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P Hofman

Publications and source records attributed to P Hofman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Laminin 5 in the human thymus: control of T cell proliferation via alpha6beta4 integrins.

Laminin 5 (alpha3beta3gamma2) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-alpha3, -beta3, and -gamma2 mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not overall inhibition of p56(lck). Using a mAb specific for alpha6beta4 integrins, we observed that while alpha3beta1 are known to be uniformly present on all thymocytes, alpha6beta4 expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and alpha6beta4 on mature thymocytes. Moreover, the soluble Ab against alpha6beta4 inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that alpha6beta4 is involved in laminin 5-induced modulation of T cell activation.

Antibodies, Monoclonal↗
PubMed1999

Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage.

AIMS/HYPOTHESIS: The Pathologische Anatomie Leiden-Endothelium (PAL-E) antigen is a marker for loss of the blood-brain barrier function in brain tumours. It is endothelium specific and is associated with the endothelial plasmalemmal vesicles (caveolae) involved in transcellular transport. To test whether blood-retinal barrier loss in diabetic retinopathy is associated with cellular changes in the endothelium, the expression of antigen PAL-E in relation to microvascular leakage in human diabetic retinopathy was investigated. METHODS: Immunohistochemical staining of frozen tissue sections of postmortem eyes obtained from 30 persons without and 41 persons with diabetes mellitus was carried out with monoclonal antibodies against PAL-E and CD31 and with antibodies against endogenous fibrinogen, albumin and IgG as indicators of vascular leakage. RESULTS: Patchy or uniform microvascular PAL-E staining was observed in the retina of 17 of the 41 eyes of diabetic patients and in 2 of the 30 normal control eyes. In the diabetic eyes, PAL-E staining co-localized with microvascular staining for endogenous fibrinogen, albumin and IgG. Strong staining for PAL-E was observed in sites without blood-tissue barriers, like the choroid. CONCLUSIONS/INTERPRETATION: In microvessels with an intact blood-retina barrier the endothelial antigen PAL-E is absent. Its expression is increased in retinal vessels of patients with diabetic retinopathy and correlates with microvascular leakage of plasma proteins. This phenotypic shift involving an antigen associated with caveolae suggests that dysfunction of the endothelium forms the cellular basis for microvascular leakage in diabetic retinopathy, rather than passive endothelial damage.

Adult↗
PubMed1999

Autopsy findings in the acquired immunodeficiency syndrome (AIDS). A report of 395 cases from the south of France.

Necropsy findings in 395 adult patients with the acquired immunodeficiency syndrome (AIDS) who died in Nice, France, between March 1983 and May 1996 were compared retrospectively with antemortem diagnoses, risk factors and number of positive T CD4 lymphocytes at the time of death. Special emphasis on bacterial infections was made in this study. Lesions observed from 1983 through 1989 and from 1990 through 1996 were compared. We assessed the role of organ lesions in the immediate cause of death. The organ system distribution of major opportunistic infections and neoplasms was similar throughout the years of the study. The most common diagnostic disease entities in all organ sites were cytomegalovirus infection, toxoplasmosis and candidiasis. Toxoplasmosis was more common in the intravenous drug abuser group. Bacterial infections were frequent and contributed to the mortality and morbidity of all risk factor groups. Kaposi' sarcoma continued to occur more frequently in the homosexual population. Cytomegalovirus infection remained one of the most common causes of death from 1983 to 1996. Mortality from fungal and bacterial infections, and mycobacteriosis increased in frequency during the course of this study whereas deaths from pneumocystosis declined. The death rate from malignant lymphoma and carcinoma increased after 1989. The clinical cause of death concurred with the pathological cause in 55% of the cases. Lung was the most frequent organ involved followed by the central nervous system the gastrointestinal tract and the heart.

AIDS-Related Opportunistic Infections↗
PubMed1999

Lack of internucleosomal DNA fragmentation is related to Cl(-) efflux impairment in hematopoietic cell apoptosis.

The heterodimeric DNA fragmentation factor (DFF) is responsible for DNA degradation into nucleosomal units during apoptosis. This process needs the caspase-dependent release of ICAD/DFF-45, the inhibitory subunit of DFF. Here we report that triggering apoptosis via a hyperosmotic shock in hematopoietic cells causes the appearance of mitochondrial and cytosolic alterations, activation of caspases, chromatin condensation, nuclear disruption, and DNA fragmentation. However, oligonucleosomal but not high molecular weight (50-150 kb) DNA cleavage is abolished if Cl(-) efflux is prevented by using NaCl to raise extracellular osmolarity or by Cl(-) channel blockers, even when apoptosis is initiated by other agents (staurosporine, anti-Fas antibody). In these conditions, all the apoptosis hallmarks investigated remain detectable, including the cleavage of ICAD/DFF-45. In vitro assays with lysates of cells in which Cl(-) efflux is blocked confirm the lack of internucleosomal DNA degradation. These findings establish that neither caspase activation nor ICAD/DFF-45 processing per se is sufficient to induce oligonucleosomal DNA fragmentation and that high molecular weight DNA degradation and chromatin condensation appear independently of it. Finally, they suggest that Cl(-) efflux is a necessary cofactor that intervenes specifically in the activation of the DFF endonuclease.

