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A Andres

Publications and source records attributed to A Andres.

At least 37 records · Page 2Linked to original sources
PubMed2001

Requirement of Notch in adulthood for neurological function and longevity.

Although Notch proteins rely upon presenilins for activation and can modulate neuritic architecture, their role in aging adults and Alzheimer's disease is unknown. Here we examine Drosophila in which Notch function was selectively diminished in adulthood. An outcrossing strategy was employed to reduce the effect of recessive modifiers of lifespan, and a temperature-sensitive allele or inducible dominant-negative Notch transgenes were used to reduce Notch function. A progressive neurological syndrome with loss of flight and shortened lifespan was observed in adults with compromised Notch function. Notch protein persists in aging adult Drosophila brains. However, no evidence of neurodegeneration in the central nervous system was detected. We conclude that Notch activity is constitutively required in the adult fly for neurological function.

Alleles↗
PubMed2001

Influence of cyclosporin, tacrolimus and rapamycin on renal function and arterial hypertension after renal transplantation.

Cyclosporin and tacrolimus have improved survival figures in organ transplantation. However, both drugs are potentially nephrotoxic. The immunosuppressive and nephrotoxic effects of both drugs appear to depend on the inhibition of calcineurin. Cyclosporin and tacrolimus cause acute (functional changes) and chronic nephrotoxicity (structural lesions in the kidney). These last important lesions include arteriolar hyalinosis, stripped interstitial fibrosis and tubular atrophy. It is possible that repeated episodes of renal ischaemia contribute to the development of chronic nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and tacrolimus also induce arterial hypertension. Therefore, the beneficial effects of immunosuppression have been limited due to nephrotoxicity and arterial hypertension. Rapamycin, a novel immunosuppressive agent, that does not inhibit calcineurin, provides immunosuppression without nephrotoxicity. In fact, in the trials performed in Europe, sirolimus-treated immunosuppression patients exhibited a much better renal function than cyclosporin-treated patients. However, sirolimus can potentiate the nephrotoxic effect of cyclosporin. Therefore, when cyclosporin and sirolimus are used in combination, a reduction of the cyclosporin dose is desirable.

Antihypertensive Agents↗
PubMed2000

Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children.

A total of 251 clinical specimens (235 gastric aspirates and 16 bronchoalveolar lavages) from 88 children were prospectively tested in a blinded manner for the presence of Mycobacterium tuberculosis complex, by use of the Amplicor M. tuberculosis test and by means of in-house polymerase chain reaction (PCR). The results were compared with those obtained by conventional culture and by direct microscopy. All of the children underwent extended follow-up to verify or exclude the clinical diagnosis of tuberculosis. The results of the different tests, when compared to the final clinical diagnosis, were a sensitivity of 60% and a specificity of 96.8% for in-house PCR, 44% and 93.7% respectively for the Amplicor test, 44% and 100% for mycobacterial culture and 12% and 100% for microscopy. Amplicor tests presented false-positive findings in children without tuberculous infection. We conclude that both in-house PCR and the Amplicor test are rapid methods that can be helpful for difficult or urgent diagnosis of tuberculosis in children. However, efforts should be aimed toward improvement of the sensitivity and specificity of an easy-to-use PCR kit.

Child↗
PubMed2000

Human motor units in health and disease.

Recent advances in clinical neurophysiology have made it possible to non-invasively stimulate single motor axons and determine the physiological characteristics of the associated motor units. Some motor units lend themselves to longitudinal studies of their electrical and contractile characteristics. The former include the conduction velocities of their motor axons and the sizes and shapes of their motor unit action potentials and the latter such contractile characteristics of the motor unit as their contractile speeds, twitch and tetanic tensions, and resistance to fatigue. The feasibility of serially examining the same motor unit has made it possible to study the responses of single motor units to conditioning as well as changes in the responses of single motor units to diseases such as amyotrophic lateral sclerosis. The non-invasive character of these approaches offers an attractive means of studying the responses of single human cells, in these cases motor neurons, in health and disease.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Accumulation of mercury in neurosecretory neurons of mice after long-term exposure to oral mercuric chloride.

Inorganic mercury (HgCl2) was administered to adult mice in drinking water (20 mg/l). Animals were sacrificed after one or two years and fixed by whole-body perfusion. Sections of the hypothalamus and neurohypophysis were subjected to silver acetate autometallography for visualization of mercury at light and electron microscopy levels. Mercury deposits, which can be seen by light microscopy as black granules, were found to accumulate within neuronal perykaria of the supraoptic and paraventricular nuclei. Electron microscopy demonstrated that mercury deposits in neurosecretory neurons were detected exclusively within lysosomes. Mercury was also present in small vesicles, 40-70 nm in diameter, and in endocytic vacuoles within the axon terminals of the neurohypophysis. No mercury could be seen in sections obtained from control animals that had been drinking uncontaminated water. Mechanisms involved in uptake and transport of mercury to neuronal bodies are discussed.

