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M C Jordan

Publications and source records attributed to M C Jordan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cytomegalovirus replication in murine microglial cell cultures: suppression of permissive infection by interferon-gamma.

The pathogenesis of encephalitis due to cytomegalovirus (CMV), particularly the role of microglial cells in the spread or control of infection, remains incompletely defined. In this study, microglial cells were isolated from the brains of newborn mice and infected in vitro with murine CMV (MCMV). Microglial cells supported productive MCMV replication, and the MCMV-infected microglia manifested a cytopathic effect (CPE) characteristic of CMV infection. Exposure of microglia to interferon-gamma (IFN-gamma) 24 h before infection markedly suppressed virus production and resultant CPE in a dose-dependent fashion. Furthermore, the addition of IFN-gamma 2 h after infection demonstrated an antiviral effect equivalent to that achieved when IFN-gamma was administered 2 h before infection. These results demonstrate that murine microglial cells are fully permissive to MCMV replication and that IFN-gamma markedly suppresses virus expression in these cells.

Animals↗
PubMed1994

Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice.

Circulating leukocytes are important in dissemination of cytomegalovirus (CMV) infection in humans. In the mouse model of murine CMV infection (MCMV), it has been shown that infection peaks on days 5 to 7 after experimental infection, when 0.01 to 0.1% of the circulating leukocytes contain viral DNA. In our laboratory, MCMV DNA was detected by in situ hybridization predominantly in the mononuclear cells on day 6 after acute infection. Infectious virus was recovered from day 6 mononuclear fractions in 16 of 16 mice compared with that from day 6 polymorphonuclear fractions in 4 of 16 mice. An eclipse phenomenon was noted in the blood leukocytes by quantitative blot hybridization: the amount of MCMV DNA present was small on day 2, diminished on days 3 and 4, and then increased markedly on days 5 and 6 in both the mononuclear and polymorphonuclear fractions immediately following viral augmentation in the liver and spleen. MCMV immediate-early and glycoprotein B (late) transcripts were present in pooled mononuclear fractions only on day 6 of acute infection but not in pooled polymorphonuclear fractions. Collectively, these data demonstrate that (i) circulating leukocytes, predominantly mononuclear, are involved in dissemination of MCMV; (ii) a primary viremia with dissemination of MCMV to reticuloendothelial organs (liver and spleen) occurs and is followed by viral amplification and a subsequent, more intense secondary viremia; and (iii) immediate-early viral mRNA and glycoprotein B mRNA transcripts are detectable only during peak infection on day 6 in mononuclear leukocytes but not in polymorphonuclear leukocytes.

Animals↗
PubMed1993

Detection of latent cytomegalovirus DNA in diverse organs of mice.

Latency is essential to the pathogenesis of cytomegalovirus (CMV) infection and disease. A survey of mouse organs that might contain latent murine CMV (MCMV) DNA was conducted using nested enzymatic amplification of a 200-bp region of exon 4 of the major immediate early gene 1. MCMV DNA was detected in diverse organs including the heart, kidney, liver, lung, spleen, brain, and salivary glands. The total number of organs in which latent MCMV DNA was detected was significantly greater in mice infected at 4 weeks of age (64/70) than in mice infected at 7 weeks of age (40/69). This phenomenon was associated with greater viral replication in the same organs during acute infection. These results indicate that latent MCMV infection is distributed much more widely than previously suspected and is directly correlated with the extent of viral replication during acute infection.

Age Factors↗
PubMed1992

Parainfluenza virus respiratory infection after bone marrow transplantation.

