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Biomedical subjects

M Franco

Publications and source records attributed to M Franco.

At least 145 records · Page 8Linked to original sources

A maternally-inherited alteration in the T cell repertoire of BALB/c mice.

A number of milk-borne exogenous mammary tumor viruses (MMTV) infect mice shortly after birth and, when expressed, produce superantigens. The expression of these superantigens mediate the progressive deletion of T cells expressing specific V beta products. Here we describe a maternally-inherited alteration in the T cell repertoire in one colony of BALB/c mice which has not been reported up to now. This alteration involves the deletion of V beta 2+ and 14+ CD4+ T cells and correlates with a high incidence of mammary tumors, suggesting the involvement of a superantigen(s) probably transmitted through an exogenous MMTV in milk.

Animals↗

Synthesis of 2-substituted-N-carboxymethyl-1,5-benzothiazepin-4-ones and -1,4-benzothiazin-3-ones and their evaluation as angiotensin converting enzyme inhibitors.

The title compounds 7a-d and 8a-e were synthesized and their in vitro inhibitory activity of angiotensin-converting enzyme (ACE) was examined. In general, these compounds possess poor ACE inhibitory activity. Among the benzothiazinone compounds, which are generally more active than the cyclohomologous compounds 7, 8b is the most effective (IC50 of 170 microM).

Angiotensin-Converting Enzyme Inhibitors↗

Aspergillus arthritis of the shoulder in a renal transplant recipient. Failure of itraconazole therapy.

We report a case of Aspergillus arthritis of the shoulder in a renal transplant recipient. Cultures of three joint fluid specimens grew Aspergillus fumigatus. Itraconazole as sole treatment resulted in initial clinical and roentgenographic improvements but failed to prevent deterioration in joint function. A relapse with fatal neurologic involvement occurred. Immune deficiency-inducing risk factors for aspergillosis include neutropenia and corticosteroid therapy. Previously published cases of Aspergillus arthritis of limb joints are reviewed. The advantages and limitations of itraconazole as single drug therapy are outlined.

Arthritis, Infectious↗

Roles of lipid modifications of transducin subunits in their GDP-dependent association and membrane binding.

Transducin is an unusually soluble and dissociable heterotrimeric G-protein, although its T alpha and T beta gamma subunits are N-acylated and farnesylated, respectively. These lipid modifications have been suggested to contribute directly to the GDP-dependent T alpha-T beta gamma association, through specific lipid recognition sites on both protein subunits. We studied the dependence of subunit association on their bound lipids and on the presence of different lipidic environments. Association of native N-acylated (nT alpha) or acyl-free recombinant (rT alpha) T alpha with farnesylated and carboxymethylated (fcT beta gamma), farnesylated (fT beta gamma), or farnesyl-free (dfT beta gamma) T beta gamma was analyzed by gradient centrifugation and gel filtration in the presence of detergent or phospholipid-cholate micelles and by cosedimentation with phospholipid vesicles. Without detergent, nT alpha GDP and fcT beta gamma associate only weakly in solution. The loss of T alpha acyl or T beta gamma farnesyl residues induces total dissociation. With detergent or lipids, isolated fcT beta gamma binds tightly to micelles or vesicles, while dfT beta gamma does not; nT alpha GDP binds weakly, while deacylated rT alpha GDP does not bind at all; and nT alpha GDP binds cooperatively with fcT beta gamma, while rT alpha GDP does not. Thus (i) the T alpha acyl chain binds weakly, whereas the T beta gamma farnesyl chain binds strongly to membrane lipids; (ii) there is no evidence for binding of the T alpha acyl chain to a polypeptide site in T beta gamma, nor for binding of the T beta gamma farnesyl chain to a polypeptidic site in T alpha, but the T alpha acyl chain seems to bind cooperatively with the T beta gamma farnesyl chain in the membrane lipids; (iii) the insertion of the two protein-attached lipids into the same membrane could contribute to the association of both subunits by favoring collision coupling of the properly oriented protein moieties on the membrane surface.

