Cytomegalovirus pericarditis: a case series and review of the literature.

Cytomegalovirus (CMV) commonly infects both normal and immunocompromised hosts. Although it usually produces an asymptomatic infection to mild illness, CMV has the potential to significantly injure many different organs. Reports of CMV causing pericardial disease, however, are limited and documentation of infection by growth of the virus from tissue or fluid is rare. As part of a prospective trial of subxiphoid pericardial biopsy in 57 adult patients with large pericardial effusions, three culture-proven cases and one serologically confirmed case of CMV pericardial disease were discovered. Subsequently, CMV was grown from the pericardium of an infant with congenital heart disease. A review of the documented cases of CMV pericarditis is provided along with a discussion of the pathogenesis and significance of this perhaps not so uncommon disease.

Coexpression of May-Hegglin anomaly and hereditary nephritis in a family.

In three generations of a family investigation for coexpression of May-Hegglin anomaly and hereditary nephritis was done by routine studies, as well as electron microscopy of renal tissue and blood cells, platelet aggregation studies, audiograms, and ophthalmologic evaluations. The propositus had typical May-Hegglin anomaly and a mild form of hereditary nephritis. One son had May-Hegglin anomaly and possible hereditary nephritis, and one daughter had May-Hegglin anomaly and probable hereditary nephritis. A grandson had May-Hegglin anomaly but no evidence of hereditary nephritis at age 23. The mild form of hereditary nephritis described here was atypical for Alport's syndrome, but together with similar reports, suggests that a combination of May-Hegglin anomaly and mild hereditary nephritis may be a distinct disorder.

Regulation of membrane chloride currents in rat bile duct epithelial cells.

This study examines the conductive properties of the plasma membrane of cells isolated from the intrahepatic portion of bile ducts. Membrane Cl- conductance was measured in single cells using whole-cell patch clamp recording techniques and in cells in short-term culture using 36Cl and 125I efflux. Separate Ca(2+)- and cAMP-dependent Cl- currents were identified. Ca(2+)-dependent Cl- currents showed outward rectification of the current-voltage relation, time-dependent activation at depolarizing potentials, and reversal near the equilibrium potential for Cl-. Ionomycin (2 microM) increased this current from 357 +/- 72 pA to 1,192 +/- 414 pA (at +80 mV) in 5:7 cells, and stimulated efflux of 125I > 36Cl in 15:15 studies. Ionomycin-stimulated efflux was inhibited by the Cl- channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) (150 microM). A separate cAMP-activated Cl- current showed linear current-voltage relations and no time dependence. Forskolin (10 microM) or cpt-cAMP (500 microM) increased this current from 189 +/- 50 pA to 784 +/- 196 pA (at +80 mV) in 11:16 cells, and stimulated efflux of 36Cl > 125I in 16:16 studies. cAMP-stimulated efflux was unaffected by DIDS. Because the cAMP-stimulated Cl- conductance resembles that associated with cystic fibrosis transmembrane conductance regulator (CFTR), a putative Cl- channel protein, the presence of CFTR in rat liver was examined by immunoblot analyses. CFTR was detected as a 150-165-kD protein in specimens with increased numbers of duct cells. Immunoperoxidase staining confirmed localization of CFTR to bile duct cells but not hepatocytes. These findings suggest that Ca(2+)- and cAMP-regulated Cl- channels may participate in control of fluid and electrolyte secretion by intrahepatic bile duct epithelial cells, and that the cAMP-regulated conductance is associated with endogenous expression of CFTR. Abnormal ductular secretion may contribute to the pathogenesis of cholestatic liver disease in cystic fibrosis.

Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization.

Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer.

Characterization of the cystic fibrosis transmembrane conductance regulator in a colonocyte cell line.

An anti-peptide antibody raised to the C-terminal sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) was used to examine CFTR immunoreactivity in the T84 colonocyte cell line. Immunoblots of T84 cell lysates detected CFTR as a 170-kDa protein that appeared as a broad band or doublet in SDS/PAGE. This protein comigrated with the predominant immunoblot signal detected in human pancreas and colon. An equivalent protein was detected as a prominent substrate for protein kinase A and for protein kinase C in T84 cell immunoprecipitates with this antibody. The immunoprecipitated protein resembled the protein detected by immunoblot in that both proteins showed the same change in electrophoretic mobility after digestion by N-Glycanase. The precipitated protein was indentified as CFTR by two criteria. First, the same protein was immunoprecipitated with an antibody to a different CFTR peptide, [Lys102]CFTR-(102-116). Second, two-dimensional phosphopeptide mapping was used to compare the immunoprecipitated protein with a bacterially expressed protein known to contain most of the predicted protein kinase A phosphorylation sites in CFTR. Because the six most prominent peptides in each map were equivalent, these maps confirm that the precipitated protein is CFTR. By using these antibodies for immunofluorescence and immunoperoxidase staining, CFTR was localized to the apical region of T84 cells grown in tumors and in monolayers. Thus, T84 cells express CFTR at sufficient levels to permit identification and immunochemical studies of this protein in its endogenously occurring form.

CFTR: development of high- affinity antibodies and localization in sweat gland.