BACKGROUND: Pneumonia complicates about half of all bone marrow transplantations, and in about a third of the cases no specific cause is identified. Although parainfluenza virus is a common cause of respiratory infection in normal children, its role in transplant recipients is unknown. METHODS: We describe the incidence and clinical course of parainfluenza infection among the 1253 recipients of bone marrow transplants at our center from 1974 through 1990. We performed viral cultures on all such recipients who had manifestations of a viral infection or fever without apparent cause. RESULTS: Among the 1253 patients, we found 27 (2.2 percent) who had parainfluenza virus infection as demonstrated by culture (12 of 580 adults and 15 of 673 children). Eight of these patients had only upper respiratory tract involvement, all of whom had positive nasopharyngeal cultures. Of the remaining 19, 8 had symptoms of both upper and lower respiratory tract involvement, and 11 had only lower respiratory involvement, of whom only 6 had positive nasopharyngeal cultures. Four required bronchoalveolar lavage for diagnosis. A median of nine days elapsed from the onset of symptoms until the culture became positive, and overall only 33 of 118 cultures obtained were positive. Respiratory failure developed in 6 of the 19 patients with lower respiratory tract involvement, and all died. CONCLUSIONS: Parainfluenza virus is a cause of serious lower respiratory tract involvement in both adults and children who undergo bone marrow transplantation. Given the insensitivity of current culturing techniques, it may be underdiagnosed.

Adolescent↗
PubMed1992

Cytomegalovirus-induced reactivation of Toxoplasma gondii pneumonia in mice: lung lymphocyte phenotypes and suppressor function.

Active cytomegalovirus (CMV) infection is associated with immunosuppression and predisposes to the development of life-threatening superinfections in immunocompromised patients. In a mouse model of virus-induced immunosuppression, acute murine CMV (MCMV) infection induced reactivation of dormant Toxoplasma gondii infection, producing Toxoplasma pneumonia. Changes in lung lymphocyte numbers and phenotypes appeared to be integral to the pathogenesis of MCMV-induced reactivation of T. gondii pneumonia. Numbers of lung CD4+ cells decreased during acute MCMV infection in mice with dormant T. gondii infection as well as in previously uninfected mice. Dually infected mice subsequently developed reactivation of Toxoplasma pneumonia. The pneumonia was characterized by a large influx of T lymphocytes, predominantly CD8+ cells, into the lungs. These lung lymphocytes markedly suppressed the ability of immune splenocytes to proliferate in response to T. gondii antigens and concanavalin A in vitro. These results suggested that the initial fall in the numbers of lung CD4+ cells observed after MCMV infection may have induced reactivation of T. gondii infection in the lungs. The subsequent pneumonia appeared to be a manifestation of a massive influx of T lymphocytes, especially CD8+ cells, into the lungs.

Animals↗
PubMed1992

High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients.

Although viremia is a hallmark of disseminated cytomegalovirus (CMV) infection, not all viremic patients have visceral organ CMV disease. We used blot hybridization with a cloned subgenomic probe to quantitate viral DNA in blood leukocytes of 60 viremic patients (25 with solid organ transplants, 20 with AIDS, and 15 marrow recipients) who had different clinical manifestations of CMV infection. The results are expressed as pg of viral DNA/10 micrograms of leukocyte DNA. Patients with AIDS or with solid organ transplants who had CMV visceral organ disease had the largest amounts of viral DNA in their granulocytes (median 632 and 237 pg, respectively). These amounts were significantly greater than those in similar viremic patients without CMV visceral disease (17 and 21 pg; P < 0.005 and 0.002, respectively). All patients in the study with > 150 pg of CMV DNA in their granulocytes had visceral CMV disease. The amounts of viral DNA in granulocytes of AIDS and organ transplant patients with CMV retinitis were low (median 22 pg). Marrow transplant patients were unique in that the amounts of CMV DNA in granulocytes were low whether CMV visceral organ disease was present (17 pg) or absent (14 pg). We conclude that high levels of circulating CMV DNA in viremic AIDS and solid organ transplant patients reflect viral involvement of visceral organs but not the retina. In marrow recipients, the severity of CMV disease, even when fatal, is not reflected quantitatively in peripheral blood leukocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir.

Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Latent murine cytomegalovirus DNA in splenic stromal cells of mice.

Latency is an integral feature of the pathogenesis of cytomegalovirus infection and disease. Using in situ hybridization, we detected viral DNA in the splenic stroma of mice with acute murine cytomegalovirus (MCMV) infection but could not detect latent infection. By using enzymatic amplification of a 700-bp region of exon 4 of immediate-early gene 1 of MCMV, viral DNA was consistently detected in whole spleens of latently infected mice. MCMV DNA was detected in 16 of 23 stromal cell fractions from latently infected animals, in only 2 of 13 residual nonstromal cell fractions, and in none of 9 additional lymphocyte or macrophage-enriched nonstromal cell preparations. We conclude that MCMV DNA is maintained predominantly, and possibly exclusively, in stromal cells in the spleens of latently infected mice.