Acylation↗

Immunohistochemical characterisation of probable intravascular haematopoiesis in the vasa rectae of the renal medulla in acute tubular necrosis.

Immunohistochemistry was applied to identify the nature of the nucleated cells that accumulate in the vasa rectae of the corticomedullary junction in acute tubular necrosis. In all 6 cases studied, there were intravascular cells that reacted with monoclonal antibodies to erythroblast, macrophages, myeloid cells, T and B lymphocytes and rare megakaryocytes. The findings are consistent with the occurrence of intravascular haematopoiesis in the renal medulla in acute tubular necrosis.

Adult↗

Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity.

To evaluate the participation of nitric oxide (NO) in chronic cyclosporin A (CsA) nephrotoxicity, the glomerular hemodynamic response to NO inhibition with N-nitro-L-arginine-methyl-ester (NAME) and stimulation of NO production with L-arginine was studied in uninephrectomized rats. Chronic CsA administration produced renal vasoconstriction, characterized by increased afferent (AR) and efferent (ER) resistances, decrease of glomerular plasma flow (QA) and ultrafiltration coefficient (Kf) that resulted in a 53% fall of single-nephron glomerular filtration rate (SNGFR). NAME infusion in vehicle group (V) elevated mean arterial pressure (MAP), AR and ER, reduced qA and Kf, and increased glomerular capillary pressure (PGC), resulting in a 28.9% fall of SNGFR. In the CsA group, NAME also increased MAP, but renal vasoconstriction was more intense; a greater rise of AR lowered PGC (P < 0.05 vs. V) further decreasing SNGFR by 38.9%. In control rats, L-arginine infusion induced a vasodilatory response of AR and ER, and elevation of QA and Kf, which resulted in a 72.6% increase in SNGFR. In the CsA group, greater vasodilation was observed and SNGFR rose by 114.9%. NO2-/NO3- urinary excretion was similar in CsA and V groups, and it was not modified by NAME in either group, but it increased five- to sixfold during L-arginine infusion in both groups. In conclusion, in CsA nephrotoxicity NO production seems to be normal and the ability of the renal endothelium to produce NO is maintained. Therefore renal vasoconstriction associated with CsA is not mediated by NO deficiency, although NO appears to attenuate it.

Animals↗

Ifosfamide extravasation.

OBJECTIVE: To report a case in which a local reaction is attributed to an ifosfamide extravasation. Previously, extravasated ifosfamide has been considered a nonirritant. CASE SUMMARY: A 54-year-old woman with a non-Hodgkin's lymphoma in stage IV B developed a local reaction in her right arm after an ifosfamide extravasation. No pressure was prescribed, no bandaging was applied on the affected area, and the limb was elevated to the heart level. In addition, chondroitinsulfatase 150 turbidity-reducing units was administered subcutaneously around the area. This procedure was repeated 12 hours later, resulting in a satisfactory decrease in the inflammatory signs and pain. DISCUSSION: The local reaction in the patient's arm cannot be attributed to the hypertonicity of the infusing solution or to the vehicle of the infusate. The antidote used was chondroitinsulfatase, an enzyme similar to hyaluronidase. It enhances the systemic uptake of the drug from the tissue. CONCLUSIONS: Extravasated ifosfamide is a potential irritant. General measures applied after its extravasation can be potentiated strongly by local subcutaneous administration of chondroitinsulfatase or hyaluronidase, repeated if necessary.

Chondroitinsulfatases↗

Synthesis and antimicrobial activity of some N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles.

Several N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles (4) were synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 4 were also tested for antifungal activity against Saccharomyces cerevisiae. The findings clearly showed that all the compounds 4 were devoid of antifungal activity, whereas the compounds 4i-m,o-r were effective against the bacterial strains used. Compounds 4k,m,p,q proved to be the most active antibacterial agents showing in some cases minimum inhibitory concentrations (MIC) lower than chloramphenicol and gentamicin, used as reference compounds. In the case of two representative bacterial strains (Gram-positive and Gram-negative, respectively), a parabolic relationship was found between the antibacterial activity of compounds 4i-m,o-r expressed as log1/MIC and the molecular lipophilicity measured as RM values.

