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Although the efficiency of underflow baffles has never been clearly proven, these underflow baffles have gained in popularity over the last few years as a viable means to intercept floatables in Combined Sewer Overflows (CSOs). These pilot scale essays, performed in a 17.0 metres basin at various flowrates, show that a critical horizontal velocity (V(CR)) may develop in the overflow chamber. Whenever this critical velocity is exceeded, floatables that would normally rise to the surface are kept within the flow and never intercepted, thus rendering the underflow baffle ineffective. The equation relating the critical horizontal velocity to the vertical velocity is found to be: V(CR) = 16 w R(H) 1/6.

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The phosphatidylserine transmembrane redistribution at the cell surface is one of the early characteristics of cells undergoing apoptosis and also occurs in cells fulfilling a more specialized function, such as the phosphatidylserine-dependent procoagulant response of platelets after appropriate activation. Although an increase in cytoplasmic Ca2+ is essential to trigger the remodeling of the plasma membrane, little is known about intracellular signals leading to phosphatidylserine externalization. Here, the role of store-operated Ca2+ entry on phosphatidylserine exposure was investigated in human erythroleukemia HEL cells, a pluripotent lineage with megakaryoblastic properties. Ca2+ entry inhibitors (SKF-96365, LaCl(3), and miconazole) inhibited store-operated Ca2+ entry in A23187- or thapsigargin-stimulated cells and reduced the degree of phosphatidylserine externalization concomitantly, providing evidence for a close link between the two processes. In cells pretreated with cytochalasin D, an agent that disrupts the microfilament network of the cytoskeleton, store-operated Ca2+ entry and phosphatidylserine externalization at the cell surface were inhibited. In a context where most of the key actors remain to be identified, these results provide evidence for the implication of both store-operated Ca2+ entry and cytoskeleton architectural organization in the regulation of phosphatidylserine transbilayer migration.

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Phosphatidylserine (PhtdSer) is an anionic aminophospholipid necessary for the development of optimal tissue factor (TF) activity at the cell surface. This study investigates the implication of a restricted lipid environment with respect to PhtdSer availability on TF expression and activity. K562 cells, showing a reduced ability to externalize PhtdSer, were transfected with human TF cDNA. PhtdSer exposure and TF activity were examined in transfected cells and compared to monocytic THP-1 cells expressing constitutive and inducible TF or megakaryocytic HEL cells showing a high PhtdSer externalization potency. TF expression was evidenced by flow cytometry and its activity measured using functional assays. PhtdSer exposure was monitored by enzymatic prothrombinase assay. One clone (DC9) expressed a stable amount of TF antigen without global modification of its membrane status. Despite a noticeable TF expression level, clone DC9 presented only a weak TF activity even after ionophore stimulation. The apparent Km, relative to factor X (FX) activation by TF-factor VIIa (FVIIa) complex, was 335 nM versus 70 nM for THP-1 cells. The velocity of the reaction was found 3-fold slower in DC9 than THP-1 cells. Ionophore treatment resulting in slightly enhanced amounts of available PhtdSer abolished this difference. The DC9 clone appears suitable for further investigations on the biology of TF expressed at the surface of cells where the contribution of PhtdSer is significantly attenuated. Such cells should enable further assessment of the role of TF as a receptor coupled to intracellular signaling pathways and its fate during apoptotic cell death.

