Lung adenocarcinoma invasion in TGFbetaRII-deficient cells is mediated by CCL5/RANTES.

Recently, we identified a lung adenocarcinoma signature that segregated tumors into three clades distinguished by histological invasiveness. Among the genes differentially expressed was the type II transforming growth factor-beta receptor (TGFbetaRII), which was lower in adenocarcinoma mixed subtype and solid invasive subtype tumors compared with bronchioloalveolar carcinoma. We used a tumor cell invasion system to identify the chemokine CCL5 (RANTES, regulated on activation, normal T-cell expressed and presumably secreted) as a potential downstream mediator of TGF-beta signaling important for lung adenocarcinoma invasion. We specifically hypothesized that RANTES is required for lung cancer invasion and progression in TGFbetaRII-repressed cells. We examined invasion in TGFbetaRII-deficient cells treated with two inhibitors of RANTES activity, Met-RANTES and a CCR5 receptor-blocking antibody. Both treatments blocked invasion induced by TGFbetaRII knockdown. In addition, we examined the clinical relevance of the RANTES-CCR5 pathway by establishing an association of RANTES and CCR5 immunostaining with invasion and outcome in human lung adenocarcinoma specimens. Moderate or high expression of both RANTES and CCR5 was associated with an increased risk for death, P=0.014 and 0.002, respectively. In conclusion, our studies indicate RANTES signaling is required for invasion in TGFbetaRII-deficient cells and suggest a role for CCR5 inhibition in lung adenocarcinoma prevention and treatment.

Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors.

Malignant mesothelioma is an aggressive neoplastic proliferation derived from cells lining serosal membranes. The biological and clinical characteristics of epithelial type malignant mesothelioma are distinct from those of biphasic and sarcomatous type tumors. The goal of our study was to examine the molecular basis for this distinction. Microarray analysis confirmed that the molecular signatures of epithelial and biphasic histologic subtypes were distinct. Among the differentially expressed functional gene categories was the ubiquitin-proteasome pathway, which was upregulated in biphasic tumors. Cytotoxicity experiments indicated that 211H cells derived from biphasic tumors were synergistically sensitive to sequential combination regimens containing the proteasome inhibitor bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of epithelial tumor origin, was apoptosis. Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients.

ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis.

Matrix metalloproteinase-1 (MMP-1), or interstitial collagenase, has been hypothesized to contribute to the progression of the human atherosclerotic lesions by digesting the fibrillar collagens of the neointimal ECM. The apolipoprotein E knockout (apoE0) mouse model develops complex atherosclerotic lesions, but mice do not possess a homologue for MMP-1. To provide an in vivo evaluation of the role of MMP-1 in atherogenesis, we created a transgenic mouse model that expresses this enzyme specifically in the macrophage, under the control of the scavenger receptor A (SCAV) enhancer/promoter. The MMP-1 transgenic mice were crossed into the apoE0 background and fed an atherogenic diet for 16-25 weeks. Surprisingly, the transgenic mice demonstrated decreased lesion size compared with control littermates. The lesions of the transgenic animals were less extensive and immature, with fewer cellular layers and a diminished content of fibrillar collagen. There was no evidence of plaque rupture. Our data suggest that remodeling of the neointimal extracellular matrix by MMP-1 is beneficial in the progression of lesions.

Mechanism of pericardial expansion with cardiac enlargement.

BACKGROUND: The normal pericardial sac accommodates a 250-350 gram heart and 15-50 ml of pericardial fluid. Cardiac enlargement and/or increases in fluid must be accompanied by an increase in pericardial volume and a concomitant expansion of the pericardial sac. The mechanism of such expansion has been debated, but theoretical considerations include fibroblastic proliferation with new connective tissue deposition versus remodeling of the pre-existent connective tissue. DESIGN: Nineteen pericardia were obtained from consecutive adult autopsies. Total pericardial fluid was measured; the absolute value of pericardial fluid volume and cardiac weight were added to create a total score. Representative pericardial tissue was stained with hematoxylin-eosin (H&E), Masson's trichrome, and Verhoeff's elastin stain (EVG). An additional archival case with the pericardium from a 900-g heart with 1,000-ml of fluid was also included. RESULTS: None of the sections showed histologic evidence of fibroblastic proliferation. Parameters indicative of collagen stretching or damage were evaluated. The greatest correlative factor in identifying an enlarged pericardium was the average of four measurements of the greatest distance between elastic fibers surrounding obliquely oriented collagen layers. Five of six cases with a cardiac score > 450 showed an average measurement of less than 15 microns, and 10 of 14 cases with a cardiac score < or = 450 showed an average measurement of > 15 microns = 0.0498). Histologic and ultrastructural evidence of collagen damage was identified in the pericardium from the 900-g heart with the 1,000-ml effusion. CONCLUSIONS: We propose that collagen stretching and slippage of obliquely oriented collagen layers contribute to the increased surface area needed to accommodate larger volumes. When these limits are exceeded, collagen damage ensues.

