Course of three biochemical bone markers after kidney transplantation.
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Adrenal Cortex Hormones↗
Biomedical subjects
R Garcia
Publications and source records attributed to R Garcia.
Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat.
OBJECTIVE: The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event. METHODS: Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt. RESULTS: Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals. CONCLUSION: Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.
Animals↗
Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence.
The sequence of chemotherapy administered prior to cranial irradiation rather than the more traditional order of radiation followed by chemotherapy is currently being evaluated. This rodent study was designed to assess the sequencing of radiation therapy and chemotherapy administered with osmotic blood-brain barrier disruption (BBBD). Drug delivery and acute toxicity were evaluated. Two clinically relevant chemotherapy regimens were given with BBBD: intraarterial methotrexate (MTX, 1 g/m2), or a combination of intraarterial carboplatin (200 mg/m2) and i.v. etoposide (200 mg/m2). In a randomized protocol, the standard rodent model of 2000 cGy as a single fraction using parallel opposed portals was administered 30 days prior to, concurrent with (24 h prior), or 30 days after these two chemotherapeutic regimens. A total of 72 animals was evaluated in this study. The administration of external beam radiation therapy either prior to or concurrent with the administration of a high molecular weight marker 14C-labeled dextran 70 (Mr 70,000), or a low molecular weight marker 3H-labeled MTX (Mr 456) resulted in a statistically significant (P < 0.01) decrease in drug delivery when compared to animals not receiving cranial irradiation. Seizures were observed in 26% of the animals that received radiation prior to the administration of intraarterial MTX after BBBD. It did not matter whether the radiotherapy was administered 30 days prior to or concurrent with MTX. Seizures were not seen in any other group. The mortality in animals receiving radiotherapy 30 days prior to chemotherapy was significantly (P = 0.03) higher than the mortality in control animals receiving chemotherapy after osmotic BBBD, but no radiation. Drug delivery was significantly decreased when the animals received prior radiotherapy; the administration of radiation prior to MTX with BBBD resulted in an increased incidence of seizures, and there was a significant increase in mortality when cranial irradiation was given 30 days prior to chemotherapy administered with BBBD. With regard to delivery and toxicity, chemotherapy with BBBD administered prior to radiotherapy may have advantages over the other sequences utilizing chemotherapy and cranial irradiation.
Analysis of Variance↗
Clinical and histopathologic study of varicella zoster virus retinitis in patients with the acquired immunodeficiency syndrome.
Varicella zoster virus retinitis in patients with the acquired immunodeficiency syndrome is known to be a devastating disease. We studied a series of six consecutive patients that sheds new light on the clinical manifestations and treatment options of this disorder. All patients had episodes of cutaneous zoster, long-term exposure to oral acyclovir, and CD4+ T lymphocyte counts less than 50 cells/mm3. Two of the six patients had simultaneous radiographically demonstrable and histologically proven varicella zoster virus encephalitis; this is an important association. Histologic examination of autopsy specimens disclosed that the retinal infection by varicella zoster virus involves the retinal pigment epithelium more heavily than the inner retina, which is consistent with the characteristic clinical impression of an outer retinal necrosis.
AIDS-Related Opportunistic Infections↗
Two point mutations within the adducin genes are involved in blood pressure variation.
The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.
Amino Acid Sequence↗
Crystal structure of an idiotype-anti-idiotype Fab complex.
Anti-idiotypic monoclonal antibody 409.5.3 is raised against an antibody that neutralizes feline infectious peritonitis virus. This antibody, used as an immunogen, elicits the production of anti-anti-idiotypic antibodies that in turn neutralize the virus. The crystal structure of the complex between anti-idiotypic Fab 409.5.3 and idiotypic Fab fragment of virus-neutralizing antibody has been solved by molecular replacement using real-space Patterson search and filtering by Patterson correlation-coefficient refinement. The structure has been refined to an R value of 0.21 based on 21,310 unique reflections between 40.0 and 2.9 A. The three-dimensional structure reveals extensive, specific interactions that involve 118 van der Waals contacts and at least 9 probable hydrogen bonds. The two Fabs are rotated 61 degrees with respect to each other around the approximate long axis of the complex and are within 26 degrees being aligned along their major axes.
Amino Acid Sequence↗
Allopurinol dose is important for attenuation of liver dysfunction after normothermic ischemia: correlation between bile flow and liver enzymes in circulation.
We have investigated the effect of two doses of allopurinol (ALL) (100 and 50 mg/kg) administered i.v. on liver function after 1 h of normothermic ischemia. ALL given in a concentration of 100 mg/kg significantly improved bile output after 1 and 24 h of reperfusion. Hepatocyte injury reflected by alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) in plasma was also significantly reduced at 24 h, but not at 1 h of reperfusion compared with controls. ALL administered at a concentration of 50 mg/kg had some protective effect. Significant correlation between circulating liver enzymes and bile output at 24 h after reperfusion indicates an important pathophysiologic link between hepatocyte function and injury in this time window.
