Cytosolic targeting domains of gamma and delta calmodulin-dependent protein kinase II.

Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) isozyme variability is the result of alternative usage of variable domain sequences. Isozyme expression is cell type-specific to transduce the appropriate Ca(2+) signals. We have determined the subcellular targeting domain of delta(E) CaMK-II, an isozyme that induces neurite outgrowth, and of a structurally similar isozyme, gamma(C) CaMK-II, which does not induce neurite outgrowth. delta(E) CaMK-II co-localizes with filamentous actin in the perinuclear region and in cellular extensions. In contrast, gamma(C) CaMK-II is uniformly cytosolic. Constitutively active delta(E) CaMK-II induces F-actin-rich extensions, thereby supporting a functional role for its localization. C-terminal constructs, which lack central variable domain sequences, can oligomerize and localize like full-length delta(E) and gamma(C) CaMK-II. Central variable domains themselves are monomeric and have no targeting capability. The C-terminal 95 residues of delta CaMK-II also has no targeting capability but can efficiently oligomerize. These findings define a targeting domain for gamma and delta CaMK-IIs that is in between the central variable and association domains. This domain is responsible for the subcellular targeting differences between gamma and delta CaMK-IIs.

Campylobacter-induced enteritis and diarrhea in captive cotton-top tamarins (Saguinus oedipus) during the first year of life.

A prospective study of 43 cotton-top tamarins, from infancy to 6 to 17 months of age, was conducted to determine the epidemiology of Campylobacter spp. infection. Nine infants followed for one year in an isolation unit, where attendants wore protective clothing, did not become infected. In the main facility where 32 of 34 animals had repeated infections with C. coli, 6% of the infections developed initially in incubators, 66% in the nursery room, and 28% after transfer to the main colony. Fifteen of these tamarins also were infected with C. jejuni. Twenty percent of the infections developed initially in the nursery room and 80% in the colony. Polyacrylamide gel electrophoresis analysis of C. jejuni cultures revealed multiple reinfections with different strains. Both types of infections were most prevalent between 3 and 9 months of age. Campylobacterjejuni infection developed most frequently between April and June and C. coli infection developed between October and December. In the nursery, diarrhea developed most frequently at times when there was no infection with Campylobacter spp. Forty percent of animals with diarrhea in the nursery had C. coli and none had C. jejuni, whereas, in the colony, 49% had C. jejuni and 11% had C. coli infections. There was no association between these infections and diet or idiopathic colitis.

delta Ca(2+)/Calmodulin-dependent protein kinase II isozyme-specific induction of neurite outgrowth in P19 embryonal carcinoma cells.

Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) has been linked to the induction of differentiation in preneuronal cells. In these cells, delta isozymes represent the majority of CaMK-IIs expressed and are activated by differentiation stimuli. To determine whether delta CaMK-IIs are causative or coincident with in vitro differentiation, we overexpressed wild-type, constitutively active, and C-terminal domains of delta and gamma CaMK-II isozymes in mouse P19 and NIH/3T3 cells using high-efficiency transfections. At 1-2 days after transfection, only constitutively active delta CaMK-II isozymes induced branched cellular extensions in both cell types. In P19 cells, retinoic acid induced neurite extensions after 3-4 days; these extensions were coincident with a fourfold increase in endogenous CaMK-II activity. Extensions induced by both retinoic acid and delta CaMK-IIs contained class III beta-tubulin in a discontinuous or beaded pattern. C-terminal CaMK-II constructs disrupted the ability of endogenous CaMK-II to autophosphorylate and blocked retinoic acid-induced differentiation. delta CaMK-II was found along extensions, whereas gamma CaMK-II exhibited a more diffuse, cytosolic localization. These data not only support an extranuclear role for CaMK-II in promoting neurite outgrowth, but also demonstrate CaMK-II isozyme specificity in these early steps of neuronal differentiation.

Transthoracic intracardiac catheters in pediatric patients recovering from congenital heart defect surgery: associated complications and outcomes.