Thymic independence of adaptive immunity to the intracellular pathogen Shigella flexneri serotype 2a.

Shigella flexneri is a facultative intracellular pathogen. While immunity to several intracellular pathogens is mediated by T lymphocytes, it is unknown whether cellular immune responses are important to adaptive immunity to S. flexneri. We show that vaccination with S. flexneri serotype 2a confers protection to mice that lack T lymphocytes or gamma interferon (IFN-gamma), specific depletion of T lymphocytes does not alter the protection, and adoptive transfer of splenocytes from vaccinated mice does not confer protection to naive mice. In contrast, vaccination conferred no protection to mice that lack B lymphocytes and adoptive transfer of immune sera conferred partial protection to naive mice. These data demonstrate that in the mouse bronchopulmonary model, adaptive immunity to S. flexneri 2a is an antibody-mediated, B-lymphocyte-dependent process and can be generated in the absence of T lymphocytes or IFN-gamma.

Adaptive immune response to Shigella flexneri 2a cydC in immunocompetent mice and mice lacking immunoglobulin A.

Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared from the lungs of intranasally inoculated mice and was Sereny negative, yet it induced 93% protection against challenge with wild-type S. flexneri. Mice that lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be required for adaptive immunity in this model system.

Detection and significance of splenomegaly on chest radiographs of HIV-infected outpatients.

AIM: The purpose of this study was to determine the prevalence of splenomegaly on chest radiographs of HIV-infected outpatients and to correlate with CD4 cell counts, opportunistic conditions, liver disease and the presence of intrathoracic disease on chest radiographs. METHODS: We reviewed sequential chest radiographs of 200 HIV Clinic outpatients at the Jacobi Medical Center, Bronx, New York, mixed with chest radiographs of 137 outpatients of unknown HIV status (control group) for the presence of splenomegaly and intrathoracic disease. Chest radiographic assessment of splenomegaly was correlated with computed tomography (CT) or ultrasound (US) in 90 out of 337 patients (27%). Clinical charts of all HIV-infected patients were reviewed for CD4 cell count, liver disease and opportunistic conditions including those associated with splenomegaly. The HIV-infected patients were divided into four groups by ascending CD4 cell count: Group 1 (0-50 cells/mm3), Group 2 (51-200 cells/mm3), Group 3 (201-500 cells/mm3) and Group 4 (>500 cells/ mm3). There were 118 men and 82 women with a mean age of 40 (range 20-60) years. Mean CD4 was 180 (range 2-1108) cells/mm3. We also reviewed all autopsies (n = 239) performed on HIV-infected patients between 1983 and 1995 at our institution to correlate splenic size with splenic pathology in that population. RESULTS: Splenomegaly was present on chest radiographs in 82 (41%) HIV-infected patients including: 36/84 (43%) Group 1, 23/49 (47%) Group 2, 18/46 (39%) Group 3, and 5/21 (24%) Group 4 (P = NS). Splenomegaly was present in 30/97 (31%) patients with no evidence of liver disease or opportunistic conditions known to be associated with splenomegaly. Forty-nine HIV-infected patients had 63 opportunistic conditions known to be associated with splenomegaly (mycobacterial and fungal infections, Kaposi sarcoma and lymphoma), half of whom had splenomegaly. Splenomegaly was present on chest radiographs in 18/137 (13%) controls. The presence or absence of splenomegaly on CT or US agreed with chest radiography in 89%. Among the autopsied patients, 135/239 (56%) had splenomegaly (splenic weight > or = 240 g). No specific pathogen was present in 93/135 (69%) enlarged spleens. In contrast, one or more opportunistic conditions were present in 26/104 (25%) normal weight spleens. CONCLUSION: In conclusion, splenomegaly is common in HIV-infected patients and was present in 41% of this series. Splenomegaly may be seen in HIV-infected patients without associated opportunistic conditions or liver disease and in the absence of specific splenic pathology. Chest radiography plays an important role in detecting splenomegaly and may lead to earlier diagnosis of HIV infection.

