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P Hofman

Publications and source records attributed to P Hofman.

At least 55 records · Page 3Linked to original sources
PubMed2001

A Jurkat T cell variant resistant to death receptor-induced apoptosis. Correlation with heat shock protein (Hsp) 27 and 70 levels.

Ligation of Fas induces an apoptotic program in Jurkat cells (Jd). We describe a Jurkat T cell variant (Jr) which shows total resistance to Fas-mediated apoptosis but which exhibits sensitivity to non-death-receptor pro-apoptotic stimuli such as staurosporine. Resistance to Fas-induced apoptosis in Jr cells is correlated with high expression of Hsps. A prior heat-shock increases Hsp27 and 70 expression and protects Jd and Jr cells from Fas- and staurosporine-induced apoptosis. Staurosporine, but not the anti-Fas antibody CH11, abrogates constitutive Hsp70 expression at 37 degrees C and staurosporine also inhibit Hsp27 expression in Jd and Jr cells at 42 degrees C. These data suggest that constitutive expression of Hsp27 inhibits Fas-mediated apoptosis, but only induced expression of Hsp70 can protect T cells from staurosporine-induced apoptosis. Thus, Hsp27 could play a role in the regulation of death receptor-mediated apoptosis, while Hsp70 could regulate mitochondrial-dependent cell death.

Apoptosis↗
PubMed2001

[A rare etiology of hepatic steatosis associated with lactic acidosis: the toxicity of antiviral nucleoside analogues].

We report three cases of hepatic steatosis associated with lactic acidosis occurring in HIV positive patients and due to a toxicity of antiviral nucleoside analogues. The clinico-pathological presentation was similar associating digestive signs (vomiting and abdominal pain), polypnea, lactic acidosis, a lethal clinical course, and an hepatomegaly with a diffuse macrovacuolar steatosis. The ultrastructural study performed in two cases showed mitochondrial alterations in hepatocytes. The toxicity of antiviral nucleoside analogues is due to a mitochondrial DNA polymerase inhibition. The incidence of this disease is actually low but probably underestimated. The diagnosis should be rapidly performed and the treatment immediatly interrupted.

Acidosis, Lactic↗
PubMed2001

[Diagnostic pitfalls in infectious disease pathology].

Numerous images observed in histopathology and cytopathology can mimic pathogens such as mycotic agents, parasites (protozoa or helminthes), bacteria or virus. An error of diagnosis may provoke the administration of a non efficient treatment which can also be toxic. The present review describes these false pathogens which can correspond to exogenous or endogenous agents. Basic morphological analysis of mycotic agents, parasites, bacteria and cytopathogenic viral effects are successively presented. Then, the main diagnostic pitfalls which can be observed during these infections are exposed. Finally, diagnostic problems occurring in case of contamination are rapidly cited.

Bacterial Infections↗
PubMed2000

Sustained polymorphonuclear leukocyte transmigration induces apoptosis in T84 intestinal epithelial cells.

Acute colitis is characterized by a large number of polymorphonuclear leukocytes (PMNLs) migrating across the columnar epithelium in response to inflammatory stimuli. Several of these inflammatory factors have been characterized as proapoptotic inducers for intestinal epithelial cells. Our aim was to elucidate the role of PMNL transmigration in the onset of intestinal epithelial cell apoptosis. We found that PMNL migration, in response to N-formyl-methionyl-leucyl-phenylalanine across monolayers of intestinal epithelial cells (T84), was associated with activation of caspase-2, -3, and -9 and poly(ADP-ribose) polymerase cleavage within epithelial cells. Moreover, dihydrocytochalasin B treatment of T84 cells induced apoptosis with similar characteristics. Although Fas and Fas ligand were expressed on T84 cells and PMNLs, treatment of epithelial cells with an antagonistic anti-Fas antibody failed to prevent apoptosis induced by migrating PMNLs. Owing to the F-actin reorganization accompanying PMNL transmigration, these findings indicate a direct relationship between PMNL migration and induction of apoptosis in epithelial cells. This apoptotic process appears to involve remodeling of the actin cytoskeleton of enterocytes independent of the Fas/Fas ligand pathway.