OBJECTIVES: To characterize transthoracic intracardiac catheter uses and associated morbidities in pediatric patients recovering from congenital heart defect surgery and to identify potential risk factors associated with their use. DESIGN: Prospective data collection and review. SETTING: An 18-bed pediatric intensive care unit (PICU) in a tertiary care university hospital. PATIENTS: All pediatric patients between October 1, 1996, and September 30, 1997, who were recovering from congenital heart defect surgery and had transthoracic intracardiac catheters in place. MEASUREMENTS AND MAIN RESULTS: Catheter use, associated morbidity, necessary interventions, and risk factors for complications of catheter use were identified. During this period, 523 catheters (276 right atrial, 155 left atrial, 68 common atrial, and 24 right ventricular or pulmonary artery catheters) in 351 PICU patients were studied. Mean age was 23.1+/-45.1 months (median, 4.98 months); 138 patients (39.3%) were <3 months old. The rate of occurrence of bleeding with catheter removal (mediastinal output in the hour after removal that was more than twice the previous average hourly output) was 36.7%, and bleeding occurred more frequently with left atrial catheters (47%; odds ratio, 2.0; p < .05). However, interventions after catheter removal were required for only 8.3% (42/504) of catheters removed, and hemodynamic compromise occurred with the removal of only 2.6% (13/504) of catheters. Interventions included fluid resuscitation (35 cases), pleural drainage (three cases), catheter wiring for retention (one case), chest tube suctioning (two cases), and surgical removal (one case). No associated deaths occurred. In a multivariate logistic regression analysis, age <3 months (odds ratio, 4.74), catheter location (left atrial: odds ratio, 4.97; pulmonary artery: odds ratio, 12.48), and platelet count of <50,000 (odds ratio, 8.59) were identified as risk factors associated with a need for intervention after catheter removal (p < .05). Other complications included blood cultures positive for organisms (1.5%), thrombus (0.6%), and catheter nonfunction (10.9%). Prematurity was a risk factor for thrombus and nonfunction. CONCLUSIONS: Use of transthoracic intracardiac catheters in pediatric patients is safe. Young infants and pediatric patients with thrombocytopenia or with catheters in the left atrial or pulmonary artery position have a greater need for interventions after catheter removal, warranting added precautions.

45-year follow-up of hepatitis C virus infection in healthy young adults.

BACKGROUND: The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown. OBJECTIVE: To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954. DESIGN: Retrospective cohort study. SETTING: A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records. PARTICIPANTS: 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954. Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years. MEASUREMENTS: The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA. Morbidity and mortality were also assessed. RESULTS: Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay. The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 [95% CI, 8.4 to 80.0]). During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 [CI, 0.94 to 13.52]). Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 [CI, 0.8 to 2.6]). Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes. One hundred nineteen HCV-negative persons (1.4%) died of liver disease. CONCLUSIONS: The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors. During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates. This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought.

Toward the development of a clinically useful approach to psychotherapy research.

The controversial move toward the development of a consensus on evidence-based or empirically supported therapies may be seen as an international crisis facing psychotherapists. Researchers long have complained that practicing therapists all too often continue to guide what they do therapeutically on the basis of their clinical experience and not the available research findings. Practicing therapists long have complained that therapy research bears only a remote resemblance to what goes on in actual clinical practice and that research reports are written for other researchers, not for clinicians. In the hope of turning our current crisis into an opportunity, this panel involved a dialogue that was designed to bridge this clinical-research gap.

Explaining recent increases in students' marijuana use: impacts of perceived risks and disapproval, 1976 through 1996.

OBJECTIVES: Marijuana use among high school seniors increased during most of the 1970s, decreased throughout the 1980s, and has been increasing again during the 1990s. Earlier analyses of the classes of 1976 through 1986 attributed the historic trends during that period to specific changes in views about marijuana. This study examined whether recent increases in marijuana use among seniors and among students in earlier grades reflect similar processes. METHODS: Multivariate regression analyses were conducted on data from large annual nationwide surveys of high school seniors from 1976 through 1996 (approximate n = 61,000) and 8th and 10th graders from 1991 through 1996 (n's = 87,911 and 82,475, respectively). RESULTS: Individual lifestyle factors (grades, truancy, religious commitment, evenings out for recreation) correlated substantially with marijuana use but did not explain the historic changes in marijuana use. Rather, decreases in perceived risk of harmfulness and in disapproval can account for the recent increases in all 3 grades and for earlier decreases among seniors. CONCLUSIONS: These findings indicate that perceived risks and disapproval are important determinants of marijuana use. Accordingly, prevention efforts should include realistic information about risks and consequences of marijuana use.