Immunoreactivity for LN2 and LN3 distinguishes small cell carcinomas from non-small cell carcinomas in the lung.

Immunoreactivity to LN2 and LN3, monoclonal antibodies that recognize components of the class II major histocompatibility complex, was assessed in 72 cases of non-small cell lung carcinoma (NSCLC) (32 biopsy specimens, 40 resection specimens) and 64 cases of small cell carcinoma (56 biopsy specimens, 8 resections) of the lung. All cases were reviewed independently by three pathologists for histological classification. Only 1 of the 64 small cell carcinomas showed immunoreactivity for LN2, and none of the 64 cases showed reactivity for LN3. Among the non-small cell carcinomas, 25 of 48 cases were positive for LN2 and 43 of 71 were positive for LN3; the sensitivity was greater for adenocarcinoma (78.5%) than for squamous cell carcinoma (37%). A combined sensitivity of 64.7% was observed when the results of LN2 and LN3 were combined, and this sensitivity was not significantly diminished in the biopsy subset of cases (59.4%). Differentiation within histological subtypes of NSCLC (ie, well, moderate, or poorly differentiated) did not alter test sensitivity. In conclusion, LN2 and LN3, used alone or in combination, appear highly specific for non-small cell carcinoma and moderately sensitive in both biopsy and resection specimens; therefore, these antibodies may be diagnostically useful in distinguishing small cell from non-small cell carcinoma of the lung.

Combined carcinoid tumor of the lung: a combination of carcinoid and adenocarcinoma.

Combined small cell carcinoma is an uncommon but well described diagnostic category of neuroendocrine lung tumors. The prognosis of these tumors appears to be similar to that of pure small cell carcinoma, although it is believed that the non-small cell components of these tumors are less chemo-responsive than the small cell components. We report a case of a 60-year-old male smoker with a 2-cm nodule that, on subsequent lobectomy, was a combination of carcinoid and adenocarcinoma. A lymph node metastasis to an ipsilateral hilar node was comprised of only the well differentiated adenocarcinoma component. The biologic behavior of such tumors is not well described and their place within, what may be described as, a spectrum of combined neuroendocrine tumors is discussed.

Cytologic detection of Trichomonas esophagitis in a patient with acquired immunodeficiency syndrome.

Trichomonads are pathogens of the female genital tract and colonizers of the oropharynx. Gastrointestinal and pulmonary diseases have been reported in association with Trichomonas species, but a direct pathogenic effect of this organism in these organ systems remains controversial. Esophageal disease due to trichomonads has not been previously reported. A 43-yr-old man with acquired immunodeficiency syndrome (AIDS) with odynophagia and esophageal erosions was evaluated by endoscopy. Cytologic brushings from three of four sites in the esophagus were positive for trichomonads. Treatment with metronidazole resulted in clearance of the organism from the esophagus and improvement in clinical symptoms. We report esophageal trichomoniasis diagnosed on esophageal brush cytology in a man with AIDS. Clinical response was confirmed by cytologic studies and odynophagia improved with metronidazole treatment. Study of cytologic preparations was superior to biopsy for identification of this organism and was particularly useful in following the post-treatment course of disease.

beta-adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy.

To establish whether catecholamines per se in the absence of significant increases in systolic load induce myocardial damage via apoptosis, rats were treated with vehicle or isoproterenol (400 microg . kg-1 . h-1). Apoptotic cardiocytes (Apo) were identified in paraffin-embedded sections using terminal deoxynucleotide transferase-mediated dUTP nick end labeling. Results were confirmed using an independent ligase assay. Systolic blood pressures were comparable in isoproterenol-treated and control rats. Twenty-four hours of treatment with isoproterenol resulted in significant numbers of Apo compared with control [7.9 +/- 2.5 vs. 0.3 +/- 0.3 (SE) cm-2, P < 0.05]. A cohort of animals was subjected to ventricular pacing to induce a tachycardia equivalent to that induced by isoproterenol, and these animals did not show an increase in Apo. The left ventricular hypertrophy induced by 2 wk of abdominal aortic banding also increased Apo ( approximately 7. 2-fold); however, 24 h of isoproterenol infusion did not induce additional Apo in these rats. Thus catecholamines, in the absence of altered systolic load, induce Apo which is not mediated solely by tachycardia. Left ventricular hypertrophy secondary to abdominal aortic banding is associated with Apo, but this does not increase sensitivity to isoproterenol-induced Apo.