Actins↗
PubMed2000

Detection of fiducial gold markers for automatic on-line megavoltage position verification using a marker extraction kernel (MEK).

PURPOSE: In this study automatic detection of implanted gold markers in megavoltage portal images for on-line position verification was investigated. METHODS AND MATERIALS: A detection method for fiducial gold markers, consisting of a marker extraction kernel (MEK), was developed. The detection success rate was determined for different markers using this MEK. The localization accuracy was investigated by measuring distances between markers, which were fixed on a perspex template. In order to generate images comparable to images of patients with implanted markers, this template was placed on the skin of patients before the start of the treatment. Portal images were taken of lateral prostate fields at 18 MV within 1-2 monitor units (MU). RESULTS: The detection success rates for markers of 5 mm length and 1.2 and 1.4 mm diameter were 0.95 and 0.99 respectively when placed at the beam entry and 0.39 and 0.86 when placed at the beam exit. The localization accuracy appears to be better than 0.6 mm for all markers. CONCLUSION: Automatic marker detection with an acceptable accuracy at the start of a radiotherapy fraction is feasible. Further minimization of marker diameters may be achieved with the help of an a-Si flat panel imager and may increase the clinical acceptance of this technique.

Algorithms↗
PubMed2000

Pseudomembranous aspergillus bronchitis in a double-lung transplanted patient: unusual radiographic and CT features.

Pseudomembranous aspergillus bronchitis is considered as an early form of invasive pulmonary aspergillosis, a well-known airway infection in immunocompromised patients. Radiologic features concerning invasive aspergillosis of the airways have been reported. However, we describe here an unusual feature of invasive aspergillus bronchitis, never reported to date, observed in a double-lung transplanted patient. Chest radiograph and CT revealed significant peribronchial thickening without any parenchymal involvement.

Adult↗
PubMed2000

The histological spectrum of visceral leishmaniasis caused by Leishmania infantum MON-1 in acquired immune deficiency syndrome.

Visceral leishmaniasis (VL) due to Leishmania infantum is endemic in Southern France and can be considered as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Co-infection with Leishmania sp. and human immunodeficiency virus (HIV) is emerging, but pathological findings of leishmaniasis in AIDS have been poorly documented, and scattered case reports have include morphological descriptions. The clinicopathologic analysis of 16 patients with HIV and VL were evaluated. The clinical presentation was characteristic of VL, with fever, hepatosplenomegaly, and pancytopenia in 6 patients, and the diagnosis was confirmed by finding amastigotes of Leishmania sp. in bone marrow smears and biopsy specimens. In 4 patients, the initial diagnosis of VL was made fortuitously in gastrointestinal biopsies performed systematically (3 patients) or in case of diarrhea (1 patient). In one duodenal biopsy, Leishmania sp. and Mycobacteria sp. were associated. Liver biopsy allowed the diagnosis of VL in 3 cases. Autopsy was performed in 9 patients, showing a disseminated leishmaniasis with very unusual localizations (adrenal and heart) in 2 cases. Cutaneous leishmaniasis involvement was noted before (4 patients), at the same time (2 patient), or after (1 patient) the diagnosis of VL. Inflammatory infiltrates noted with Leishmania sp. infection were made by CD68 macrophages with (8 patients) or without (8 patients) associated CD8 positive lymphocytes. Immunoperoxidase study using polyclonal anti-Leishmania sp. antibodies contributed to the diagnosis in all cases. Electron microscopy of 2 digestive biopsy specimens showed the ultrastructural characteristics of Leishmania sp. amastigotes. The zymodeme MON-1 of L infantum was identified by isoenzyme electrophoresis in all patients. The mean of CD4 counts was 37/mm3 at the time of diagnosis, and the mean duration before the death was 8 months. As shown in this study, VL in AIDS can be diagnosed in gastrointestinal or liver biopsies. Diagnosis of VL was made when the CD4 count was very low and was correlated with a poor prognosis.

