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Biomedical subjects

J F Michiels

Publications and source records attributed to J F Michiels.

At least 55 records · Page 3Linked to original sources

[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↗

[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↗

Differential SP220K expression in renal carcinoma and oncocytoma cells.

SP220K is a newly described serine proteinase which displays guanidinobenzoatase activity in its inactive form and gelatinolytic activity in its active form. SP220K expression was studied in 20 renal clear-cell carcinomas and in a series of renal oncocytomas, a rare benign tumor derived from the kidney tubule epithelium. We provide evidence that SP220K expression, as assessed by guanidinobenzoatase activity, gelatin zymography and Western blot immunodetection, was increased markedly in cancer basolateral membranes compared to kidney cortex controls, whereas no signal was detectable in basolateral membranes from the 5 renal oncocytomas studied. Cytoplasms of carcinoma cells were immunodetected consistently, whereas no expression was seen in oncocytic cells from any of the oncocytomas studied (12/12). Endothelial cells were immunodetected in all 3 tissue types. Our data favor a potential mechanistic relationship between expression of the matrix proteinase SP220K and invasive phenotype in kidney epithelium proliferative processes.

Adenoma, Oxyphilic↗

Cyclophosphamide cystitis as a model of visceral pain in rats: minor effects at mesodiencephalic levels as revealed by the expression of c-fos, with a note on Krox-24.

The evoked expression of the immediate-early gene-encoded proteins c-Fos and Krox-24 was used to study activation of mesodiencephalic structures as a function of the development of cyclophosphamide (CP) cystitis in behaving rats. This article is the third of a series and completes previously published data obtained at both spinal and hindbrain levels. CP-injected animals received a single dose of 100 mg/kg i.p. under transient volatile anesthesia and survived for 1-4 h in order to cover the entire postinjection period during which the disease develops. Survival times longer than 4 h were not used owing to ethical considerations. Results from CP-injected groups are compared with those from either noninjected controls or saline-injected animals having survived for the same times as CP-injected ones. Quantitative results come from c-fos expression. At mesodiencephalic levels a high and widespread basal c-fos expression was observed in control animals; maximum staining was observed at the midthalamic level. Four groups of nuclei were identified with regard to the density of staining. The first group included nuclei showing clustered, intensely labeled cells; these areas were restricted in extent and related to the maintenance of circadian rythms (intergeniculate leaf, suprachiasmatic nucleus, dorsal parts of either paraventricular thalamic nuclei or central gray), sleep-arousal cycle (supramamillary nucleus), or changes in arterial pressure (laterodorsal tegmental nucleus). The second group included nuclei showing scattered, moderately labeled cells; these areas were widespread at all rostrocaudal levels and related to either autonomic/neuroendocrine regulations (central gray, lateral habenula, hypothalamus) or motor behavior, orienting reflex and oculomotor coordination (unspecific subdivisions of both colliculi and their adjoining mesencephalic regions, zona incerta dorsal). The third group included nuclei with evenly distributed, faintly labeled cells; these areas, which, with few exceptions, covered almost the entire diencephalon, mainly concerned nuclei of multisensory convergence having functions in either discriminative tasks (laterodorsal and lateroposterior thalamic nuclei) or emotional responses (intralaminar and midline thalamic nuclei). The fourth group included nuclei free of labeling; these were areas that received the bulk of unimodal sensory/motor inputs (central inferior colliculus, pretectal optic nuclei, ventral medial geniculate nucleus, ventral anterior pretectal nucleus, dorsal lateral geniculate nucleus, ventrobasal complex; zona incerta ventral, parafascicular thalamic nucleus) and are thus the most discriminative regarding specific modalities. Variations in staining were of the same magnitude in both saline- and CP-injected animals. A sequential study spanning every postinjection hour revealed maximum staining at 1 h postinjection, which was followed by a progressive, time-related decrease. Increases in the number of labeled cells 1 h postinjection were significant in only a restricted number of nuclei showing low basal expression (Edinger-Westphal nucleus and paraventricular, supraoptic, and lateral hypothalamic nuclei); time-related reductions in staining that were correlated to sleep or quiescence behaviors finally resulted in staining equal to or below that seen in control animals. No structures showed significantly increased staining in relation to the full development of cystitis, i.e., with the increase of visceronociceptive inputs. Comparing the present results with those previously obtained at more caudal levels, it appears that subtelencephalic levels primarily driven by visceronociceptive inputs, i.e., those that increase and/or maintain their activity in parallel with the degree of nociception, are confined to brainstem-spinal cord junction levels and only comprise certain subdivisions of the nucleus of the solitary tract (nucleus medialis, nucleus commissuralis, and ventralmost part of area po