Fibrous long-spacing collagen in bacillary angiomatosis.

Fibrous long-spacing (FLS) collagen is a distinct ultrastructural form of collagen present in normal tissue, various tumors, and tissues degraded by bacterial collagenases in vivo and in vitro. An association between FLS collagen and bacillary angiomatosis has not been previously described. Six cases of bacillary angiomatosis, including one autopsy case with disseminated disease, were examined ultrastructurally. In addition, Kaposi sarcoma (3), pyogenic granuloma (3), capillary hemangioma (3), and cavernous hemangioma (2) were examined for comparison. A vascular proliferation in a lymph node from a patient with AIDS (1) and a case of pulmonary capillary hemangiomatosis (1), also in an AIDS patient, were studied. Abundant FLS collagen was identified in 4 of 6 cases of bacillary angiomatosis, in close association with the organisms. FLS collagen was not seen beyond the immediate vicinity of the organisms. The FLS collagen in bacillary angiomatosis was seen in skin biopsies and in lung and skeletal muscle in the autopsy case; in the latter case, as well as in the two AIDS-associated, nonbacillary angiomatosis, non-Kaposi sarcoma vascular proliferations, there was a striking distribution of FLS collagen around small blood vessels. Occasional FLS collagen was observed in all three pyogenic granuloma. When present in pyogenic granuloma, FLS collagen was intermixed with subendothelial collagen. Abundant FLS collagen was identified in close association with the organisms of bacillary angiomatosis in four cases; this morphologic alteration was seen in skin as well as lung and skeletal muscle. An association between FLS collagen and endothelial cells in normal tissue (Descemet's membrane) and in certain vascular proliferations appears to exist.

Splenic para-amyloid material: a possible vasculopathy of the acquired immunodeficiency syndrome.

We have observed perivascular para-amyloid in the spleens of acquired immune deficiency syndrome (AIDS) patients at autopsy. Whether this phenomenon is unique to AIDS patients or is a common degenerative phenomenon in the spleen has not been determined. Autopsy spleens from 355 patients (171 AIDS, 184 non-AIDS) were graded for presence of splenic para-amyloid material (SPAM) on a scale of 0 to 3. The average ages of the AIDS and non-AIDS groups were 38.4 and 60.4 years, respectively. All SPAM-positive AIDS cases had age-matched non-AIDS controls. Selected positive cases were examined ultrastructurally. Of the 171 AIDS patients, 55 had SPAM; in 30 cases, it was considered grade 2 or 3. Although none of the non-AIDS cases were graded 2 or 3, eight of them were grade 1. SPAM is highly correlated with AIDS (32.1 v 4.3%; P < .0001), with a specificity of 95.6% and a positive predictive value of 87.3%. These perivascular deposits correspond to areas of periarteriolar lymphoid sheaths and appear to be in continuity with arteriolar adventitia. Ultrastructurally, they contain collagen, long-spaced collagen, fibrillin, and occasional residual cells. No viral particles were noted. SPAM appears to be more prevalent and in greater quantity in AIDS patients. It does not correlate with advanced age; it can be mistaken for amyloid. Its consistent association with the adventitia of vessels raises the possibility of a new vasculopathy of AIDS; it also may be related to follicular involution and hyalinization associated with regression of prior follicular hyperplasia.

An essential role for gamma interferon in innate resistance to Shigella flexneri infection.