AIDS-Related Opportunistic Infections↗
PubMed2000

Increased Escherichia coli phagocytosis in neutrophils that have transmigrated across a cultured intestinal epithelium.

The functionality of polymorphonuclear leukocytes (PMNs) once they migrate into the digestive lumen is still ill defined. More specifically, phagocytic function and bactericidal action of PMNs after transepithelial migration have not received much attention. The aim of the present study is to compare PMN behavior before and after transepithelial migration, in particular (i) phagocytosis and bactericidal activity; (ii) expression of surface molecules, particularly those involved in phagocytosis; and (iii) apoptosis. Cultured human intestinal epithelial T84 cell monolayers were used. The effect of transepithelial migration on phagocytosis was evaluated by immunofluorescence and electron microscopy and by flow cytometric assessment of the engulfment of a strain of Escherichia coli transfected with the green fluorescent protein. Superoxide production by PMNs was investigated by luminol-mediated chemiluminescence. Expression of various surface molecules on PMNs was evaluated by flow cytometry, while PMN apoptosis was assayed by morphologic changes and DNA fragmentation. E. coli phagocytosis by the PMNs was markedly increased after transepithelial migration without modification of superoxide production. CD11b/CD18 and CD47 expression was increased upon PMN transmigration, whereas CD16 expression was decreased and CD29, CD46, CD49e, CD49f, CD55, CD59, CD61, CD95 levels remained unchanged. Apoptosis in transmigrated PMNs was slightly advanced and was observed after 12 h compared to 16 h for nontransmigrated PMNs. In conclusion, the phagocytic capacity of the PMNs is augmented after transepithelial migration, with a dramatic increase in the level of CD11b/CD18 and preservation of the superoxide production. These results suggest a higher bactericidal activity of the PMNs once they have translocated into the digestive lumen.

Antigens, CD↗
PubMed2000

Effect of Helicobacter pylori on polymorphonuclear leukocyte migration across polarized T84 epithelial cell monolayers: role of vacuolating toxin VacA and cag pathogenicity island.

Helicobacter pylori infection can induce polymorphonuclear leukocyte (PMNL) infiltration of the gastric mucosa, which characterizes acute chronic gastritis. The mechanisms underlying this process are poorly documented. The lack of an in vitro model has considerably impaired the study of transepithelial migration of PMNL induced by H. pylori. In the present work, we used confluent polarized monolayers of the human intestinal cell line T84 grown on permeable filters to analyze the epithelial PMNL response induced by broth culture filtrates (BCFs) and bacterial suspensions from different strains of H. pylori. We have evaluated the role of the vacuolating cytotoxin VacA and of the cag pathogenicity island (PAI) of H. pylori in PMNL migration via their effects on T84 epithelial cells. We noted no difference in the rates of PMNL transepithelial migration after epithelial preincubation with bacterial suspensions or with BCFs of VacA-negative or VacA-positive H. pylori strains. In contrast, PMNL transepithelial migration was induced after incubation of the T84 cells with cag PAI-positive and cagE-positive H. pylori strains. Finally, PMNL migration was correlated with a basolateral secretion of interleukin-8 by T84 cells, thus creating a subepithelial chemotactic gradient for PMNL. These data provide evidence that the vacuolating cytotoxin VacA is not involved in PMNL transepithelial migration and that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular signal across T84 monolayers, inducing a subepithelial PMNL response.

Antigens, Bacterial↗
PubMed2000

Early expression of beta- and gamma-subunits of epithelial sodium channel during human airway development.

