min). At this time, the following data were also obtained from rats with nephritis: (i) sections of liver, examined by immunofluorescence, showed rat IgG in Kupffer cells reflecting the presence of immune complexes (IC), as was demonstrated in blood by the Raji cell assay; and (ii) rosette formation of IgG-sensitized Affigel 701 beads with Kupffer cells demonstrated decreased Fc receptor-ligand binding in comparison to those of control rats (percentage rosettes: 18.3 +/- 7.2 versus 40.9 +/- 7.9; P less than 0.01). To assess the dynamics of the mononuclear phagocytic system (MPS) in the uptake of immune complexes, in another set of experiments the A-IgG was administered 18 hr after the injection of OVA (Group II). Although a delayed blood clearance of A-IgG was also observed (t1/2 = 4.1 +/- 1.2 min) there were neither circulating IgG-immune complexes nor IgG deposits in the liver, and the percentage of rosette-forming Kupffer cells was increased (75.6 +/- 7.4%). To explain the apparently discordant results between the t1/2 and percentages of rosette-forming Kupffer cells in Group II, binding assays (at 4 degrees and 37 degrees), endocytosis, and catabolism of labelled A-IgG for Kupffer cells were studied. The binding studies at 4 degrees showed that the number of receptor sites per cell was similar in rats with nephritis (6.5 +/- 3.3 X 10(4] and control rats (7.0 +/- 3.1 X 10(4]. However, in rats with nephritis, the affinity constant Ka was significantly lower (0.86 +/- 0.4/M X 10(8] than in control rats (37.4 +/- 13.9/M X 10(8); P less than 0.01). The endocytosis rates of rats with nephritis were significantly decreased throughout the whole period of study compared to control rats, while the catabolism was only different during the final period of the study. On the whole, these data suggest that rats with induced chronic nephritis present an impairment in the immune clearance of IgG aggregates, probably due to decreased processing by Kupffer cells.

Animals↗
PubMed1987

Blind evaluation of the effect of octreotide (SMS 201-995), a somatostatin analogue, on small-bowel fistula output.

In a blind crossover trial for 4 days, after at least 7 days on conventional treatment, 14 patients with postoperative small-bowel fistula were randomised to 2 days on a somatostatin analogue, octreotide (SMS 201-995), followed by 2 days on placebo (group 1) or vice versa (group 2), after which all patients were treated with octreotide until the fistula closed or reoperation was deemed necessary. In group 2 mean fistula output was reduced from 698 ml per 24 h pretreatment to 246 mg per 24 h after 2 days on octreotide; output increased from 228 ml per 24 h to 497 ml per 24 h when treatment with octreotide was interrupted by placebo. In 11 patients fistulae closed spontaneously in an average of 4.5 days after continous treatment with octreotide.

Adult↗
PubMed1987

Influence of a low sodium diet on the renal response to amino acid infusions in humans.

In experimental animals, a high protein diet has been shown to accelerate end-stage renal disease by inducing glomerular hyperperfusion. In this study, we found that intravenous administration of amino acid, used as one component of parenteral nutrition, to normal volunteers resulted in a significant increase in renal blood flow (from 517 +/- 29 to 754 +/- 60 ml/min) and glomerular filtration rate (from 106 +/- 6 to 165 +/- 12 ml/min) without altering systemic blood pressure, renal excretion of electrolytes, plasma renin activity, or plasma aldosterone concentration, and excretory rates of prostaglandins E2 were increased (from 665 +/- 61 to 1,034 +/- 153 pg/min). These amino acid-induced renal hemodynamic effects were abolished when the volunteers received a low sodium diet (20 mEq/day) for three days before the amino acid infusions. However, the hemodynamic effects were restored when the subjects receiving low sodium diets were pretreated with captopril. Under these conditions, amino acid infusions increased renal blood flow (from 388 +/- 11 to 597 +/- 27 ml/min) and glomerular filtration rate (from 80 +/- 4 to 118 +/- 9 ml/min). Reduction of prostaglandin synthesis with indomethacin in volunteers receiving a normal sodium intake was also capable of significantly decreasing the amino acid effects on renal hemodynamics. The results indicate that the renal hemodynamic effects of amino acid infusion are strongly influenced by angiotensin II and prostaglandin formation.

Adult↗
PubMed1987

Ectopic Cushing's syndrome with periodic hormonogenesis--a case suggesting a pathogenetic mechanism.

We report on a case of ectopic Cushing's syndrome due to a thymic carcinoid tumour with periodic hormonogenesis. Periods of hormonal production averaged 27 days. Prior to bilateral adrenalectomy, mean (s.d) values of ACTH and cortisol were 202.1 (50.3) pg/ml and 46 (14.7) micrograms/dl, ACTH rising to 3996 +/- 425 pg/ml (P less than 0.01) and cortisol falling to 6.3 +/- 1.5 micrograms/dl (P less than 0.01) in the immediate postoperative period. During the late postoperative period (2-13 months following surgery) ACTH levels fell to 509.3 (123.8) pg/ml (P less than 0.01), but remaining even higher (P less than 0.01) than before adrenalectomy. The pattern of ACTH in the present case suggests the existence of a negative feedback exerted by the cortisol over tumoral ACTH.

ACTH Syndrome, Ectopic↗
PubMed1987

Presence of shared idiotypes in serum and immune complexes in patients with IgA nephropathy.

Patients with IgA nephropathy often present a large array of antibodies against diet antigens and this disease can be experimentally induced by alimentary antigens. In this report, we have described the isolation from a patient with IgA nephropathy of antibovine serum albumin (BSA)-antibody idiotypes that are specifically recognized by auto-and heteroantiidiotypic antibodies. The fact that antigen (BSA) but not monomeric or aggregated human IgG inhibited the binding of antiidiotypic antibodies to the idiotypes, suggested that the idiotypic determinants are in or near the antigen binding site and that it is not a rheumatoid factor. By means of the heteroantiidiotypic antibodies raised in rabbits we observed the presence of increased levels of shared idiotypes in serum and/or immune complexes (IC) of 48 out of 70 (68.5%) genetically unrelated patients with IgA nephropathy. The close correlation (P less than 0.005) between the presence of IgA-IC, measured by Raji cell assay, and the existence of high levels of serum idiotypes, suggest that a portion of circulating IC could consist of idiotype-antiidiotype. A strong concordance between the presence and levels of idiotypes and the clinical activity, as defined by the existence of haematuria, was also noted. The discrepancies and absence of correlation observed in our study among the levels of anti-BSA antibodies of different classes and serum levels of idiotypes, circulating IC and haematuria could suggest that the antibodies reacting with the heterologous antiidiotypic antibodies could be directed to other more pathogenic antigens than dietary antigens. All together, our results suggest that IgA nephropathy might belong to the group of diseases that occur in susceptible individuals with a limited potential in the immunological response repertoire.

Animals↗