Shigella spp. are the major cause of bacillary dysentery worldwide. To identify immune effectors associated with protection of the naive host during infection, the susceptibility to pulmonary Shigella infection of each of various mouse strains that have a targeted deletion in a specific aspect of the immune system was evaluated. Our results demonstrate that mice deficient in gamma interferon are 5 orders of magnitude more susceptible to Shigella than are wild-type mice, whereas mice deficient in B and T lymphocytes or in T lymphocytes alone exhibit no difference in susceptibility. Significantly lower numbers of shigellae were recovered from immunocompetent compared with gamma-interferon-deficient mice after infection. While immunocompetent mice were able to clear a sublethal Shigella inoculum by day 5 postinfection, progressively increasing numbers of shigellae were cultured from the lungs of gamma interferon-deficient mice over the same period. Histopathology of the lungs from immunocompetent mice infected with a sublethal Shigella inoculum showed mild inflammatory changes, whereas the lungs from gamma interferon-deficient mice demonstrated progressively worsening acute bronchiolitis with ulceration. Further, the time to death in gamma interferon-deficient mice correlates inversely with the size of the Shigella inoculum. To identify the cellular source of gamma interferon, we infected SCID mice, T-cell-receptor-deficient mice, beige mice (a mouse strain deficient in natural killer [NK] cell activity), and mice depleted of NK cells using anti-asialo-GM1. Each NK cell-deficient mouse strain exhibited a 10-fold-greater susceptibility to Shigella infection than immunocompetent mice. To test the protective effects of gamma interferon in vitro, survival of intracellular Shigella was examined in primary macrophages from wild-type mice, primary macrophages from gamma interferon-deficient mice, a macrophage cell line, and a fibroblast cell line. Following activation with gamma interferon, each cell type eradicated intracellular Shigella, while nonactivated macrophages fostered Shigella replication and nonactivated fibroblast cells fostered both Shigella replication and intercellular spread. Taken together, these data establish that NK cell-mediated gamma interferon is essential to resistance following primary Shigella infection.

Inf lammatory Mass with Fibrinoid Necrosis of Vessels Caused by Methylene Blue Marking of a Colonic Polyp.

Methylene blue is a relatively non-toxic dye that is used in a variety of procedures including the marking of margins and skin flaps, identifying sinus and fistulous tracts, localizing islet cell tumors, and marking colonic polyps. It has been used intravascularly for the labeling of arteriovenous malformations or to find small bleeding sites. Few adverse effects have been reported with its use. We report an unusual case of an inflammatory mass secondary to transmural injection of methylene blue that resulted in fibrinoid necrosis of arterial media mimicking a necrotizing vasculitis.

Review and hypothesis: the eosinophil and peripartum heart disease (myocarditis and coronary artery dissection)--coincidence or pathogenetic significance?

OBJECTIVES: To examine a possible relationship between peripartum heart disease (myocarditis and spontaneous coronary dissection) and the presence of eosinophils. BACKGROUND: Eosinophils have been shown to have potential collagenolytic and cytotoxic activity. Eosinophils may play a role in postpartum uterine involution. The presence of eosinophils in spontaneous coronary dissection and myocarditis in the postpartum period raises the possibility of a role for eosinophils in these diseases. METHODS: We reviewed the files of one of us (S.M.F.) for cases of peripartum myocarditis and spontaneous coronary dissection and assessed the frequency of eosinophilic inflammation. Seventeen postpartum myocarditis and/or cardiomyopathy cases were found and two spontaneous coronary dissections. Fifteen sex- and age-matched controls on non-postpartum myocarditis and borderline myocarditis were evaluated and eosinophil counts per unit area compared. Also, a Medline search of all previously published cases of spontaneous coronary dissection was performed back to 1966. RESULTS: Of the 16 heart biopsies and one autopsy in the peripartum period, 10 were shown to contain easily identified eosinophils (6 myocarditis, 1 borderline, 3 cardiomyopathy). When presence of eosinophils was compared with the control group, a statistically significant difference was obtained (P = 0.036). The two new spontaneous coronary dissection cases had eosinophils along the dissection plane; the literature search produced 13 of 24 autopsied peripartum spontaneous coronary dissections with eosinophils for a total of 15 of 26 with our cases. CONCLUSIONS: An association exists between eosinophils and peripartum cardiac disease (myocarditis and spontaneous coronary dissection). The role of eosinophils in labor, uterine involution and collagenolysis and the possible relation to cardiac disease are discussed.

Distribution of endothelin immunoreactivity in human kidney correlates with antemortem acute renal failure: a possible postmortem immunohistochemical test.