Alanine Transaminase↗
Magnetic resonance signal alterations of the brain in asymptomatic patients treated with high-dose cisplatin for ovarian carcinoma.
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Brain↗
Air bag implicated in temporomandibular joint injury.
A patient's impact with an automatic air bag deployed during a vehicular collision causes injury to the temporomandibular joints (TMJs). The injury was confirmed using magnetic resonance imaging (MRI).
Accidents, Traffic↗
Captopril treatment does not restore either the renal or the ANF release response during volume expansion in moderate to severe high output heart failure.
OBJECTIVE: Atrial natriuretic factor (ANF) release and the renal response to moderate volume expansion have been shown to be conserved in rats with a mild to moderate degree of high output heart failure (aortocaval shunt). The aim of this study was to investigate whether these variables are also conserved in animals with moderate to severe heart failure induced by an aortocaval shunt. The effect of angiotensin converting enzyme (ACE) inhibition by captopril on these responses was also investigated. METHODS: An aortocaval shunt was developed in Sprague-Dawley rats weighing 180-200 g; sham operated rats served as controls. Three weeks after surgery, three experimental groups were established: aortocaval shunt and sham operated controls, and aortocaval shunt rats treated with captopril during the last week before the experiments were started. Four weeks after surgery, haemodynamic variables, ANF release, diuresis, and natriuresis were evaluated following a moderate volume expansion. RESULTS: Mean arterial blood pressure was lower in shunt animals and still lower in the ACE inhibited group than in the sham operated controls. Central venous pressure and left ventricular end diastolic pressure (LVEDP) were significantly higher in untreated shunt rats than in their controls. ACE inhibition returned the raised central venous pressure, but not LVEDP, to control values. Shunt rats had lower baseline urinary sodium excretion (UNaV), urinary volume, and packed cell volume than their sham operated controls. ACE inhibition reversed baseline urinary volume to control values. Baseline COOH terminal and HN2 terminal ANF were greatly increased in both treated and untreated shunt rats. Volume expansion was performed three times in conscious animals at 15 min intervals with human plasma protein fraction. Its effect on LVEDP was similar in all three groups, but the increase in central venous pressure was much higher in untreated shunt animals. UNaV, urinary volume, and the release of COOH terminal and NH2 terminal ANF in response to volume expansion were blunted in both treated and untreated shunt rats when compared with their sham operated counterparts. Both absolute and relative heart weights were significantly lower in captopril treated shunt animals than in the untreated shunt group, the latter presenting very significant cardiac hypertrophy. CONCLUSIONS: Aortocaval shunt animals with moderate to severe heart failure show a blunted ANF release and renal response to volume expansion, which, despite significant haemodynamic improvement, are not restored by ACE inhibition.
Animals↗
Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.
OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.
Acquired Immunodeficiency Syndrome↗
Systemic strongyloidiasis in patients infected with the human immunodeficiency virus. A report of 3 cases and review of the literature.
We report 3 cases of systemic strongyloidiasis in HIV-infected individuals and review 11 additional cases reported in the English-language literature. Systemic strongloidiasis is a rare and potentially fatal complication of late-stage HIV disease. A combination of gastrointestinal and respiratory symptoms in an HIV-infected patient who has been to an endemic area should prompt the clinician to search for S. stercoralis in stool and sputum specimens. Treatment failures occur commonly, and careful follow-up is warranted. New antihelminthic drugs (such as ivermectin) seem promising and need to be evaluated in controlled studies.
AIDS-Related Opportunistic Infections↗
Isolation and function of human and pig islets.
This report confirms reproducible methods to isolate and assess viability and function of pig and human islets. We processed 10 pig and five human pancreata. The pancreata were digested by a modification of Ricordi's automated method for islet isolation. The number of islet equivalents (150 microns diameter islets) was 335,190 +/- 79,345 islets per pig pancreas (5,146 +/- 1,274 islets/g pig pancreas) and 323,630 +/- 147,810 per human pancreas (6,252 +/- 2,572 islets/g human pancreas). The majority of islets were in the range of 50-200 microns diameter, and 20% of the islet population had a size distribution of 200 microns diameter in both porcine and human models. The purity of the final preparations exceeded 90%. The secretory response of perifused islets showed a biphasic insulin release pattern in both species. Perifused fresh pig islets released 2.5 pmol/L islet-1 min-1 at 2.0 mM glucose and 6.2 pmol/L islet-1 min-1 at 16.7 mM glucose. After 7 days culture at 37 degrees C, human islets released 1.32 pmol/L islet-1 min-1 at 2.0 mM and 12.24 pmol/L islet-1 min-1 at 16.7 mM. These results indicate that this procedure is useful to obtain pure, large, and functional islets from pig and human pancreata.