Family history as a risk factor for ulcerative colitis-associated colon cancer in cotton-top tamarin.

BACKGROUND & AIMS: Little is currently known about the relationship between family history of colon cancer and ulcerative colitis-associated colon cancer. A nested case-control study was performed to evaluate the association between family history of colon cancer and spontaneously occurring colon cancer in cotton-top tamarins (Saguinus oedipus). METHODS: Subjects were chosen from a colony of cotton-top tamarins held in captivity between 1968 and 1995. The cancer status of parents and grandparents was compared for 48 animals with colon cancer and 58 controls, all with histological confirmation of ulcerative colitis. Multivariate odds ratios were calculated using logistic regression. RESULTS: A parental history of colon cancer was positively associated with risk of colon cancer (multivariate odds ratio, 2.7; 95% confidence interval, 1.1-6.3). Risk also increased as an animal's total number of family members with colon cancer increased (multivariate odds ratio, 1.7 for each increase in the total number of family members with cancer; 95% confidence interval, 1.1-2.8). CONCLUSIONS: The results suggest that cotton-top tamarins with ulcerative colitis are at significant increased risk for developing colon cancer if they have a family history of colon cancer. Further investigation of this relationship in both tamarins and humans is warranted.

Five spontaneous deaths associated with Clostridium difficile in a colony of cotton-top tamarins (Saguinus oedipus).

Clostridium difficile toxin was detected in the feces of five cotton-top tamarins (Saguinus oedipus) that died spontaneously over a period of 10 weeks. Deaths occurred subsequent to antibiotic therapy for infectious diarrhea associated with Campylobacter spp. Relevant clinical signs of disease prior to death included weight loss, watery diarrhea, hematochezia, weakness, and sudden collapse. On histologic examination of the colon at necropsy, pseudomembranous colitis was evident in two cases, a lesion consistent with C. difficile lesions in humans. This finding prompted submission of feces for C. difficile toxin analysis from these five cases. Four of the tamarins were from a single room, and the fifth was housed nearby. The proximity of the cases raises the possibility of environmental contamination by resistant C. difficile spores or fecal spread of the organism as reported in hospitals, day-care centers, and nurseries. The relative importance of C. difficile and its potential role as an unrecognized cause of enteric disease secondary to antibiotic therapy in nonhuman primates is discussed.

Amplification of stromelysin-3 transcripts from carcinomas of the colon.

Stromelysin-3 has been recently described in association with the stroma of different types of cancer including colorectal carcinomas. This article reports the detection of transcripts for stromelysin-3 (matrix metalloproteinase-11 [MMP-11]) in extracts of tissue from colorectal carcinomas using the technique of reverse transcription-polymerase chain reaction (RT-PCR). In 12 cases of primary colon carcinoma, stromelysin-3 messenger RNA (mRNA) was detected after 25 cycles, whereas this procedure did not reveal stromelysin-3 mRNA expression in one rectal carcinoma micrometastasis to the liver or in normal colon tissue (controls) after 30 cycles of PCR. However, stromelysin-3 mRNA was detected in normal colon specimens after 45 cycles. The high sensitivity of this technique allows application for the investigation of the expression of stromelysin-3 in small amounts of tissue.

A prospective study of the epidemiology of colitis and colon cancer in cotton-top tamarins (Saguinus oedipus).

BACKGROUND & AIMS: Spontaneous colitis and colon cancer in the cotton-top tamarin have been shown to resemble human ulcerative colitis and its associated cancer. The effect of environment and diet on the evolution of the disease was studied in animals from birth to 5 years of age. METHODS: Newborn tamarins were assigned to three groups reared in (1) a colony in which colitis was highly prevalent and fed a standard diet; (2) an isolation unit and fed a standard diet or one of two semipurified diets; and (3) a multispecies nursery, returned to the colony, and fed the same semipurified diets. Mucosal biopsy specimens from the descending colon were taken at 4-month intervals. RESULTS: Acute colitis and chronic mucosal changes were significantly higher in the colony than in the isolation unit. Diet had no effect on acute colitis, but chronic mucosal changes were significantly higher in animals fed a standard diet than semipurified diets. CONCLUSIONS: Data suggest that acute colitis was associated with environment. Factors in the environment, including a transmissible agent, are discussed. Chronic mucosal changes were modified by diet. Cancer was associated with acute colitis and chronic changes and seems to be associated with diet.