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AIMS: The oesophageal mucosa is a frequent target of opportunistic infections in human immunodeficiency virus (HIV) infection. Langerhans cells (LC) are known as a target and reservoir of HIV in the skin. The aim of this study was to characterize oesophageal LC in HIV-infected patients. METHODS AND RESULTS: Thirty oesophageal biopsies were obtained from 29 patients (median age 35.5), all in stage IV of the HIV Center of Disease Control Classification. We performed histological assessment of the oesophageal mucosa and immunohistochemical detection of oesophageal LC using an anti-CD1a antibody, followed by morphometric analysis. Biopsies from 17 noninfected patients were studied using the same procedure. LC in oesophageal mucosa of the HIV positive patients showed a significantly and dramatically decreased number (LC(N) median = 5.85/mm2) and surface/epithelial surface (LC (S) ratio = 0.09) when compared with HIV-negative controls (LC(N) median = 29.7/mm2, LC(S) ratio = 1.83) with P = 0.003 for LC(N) and P < 0.0001 for LC(S). CONCLUSION: These data suggest that oesophageal LC are, like their epidermal counterparts, a preferential target for HIV infection. Their alterations may provide a clue to the pathogenesis of the decreased local oesophageal immunity and to the occurrence of opportunistic infections.

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Hyperplastic polyps originating from islands of gastric mucosa can be observed in the duodenum. We report 3 cases of duodenal hyperplastic polyps on antral or fully developed fundic mucosa. They macroscopically presented as small confluent polyps or as large villous polyps. Their microscopic features were the same as those observed in hyperplastic gastric polyps. This type of polyp must be added to the list of tumor like lesions of the duodenum that may endoscopically present as polyps.

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The study of one commercial preparation of human alpha 1-acid glycoprotein (AAG) by isoelectric focusing and by different chromatographic methods, previously developed to purify and fractionate the genetic variants of AAG, revealed an abnormal heterogeneity for this preparation. In addition to the three main variants (F1, S and A) of AAG normally present, this preparation contained five other AAG variants (called here sigma, alpha, beta, delta and gamma), accounting for ca. 40% of the total. As it is very unlikely that the latter variants are rare AAG variants, the abnormal heterogeneity of this AAG preparation is most probably due to structural alterations occurring during the large scale isolation. The alpha and the sigma, beta, delta and gamma variants could correspond to altered forms of the A and the F1 and S variants, respectively, because of their similar retention behaviour on immobilized copper(II) ions and their similar drug binding properties. However, the elution of the variants from the immobilized metal affinity column suggested that sigma, alpha, beta, delta and gamma were desialylated. Chromatography on hydroxyapatite enabled the separation of the F1, S and A variants from the sigma, alpha, beta, delta and gamma variants. The inability of the latter variants to bind to hydroxyapatite suggests that the structural alterations might involve acidic amino acid residues. This proposal agreed with the isoelectric focusing study of variants sigma, alpha, beta, delta and gamma. Since the different separation methods used were able to resolve the variants of this AAG, this protocol could be used for characterization of commercial AAG proteins.

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Human alpha 1-acid glycoprotein (AAG), a plasma drug transport protein, has three main genetic variants, the A variant and the F1 and S variants, which are encoded by two different genes. The binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main gene products of AAG-the A variant and a mixture of the F1 and S variants (60% F1 and 40% S)-separated by chromatography from native commercial AAG, a mixture of almost equal proportions of the F1, S and A variants, was studied by equilibrium dialysis. A selective binding of disopyramide and methadone to the A variant and a preferential binding of dipyridamole to the F1S variant mixture were found. Lignocaine and chlorpromazine had a slight preference for binding to the A variant and to the F1S mixture, respectively, but progesterone showed no selectivity with regard to any of the variants of AAG. The differences in drug-binding demonstrated between the A variant and the F1S mixture confirmed those of a previous study, in which a selective binding of imipramine to the A variant and of warfarin and mifepristone to the F1S mixture have been found. These results indicate specific drug transport roles for each AAG variant, according to its separate genetic origin. The results of control binding experiments performed with (unfractionated) commercial AAG and the series of tested ligands concurred with that for the separate AAG variants, with respect to the proportion of the A variant (27%) and that of the F1 and S variants (73%) in the commercial protein. In addition, disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone were used in equilibrium dialysis displacement experiments to study interactions on binding sites labelled with imipramine for the A variant and with warfarin for the F1S variant mixture. The four latter ligands were found to competitively inhibit the binding of warfarin to the F1S variant mixture and all of them that of imipramine to the A variant. The ligands association constants to each AAG variant obtained from such inhibitory experiments were comparable to those determined in the direct binding studies. As the stochlometry of the interactions of the A variant and the F1S variants, respectively, with their specific ligands was approximately one (1), it was concluded that these ligands bind to each of these variants via a single common binding site. These results indicate that the AAG molecule would have for its ligands at least two separate binding sites, showing different specificity and localization, and not one site, as it is generally assumed. The possible pharmacological and clinical consequences of the binding results with the separate AAG variants are discussed.