Animals↗
PubMed1990

Quantitation of cytomegalovirus DNA by blot hybridization in blood leukocytes of viremic patients.

We describe a technique for quantitation of viral DNA in blood leukocytes during viremic infection with human cytomegalovirus (CMV). Using a cloned subgenomic DNA probe and a blot hybridization assay, small amounts of viral DNA within samples of leukocyte DNA could be quantitated reproducibly using a videodensitometer. Critical components of the assay were: (1) a direct relationship between optical density and known amounts of viral DNA diluted in cellular DNA as positive standard samples and, (2) determination of the proper duration of autoradiographic exposure. The technique was sufficiently sensitive to detect 10 picograms of CMV DNA in the presence of microgram quantities of host cell DNA. In addition, samples containing minute amounts of CMV DNA could reliably be distinguished from samples that were negative. We have used the technique to characterize the pathogenesis of CMV viremia and to monitor the effects of antiviral chemotherapy. This procedure could easily be applied to pathogenetic studies of a variety of other infectious agents.

Cytomegalovirus↗
PubMed1990

Cardioprotection by Cu,Zn-superoxide dismutase is lost at high doses in the reoxygenated heart.

Limited dose-response curves for superoxide dismutase (SOD) were assessed in isolated and in vivo hearts. SOD at 2.3, 7, 20, or 50 mg/L suppressed CK release in Langendorff rat hearts by 61%, 63%, 72%, and 30%, respectively. SOD at 0.5, 1, 5, and 50 mg/L suppressed LDH release in Langendorff rabbit hearts by 32%, 48%, 54%, and -12%, respectively. In rabbit hearts subjected to coronary artery ligation and reperfusion in vivo, SOD at 2, 5, or 15 mg/kg reduced infarct size by 10%, 30% or 19%, respectively, while 50 mg/kg increased infarct size by 28%. In conclusion, while SOD was protective at low doses in all models, protection was lost at higher doses in the isolated rat and rabbit hearts, and exacerbation of damage was seen in the in vivo rabbit hearts.

Animals↗
PubMed1990

Left ventricular unloading during reperfusion does not limit myocardial infarct size.

To determine whether venting the left ventricle during coronary reperfusion limits myocardial infarct size, we studied paced (200 beats/min) Langendorff rabbit hearts, perfused with blood from a support rabbit. A left coronary artery was occluded for 60 minutes, followed by 2 hours of reperfusion. Four experimental conditions, as follows, were used: In group 1 (control), the hearts contracted isovolumetrically on a fluid-filled balloon in the left ventricle during both occlusion and reperfusion. In group 2, the balloon was present only during occlusion, and the heart was vented during reperfusion. Hearts in group 3 were vented during occlusion and developed pressure during reperfusion. In group 4, the left ventricle was vented during occlusion and reperfusion. Perfusion pressure (91.2 +/- 0.9 mm Hg) and coronary flow (0.88 +/- 0.03 ml/min/g) were not different between groups. Left ventricular pressures (mean of all groups) were 87.3 +/- 1.5 mm Hg systolic and 6.5 +/- 0.6 mm Hg diastolic. Infarcted myocardium was assessed by triphenyl tetrazolium staining and expressed as a percentage of the area at risk, as measured by fluorescent particles. Venting during both ischemia and reperfusion (n = 10) did result in significantly smaller infarcts than in the unvented controls (n = 10), that is, 13 +/- 5% vs. 41 +/- 6%, respectively. Venting only during reperfusion (n = 10) or occlusion (n = 11) did not significantly limit infarct size (57 +/- 6% and 32 +/- 5%, respectively), as compared with controls. Thus, the clinically feasible intervention of left ventricular venting during reperfusion was not cardioprotective.

Animals↗
PubMed1990

Demographic and dietary determinants of constipation in the US population.