Administration, Oral↗
PubMed1997

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Adolescent↗
PubMed1997

Membranous glomerulonephritis associated with hepatitis C virus infection in renal transplant patients.

BACKGROUND: Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. METHODS: From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). RESULTS: Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (<2 g/24 h.). CONCLUSIONS: In summary, HCV is preferentially associated with MGN in renal transplant patients, rather than with membranoproliferative glomerulonephritis as in the normal adult population. MGN associated with HCV infection has a similar clinical picture and outcome to posttransplant idiopathic de novo MGN, with persistent massive proteinuria and progressive deterioration of renal function.

Adult↗
PubMed1997

Increased lipoproteins and fibrinogen in chronic renal allograft dysfunction.

Chronic rejection - also called chronic renal allograft dysfunction (CRAD) - is the main cause of long-term loss of the transplanted kidney, but its pathogenesis is not well known. The aim of this study was to know if lipoproteins, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and platelet aggregation show more abnormalities in renal transplant patients with CRAD than in those with stable renal function. Sixty patients with renal allograft have been studied; 20 patients with CRAD and 40 controls matched for age, gender and time after transplantation. In a univariate analysis patients with CRAD had higher total serum triglycerides (214+/-153 vs. 133+/-39 mg/dl; p = 0.04) and very-low-density lipoprotein (VLDL) triglycerides (128+/-116 vs. 59+/-29 mg/dl; p = 0.04). Apolipoprotein B levels were also increased in patients with CRAD although this difference was only borderline significant (131+/-58 vs. 98+/-16 mg/dl; p = 0.05). Similarly, there was a trend toward increased total, VLDL, and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol in CRAD patients, but these differences did not reach statistical significance. Apolipoprotein A-1 and lipoprotein(a) levels were similar in both groups. Neither platelet aggregation nor PAI-1 levels differed between both groups. In contrast, fibrinogen was increased in patients with CRAD (373+/-81 vs. 322+/-62 mg/dl; p = 0.01). In a multivariate analysis triglycerides and fibrinogen were positively correlated to CRAD. These findings add further support to the hypothesis that lipid abnormalities may be involved in the pathophysiology of CRAD. In addition, this is the first report showing that fibrinogen levels are increased in patients with CRAD. Further studies are needed to evaluate a potential role of fibrinogen in the development of CRAD.

Adult↗
PubMed1997

In vivo insulin-dependent glucose uptake of specific tissues is decreased during aging of mature Wistar rats.

Aging has been associated with peripheral insulin resistance in both humans and rats. However, the specific tissues that become insensitive to insulin before glucose homeostasis is altered remain to be elucidated. In the present work we studied the glucose metabolic index of a number of tissues known to be insulin sensitive in 3- and 24-month-old Wistar rats by measuring 2-deoxy-D-[1-3H]glucose uptake both under euglycemic-hyperinsulinemic conditions and in the basal state. Analysis of the glucose infusion rate to maintain normoglycemia during the clamp confirmed that the old rats show overall insulin resistance at both saturating and subsaturating insulin concentrations. The maximal response of glucose uptake to insulin as well as insulin sensitivity in red and white quadriceps were unaltered in old rats. In contrast, glucose uptake by soleus and diaphragm was poorly stimulated in old animals, and a marked decrease in insulin sensitivity was observed in both tissues. In heart, only the sensitivity to the hormone, not the maximal response, was impaired in old rats. In white adipose tissue, no significant stimulation was detected. We conclude that during aging in Wistar rats and before fasting plasma insulin and glucose levels become altered, specific tissues develop insulin resistance, whereas other remain insulin sensitive. We postulate that fat tissue plays a qualitative important role in eliciting the insulin resistance in old animals. Due to the metabolic characteristics of the aged Wistar rat, the changes reported might reflect what occurs in nonobese elderly humans, nongenetically committed to develop type 2 diabetes.

Adipose Tissue↗
PubMed1996

Aging abolishes the renal response to L-arginine infusion in essential hypertension.

A defect in the endothelium-dependent vasorelaxation could contribute to the development of arterial hypertension through the facilitation of renal vasoconstriction and sodium retention. In this study, we tested the hypothesis that aging impairs kidney function in essential hypertension through a derangement of nitric oxide-dependent renal mechanisms. To this end, we compared the renal response to an intravenous infusion of the precursor of nitric oxide synthesis, L-arginine, in young and aged essential hypertensives. In young hypertensives, L-arginine induced a significant increase in renal plasma flow, glomerular filtration rate, natriuresis and kaliuresis, without changes in filtration fraction. These effects were not observed in aged hypertensives. Neither PRA nor PA were affected by L-arginine infusion in any group. These results indicate that aging produces a derangement of endothelial function in essential hypertension.

Adult↗