Multifocal osteogenic sarcoma in Paget's disease.

The most serious complication of Paget's disease is sarcomatous degeneration of pagetic bone. Multifocal sarcomatous degeneration occurs mainly in polyostotic Paget's disease. Multifocal Paget's sarcoma is uncommon and can arise in any site. We report two cases of synchronous multifocal sarcomatous degeneration. The two patients were elderly women (aged 77 and 86 years, respectively) who developed sarcomatous lesions concomitantly, in the first case report in left ilium, left tibia, and first lumbar vertebra and in the second case report in the skull, right ilium, and sacrum. Whether these cases are due to the simultaneous development of several primaries or to metastases from a single primary remains unclear.

Fibre-type distribution and subcellular localisation of alpha and beta enolase in mouse striated muscle.

Enolase is a dimeric glycolytic enzyme exhibiting tissue specific isoforms. During ontogenesis, a transition occurs from the embryonic alphaalpha towards the specific alphabeta, and betabeta isoforms in striated muscle. Immunocytochemical analyses on transverse sections of adult mouse gastrocnemius muscle, allowed us to compare the expression of alpha and beta subunits to that of myosin heavy chain (MHC) isoforms. Levels of beta immunoreactivity followed the order IIB > IIX > IIA > I. This gradient parallels the ATPase activity associated to MHC isoforms, indicating that the expression of beta enolase in myofibres is finely regulated as a function of energetic requirements. By contrast, variations in alpha immunolabelling intensity appeared independent of fibre types. Longitudinal muscle sections exhibited a striated pattern of alpha immunoreactivity. Confocal microscopy analyses demonstrated that alpha was localised at the M band. Most beta immunoreactivity was diffuse all over the sarcoplasm. However, some beta immunoreactivity was striated and localized at both Z and M bands. Thus, betabeta enolase could participate to multi-enzyme complexes present at the I band, and involved with local ATP production. Our results support the notion that isozymes differ in their ability to interact with other macromolecules, thus segregating to different subcellular sites where they would respond to specific functional demands.

The -700/-310 fragment of the apolipoprotein A-IV gene combined with the -890/-500 apolipoprotein C-III enhancer is sufficient to direct a pattern of gene expression similar to that for the endogenous apolipoprotein A-IV gene.

Spatial gene expression in the intestine is mediated by specific regulatory sequences. The three genes of the apoA-I/C-III/A-IV cluster are expressed in the intestine following cephalocaudal and crypt-to-villus axes. Previous studies have shown that the -780/-520 enhancer region of the apoC-III gene directs the expression of the apoA-I gene in both small intestinal villi and crypts, implying that other unidentified elements are necessary for a normal intestinal pattern of apoA-I gene expression. In this study, we have characterized transgenic mice expressing the chloramphenicol acetyltransferase gene under the control of different regions of the apoC-III and apoA-IV promoters. We found that the -890/+24 apoC-III promoter directed the expression of the reporter gene in crypts and villi and did not follow a cephalocaudal gradient of expression. In contrast, the -700/+10 apoA-IV promoter linked to the -500/-890 apoC-III enhancer directed the expression of the reporter gene in enterocytes with a pattern of expression similar to that of the endogenous apoA-IV gene. Furthermore, linkage of the -700/-310 apoA-IV distal promoter region to the -890/+24 apoC-III promoter was sufficient to restore the appropriate pattern of intestinal expression of the reporter gene. These findings demonstrate that the -700/-310 distal region of the apoA-IV promoter contains regulatory elements that, in combination with proximal promoter elements and the -500/-890 enhancer, are necessary and sufficient to restrict apoC-III and apoA-IV gene expression to villus enterocytes of the small intestine along the cephalocaudal axis.

An autopsy study of the prostate in acquired immunodeficiency syndrome: evidence for excessive apoptosis and intracytoplasmic epithelial inclusions.

We describe a combination of epithelial cell apoptosis and intracytoplasmic inclusions in prostatic epithelium in 6 patients who died from the acquired immunodeficiency syndrome. Two different types of apoptosis were detected: simple cell shrinkage and exploding glandular cells. No intracellular or extracellular viral particles were detected, either ultrastructurally or immunohistochemically. Intracytoplasmic inclusions are apoptotic bodies in a state of degradation and in close association with lipofuscin. The cell degeneration we observed confirms the theory that increased apoptotic cell depletion is responsible for weight loss in the acquired immunodeficiency syndrome. In the prostate itself, the combination of excessive apoptosis and active phagosomal digestion of apoptotic bodies presents a "human model" of postcastration rat ventral prostate, under the conditions of severe immune deficiency.

Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus.

The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.

Thrombotic microangiopathy and cytomegalovirus disease in patients infected with human immunodeficiency virus.

Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.

Antibodies to the 280-kd coated pit protein, target of teratogenic antibodies, produce alterations in the traffic of internalized proteins.