Determination of total organic emissions from hazardous waste combustors.

U.S. Environmental Protection Agency risk assessment guidance currently under development for evaluation of permitting information from hazardous waste combustors requires a quantity referred to as "total organic carbon". The risk guidance does not define this term precisely, nor does it explain how it should be determined. This paper discusses basic principles of sampling and analysis of stack emissions for "total organics", best currently available technology, and the status of two ongoing projects designed to provide guidance and to improve analysis procedures. Determination of total organics from stack emissions is much more complicated than might be expected, and more published guidance is badly needed. The best scheme available for analysis of stack emissions for total organics to be used in material balance style "bookkeeping" includes determination of organics content in three boiling point ranges: <100 °C, 100 °C-300 °C, and >300 °C. Total organic carbon is not a useful quantity, since it includes soot, polymeric material, and other nonextractable organic materials. Total organics has been found to be an imperfect but less misleading term. Various calculations can be made and conclusions can be drawn on the basis of the contents of the individual boiling point ranges, as determined by the recommended methodology. The analysis strategy is complicated and difficult, and it contains limitations and compromises. It does not, however, require exotic analysis instrumentation, nor is it very expensive. Each of these facets of the methodology is discussed in this paper, and a status report is provided on development of a guidance document and a research project intended to produce improved methods.

Chromatin organization, meiotic status and meiotic competence acquisition in mouse oocytes from cultured ovarian follicles.

Changes in chromatin organization, meiotic status and the development of meiotic competence in oocytes retained within mouse ovarian follicles from day 0 to day 6 in culture were examined. The effects of exposure for 24 h to human luteinizing hormone (hLH) during the last day in culture was also determined. Preantral follicles from 22- to 24-day-old (prepubertal) mice develop antra and undergo significant growth from day 0 to day 4 in culture, after which the growth rates slow. The statistical significance of meiotic progression was examined using exact logistical regression analysis, which is particularly useful when the data are sparse and unbalanced. The transition from rimmed to unrimmed germinal vesicle stages was found to occur between day 2 and day 4 of follicle culture and was not influenced by exposure to hLH. Treatment with hLH caused a significant increase in the proportion of intrafollicular oocytes resuming meiosis. Assays of meiotic competence performed in vitro in oocytes retrieved from cultured follicles demonstrated that the transition from an unrimmed to a rimmed state is closely coincident with the acquisition and expression of meiotic competence. Forty-six per cent of competent oocytes from follicle cultures at day 3 progressed to metaphase II. These results indicate that the follicle culture system used in these studies supports the transformation of enclosed oocytes from a precompetent to a competent state and can maintain meiotic arrest for up to 6 days in culture. However, an increasing proportion of oocytes exhibit abnormal meiotic progression with continued follicle culture beyond 4 days.

Renal interleukin-1 expression during endotoxemia and gram-negative septicemia in conscious rats.

Endotoxin-induced cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) are thought to contribute to the proinflammatory effects of endotoxin in gram-negative infections. Using a conscious rat model of sepsis, induced by intravenous challenge with LD95 doses of endotoxin (n = 24) or live Escherichia coli (E. coli) (n = 24), we examined frozen sections of kidney at various intervals for evidence of IL-1 alpha and TNF alpha expression. A transient glomerular endothelial IL-1 alpha expression was demonstrated at 30 and 90 min after initiation of the sepsis in both endotoxin and E. coli-treated animals using immunohistochemistry. The endothelial IL-1 alpha expression as determined by immunohistochemistry occurred at the same time as IL-1 alpha mRNA expression, as determined by Northern blot analysis. The glomerular endothelial IL-1 alpha expression coincided with a slight but significant increase in the number of the glomerular polymorphonuclear leukocytes as identified by naphthol AS-D chloroacetate esterase enzyme histochemical reaction. Glomerular endothelial IL-1 alpha expression was virtually absent by 180 and 360 min. No TNF alpha expression was detected in the renal tissues at any time interval. Neither alpha-naphthyl acetate esterase-positive nor acid phosphatase-positive monocytes/macrophages were identified in the glomeruli. Our findings provide direct in vivo evidence that the IL-1 alpha gene product is expressed locally in the kidney by glomerular endothelial cells in this septic rat model.

