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Adenovirus has been implicated as a cause of opportunistic infections in immunocompromised patients, frequently with multiorgan involvement and a fatal outcome. We describe a case of necrotizing adenoviral prostatitis in a 35-year-old man with terminal AIDS and generalized adenoviral infection. The histopathologic findings of intraacinar necrotizing inflammation, prominent viral nuclear inclusions in residual epithelium, and mild T-lymphocyte and macrophageal inflammatory reaction were observed in the prostate. The presence of adenovirus was confirmed by electron microscopy and immunohistochemistry. Squamous metaplasia was present in the surrounding acini. This case of adenoviral prostatitis appears to be the first report of its kind in medical literature and demonstrates another aspect of the diversity of organ manifestations seen in this infection. This lesion should be included in the differential diagnosis of necrotizing prostatic diseases.

Background & Aims: Klebsiella oxytoca has been isolated from stools and colonic biopsy specimens of patients with Clostridium difficile-negative antibiotic-associated hemorrhagic colitis (AAHC), but the pathogenic role of the germ has not been established. The purpose of this study was to investigate the presence of K. oxytoca in patients with AAHC from a prospective cohort of patients with acute colitis, and to test the cytotoxicity on HEp-2 cells of K. oxytoca strains from patients with AAHC and healthy carriers., Methods: Colonic biopsy specimens and a sample of colonic fluid from 93 consecutive patients with acute colitis were cultured on selective media for 7 established pathogens and K. oxytoca. The 2 K. oxytoca strains isolated in the 4 patients with C. difficile-negative AAHC of this cohort and 105 additional K. oxytoca strains from patients with C. difficile-negative AAHC (n = 15) and healthy carriers (n = 90) were tested for cytotoxicity using a HEp-2 cell culture assay., Results: K. oxytoca was isolated in 50% (2 of 4) of the patients of the prospective cohort with C. difficile-negative AAHC compared with 2% (1 of 41) of the patients with acute colitis caused by established pathogens (P = 0.02). The rate of cytotoxic strains of K. oxytoca was higher in patients with AAHC (82%) than in healthy carriers (42%, P = 0.003)., Conclusions: We conclude that K. oxytoca is isolated with a significant high rate in patients with C. difficile-negative AAHC, and that K. oxytoca strains from patients with AAHC are cytotoxic more frequently on HEp-2 cells than strains from healthy carriers. These results strengthen the hypothesis of a causative role of K. oxytoca in some of the patients with AAHC.

The apoA-I/C-III/A-IV gene cluster, like most intestine-specific genes, displays a specific pattern of expression along the intestinal cephalocaudal and crypt-to-villus axes. We have shown that this specific pattern of expression requires the distal apoA-IV promoter and the apoC-III enhancer. Using a new set of transgenic mice, we demonstrate here that the restriction of apoA-IV gene transcription to villus enterocytes requires a hormone-responsive element (HRE) located within the apoA-IV distal promoter. We showed, using nuclear extracts from villus or crypt epithelial cells, that this HRE bound the transcription factor hepatic nuclear factor 4 (HNF-4). We also found that the HNF-4gamma isoform was produced only in the villus, whereas the HNF-4alpha isoform was produced along the entire length of the crypt-to-villus axis. Our results demonstrate that the HRE of the distal apoA-IV promoter is responsible for the restriction of gene expression to villus epithelial cells and that this HRE binds HNF-4 isoforms. The in vivo observation of parallel gradients for apoA-IV and HNF-4gamma gene expression raises questions concerning whether this transcription factor plays a specific role in the control of enterocyte differentiation.

Background: Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known., Patients and Methods: Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry., Results: Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients., Conclusion: These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.

Unlabelled: Morphologically, polymorphic prostatic lipochrome pigment has been classified and subclassified in the last few years. Type 2B lipochrome pigment granules (LPGs) are frequently found in prostatic epithelium in patients who had died of AIDS. Intensive apoptosis is observed in the same epithelium which lends support to the hypothesis of heterophagocytic (apoptotic) origin of type 2B pigment granules. Detection of nuclear chromatin material is necessary for the differentiation of an autophagosomal from a heterophagosomal structure in the cellular cytoplasm., Object of the Study: Application of in situ hybridization (ISH) for elucidating the origin of subtype 2B LPGs in the prostate epithelial cells of patients who had died of AIDS., Methods: ISH was used on routine necropsic prostate epithelial samples from three patients who had died of AIDS. A DNA probe raised against total human DNA was employed., Results: Multiple hybridization signals were detected in type 2B LPGs which shows the presence of nuclear material in those structures. The chromatin material localized to the periphery of pigment granules., Conclusion: Type 2B LPGs have a heterophagocytic origin and represent phagocytosed apoptotic bodies in the phase of phagolysosomal degradation. They can be used as a morphologic tissue marker of intensive epithelial apoptosis.

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.

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.

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.

Three cases are presented of lymphocytic colitis with chronic diarrhoea concurrent with longterm use of Cyclo 3 Fort, a phlebotonic drug used in France. The histological and immunopathological features of lymphocytic colitis are described. We show that lymphocytic colitis is drug induced, particularly in one patient where the immunopathological features of mucosal immune cell activation were induced by drug rechallenge. It is concluded that lymphocytic colitis may be drug induced, secondary to a chronic activation of the mucosal immune system by one or several components of the drug.

In patients with the acquired immunodeficiency syndrome (AIDS), manifestations of generalized Mycobacterium avium intracellulare infection are non-specific and pneumopathy is rarely encountered. We report a case of a patient with AIDS who had clinical and radiological manifestations of multifocal alveolar pneumopathy which was found on autopsy to be due to disseminated Mycobacterium avium intracellulare.