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Herpetic esophagitis (HE) associated with human immunodeficiency virus (HIV) is a rare condition mainly reported as isolated cases. We thus decided to study this association and analyze the possible predisposing factors, clinical and endoscopic presentations, and clinical response to treatment. Thirty-four HIV-1-infected patients were identified: 27 had histologically or virologically confirmed HE and seven had probable HE, a retrospective diagnosis based on the efficacy of acyclovir given alone. The median CD4 cell count was 15/mm3. Recent predisposing factors (such as nasogastric procedures, steroid therapy, and anticancer therapy) were noted with regard to 16 of the 34 patients (47%). Odynophagia and/or chest pain occurred in 30 patients (88%). At the time of diagnosis of HE, extraesophageal herpes was found in only 13 patients (38%). Superficial ulcers of the distal third of the esophagus were present in 17 (50%). Among 20 of the 27 patients with confirmed HE that could be evaluated, therapy with acyclovir led to complete resolution in 16 and partial response in 3; 1 patient died of HE. Five patients (15%) suffered confirmed or possible relapses. The mean interval between the diagnosis of HE and death was 8.8 months. Herpes simplex virus may be responsible for ulcerated esophagitis that occurs in the advanced stages of AIDS and that can be safely treated with acyclovir before a definitive diagnosis is made.

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We report a case of splenic pneumocystosis in a human immunodeficiency virus-positive individual treated prophylactically with aerosolized pentamidine. Despite this infection with Pneumocystis carinii, the bronchoalveolar lavage revealed no microorganisms. The use of aerosolized pentamidine as prophylaxis for Pneumocystis carinii is not protective against extrapulmonary pneumocystosis because of inadequate systemic distribution of the drug.

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In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a persistent infection was demonstrated in all rats. These results confirm the anticryptosporidial activity of paromomycin and underscore the limitations of this compound because of its potential toxicity at such high dosages and its inability to eradicate the infection.

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OBJECTIVES: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis. METHODS: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy. RESULTS: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29. CONCLUSION: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

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After having been considered as an essentially digestive disease, Whipple's disease has appeared more and more to be a multivisceral disease with two main characteristics: on one hand Whipple's disease yields a diffuse infiltration of tissues by abnormal macrophages without any other inflammatory reaction; on the other hand, aspects of microbial invasion by intra or extracellular unique rod-shaped Gram+bacteria are found. This unusual pathological complex has alternatively been considered as suggestive of an immunological defect or as a very unusual type of bacterial infection. Though recent studies support the hypothesis of a primary microbial infection due to a hitherto undescribed bacterium (Tropheryma whippelii) or more or less related bacteria belonging to the actinomycetes family, they do not totally exclude a primary or acquired impairment of antigen processing by macrophages. Speculations about this fascinating pathophysiological model and about its optimal therapeutic modalities are not likely to reach a conclusion in the near future.

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Disseminated infection by Fusarium is being increasingly reported in immunocompromised patients. We report the first case of Fusarium oxysporum disseminated infection with well-documented fungal myocarditis. Despite antifungal therapy and hematologic recovery, the patient died in cardiogenic shock, myocardial involvement clearly contributing to the fatal outcome.