Lack of suppressed renal thrombomodulin expression in a septic rat model with glomerular thrombotic microangiopathy.

BACKGROUND: The thrombomodulin-dependent protein C anticoagulant pathway plays a major physiologic role in the down-regulation of the coagulation process. In cell culture, inflammatory cytokines or endotoxin can down-regulate endothelial thrombomodulin (TM) suggesting that suppressed TM expression may contribute to thrombotic complications noted in Gram-negative sepsis. EXPERIMENTAL DESIGN: In the present study, we have examined TM expression in the kidneys of septic rats utilizing indirect immunofluorescence and have quantified TM antigen and TM activity in extracts of the same kidneys by enzyme-linked immunosorbent assays and protein C activation assays, respectively. Conscious Sprague-Dawley rats were injected intravenously with LD95 doses of live E. coli (N = 30), or endotoxin (N = 30). Control animals (N = 30) were injected with equivalent volumes of saline. The rats were killed 30, 90, 180, 360, and 720 minutes after the initiation of sepsis. RESULTS: Glomerular capillary thrombosis developed by 180 minutes in approximately half of the animals after the initiation of sepsis. We failed to demonstrate suppressed TM expression in the kidneys of septic animals using immunofluorescence. Neither enzyme-linked immunosorbent assays, nor protein C activation assays showed decreased levels in TM antigen expression or activity at different time points during the sepsis. CONCLUSIONS: These results indicate that suppressed TM expression does not contribute to the development of the glomerular capillary thrombosis in this septic rat model.

Proliferative activity of intrinsic cell populations in the normal human kidney.

The proliferative activity of various normal human renal cell populations is unknown. Recently, antibodies to cell proliferation-associated nuclear proteins, such as proliferating cell nuclear antigen (PCNA) and KI-67, which are applicable to archival paraffin sections, became available. With antibodies to PCNA and Ki-67 after microwave pretreatment of the paraffin sections, the proliferation indexes (ratio of positive nuclei with PCNA and Ki-67 antibodies/all nuclei counted x 100, i.e. percentage of positive cells) of 12 different intrinsic renal cell populations in 20 normal human kidneys have been determined. The following proliferation indexes (percentages of positive cells) were found with the PCNA and the Ki-67 antibodies, respectively: proximal tubular epithelium, 0.22, 0.24; thin limb of Henle, 0.29, 0.30; thick ascending limb of Henle, 0.32, 0.29; distal tubular epithelium (distal convoluted tubules and cortical collecting ducts, 0.33, 0.44; medullary collecting ducts, 0.32, 0.3; glomerular mesangial cells, 0.07, 0.12; glomerular visceral epithelial cells, 0.04, 0.08; glomerular parietal epithelial cells, 0.07, 0.1; glomerular capillary endothelium, 0.42, 0.47; peritubular capillary endothelial cells, 0.38, 0.43; endothelium of large intrarenal vessels (arteries and veins), 0.09, 0.12. Thus, normally capillary endothelium (glomerular and peritubular) appears to have the highest proliferation index in the human kidney by these techniques. These results indicate major variation in the proliferative activity of normal human renal cell populations, along with a significant correlation between PCNA and Ki-67 staining. Furthermore, this study provides normal values for the proliferative activity of different human renal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ DNA hybridization study of 'primary' cytomegalovirus (CMV) oophoritis.

We report the case of a 50 year old woman with metastatic breast carcinoma refractory to chemotherapy who died of candidal septicemia after autologous bone marrow transplantation. Although there was no apparent active cytomegalovirus (CMV) infection (negative cultures and serology for active infection), autopsy revealed histologic evidence of CMV inclusions limited to both ovaries. DNA in situ hybridization was performed on multiple organs, and additional foci of infection in one fallopian tube and the adrenal glands were detected. Previous reports of isolated CMV oophoritis may represent sampling error. An ascending route of infection is suggested. Tubo-ovarian changes due to CMV infection may occur more frequently than suspected; they are difficult to diagnose because even actively CMV infected cells may not be detected by routine histology alone, and because, after the active infection 'heals', no evidence of the virus can be found on histologic examination.

Absence of association between cytomegalovirus infection and obliterative transplant arteriopathy in renal allograft rejection.