Apoptosis↗
PubMed1999

Neutrophil F-actin and myosin but not microtubules functionally regulate transepithelial migration induced by interleukin 8 across a cultured intestinal epithelial monolayer.

The role of the polymorphonuclear leukocyte (PMN) cytoskeleton during the transmigration across colonic epithelial cells is not very well understood. In order to study the role of different components of the PMN cytoskeleton during transepithelial migration across a colonic epithelial cell monolayer (T84), PMN were preincubated with drugs affecting either the actin cytoskeleton (cytochalasin B, iota toxin of Clostridium perfringens, and phalloidin) or the microtubules (colchicine and taxol). The role of PMN myosin during transepithelial migration was investigated using the inhibitor 2,3-butanedione monoxime (BDM) and DC3B toxin. PMN intracellular Ca2+, during neutrophil adhesion and translocation across the epithelium, was assessed by the Ca2+ chelator 1, 2bis-(2-aminophenoxy)-ethane-N,N,N', N'-tetra-acetic acid tetrakis (acetoxymethyl) ester (BAPTA-AM). Transmigration of PMN was initiated by applying either interleukin-8 or formyl-met-leu-phe (fMLP). While colchicine and taxol preexposure did not influence PMN transepithelial migration, treatment with cytochalasin B, iota toxin, phalloidin, BDM, DC3B toxin and BAPTA-AM greatly diminished migration of PMN across T84 monolayers. Similarly, cell-cell contacts established between PMN and epithelial cells during the transmigration were diminished after treatment of PMN with iota toxin or cytochalasin B. These data show that the neutrophil actin cytokeleton and myosin, but not the microtubules, evoke a Ca2+ -dependent motility that facilitates migration across the colonic epithelial barrier.

ADP Ribose Transferases↗
PubMed1999

Impairment of HIV polymorphonuclear leukocyte transmigration across T84 cell monolayers: an alternative mechanisms for increased intestinal bacterial infections in AIDS?

Our objective was to study the influence of HIV infection of polymorphonuclear leukocytes (PMN) on transepithelial migration. To date, reports of functional PMN chemotaxis in AIDS are contradictory. This is the first attempt to assess this function via an in vitro model allowing transmigration of neutrophils through an intestinal epithelial barrier. PMN were isolated from 45 HIV-infected patients and 45 healthy volunteers. PMN transmigration across T84 epithelial cells was initiated by applying either various concentrations of formyl-met-leu-phe peptide (f-MLP) or interleukin-8 and assayed by quantification of myeloperoxidase activity. CD11b, CD18, and CD47 expression on PMN was compared before and after transepithelial migration by flow cytometry analysis. CD11b expression was studied by electron microscopy. Apoptosis of transmigrated HIV PMN and control PMN was investigated by morphology and DNA fragmentation characterization. Compared to control PMN, HIV PMN exhibited a decrease in transepithelial migration that directly correlated with CD4+ counts. Basal and transepithelial migration-mediated expression of CD11b, CD18, and CD47 were unmodified in HIV PMN compared to control PMN. Electron microscopy labeling confirmed no difference in CD11b expression on HIV and control PMN. The index of apoptosis in transmigrated HIV PMN and control PMN was identical. These data provide evidence of a defect in the f-MLP-induced chemotaxis of PMN from HIV-infected patients across an intestinal epithelial barrier. This defective migration is not due to a quantitative modification of CD11b, CD18 and CD47 on HIV PMN suggesting a more subtle alteration. The impairment in the transmigration function may contribute in vivo to an increased susceptibility to intestinal bacterial infection in HIV-infected patients.

Adult↗
PubMed1998

CD10 inhibitors increase f-Met-Leu-Phe-induced neutrophil transmigration.