Anti-Bacterial Agents↗

[Infectious endocarditis in non-addict patients without predisposing heart disease. Differential features].

INTRODUCTION AND AIMS: Although uncommonly, infective endocarditis in non-addict patients may involve people without predisponente heart disease. The aim of our study was to assess the clinical and prognostic features of this type of endocarditis and to compare them with those of the more common type of endocarditis with underlying lesion. METHODS: With this aim, we have reviewed 71 consecutive cases of non-addict infective endocarditis diagnosed in our hospital in the last 7 years; there was no preexisting cardiac lesion in 9 patients (13% of all endocarditis and 21% of native valve endocarditis), while underlying heart disease, including mitral valve prolapse, was present in the remaining 62 patients. RESULTS: Mean age was significantly lower in 9 patients without preexistent lesion (28 +/- 18 versus 46 +/- 17 years, p < 0.01), while there was no differences for gender. Infection involved the aortic valve in 56%, the tricuspid or pulmonary valve in 33% and the mitral valve in only 11% of the patients without underlying cardiopathy (for 44%, 4% and 49%, respectively, in patients with cardiopathy). Staphylococcus aureus caused 67% of cases in patients without cardiopathy and only 9% in those with cardiopathy. Surgery was required in a similar proportion by both groups of patients (55% and 56%), although mortality was more than twice higher in patients with prior cardiac lesions (25% versus 11%). CONCLUSIONS: A significant proportion of non-addict infective endocarditis involves patients without predisponente heart disease. These cases have some differential features (younger age, aortic and right heart valves involvement, S. aureus as the main causative agent and lower mortality) in comparison to those of endocarditis in patients with underlying cardiopathy.

Adolescent↗

[The echocardiographic findings in patients with brain death. The implications for their selection as heart transplant donors].

INTRODUCTION AND AIMS: Brain death causes myocardial impairment by some mechanisms not yet well understood. The aim of this work was to assess the echocardiographic features found in these patients and their implication in donor selection for heart transplantation. METHODS: With this aim, we have studied 38 consecutive patients with brain death assessed as possible donors for heart transplant in our hospital in the last 3 years. Age was 23 +/- 13 years; 77% were male. No history of cardiac disease was present in any patient. An adequate transthoracic echocardiogram was obtained in 74% of patients; transesophageal view was used in the remaining 26%. RESULTS: Echocardiogram was strictly normal in only 14 patients (37%). Mild valvular alterations were found in 5 patients (13%); a dilated aortic root in 1 (3%); moderate concentric left ventricular hypertrophy in 5 (14%); mild pericardial effusion in 1 (3%); mild septal hypokinesia with normal left ventricular ejection fraction in 4 (10%); abnormal left ventricular diastolic function in 7 (18%); and diffuse hypokinesia with ejection fraction less than 60% in 14 (37%). In 7 patients (18%) ejection fraction was lower than 40% (one of them was cocaine-addict). Mean ejection fraction was 59 +/- 15% (23 to 83%). Only 2 of the 19 (10%) donor hearts implanted in our hospital showed early dysfunction after transplant, but no relation to pretransplant ejection fraction was found. Ejection fraction increased from 62% pretransplant to 73% at one week after transplant in the other 17 cases. CONCLUSIONS: Brain death commonly causes alterations of left ventricular function, and this impairment is severe in almost 20% of cases. These echocardiographic features must be known when selection of donors for heart transplantation is concerned.

Adolescent↗

Videothoracoscopic wedge resection for peripheral pulmonary nodules.