Adult↗
Prevalence of antibodies to different Leptospira interrogans serovars in pigs on large farms.
A seroepidemiological survey was carried out in the province of Badajoz (south-western Spain) in order to determine the presence and spread of Leptospira interrogans. The 521 sera tested were drawn from breeding sows on 28 large farms (15 with fewer than 60 and 13 with over 60 breeders). Immunological testing was performed using the Martin-Pettit micro-agglutination technique. Pigs with titres equal to or greater than 1:100 were considered positive. Haemolysed and/or contaminated test sera were reprocessed following filter-paper treatment. A total of 10.56% of pigs tested proved positive, 39.28% of farms being affected. The following L. interrogans serovars were detected: pomona (6.53%), castellonis (1.15%), sejroe (1.15%), grippotyphosa (0.96%), australis (0.38%), hebdomadis (0.19%) and icterohaemorrhagiae (0.19%).
Animals↗
Allergic contact dermatitis from colour developers: absence of cross-sensitivity to para-amino compounds.
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Adult↗
Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.
AIM: To analyse the pathogenic mechanism of HIV related thrombocytopenia. METHODS: Forty one patients with thrombocytopenia and HIV-1 infection were investigated over two years. Anticardiolipin antibodies were measured using an enzyme linked immunosorbent assay and antiplatelet antibodies were measured using an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and rheumatoid factor were also carried out in all patients and 80 control subjects (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were transfused in 13 patients. P24 antigen were also measured in 12 bone marrow aspirates. RESULTS: Antiplatelet antibodies and circulating immune complexes were found exclusively in the thrombocytopenic group; values for antiplatelet antibodies and circulating immune complexes were both higher in homosexual and bisexual patients. Three kinds of pattern were observed using 111 In-labelled platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in just one case. The two most influential factors in the sequestration pattern were antiplatelet antibodies in the splenic uptake and circulating immune complexes in the hepatic and marrow sequestration. All patients, except three, had decreased platelet recovery. In those patients with a CD4 lymphocyte count of less than 200 x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were chosen for immunohistochemical study, p24 antigen was detected in the megakaryocytes, verifying that HIV-1 infects such cells. CONCLUSIONS: The pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted. Antiplatelet antibodies and circulating immune complexes would cause peripheral destruction in the spleen, liver, and bone marrow, in that order; and, on the other hand, there would be an ineffective immune thrombopoiesis and direct infection of the megakaryocytes which could cause a change in the function and maturity of these cells.
Antigen-Antibody Complex↗
Suitability of Neisseria gonorrhoeae lipooligosaccharides for epidemiological studies.
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Gonorrhea↗
Endothelin-stimulated secretion of natriuretic peptides by rat atrial myocytes is mediated by endothelin A receptors.
Endothelin (ET), a potent vasoconstrictor peptide, is known to enhance the secretion of atrial natriuretic factor (ANF) by the heart. In the present study, we investigated the potency of ET isopeptides to stimulate ANF and brain natriuretic peptide (BNP) secretion in primary cultures of neonatal atrial myocytes, and we characterized the receptor mediating these effects. All ET isopeptides caused a twofold increase of ANF and BNP secretion with the following order of potency: ET-1 approximately ET-2 > sarafotoxin 6b >> ET-3. Secretion of the natriuretic peptides was blocked by BQ-123, an ETA-receptor antagonist, but was not affected by either IRL-1620 or [Ala1,3,11,15]ET-1, two ETB-receptor agonists. ET receptors were localized by autoradiography on the surface of atrial myocytes, indicating that contaminating cells were not responsible for 125I-ET-1 binding. Competition binding analyses were then used to assess the ET-receptor subtype on atrial myocyte membrane preparations. A high-affinity (100 pmol/L) binding site with high density (approximately 1500 fmol/mg) was found to preferentially bind the ET isopeptides in the following order: ET-1 > or = ET-2 > or = sarafotoxin 6b > ET-3. Binding was totally displaced by BQ-123 but not by IRL-1620. The ET binding site therefore had the characteristics of an ETA-like receptor. Analysis by cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that it possessed a molecular mass of approximately 50 kD. Northern blot analysis of both ETA- and ETB-receptor mRNAs allowed only the detection of the former, indicating that the ETB receptor may be expressed in very small amounts. These results demonstrate that ANF and BNP secretion by atrial myocytes is enhanced by ET via binding to an ETA-like receptor.
Animals↗