The role of endothelin in the normal kidney function, as well as in disease states, has been studied in animal models. In addition, it was shown previously that endothelial, mesangial, and epithelial components of the nephron produce endothelins, in particular ET-1. We performed immunohistochemistry for ET-1 reactivity on 31 autopsy and four surgically removed kidneys. Eighteen cases had clinical diagnoses of acute renal failure (ARF) In the remaining 17 cases with normal or unchanged renal function before death or surgery, ET-1 immunoreactivity was present in tubular epithelium, with the most intense staining in the medullary collecting tubules. In 13 of 18 cases of ARF, tubular staining was either replaced or accompanied by interstitial reactivity in the inner and outer medulla, corresponding to the location of the vasa recta and interlobular arteries identified by factor VIII immunostaining. Controlled autolysis performed on normal kidney over 72 hours postmortem produced tubular epithelial degradation with reduced epithelial cell endothelin reactivity, but not an interstitial pattern. In situ hybridization for ET mRNA localized expression to tubular and collecting duct epithelium in both normal and acute renal failure cases. The change in the localization of ET-1 immunoreactivity from tubular epithelium to the interstitium in these ARF cases does not appear to be the result of increased vascular endothelial production of endothelin. This altered immunoreactivity pattern for ET-1 may be a marker of antemortem tubular damage and can be used as an adjunct in the autopsy diagnosis of ARF.

Comparison of changing autopsy trends in the Bronx population with acquired immunodeficiency syndrome.

The opportunistic infections, malignancies, and causes of death related to acquired immunodeficiency syndrome (AIDS) are changing, perhaps as a result of improved treatment, prophylaxis, and education. With its high percentage of persons who acquired the human immunodeficiency virus from intravenous drug (IVD) use, the population of patients with AIDS in the Bronx is potentially unique. All of the 257 consecutive adult human immunodeficiency virus and/or AIDS cases from two Bronx teaching hospitals from 1982 through 1995 were collected. The reports were reviewed for patient demographics, opportunistic infections, malignancies, and causes of death. One hundred thirteen cases from 1982 through 1988 were compared with 144 cases from 1989 through 1995, separated by the institution of antiretroviral therapy and Pneumocystis carinii (PCP) prophylaxis in the latter period. Male homosexuality as a risk factor significantly decreased from 24.8% of the cases in our study from the 1982/88 period to 12.5% during the 1989/95 period (P = 0.014), but IVD use cases showed no change. Cases of AIDS in heterosexual patients increased from 23.9 to 36.1% (P = 0.041) but did not achieve statistical significance unless the unknown risk category (a population shown to be infected predominantly through heterosexual transmission) was included. The prevalence of PCP at autopsy as an opportunistic infection decreased from 37.2 to 25% (P = 0.04), and its prevalence as a cause of death decreased from 31.9 to 13.9% (P = 0.007). This decrease was seen in the homosexual and heterosexual populations but not in the population of IVD users. The homosexual population, as opposed to the population of IVD users, may have taken greater advantage of PCP treatment and prevention. As a result, bronchopneumonia, not PCP, is now the leading cause of death among the patients with AIDS in this study. These findings have important implications for therapy and prophylaxis to control the spread of AIDS and its related infections, particularly in an inner city population troubled by drug use and poverty.

Autopsy patterns of disease among subgroups of an inner-city Bronx AIDS population.

The Bronx, New York, has a large, inner-city, AIDS population which contains a greater proportion of women and intravenous drug users and a lower percentage of homosexuals than the U.S. AIDS population overall. Because this population is reflective of the evolving trends in the national AIDS population, our objective was to gain an understanding of patterns of infections, malignancies, and cause of death among these individuals. All autopsies (252) performed on patients with AIDS at two hospitals affiliated with a major academic center in the Bronx between 1982 and 1995 were reviewed. Cytomegalovirus (CMV) as an infection or as a cause of death (COD) occurred more commonly among patients who had been infected with HIV through sexual relations (p = 0.0002 and p = 0.0011, respectively). Bacterial pneumonia was the most common source of pulmonary infection, although Pneumocystis carinii pneumonia was more often a cause of death. A higher frequency of aspergillus infection in female subjects was also noted (p = 0.010). These and other observations may have ramifications for treatment and prevention in analogous AIDS inner-city populations.