BACKGROUND: This study was done to evaluate the use of the endoscopic multifire linear stapler for videothoracoscopic wedge resection (VTWR) of peripheral pulmonary nodules and to define the indications, advantages, and drawbacks of this minimally invasive technique. STUDY DESIGN: A case study review of 57 consecutive video-assisted thoracic operations for wedge resection of peripheral pulmonary nodules performed upon 55 patients admitted to a community hospital from June 1991 through July 1993 is presented. RESULTS: There were 44 malignant and 13 benign lesions. Of the malignant peripheral pulmonary nodules (PPN), there were 19 adenocarcinomas, ten squamous cell carcinomas, two undifferentiated large-cell carcinomas, three bronchoalveolar carcinomas, two carcinoid tumors, one neuroendocrine tumor, and seven metastatic carcinomas. The benign nodules included five hamartomas, two granulomas, one aspergilloma, one nodular amyloidosis, one Wegener's granulomatosis, one focal pulmonary infarct, and two interstitial fibroses. Videothoracoscopic wedge resection alone was performed upon 37 patients, 17 of whom had primary carcinoma of the lung; seven had metastatic lesions, and the remainder had benign disease. Of the 17 patients with primary carcinoma of the lung who had VTWR alone, eight patients had marked impairment of pulmonary function, six had significant co-morbid disease, two had peripheral carcinoid tumors, and one had bilateral metachronous carcinomas. Videothoracoscopic wedge resections with concomitant lobectomies were performed upon 20 patients with primary carcinoma of the lung, including one patient with bilateral synchronous carcinomas. Five of the patients with nodules ranging from 2 to 3 cm in diameter were found to have metastasis to regional nodes. None of the patients who had lobectomies for peripheral carcinomas less than 2 cm in diameter had regional nodal metastases. There was no perioperative mortality and no significant morbidity. CONCLUSIONS: Videothoracoscopic wedge resection is a useful alternative to traditional transthoracic resection for suspicious, undiagnosed PPN, for low grade malignant neoplasms, such as carcinoid, for peripheral metastatic lesions, for bilateral synchronous or metachronous tumors, for the occasional clinically localized peripheral small-cell carcinoma as a surgical adjunct to chemotherapy, and for small, peripheral, T-1, N-0, M-0 bronchial carcinomas in compromised patients at high risk with marginal pulmonary reserve. The procedure is effective, minimally invasive, and has potential advantages over conventional thoracotomy, including less postoperative pain and morbidity, shorter hospitalization period and convalescence, and an earlier return to work and normal activities.

Humans↗

[Infectious endocarditis due to Q fever: a recurrent disease. Apropos a new case].

We report a case of a patient with an aortic prosthetic valve who had Q fever endocarditis, glomerulonephritis and rapidly progressive renal failure. He was seen in 1987 and successfully treated by heart valve surgery and a one-year course of doxycycline. Five years later, the patient had another episode of Q fever endocarditis, involving the native mitral valve, complicated with acute renal failure and severe mitral regurgitation that required hemodialysis and mitral valve replacement. The outcome was again successful. This case report raises the question of whether Q fever endocarditis can be eradicated, and also the required duration of antibiotic therapy for this disease.

Acute Kidney Injury↗

[An analysis of the factors and phenomena associated with the formation of a spontaneous echo contrast in the left atrium].

INTRODUCTION AND AIMS: To determine the factors related to the formation of spontaneous echo contrast in left atrium. PATIENTS AND METHODS: We have analyzed our series of 1,066 patients undergoing transesophageal echocardiography until December 1991. It was found in left atrium in 387 patients (36%) and was associated with another pathology in 99%. We defined spontaneous echo contrast as mild in 64% and severe in 36%. RESULTS: The prevalence of spontaneous echo contrast was greater in patients with atrial fibrillation (p < 0.001), mitral stenosis (p < 0.001), double mitral lesion (p < 0.001), prosthesis (p < 0.001), embolism (p < 0.05) and a dilated left atrium (left atrial dimension greater than 60 ml) (p < 0.01). The presence of mitral regurgitation made it less frequent (p < 0.05). Thrombi were visualized in 104 patients and they were more frequent in the presence of spontaneous echo contrast. Severe spontaneous echo contrast was significantly more frequent in patients with atrial fibrillation (p < 0.001), mitral stenosis (p < 0.05) and thrombi (p < 0.001). CONCLUSIONS: Spontaneous echo contrast in left atrium is a common finding in transesophageal studies and it is associated with another pathology in 99%. It is more frequent in patients with atrial fibrillation, mitral stenosis, embolism or prosthesis. Left atrial enlargement is one of the more important factors. It is less frequent in patients with mitral regurgitation. Thrombi are less frequent in patients without spontaneous echo contrast. Severe spontaneous echo contrast is significantly associated with mitral stenosis, atrial fibrillation and left atrial thrombi.