A variety of bacterial enterocolitis in their active stages are characterized by the migration of polymorphonuclear leukocytes (PMNs) across epithelial surfaces. These mechanisms could explain some effects of enterotoxins observed in the intestinal mucosae. Here, using specific inhibitors, we investigated the potential role of CD10 (E.C. 3.4.24.11), present at the surface of human neutrophils, on formyl-Met-Leu-Phe (fMLP)-induced PMN migration across cultured monolayers of the human intestinal cell line T84. Transmigration of human neutrophils across T84 epithelial cells was observed for concentrations of fMLP as low as 10(-9) M, whereas maximal effect was achieved at 10(-7) M as determined by transepithelial resistances and PMN myeloperoxidase assays. RB25, a CD10 inhibitor, reduced by two orders of magnitude the concentration of fMLP required to obtain full neutrophil transmigration across T84 epithelial cell line. RB25 response was concentration dependent with half-maximal and maximal effect occurring at 10(-9) and 10(-7) M, respectively. These concentrations of RB25 corresponded exactly to the half-maximal and maximal inhibition of endopeptidase 24.11 at the neutrophil cell surface. However, the effect of CD10 inhibitors on PMN transmigration cannot be accounted for by a direct action on T84 epithelial cells, since these cells fail to express any detectable endopeptidase 24.11 activity. Moreover, blocking of CD10 enzymatic activity by various and selective inhibitors potentiated the effect of low concentrations of fMLP on PMN transmigration. Finally, RB25 failed to affect interleukin-8 (IL-8)-induced PMN transmigration across T84 epithelial cells, in agreement with the preference of CD10 for small peptidic substrates. Taken together, these results demonstrate that inhibition of CD10 significantly reduced the concentration of fMLP needed for eliciting transmigration of PMN across intestinal epithelia.

Benzylidene Compounds↗
PubMed1998

Ciliary muscle capillaries have blood-tissue barrier characteristics.

It was determined whether the capillaries in the ciliary muscle are of the blood-tissue barrier or of the permeable non-barrier type. Ciliary body and iris of normal human and animal eyes were examined by electron microscopy and by immunohistochemical staining with a panel of antibodies recognizing endothelial blood-brain barrier markers. In addition, horseradish peroxidase (HRP) tracer studies of the anterior segment were carried out in rabbits. Our results demonstrated that the capillary endothelium in human and rabbit ciliary muscle has few luminal pinocytotic vesicles and a morphological aspect suggesting the presence of tight junctions. Ciliary muscle and iris capillaries stained positive for the blood-brain barrier markers Glucose-Transporter-1 and P-Glycoprotein, while staining for the PAL-E antigen and the transferrin receptor was absent. In the rabbit ciliary muscle, vascular leakage of exogenous HRP tracer was absent. It was concluded that this functional barrier and the observed phenotype of ciliary muscle capillaries are consistent with a blood-tissue barrier function similar to that of the iris microvasculature.

Aged↗
PubMed1998

Escherichia coli cytotoxic necrotizing factor 1 effaces microvilli and decreases transmigration of polymorphonuclear leukocytes in intestinal T84 epithelial cell monolayers.

Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like protein from pathogenic Escherichia coli strains, induces an actin cytoskeleton reorganization consisting of the formation of prominent stress fibers by permanent activation of the small GTP-binding protein Rho. Since p21Rho regulates tight-junction permeability and perijunctional actin reorganization in epithelial intestinal cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez, P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we used polarized T84 epithelial intestinal cell monolayers to examine whether CNF1 could affect microvillus structure, transepithelial resistance, and polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with CNF1 did not influence transepithelial resistance, suggesting that barrier function and surface polarity were not affected by the toxin. However, CNF1 effaced intestinal cell microvilli and induced a strong decrease of PMN transepithelial migration in either the luminal-to-basolateral or the basolateral-to-luminal direction. CNF1 could thus be a virulence factor exhibiting a new type of combined activity consisting of effacing of microvilli and occlusion of the epithelial barrier to PMNs. Attenuated transepithelial migration of PMNs could result in the enhanced growth and protection of luminal bacteria.

Bacterial Toxins↗
PubMed1998

[Placental infection in Rwanda: comparison an HIV infected population and a control population].

We report an histological study from term placentas of 286 HIV positive women born in Rwanda. We observed chorioamnionitis without any pathogen in 15% of the cases, cocci Gram positive infection in 12 observations and malaria infection in 75% of placentas. We noted 71 cases of active malaria infection with Plasmodium falciparum trophozoites in the erythrocytes of the intervillous spaces, and 135 cases of chronic infection with malaria pigment without any parasite. An ultrastructural study performed in 8 cases of active malaria infection showed characteristic features of trophozoites and schizontes, and malaria pigment. No viral particle were seen. We did not observe any significative difference concerning the incidence of chorioamnionitis and of malaria infection in 275 HIV negative placentas. In the literature as well as in the present study, the main lesions observed in the placentas of AIDS patients were chorioamnionitis. Opportunistic infections and neoplasias of the placenta are exceptional. Detection of HIV proteins by immunochemistry or in situ hybridization is possible, but the HIV could not be identified in the trophoblast by electron microscopy. Mechanisms of the materno-fetal transmission for HIV are currently unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Kimura's disease of the lymph node. Histology, immunohistochemistry, and differential diagnosis].