The amiloride-sensitive epithelial Na(+) channel (ENaC) is an apical membrane protein complex involved in active Na(+) absorption and in control of fluid composition in airways. There are no data reporting the distribution of its pore-forming alpha-, beta-, and gamma-subunits in the developing human lung. With use of two different rabbit polyclonal antisera raised against beta- and gamma-ENaC, immunohistochemical localization of the channel was performed in fetal (10-35 wk) and in adult human airways. Both subunits were detected after 17 wk of gestation on the apical domain of bronchial ciliated cells, in glandular ducts, and in bronchiolar ciliated and Clara cells. After 30 wk, the distribution of beta- and gamma-subunits was similar in fetal and adult airways. In large airways, the two subunits were detected in ciliated cells, in cells lining glandular ducts, and in the serous gland cells. In the distal bronchioles, beta- and gamma-subunits were identified in ciliated and Clara cells. Ultrastructural immunogold labeling confirmed the identification of beta- and gamma-ENaC proteins in submucosal serous cells and bronchiolar Clara cells. Early expression of ENaC proteins in human fetal airways suggests that Na(+) absorption might begin significantly before birth, even if secretion is still dominant.

Adult↗
PubMed2000

Normal cognitive performance in patients with chronic alcoholism in contrast to patients with Korsakoff's syndrome.

This study investigated which cognitive deficits are associated with chronic alcoholism. Neuropsychological profiles and MRI brain structure volumes of 14 patients with Korsakoff's syndrome, 15 patients with chronic alcoholism, and 16 healthy control subjects were compared. The patients with alcoholism had a normal cognitive performance and normal brain structure volumes. The patients with Korsakoff's syndrome had performance deficits on tests of memory, visuoperceptual, and executive functions, as well as reduced brain structure volumes. The results suggest that the cognitive deficits cannot be ascribed to mere chronic consumption of alcohol. If cognitive deficits are present in patients with chronic alcoholism, this may point to an underlying brain disorder.

Adult↗
PubMed2000

[Ultrastructural findings of epimacular membrane and detached posterior hyaloid in vitreomacular traction syndrome].

PURPOSE: Vitreomacular traction syndrome is characterized by an incomplete posterior vitreous detachment and by the cortical vitreous remaining attached to the macula. In certain case epimacular membrane is clinically well defined. We studied the electron microscopic features of epiretinal tissue and posterior hyaloid removed from the posterior pole. MATERIAL AND METHODS: [corrected] Six epimacular membranes were removed during a pars plana vitrectomy, placed in 2.5% glutaraldehyde solution, embedded in Epoxy resin, and examined in a transmission electron microscope. The detached posterior hyaloid was removed and analyzed separately in two cases. RESULTS: The analysis disclosed five morphologically cell types. Fibrous astrocytes were predominant in five cases. Other cell types were less frequent and were identified as fibroblasts, macrophages and myofibroblasts. In one case epithelial-like cell type was predominant. The stroma was mainly composed of a thin layer of 15-nm diameter collagen evoking a vitreous origin. Internal limiting membrane was present in one case only. Detached posterior hyaloid was constituted by the same cellular constituents on thin layer of vitreous collagen. DISCUSSION: The cellular proliferation is principally constituted by fibrous astrocyte and occurs on the inner surface of cortical vitreous. Some glial cells seem to present an epithelial differentiation. CONCLUSION: The attached and detached posterior hyaloid in vitreomacular traction syndrome is the place of glial cells migration and proliferation.

Humans↗
PubMed2000

[Solid and pseudopapillary tumor of the pancreas: immunohistochemical and ultrastructural study of 2 pediatric cases].

We report 2 cases of solid and pseudopapillary tumors of the pancreas occurring in female children. Lesions were made of uniform small cells arranged in solid areas associated with pseudopapillary and cystic patterns. Immunohistochemistry study was positive for neuron-specific enolase, alpha-1 anti-trypsin and vimentin. Ultrastructural study showed an abundant cytoplasm, rich in mitochondria, containing a lot of granules of variable sizes, often disintegrated, and some lipid droplets. The differential diagnosis of this lesion included endocrine tumor, pancreatoblastoma and acinar cell carcinoma. It is a rare tumor of the pancreas with a favorable prognosis after complete resection.