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A dexamethasone-treated rat model of cryptosporidiosis was used to evaluate the curative activity of paromomycin. Although eradication of the parasite could not be demonstrated, statistically significant decreases in oocyst excretion and in the intensity of ileal parasitism were observed in animals receiving 100 mg of paromomycin per kg of body weight per day.

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OBJECTIVE: To determine criteria for the diagnosis of cytomegalovirus (CMV) colitis and to analyse stages of the course and prognosis of CMV colonic involvement in HIV-1-infected patients. DESIGN: Prospective search for CMV colonic involvement with systematic biopsies to search for CMV intranuclear inclusion bodies and for CMV culture. The evolution of CMV colonic involvement was estimated using further coloscopies and autopsy. SETTING: Infectious diseases department in a tertiary referral teaching hospital in Paris, France. PARTICIPANTS: Fifty-five consecutive patients with HIV-1 infection, who had not previously received anti-CMV drugs, and who had at least one coloscopy performed. RESULTS: According to initial coloscopy, colitis, either ulcerative or inflammatory, was found in nine (16%) out of the 55 patients, CMV intranuclear inclusions were present in the colon of four (7%) patients, and colonic cultures were positive for CMV in 15 (27%) patients. The results of the initial coloscopy showed a positive correlation between endoscopic colitis (either ulcerative or inflammatory), CMV inclusions and positive CMV culture from colonic biopsies. The absence of endoscopic ulcerative lesions had a 98% (49 out of 50) negative predictive value for recording CMV inclusions in the colon (95% confidence interval, 89-100). CMV inclusions were recorded in three out of five ulcerative colitis. Male homosexuality, HIV-1 infection stages IVB, C1, D or E, according to the Centers for Disease Control and Prevention classification, CD4 lymphocyte count < 200 x 10(6)/l and CMV viraemia also correlated positively with CMV colonic involvement. During the observation period (mean, 7.3 months), the estimated incidence of CMV colitis according to coloscopic studies was 13%. Deterioration in condition was the most frequent spontaneous evolution of CMV colonic infection, whereas anti-CMV treatment resulted in an improvement. Ulcerative lesions occurred earlier in patients with colonic CMV inclusions or positive colonic CMV culture than in patients without CMV colonic involvement at the initial coloscopy. CMV colitis occurred late in the course of HIV-1 infection, on average 4 months before death. The presence of CMV inclusions was an indicator of poor prognosis with earlier occurrence of CMV viraemia and retinitis and no survival after 9 months. CONCLUSIONS: These results confirm that the colon is a target organ for CMV in HIV-1-infected patients. Coloscopy should be used to diagnose CMV colitis, because of the close correlation between endoscopic and histological data (i.e., intranuclear inclusions). This combination allows us to propose an evolutive staging of CMV colonic involvement and provide stratification criteria to assess the efficacy of anti-CMV drugs.

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The case of an immunocompetent woman who died of disseminated cytomegalovirus infection with encephalitis and skin ulcerations is reported. The duration of the disease, from onset to death, was five months. Cytomegalovirus was found in the blood, urine, skin, muscle, liver and periventricular brain tissue, but not in frontal cortex tissue. This case underlines the fact that cytomegalovirus may exceptionally cause life-threatening illness in immunocompetent adults.

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The infection of liver cells by HIV-1 was investigated in vivo. Liver biopsies from 13 anti-HIV-1 antibody-positive patients were studied and HIV-1 DNA was revealed by polymerase chain reaction (PCR) in eight. In situ hybridization demonstrated the presence of HIV-1 RNA in all eight PCR-positive liver specimens. Mononuclear inflammatory cells in the portal tracts and Kupffer cells were labeled by a HIV-1 35S-RNA probe in all cases and by an anti-p24 monoclonal antibody, in seven cases. In addition, hepatocytes also clearly scored positive for HIV-1 RNA in three cases. These results demonstrate the infection of both parenchymal and non-parenchymal liver cells by HIV-1 in vivo and therefore show that HIV-1 can infect an epithelial CD4-negative cell type.

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The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.

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