Kimura's disease, a chronic inflammatory condition of unknown cause, occurs predominantly in young Asian adult men. The disease involves subcutaneous tissues and lymph nodes in the head and neck region. We report a new case occurring in a young woman. The diagnosis was made late on a retroauricular lymph node examination. Immunohistochemical study showed that B lymphoid area remained, located in the germinal center showing some fibrosis involvement, and in the subcortex. T lymphoid zones were observed in the paracortex. Strong IgE positivity was noted in germinal centers. Vessels were positive with CD31, CD34, factor VIII and smooth muscle actin antibodies. Warthin-Finkeldey cells were negative for lymphoid and macrophagic markers used in this study. Differential diagnosis is discussed.

Actins↗
PubMed1998

[Epithelial tumors with thymus differentiation of the thyroid gland and the neck].

Epithelial tumors with thymus-like differentiation occurring in the thyroid gland and the neck, delineate four entities with distinct histological features and different behaviour. The spindle epithelial tumors with thymus-like differentiation are potentially malignant tumors occurring in the thyroid gland of young patients. They are highly cellular with pattern of spindle cells and tubulopapillary formations and mucinous glands. Carcinomas showing thymus-like differentiation of the thyroid gland are histologically identical to some thymic carcinomas. The ectopic hamartomatous thymoma is strictly benign and occurs in the soft tissues of the lower neck. It is characterized by spindle and solid or cystic islands of epithelial cells associated with adipose cells. The ectopic cervical thymoma is usually benign and histologically similar to mediastinal thymomas. All these tumors are particularly rare and arise from ectopic thymus or remnants of branchial pouch. The differential diagnoses of these tumors can be difficult and include some other proliferations occurring in the neck.

Adipose Tissue↗
PubMed1998

[Pulmonary lymphangioleiomyomatosis. Immunohistochemical and ultrastructural study of two cases].

The authors report two cases of pulmonary lymphangioleiomyomatosis which were diagnosed by surgical biopsies. Immunohistochemical study showed positive staining of the smooth muscle cells using antibodies directed against smooth muscle actin, specific muscle actin, HMB45 and vimentin. Ultrastructural study showed some smooth muscle differentiation features, with numerous myofilaments and some dense bodies near the plasma membrane. In one case, the patient was treated by a double-lung transplantation. LAM is a non-familial disease occurring exclusively in females. The etiology is unknown. This disease can be complicated by chronic respiratory failure. Extrapulmonary sites are not rare, particularly in the uterus. Anti-estrogen treatment can slow the course of the disease. Lung transplantation is actually the only effective treatment at the present time therapy. The differential diagnosis of this disease is discussed.

Actins↗
PubMed1998

[Cutaneous malacoplakia. An immunohistochemical and ultrastructural case study].

The authors report a case of a 70 year-old man with a past of myelodysplasia and presenting a voluminous lesion of the thigh corresponding to a cutaneous malacoplakia. Histologic study showed a dermo-hypoderma granuloma with numerous Von Hansemann cells containing some Michaelis-Gutmann bodies. Immunohistochemical study showed a positivity of these cells with the antibodies against CD68 (KP1, Mac 387, PGM1), the lysozyme and the alpha-chemotrypsine. Ultrastructural study confirmed the histiocytic origin of this infiltration by showing some regular and voluminous inclusions with a clear center and a peripheral and dense ring, and also some bacteria measuring 3 to 5 microns. Bacteriological study isolated an Escherichia coli. The evolution was favourable after surgical excision and antibiotherapy. Cutaneous malacoplakia is a very rare disease, usually with a perineal localization, and occurring in immunodeficient host. Michaelis-Gutmann bodies are sometimes difficult to identify by light microscopy underlying the rule of the immunohistochemical and the ultrastructural studies to perform the diagnosis.

Aged↗
PubMed1997

Apoptosis of immature thymocytes mediated by E2/CD99.

E2/CD99 is a 32-kDa transmembrane molecule that does not belong to any known family of proteins. It appears to regulate adhesion properties of T cells as previously reported, in particular, the induction of homotypic adhesion in CD4+ CD8+ thymocytes. Apoptosis induced via E2/CD99 displays characteristic morphologic features, but includes early mitochondrial alterations and phosphatidylserine exposure at the outer leaflet of the plasma membrane. It is not followed by detectable DNA fragmentation, and its time course is much longer than apoptosis induced via the Fas/CD95 pathway. It requires 18 h for completion. E2/CD99-induced apoptosis does not require any RNA or protein synthesis and still occurs following blockage of the Fas pathway. It is, however, dependent on CPP32 and IL-1beta-converting enzyme-type cysteine proteases, as shown by blockade with their respective specific inhibitors. This effect is restricted to double-positive thymocytes carrying an intermediate density of CD3 and including all CD69+ cells. Thus, E2/CD99 apears to mediate a distinctive apoptotic signal at a critical stage of thymocyte differentiation, i.e., when positive selection is known to occur.

12E7 Antigen↗