We investigated the association between self-reported constipation and several demographic and dietary variables in 15,014 men and women 12-74 years of age examined between 1971-75 during the first Health and Nutrition Examination Survey. Overall, 12.8 percent reported constipation. Self-reported constipation correlated poorly with stool frequency. Nine percent of those with daily stools and 30.6 percent of those with four to six stools/week, reported constipation. Constipation was more frequent in Blacks (17.3 percent), women (18.2 percent), and those over age 60 (23.3 percent); after adjusting for age, sex, and race it was more prevalent in those with daily inactivity, little leisure exercise, low income, and poor education. Constipated subjects reported lower consumption of cheese, dry beans and peas, milk, meat and poultry, beverages (sweetened, carbonated and noncarbonated), and fruits and vegetables. They reported higher consumption of coffee or tea. They consumed fewer total calories even after controlling for body mass and exercise.

Activities of Daily Living↗
PubMed1990

Viral pneumonia in recipients of solid organ transplants.

Viral pulmonary infections are a major cause of morbidity and mortality in solid organ transplant recipients. The herpes viruses-cytomegalovirus, herpes simplex virus, varicella zoster virus, and Epstein-Barr virus--cause most of the viral infections in this population. Respiratory syncytial virus, adenovirus, and human immunodeficiency virus also cause pneumonitis in the transplant recipient. Differences in the clinical and laboratory presentation of pneumonitis due to the various viral agents can provide clues to the etiology. However, definitive diagnosis requires laboratory identification of the virus or appropriate serologic changes. With cytomegalovirus, herpes simplex virus, Epstein-Barr virus, and adenovirus, one must take care to distinguish between asymptomatic shedding of the virus and disease produced by the virus. Advances in diagnostic techniques such as rapid antigen detection, nucleic acid hybridization, and gene amplification may allow an earlier diagnosis of viral pneumonia. Advances in risk reduction with appropriate pairing of donors and recipients, improved immunosuppressive regimens, vaccination, and prophylactic administration of antiviral agents may reduce the incidence of viral infection. Finally, advances in anti-viral therapy have made possible the successful treatment of pneumonia due to some of the viral agents.

Adenoviridae Infections↗
PubMed1989

Reactivation of Toxoplasma gondii by cytomegalovirus disease in mice: antimicrobial activities of macrophages.

Reactivation of Toxoplasma gondii infection often occurs concurrently with active cytomegalovirus (CMV) disease in immunocompromised patients, and CMV disease results in immunosuppression. To determine if murine CMV (MCMV) infection decreases resistance to T. gondii, mice with latent T. gondii infection were infected with MCMV. T. gondii infection reactivated, manifested primarily as pneumonia. Lung macrophages supported the growth of T. gondii before, during, and after T. gondii reactivation. Peritoneal macrophages inhibited the growth of T. gondii as pneumonia developed and became permissive as pneumonia resolved. Mice with latent T. gondii infection could survive larger doses of MCMV than could controls. Thus, MCMV infection led to reactivation of latent T. gondii infection in mice. Activation of lung macrophages, assessed by their ability to inhibit replication of T. gondii in vitro, was not associated with control of T. gondii infection.

Animals↗
PubMed1988

Respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus disease was documented in 11 immunocompromised adults, aged 21 to 50. Underlying conditions included bone marrow transplant (6 patients), renal transplant (3 patients), renal and pancreas transplants (1 patient), and T-cell lymphoma (1 patient). Diagnosis of infection was based on specimens from bronchoalveolar lavage, sputum, throat, sinus aspirate, and lung biopsy. The virus was detected simultaneously by antibody in either an immunofluorescence or enzyme-linked immunosorbent assay in 3 of 4 patients whose culture results were positive for respiratory syncytial virus. The virus was an unexpected finding, despite widespread infection in the community. Clinical symptoms included low-grade fever, nonproductive cough, rhinorrhea or nasal congestion, and radiographic evidence of interstitial infiltrates and sinusitis. Aerosolized ribavirin therapy was used in the 6 recipients of bone marrow transplants, 3 of whom required assisted ventilation but died. Death caused by virus infection was documented in 4 of 11 patients. Respiratory syncytial virus disease must be considered in the differential diagnosis of fever and pulmonary infiltrates in immunocompromised adults.

Adult↗