Animals↗

AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors.

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.

Adult↗

Histiocytoid cardiomyopathy: a cause of sudden death in infancy.

We report the case of an infant aged of 14 months deceased of sudden death. The diagnosis of histiocytoid cardiomyopathy was made on a necropsic basis. The pathologic examination showed a cardiac hypertrophy characterized by yellowish areas with irregular outlines, disseminated in the myocardium, and made of histiocyte-like cells with foamy or granular cytoplasm. These cells reacted positively with desmin and myoglobin labels, and had rare and disorganised myofibrils in electron microscopy, proving their muscular origin. The illness affects infants and usually causes severe cardiac troubles leading to death without treatment. This case is the fourteenth associated with sudden death.

Cardiomyopathies↗

Oral inflammatory pseudotumour: immunohistochemical investigation of a case involving the submandibular gland and review of the literature.

Inflammatory pseudotumours (IPs) are rare lesions. Most commonly reported in the lung, they are almost ubiquitous, but few oral cases have been described. Their rapid growth, local invasiveness and recurrence, and their ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) aspects are confusing and mimic benign or malignant neoplasms. Their recognition and distinction from malignant tumors is of importance but their histopathological diagnosis may represent a challenge. In the case reported involving the submandibular gland, the spindle cells had the immunohistochemical profile of myofibroblasts, broader cells with a larger nucleus were CD68 and/or Mac387 positive and the dense plasmacytic infiltrate was polyclonal. Histopathology of IPs covers a spectrum of appearances according to the cellularity and the degree of fibrosis. The recognition of a variable mixture of three main cell types: histiocytes or macrophages, myofibroblasts or fibroblasts and abundant plasma cells, with low mitotic activity and absence of cytological abnormalities in an ill circumscribed and rather fibrous lesion is recommended for the diagnosis of oral IP.

Fibroblasts↗

Anatomic distribution of melanocytes in normal nail unit: an immunohistochemical investigation.

Very few histologic reports describe normal melanocytes of the nail unit. Previous studies predominantly address the distal nail matrix melanocytes; we found no review of nail-bed melanocytes in the literature. The proximal nail matrix melanocytes are difficult to identify; the cells cannot be identified by L-DOPA staining. More recently, their scarcity was confirmed by immunohistochemistry with a large panel of antibodies directed against melanocytes. We wished to detect the proximal nail matrix dormant melanocytes and compare their density and distribution with that of the other melanocytes in the distal matrix and nail bed and to establish criteria of normality that may help clarify the pathologic features of benign nevoid melanonychia in the nails of whites. A panel of five monoclonal antibodies (MoAbs), including HMB45 and TRP1 directed against antigens localized in early melanosomal vesicles, was investigated in frozen sections of six nail specimens from whites. Both vertical and horizontal sections were assessed to determine the presence of dormant melanocytes. Results showed that the proximal nail matrix melanocytes were clearly identified with MoAbs HMB45 and tyrosinase-related protein-1 (TRP-1). By contrast, melanocytes stained by MoAb against tyrosinase and L-DOPA reaction were evident, especially in the distal matrix. With MoAb TRP-1, the epithelial sheets showed counts of approximately 217+/-84/mm2 in the proximal matrix and of 132+/-34/mm2 in the distal matrix; the nail bed counts were only 45+/-25/mm2. The split epithelial sheets had 103+/-17/mm2 L-DOPA-positive melanocytes in the distal third of the matrix, but only a few of them were detected in the proximal matrix and none were noted in the nail bed. We clearly identified proximal nail melanocytes using MoAb HMB45 and TRP1. The total number of matrix melanocytes can be estimated as approximately 217/mm2. In proximal matrix, the dormant melanocytes compartment was predominant. In the distal matrix, two compartments were identified: a functionally differentiated and a dormant compartment. Contrary to classical opinion, longitudinal melanonychia originates more frequently in the distal matrix, not secondary to the larger melanocyte density but because only the distal matrix contains an active melanin synthesis compartment. Furthermore, the superficial distribution of proximal nail melanocytes in vertical sections showed a histologic feature that may simulate the pagetoid pattern of melanoma in situ.