Cytomegalovirus (CMV) was recently identified, using in situ hybridization, in the coronary arteries of patients with cardiac transplant rejection, suggesting a role of CMV in the development of obliterative transplant arteriopathy in cardiac allografts. We sought to verify this observation by examining arteries in kidney transplants with intimal thickening due to chronic rejection. Eleven renal biopsies and 13 nephrectomies from 24 patients, all showing obliterative transplant arteriopathy, were collected for this study. Of these patients, six were seropositive for CMV before transplantation, three were identified as seropositive following renal transplantation, nine had no evidence of CMV infection, and clinical data were not available for an additional six patients. Paraffin-embedded renal sections were examined for the presence of CMV by immunohistochemistry in situ hybridization and polymerase chain reaction. By these methods, only one case (1/24) was demonstrated to have CMV infected cells in the renal interstitium, tubules, and glomeruli, but none (0/24) showed CMV to be located in any of the renal arteries or arterioles. Thus, our results suggest that obliterative transplant arteriopathy can occur in the absence of demonstrable CMV and is probably unrelated to direct CMV infection of the graft.

Nonpapillary and papillary renal cell carcinoma: a cytogenetic and phenotypic study.

Cytogenetic and molecular genetic studies allow the common renal cell neoplasms to be separated into two main types: (1) Nonpapillary renal cell carcinomas (RCC) which have a loss of 3p13-pter sequences and (2) Papillary renal cell tumors having tri- or tetrasomies of chromosome 7 and trisomy 17. To investigate renal proximal (PT) and distal (DT) tubular epithelial phenotype expression in these genetically distinct neoplasms, a panel of antibodies and lectins selectively reactive with normal adult PT and DT was applied to 10 nonpapillary and seven papillary RCC. All tumors except one papillary RCC demonstrated characteristic karyotypes. Phenotype expression varied depending upon changes in the histopathologic patterns within a tumor. Among tumors composed of only one cell type, columnar, eosinophilic cells showed only PT staining and small, basophilic cells showed only DT staining. One tumor revealed a transition from small, basophilic cells to columnar, eosinophilic cells. The basophilic cells stained for DT markers and the eosinophilic cells for PT markers. One tumor consisted of nests of clear cells between indistinct papillary structures. The clear cells stained for both PT and DT markers. All 10 nonpapillary RCC demonstrated PT staining; nine exhibited DT markers. Staining was most intense in areas of tumor showing higher nuclear grades, tubuloglandular differentiation or in granular, eosinophilic cells and was absent or weak in solid groups of low nuclear grade clear cells. Papillary and nonpapillary RCC demonstrated lectin-binding or antigens associated with both PT and DT indicating a capacity for multipotential metanephric differentiation in each type of neoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Is cytomegalovirus associated with renal disease in AIDS patients?

Although it has been suggested that cytomegalovirus (CMV) infection of the kidney might facilitate the development of human immunodeficiency virus-associated nephropathy (HIVAN) or other morphologic renal changes in patients with AIDS, no systematic study has been performed on kidneys from AIDS patients. We examined 75 autopsy kidneys, two renal biopsy specimens, and a nephrectomy specimen from 78 HIV-infected patients (five with HIVAN) for the presence of CMV. Immunocytochemistry (ICC) utilizing a monoclonal antibody against the late antigen of CMV and in situ hybridization (ISH) with a biotinylated DNA probe for CMV sequences were used. The detection system for both ICC and ISH was streptavidin-conjugated alkaline phosphatase with Fast Red TR chromogen. CMV was detected in only 10 of the 78 kidneys examined (12.8%): eight by both methods, one by ISH only, and another by ICC only. All 10 positive kidneys were obtained from autopsies of patients with AIDS. The average number of positive cells (in approximately 15 x 10 mm sections) was 22 with ICC and 10 with ISH. Glomerular intracapillary cells (possibly endothelial cells) were the most commonly stained, followed by positive cells in the interstitium and peritubular capillaries. Relatively few tubular epithelial cells were stained. The majority of positive cells by either ICC or ISH did not show nuclear or cytoplasmic inclusions; however, only two of the 10 positive kidneys did not contain cells with typical Cowdry type-A intranuclear CMV inclusions. The most frequent pathologic finding in the kidneys positive for CMV by either ICC or ISH was acute tubular necrosis (in six of 10, 60%).(ABSTRACT TRUNCATED AT 250 WORDS)