Rabbit antisera were raised to six synthetic peptides corresponding to amino acid sequences contained in the protein product of the cystic fibrosis gene, CFTR. For two peptides, [Lys102]CFTR(102-116) and CFTR(1468-1480), antibody-peptide binding was of high affinity in that half-maximal binding occurred at peptide concentrations below 10 nM. Monospecific antibodies were prepared using these peptides, and these antibodies were used to stain human skin. Specific staining was detected in the cells lining the reabsorptive duct of the sweat gland. Within these lumenal cells, staining was most prominent at the apical domain but was also detected near the basolateral surface. This finding agrees well with predictions based on the effects of cystic fibrosis on sweat gland function, and suggests that these antibodies will be useful for studying CFTR in other human tissues.

Effects of TNF alpha on the expression of class II MHC molecules in macrophages induced by IFN gamma: evidence for suppression at the level of transcription.

Tumor necrosis factor-alpha (TNF-alpha) induces surface expression of class II major histocompatibility (MHC) molecules (la molecules) in many cells, including macrophage-like cell lines. When we tested the effects of this cytokine on murine peritoneal macrophages, TNF alpha had little effect on surface expression of la. The strong expression of such molecules induced by interferon-gamma (IFN gamma) was, however, suppressed moderately by TNF alpha. These effects were reflected at the level of specific messenger RNA (mRNA) as detected by Northern blot analysis. Furthermore, the locus of control appears to be transcriptional; in nuclear run-on assays, TNF alpha suppressed the IFN gamma-induced enhancement of transcription for the murine beta-chain of I-A (I-A beta.). Taken together the data suggest that TNF alpha has little effect on class II MHC genes and surface expression in murine peritoneal macrophages, that TNF alpha is a modest suppressant of such molecules when their levels are raised by IFN gamma, and that these suppressive effects are mediated at the level of transcription.

Adenoid cystic carcinoma of the cervix in women under age 40.

Adenoid cystic carcinoma of the cervix, traditionally associated with a poor prognosis, occurs in postmenopausal patients in the vast majority of cases reported. Only four cases have been reported in women less than age 40, and none in women less than age 30. Three new cases of adenoid cystic carcinoma of the cervix are reported in women aged 24, 27, and 38 years. All three patients were treated with radical pelvic surgery; lymph node metastases and vascular involvement were prominent. Adjuvant chemotherapy with cisplatin was used in two patients, one of whom has had long-term survival. A review of the literature is also presented.

Flow cytometry shows recurrent aneuploid clone after remission in megakaryocytic leukemia.

Flow cytometry using a DNA label can quantitate aneuploid clones in malignant tissue. We illustrated the clinical value of this technique in a 71-year-old woman with acute megakaryocytic leukemia, which was diagnosed by staining of the blasts with factor VIII antigen and their morphologic resemblance to megakaryoblasts. Marrow cells were removed from needle biopsies by vortexing in RPMI medium, centrifuged in Ficoll-Hypaque, stained with a propidium-iodide/NP-40 mixture, and analyzed at 488 nm using an argon laser. During 3 weeks of low-dose cytosine arabinoside (ara-c) infusion therapy, hyperdiploid peak A dropped from 35% (day 0) to 2.3% (day 14) to 0% (day 21), with development of marrow hypoplasia. Similarly, hyperdiploid peak B, went from 7.6% to 9.1% to 3.5%. Subsequently, her marrow recovered normal morphology and lost the aneuploid peaks. Her blood counts recovered to near normal. Four months later, she relapsed and had a return of the day-21, incompletely eradicated peak B. There was no evidence of peak A. Repeated treatment with ara-c resulted in temporary suppression of the disease, but she died 3 months later with progressive hepatosplenomegaly. Analysis of cells from her enlarged liver, heavily infiltrated with blasts, showed a large hyperdiploid peak B. In this patient, ara-c therapy induced a remission with permanent eradication of one clone, but incomplete eradication of a second clone, which ultimately led to her relapse and death.

Intraabdominal granuloma reaction in rats after introduction of maize-starch powder.

A total of 32 Wistar rats were given 1, 10, 100 and 1000 mg glove powder (Biosorb) intraperitoneally for 4, 11, 18 or 25 days. Four control rats received physiological saline. Examination of the abdominal cavity displayed granulomatous inflammation which was clearly dose-dependent in the experimental animal, but not in the controls. A biphasic time-sequence of the granulomatous reaction was observed in those rats receiving 100 and 1000 mg Biosorb with a minimum at day 18. The mean size of the granules (8.1 microns) within the inflammatory tissue was almost identical with the size of powder granules found on the external surface of the gloves (8.8 microns). X-ray microanalysis demonstrated maize-starch additives of magnesium and aluminium. The study indicates a foreign body reaction to maize-starch. In addition, immunological factors may play a role later in the development of the disease.

Mortality in rats on long-term parenteral nutrition.

The long-term effect of total parenteral nutrition (TPN) was studied in rats. A failure to thrive developed and all animals died within 40 days of TPN. Autopsy invariably demonstrated the increased weight and volume of the liver and spleen. Multiple fat emboli were found in the lungs of all animals, and multiple epithelioid cell granulomas in the liver of all and in the spleen of most animals. Chronical low grade infection could not be demonstrated. Microorganisms were not found in blood or tissue specimens and endotoxin could not be demonstrated in plasma samples.