Previous studies have identified two high-molecular weight (280 and 330 kd) glycoproteins expressed by coated pits of the proximal renal tubule and yolk sac and have further established that, in vivo, antibodies to gp280 but not to gp330 induce fetal malformations. In the present study, we report the effect of these antibodies on the endocytic process by yolk sac visceral epithelial cells of rat embryos explanted at day 10 of gestation. Antibodies to gp280 markedly altered development of the yolk sac and embryo, induced malformations, inhibited by 40% the uptake of [14C] sucrose and perturbed the intracellular traffic of internalized proteins. Under control conditions, rat immunoglobulin G present in the culture medium was immunolocalized in lysosomes of epithelial cells, whereas in the presence of antibody, it was detected in small vesicles scattered through the apical cytoplasm. Alterations of the endocytic pathway were confirmed by experiments analyzing the uptake of peroxidase added to the medium for 2 to 60 minutes. The initial compartments of endocytosis visualized by peroxidase were increased in size and abnormal in shape and the transfer of the internalized peroxidase to the lysosomal compartment was delayed. In contrast, antibodies to gp330 had a minimal effect on embryonic development and did not induce fetal malformations. Endocytosis was only modestly altered; uptake of [14C] sucrose was decreased by 25%, and only minor modifications of the intracellular transit of peroxidase could be detected. We suggest that the key role of anti-gp280 antibodies is via trapping of the target antigen in the early endocytic compartment thus preventing its normal function in lysosomal transfer.

Granulocytic sarcoma of the small intestine: a case report.

We report the case of a patient with an ileal tumor initially diagnosed as a lymphoma. The development of acute myeloblastic leukemia 8 months later made it clear that the initial tumor was a granulocytic sarcoma (GS). This case emphasizes the possible difficulties of histologic diagnosis and the importance of the routine use of histochemical and immunologic techniques in the diagnosis of extranodal lymphomas.

[Role of the digestive tract immune system in the control of bacterial translocation in gnotoxenic mice]. / Rôle du système immunitaire digestif dans le contrôle de la translocation bactérienne chez la souris gnotoxénique.

The aim of this work was to study the role of gut associated lymphoid tissue in the control of bacterial translocation. Two strains of Escherichia coli were orally inoculated to 71 axenic mice. Ten days after, the 2 initial strains and 2 others, resulting from plasmidic exchanges, were present in the digestive tract of the mice which were divided in two groups: the first group (n = 41) received one intraperitoneal injection of cyclophosphamide 100 mg/kg; the second control group (n = 30) received isotonic saline. The following parameters were studied 3, 5 and 9 days after the injection: the population level of the 4 strains in the caecum, their translocation to mesenteric lymph nodes, liver, spleen and circulating blood, the density per unit surface of lamina propria plasma cells and intraepithelial lymphocytes in duodenal and caecal mucosae. The population in each strain found in the caecum was different from the 3 others but similar within the two groups of animals and remained unchanged with time. In the control group, bacterial translocation to the mesenteric lymph nodes decreased (p less than 0.01), while the density of plasma cells increased (p less than 0.01) from the 3rd to the 9th days. In the cyclophosphamide treated group, translocation to the mesenteric lymph nodes increased (p less than 0.01), while the density of intestinal plasma cells decreased (p less than 0.05) from the 3rd to the 9th days. Density of intraepithelial lymphocytes did not vary with time in each group and from one group to another. Bacterial translocation to liver, spleen and systemic blood was weak and did not increase in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vertebral compression with intrasomatic vacuum images. Apropos of 2 cases with histological control by trocar biopsy]. / Tassements vertébraux avec images de vide intra-somatique. A propos de deux observations avec contrôle histologique par biopsie au trocart.

The significance of a gas shadow, known as an intra-somatic space, seen in cases of vertebral compression is discussed in relation to two cases with histological confirmation by means of trocar aspiration biopsy of the vertebra. The presence of this image is in favour of a neoplastic or infectious aetiology; however, in view of the limited experience, histological confirmation by aspiration biopsy of the vertebra is indicated in the presence of one or more reasons for suspecting a neoplastic aetiology. The most satisfactory pathophysiological hypothesis to explain the appearance of an intra-somatic space is that this image generally appears in cases of osteoporotic vertebral compression complicated by a certain degree of osseous ischaemia.

Tumoral calcinosis: light and electron microscopic study with electron diffraction and x-ray microanalysis of the mineral deposit.

Samples of deposits taken from sites close to articulations in a young black African suffering from tumoral calcinosis with hyperphosphoraemia were studied by light and electron microscopy techniques. Light microscopy demonstrated lesions of a foreign body granuloma type in contact with calcium salt deposits suggesting that the process was of an active nature. Electron microscopy, and the demonstration of acid phosphatase activity, led to the identification of two cell types: mono or multinuclear macrophage type cells which phagocytose the deposit, and fibroblastic type cells. No signs of damage to the microvessels or the interstitial collagen were noted which could serve as a basis or a physiopathological explanation of the deposition. The deposits were analysed by energy dispersive X-ray microanalysis and by electron diffraction and were considered to be hydroxyapatite.