Aged↗

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

AIDS-Related Opportunistic Infections↗

Examination of extraintestinal tissue cysts of Isospora belli.

Relapse is common in immunocompetent and immunosuppressed humans infected with Isospora belli and is believed to be associated with the presence of extraintestinal stages. In the present study, we examined this important stage in an AIDS patient using histological, immunohistological, histochemical, and ultrastructural methods to better understand the development and structure of this stage and to develop better means of detecting infections. Antisera made in rabbits to Isospora suis, Toxoplasma gondii, Hammondia hammondi, Sarcocystis neurona, Neospora caninum, and Caryospora bigenetica were tested against I. belli tissue cysts in the avidin-biotin peroxidase complex (ABC) immunohistological test. Most antisera reacted positively in the ABC test at dilutions of 1:100 but not at dilutions of 1:250. Some antisera to N. caninum and H. hammondi reacted positively at dilutions of 1:1,000 in the ABC test. Most reactive antisera stained the tissue cyst wall and not the enclosed zoite. Eight histochemical tests were examined and most were nonreactive with I. belli zoites or tissue cysts. Transmission electron microscopy revealed that the tissue cyst wall was composed of granular material and was directly beneath the parasitophorous vacuole membrane. Zoites were in the center of the tissue cysts and were surrounded by fibrillar material that appeared to originate from the zoite surface. Tubulelike structures were present in the granular tissue cyst wall and in the fibrillar material that surrounded the zoite. Zoites contained a crystalloid body. New findings in the present study consisted of identifying what are probably early tissue cysts that lack a developed tissue cyst wall, demonstrating that more than 1 tissue cyst can occupy a host cell, describing the distribution of micronemes and the shedding of zoite membranes, and identifying tubular structures in the inner tissue cyst wall and inner compartment.

Animals↗

[Familial hemophagocytic lymphohistiocytosis. Differential diagnosis with secondary hemophagocytic syndromes].

We report 2 cases of familial hemophagocytic lymphohistiocytosis in two children, hétérozygous twins, born from consanguine parents. This disease is characterised by disseminated lymphohistiocytic infiltrates with hemophagocytosis, that most commonly involves bone marrow, spleen, lymph nodes, liver and central nervous system. Differential diagnosis is difficult with infection-induced hemophagocytic syndromes. The only distinguishing feature in pathology is the expression of CD21, CD30 and CD35 antigens by histiocytes. Differenciation is made by an association of clinical and pathologic characteristics: a familial history, lack of infection or neoplasm, and immunohistochemical results. Diagnostic must be rapidly made, because this disease is always fatal without treatment.

Biopsy↗

[Diagnosis of intravascular lymphoma on a muscular biopsy].

Intravascular lymphomatosis is characterized by a proliferation of malignant lymphoid cells within the lumen of arteriola, capillaria or venula. It is a very rare neoplasia (less than 200 cases reported). Many organs can be involved, but preferentially the central nervous system. The diagnosis is sometimes performed only by a post mortem study. We report a case of a 74 year-old man with biological markers of inflammation, progressive dyspnea and myalgia. A muscular biopsy revealed the diagnosis.

Aged↗