Adolescent↗
PubMed2000

Escherichia coli cytotoxic necrotizing factor-1 (CNF-1) increases the adherence to epithelia and the oxidative burst of human polymorphonuclear leukocytes but decreases bacteria phagocytosis.

Recruitment of polymorphonuclear leukocytes (PMNL) is a hallmark of both urinary and digestive infections caused by Escherichia coli. Cytotoxic necrotizing factor 1 (CNF-1) is a toxin produced by uropathogenic E. coli strains that mediates its effects via the activation of small GTP-binding proteins. However, the role and the consequences of CNF-1 on PMNL physiology remain largely unknown. In this study, we provide evidence that CNF-1 dramatically affects the PMNL cytoskeleton architecture by inducing an increased content of F-actin. Furthermore, we demonstrate that CNF-1 increases functional features of PMNL, such as superoxide generation and adherence on epithelial T84 monolayers, but significantly decreases their phagocytic function. Our results suggest that CNF-1 may behave as a virulence factor in urinary or digestive infection by stimulating PMNL cytotoxicity as a result of its enhancing effect on their adherence to epithelial cells as well as the production of radical oxygen products. Moreover, the decreased phagocytosis of PMNL induced by CNF-1 likely facilitates growth of bacteria. In these conditions, CNF-1 would intervene in the initiation and in the perpetuation of the inflammatory process.

Actins↗
PubMed2000

[Diathermic scleral retraction].

Diathermic scleral retraction appears to be an efficient technique, with little aggressivity, allowing both scleral indentation and radial and circumferential shortening of the ocular wall. We compared experimental results of a diathermic technique with those obtained by other authors using infrared laser scleral photocoagulation. The large number of variables, especially IOP, complicates standardization, but the results of the two methods on cadaver eyes were found to be quite similar. Diathermic scleral retraction creates a buckle effect and a 10 to 30% scleral shortening. This retractile effect decreases with rising IOP. This method would appear to have therapeutic interest for the management of retinal detachments with anterior proliferation and for the treatment of residual detachments after prolonged tamponade with silicon oil. These techniques of scleral shortening necessitate other experimental studies to evaluate their effects in the long-term, but the absence of induced chorioepithelial lesions would indicate therapeutic applications.

Diathermy↗
PubMed2000

VEGF-A induced hyperpermeability of blood-retinal barrier endothelium in vivo is predominantly associated with pinocytotic vesicular transport and not with formation of fenestrations. Vascular endothelial growth factor-A.

PURPOSE: In tissues outside the brain, vascular endothelial growth factor-A (VEGF) causes vascular hyper-permeability by opening of inter-endothelial junctions and induction of fenestrations and vesiculo-vacuolar organelles (VVOs). In preliminary studies, we observed that in blood-retinal barrier endothelium, other cellular mechanisms may underlie increased permeability caused by VEGF. This was further investigated in material of an in vivo experimental model of VEGF-induced retinopathy. METHODS: Two monkeys received 4 intravitreal injections of 0.5 microg VEGF in one eye and PBS in the other eye prior to sacrifice at day 9. One monkey received 12 injections of 1.25 microg VEGF in one eye and PBS in the other eye prior to sacrifice at day 24. As a control, an untreated eye of a fourth monkey was studied. RESULTS: In the high-dose VEGF-injected eye, fluorescein angiography showed intense retinal micro-vascular leakage. This leakage was also demonstrated by immunohistochemistry demonstrating extravasation of endogenous fibrinogen and IgG. However, in these leaky blood vessels the number of pinocytotic vesicles (caveolae) at the endothelial luminal membrane were significantly higher and, only in the VEGF-injected eyes, these pinocytotic vesicles transported plasma IgG. By electron microscopy, no fenestrations or VVOs were found in the endothelial cells of the VEGF-injected eyes. CONCLUSION: We conclude that increased vascular permeability for plasma proteins induced by VEGF in blood-retinal barrier endothelium is predominantly caused by a mechanism involving active trans-endothelial transport via pinocytotic vesicles and not by formation of endothelial fenestrations or VVOs.

Animals↗