Acute Disease↗

Myristoylation is not required for GTP-dependent binding of ADP-ribosylation factor ARF1 to phospholipids.

Membrane binding of ADP-ribosylation factors (ARFs) is GTP-dependent and seems to require amino-terminal myristoylation. Recently it has been proposed that myristoylation is needed not for the activation of ARF by GTP but for its subsequent association to membranes. Here we show that unmyristoylated bovine ARF1, expressed in bacteria, can be efficiently loaded with GTP gamma S (guanosine 5'-O-(thio)triphosphate) at 1 microM free Mg2+, in the presence of phospholipids. Unmyristoylated ARFGTP gamma S cosediments with phospholipid vesicles and totally binds to phospholipid-cholate micelles, as seen by gel filtration chromatography. We therefore propose that, in vivo, myristoylation is required for the interaction of ARFGDP with its membrane-bound exchange factor rather than for the association of ARFGTP with lipid membranes. Phospholipid-bound ARFGTP gamma S can also stably interact with and activate the catalytic subunit of cholera toxin, suggesting that ARFGTP provides a membrane anchor for cholera toxin and thereby facilitates its access to membrane-bound substrates.

ADP-Ribosylation Factor 1↗

Factors determining late success after mitral balloon valvulotomy.

Mitral balloon valvulotomy (MBV) has proved to be an effective method in the treatment of patients with mitral stenosis. Although several factors determining an optimal immediate result have been described, there is little information regarding long-term follow-up, as well as factors influencing late success after MBV. This study analyzes 350 patients (mean age 46 +/- 12 years) treated by MBV who were clinically followed up between 6 months and 6 years. At least 1 echo-Doppler follow-up study was obtained in 298 patients 28 +/- 14 months after MBV; hemodynamic reevaluations were performed in 66 patients after 23 +/- months. Late success was considered if the patient was in functional class I to II and free of major events (death, restenosis and valve surgery). Restenosis was defined as a 50% loss of initial gain with regard to valve area by echocardiography, which was confirmed hemodynamically. After a mean follow-up of 38 +/- 15 months, 296 patients (84%) remained in functional class I to II, without surgery or the need for an increase in medical treatment. The 5-year Kaplan-Meier survival rate was 94 +/- 1%, whereas restenosis, valve surgery and major event-free probability were 90 +/- 3%, 91 +/- 2% and 85 +/- 2%, respectively. Multivariate study (Cox regression model) identified the presence of sinus rhythm (p < 0.001) and the absence of calcium at fluoroscopy (p < 0.003) as the only independent factors of late success.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunohistochemical characterization of mononuclear cells in delayed hypersensitivity reactions to Paracoccidiodes brasiliensis (paracoccidioidin test).

The density and distribution of T cells, T helper cells, macrophages and B cells at the site of skin tests with a cytoplasmic Paracoccidioides brasiliensis antigen (paracoccidioidin) was studied at 24 and 48 h post-challenge in 10 patients with the chronic form of paracoccidioidomycosis and in 5 non-infected individuals. The in situ study was carried out using immunoperoxidase techniques and monoclonal antibodies. The controls showed negative skin test. In the patients, the great majority of the cells in the perivascular foci were T cells (CD43-positive cells) making up 47% and 48.6% of the total number of cells at 24 and 48 h respectively. Most of the T cells showed a T helper phenotype (CD45RO-positive cells). Approximately 25% of the cells were macrophages (CD68-positive cells) and there were very few B lymphocytes (CD20-positive cells). The present data on the microanatomy of paracoccidioidin skin test sites were consistent with a delayed type hypersensitivity pattern. Our results were comparable to those reported on skin tests for other granulomatous chronic diseases.

Adult↗