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Biomedical subjects

M Franco

Publications and source records attributed to M Franco.

At least 19 recordsLinked to original sources
PubMed1992

Functional modifications of transducin induced by cholera or pertussis-toxin-catalyzed ADP-ribosylation.

Transducin (T alpha beta gamma), the heterotrimeric GTP-binding protein that interacts with photoexcited rhodopsin (Rh*) and the cGMP-phosphodiesterase (PDE) in retinal rod cells, is sensitive to cholera (CTx) and pertussis toxins (PTx), which catalyze the binding of an ADP-ribose to the alpha subunit at Arg174 and Cys347, respectively. These two types of ADP-ribosylations are investigated with transducin in vitro or with reconstituted retinal rod outer-segment membranes. Several functional perturbations inflicted on T alpha by the resulting covalent modifications are studied such as: the binding of T alpha to T beta gamma to the membrane and to Rh*; the spontaneous or Rh*-catalysed exchange of GDP for GTP or guanosine 5-[gamma-thio]triphosphate (GTP[gamma S]), the conformational switch and activation undergone by transducin upon this exchange, the activation of T alpha GDP by fluoride complexes and the activation of the PDE by T alpha GTP. ADP-ribosylation of transducin by CTx requires the GTP-dependent activation of ADP-ribosylation factors (ARF), takes place only on the high-affinity, nucleotide-free complex, Rh*-T alpha empty-T beta gamma and does not activate T alpha. Subsequent to CTx-catalyzed ADP-ribosylation the following occurs: (a) addition of GDP induces the release from Rh* of inactive CTxT alpha GDP (CTxT alpha, ADP-ribosylated alpha subunit of transducin) which remains associated to T beta gamma; (b) CTxT alpha GDP-T beta gamma exhibits the usual slow kinetics of spontaneous exchange of GDP for GTP[gamma S] in the absence of Rh*, but the association and dissociation of fluoride complexes, which act as gamma-phosphate analogs, are kinetically modified, suggesting that the ADP-ribose on Arg174 specifically perturbs binding of the gamma-phosphate in the nucleotide site; (c) CTxT alpha GDP-T beta gamma can still couple to Rh* and undergo fast nucleotide exchange; (d) CTxT alpha GTP[gamma S] and CTxT alpha GDP-AlFx (AlFx, Aluminofluoride complex) activate retinal cGMP-phosphodiesterase (PDE) with the same efficiency as their unmodified counterparts, but the kinetics and affinities of fluoride activation are changed; (e) CTxT alpha GTP hydrolyses GTP more slowly than unmodified T alpha GTP, which entirely accounts for the prolonged action of CTxT alpha GTP on the PDE; (f) after GTP hydrolysis, CTxT alpha GDP reassociates to T beta gamma and becomes inactive. Thus, CTx catalyzed ADP-ribosylation only perturbs in T alpha the GTP-binding domain, but not the conformational switch nor the domains of contact with the T beta gamma subunit, with Rh* and with the PDE.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Mechanisms involved in the progression to glomerular sclerosis induced by systemic hypertension during mild puromycin aminonucleoside nephrosis.

To evaluate the contribution of systemic hypertension in the progression of nephropathies to glomerular sclerosis, a mild form of puromycin aminonucleoside (PAN) nephrosis was associated with Goldblatt hypertension and studied after 18 weeks. We studied four groups: Group I, controls; Group II, Goldblatt hypertension; Group III, PAN nephrosis; and Group IV, both conditions. Systolic blood pressure, 24-h proteinuria, serum cholesterol, triglycerides, glomerular hemodynamics, and histological studies were compared among the groups. Rats in groups II and IV developed systemic hypertension, but only group IV rats showed persistent proteinuria. No alterations in lipid metabolism were present in any of the groups. The most striking findings in the micropuncture studies were a significant increase of glomerular capillary pressure in group IV rats (63.15 +/- 1.34 mm Hg) as compared to controls (48.74 +/- 0.97 mm Hg) and to groups II and III (55.31 +/- 2.11 and 48.17 +/- 1.23 mm Hg, respectively), and a marked fall in Kf in groups III and IV. Only group IV showed significant histological alterations such as glomerular sclerosis, interstitial damage, and increased glomerular area. These results suggest that, in the presence of an underlying nephropathy, a greater fraction of systemic pressure is transmitted to the glomerular capillaries when systemic hypertension is present; the resulting elevation in glomerular pressure and proteinuria seems to be responsible for the progression to glomerular sclerosis.

Animals↗
PubMed1992

Renal interstitial foam cells are macrophages.

Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells.

Adolescent↗
PubMed1992

Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis.

Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis. Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis. In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C. albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later. Control mice of the same strain were infected with C. albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral challenge. Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined. The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C. albicans mainly in regions of the cardial-atrium fold of the stomach. Well-defined abscesses with entrapped C. albicans hyphae were observed in the region of the cardial-atrium fold of control mice. A significant increase in the number of C. albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals. The murine model of GI candidiasis reported here permits examination of the nature of C. albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection.

Animals↗
PubMed1992

Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice.

Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection.

Animals↗
PubMed1992

Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia.

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The use of a mixture of somatic and culture filtrate antigens in the evaluation of the immune response to Paracoccidioides brasiliensis.

Three Paracoccidioides brasiliensis antigens, namely a culture filtrate preparation, a somatic antigen and a mixture of equal parts of the two, were tested by two serological techniques against sera from patients with paracoccidioidomycosis, and in an in vivo delayed hypersensitivity model in mice. The antigen mixture was more sensitive than the two individual antigens for the evaluation of the humoral and cellular immune response to P. brasiliensis, both in man and in experimental animals.

Animals↗
PubMed1991

Effect of circulating factors on vascular smooth muscle contraction and its calcium uptake in uremia.

Uremia is often associated with alterations in calcium metabolism and vascular smooth muscle function in hypertension and atherosclerosis. The ways in which these conditions inter-relate are not clearly understood. In order to study the possibility that circulating factors might influence smooth muscle function, experiments were performed on rat aortic strips. The serum from both uremic patients and rats enhanced the norepinephrine-induced contraction (NEIC) and net 45-calcium uptake in rat aortic strips. In a similar manner, the serum of parathyroidectomized uremic rats also increased the NEIC, whereas verapamil reduced the aortic response to levels below those of the control, in the presence of uremic serum. These findings suggest that in both chronic (patients) and early (rats) stages of uremia, there is a circulating factor, different from parathyroid hormone, that affects calcium uptake and vascular smooth muscle contraction.

Adult↗
PubMed1991

[The management by medical treatment of an intracranial mycotic aneurysm in a patient with infectious endocarditis with negative blood cultures and hypertrophic myocardiopathy].

A case of intracranial mycotic aneurysm due to culture-negative infective endocarditis involving a patient with hypertrophic cardiomyopathy is reported. The patient, a 22-year-old woman with no history of known prior disease, had fever, headache and focal neurologic symptoms 3 days before admission. An echocardiogram performed after admission disclosed an obstructive hypertrophic cardiomyopathy and a gross vegetation on septal leaflet of mitral valve. Cerebral angiography revealed a mycotic aneurysm involving a peripheral branch of the left middle cerebral artery. Causal agent was not identified, and empiric treatment with penicillin G and streptomycin achieved medical cure and disappearance of the aneurysm 2 weeks later. Four months after endocarditis had been cured, the patient was electively operated because of progression of mitral regurgitation. Six months later, she is asymptomatic.

Adult↗
PubMed1990

Arrestin from nucleated red blood cells binds to bovine rhodopsin in a light-dependent manner.

Using a panel of monoclonal antibodies, it has previously been demonstrated that the cytosol of nucleated red cells (trout and turkey) contains a protein similar to arrestin, a soluble protein found so far only in the photosensitive cells and which, by binding to photoexcited rhodopsin, inhibits the phototransduction process. The role of this arrestin-like protein in non-photosensitive cells is questionable. In this report we present evidence that partially purified red blood cell arrestin (RBC arrestin) behaves functionally like bovine retinal arrestin: it binds to phosphorylated bovine rhodopsin only when this receptor has been photoactivated. Thus RBC arrestin and bovine retinal arrestin are closely related both structurally and functionally. By analogy with the function of retinal arrestin, it is proposed that RBC arrestin is involved in desensitization of membrane transport proteins and/or adrenergic receptors.

Animals↗
PubMed1990

Reticulin antibodies: relationship with endocardium-vessel-interstitium antibodies and heterophilic antibodies.

1. Indirect immunofluorescence was used to compare reticulin antibodies, endocardium-vessel-interstitium (EVI) antibodies and heterophilic antibodies in serum samples from patients with degenerative and inflammatory diseases, Chagas' disease, or paracoccidioidomycosis and from healthy blood donors. 2. The antigen substrates used were rat, mouse and human liver for reticulin antibodies, mouse and human heart and skeletal muscle for EVI factor, and rat heart and rat, mouse and human kidney and stomach for heterophilic antibodies. 3. The three antibodies produced extremely similar fluorescent patterns and were present simultaneously in a large proportion of reticulin-positive serum samples. 4. The three antibodies were significantly absorbed by heterophilic antigens such as sheep and rat red blood cells and guinea pig kidney, by Trypanosoma cruzi (an antigen associated with EVI factor) and by Paracoccidioides brasiliensis. However, they did not react with several human tissues. 5. These results suggest that reticulin and EVI antibodies can be considered to be heterophilic antibodies.

Animals↗