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Biomedical subjects

S A Spector

Publications and source records attributed to S A Spector.

At least 145 records · Page 8Linked to original sources
PubMed1990

Localization of human cytomegalovirus in peripheral blood leukocytes by in situ hybridization.

The in vivo interaction of human cytomegalovirus (HCMV) with leukocytes from a group of immunosuppressed patients was studied using specific subgenomic DNA probes and in situ cytohybridization. Study subjects had no recognized disease due to HCMV or had HCMV retinitis or colitis. Viral nucleic acid was detected in lymphocytes, monocytes, and polymorphonuclear leukocytes (PMNL). PMNL were consistently hybridization-positive for HCMV RNA and DNA in patients with HCMV viremia. Monocytes were occasionally positive by hybridization and lymphocytes were rarely positive. These findings demonstrate that the HCMV genome is expressed in PMNL of viremic patients and that PMNL may play an important role in virus dissemination.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Human immunodeficiency virus pseudotypes with expanded cellular and species tropism.

One mechanism for expanding the cellular tropism of a virus is through the formation of phenotypically mixed particles or pseudotypes, a process commonly occurring during viral assembly in cells infected with two or more viruses. We report here that dual infection of cells with human immunodeficiency virus (HIV) and a murine amphotropic retrovirus leads to the production of HIV pseudotypes that have acquired the host range of the amphotropic retrovirus and are capable of infecting not only CD4- human cells but also mouse cells. The replication of the HIV pseudotypes in the various CD4- cells was determined by measuring the appearance of HIV antigens in the supernatants, by cocultivation of CD4+ CEM cells with the infected CD4- cells, and in some cases by assaying the culture supernatants directly for infectious virus. Of the cells tested, human foreskin fibroblasts were the best host cells, and by in situ cytohybridization, we were able to document that all cells in the culture were infected. In addition, the temporal appearance of HIV-specific proteins in the HIV pseudotype-infected fibroblasts was similar to that seen in CD4+ CEM cells. If the human fibroblasts were first infected with the amphotropic retrovirus, they demonstrated the property of superinfection exclusion and were resistant to subsequent infection by the HIV pseudotype. In other cell lines, including the human glioblastoma-derived cell line U373MG, HeLa cells, BALB/c mouse embryo cells, and SC-1 wild mouse cells, although the HIV pseudotype infection appeared to be less efficient, substantial amounts of HIV were nevertheless produced. These results indicate that the HIV (amphotropic retrovirus) pseudotypes may be useful for studying the molecular biology of HIV infections in a wide range of cells.

Animals↗
PubMed1990

Diagnosis of cytomegalovirus infection.

The diagnosis of cytomegalovirus (CMV) infection in bone marrow transplant recipients is most accurately accomplished by the identification of CMV in the organ of concern; identification of CMV in bronchoalveolar lavage fluid can also be helpful in diagnosing CMV interstitial pneumonia. When tissue specimens are available, the identification of cytomegalic cells is often helpful in establishing CMV as the pathogen. Immunocytochemistry and in situ hybridization can increase the sensitivity and specificity of the CMV diagnosis; when nonisotopic detection systems are used, each can be performed the same day the specimen is obtained. Direct viral culture can also be used to establish a diagnosis. Although culture of CMV on human fibroblasts is still considered the diagnostic "gold standard," identification of the virus in culture may take several days to several weeks. The use of the shell-vial viral culture procedure, in conjunction with monoclonal antibodies directed at immediate early CMV antigens, has made it possible to detect CMV in culture within 24 hours. The use of nucleic acid hybridization procedures, including amplification of CMV sequences by the polymerase chain reaction, is highly sensitive; however, the application of these hybridization procedures to the diagnosis of CMV disease remains unclear.

Bone Marrow Transplantation↗
PubMed1990

Quality of life in a placebo-controlled trial of zidovudine in patients with AIDS and AIDS-related complex.

We measured quality of life using the Karnofsky Performance Status and Quality of Well-Being scale (QWB) for 31 patients with AIDS and AIDS-related complex in a placebo-controlled trial of zidovudine. Sixteen patients were randomized to zidovudine and 15 to placebo. We recorded nine scores for each patient during 1 year. During the blinded trial, 3 patients receiving placebo died; at 1 year, one had died in the zidovudine group and 10 in the placebo group. Repeated-measures analysis of variance demonstrated that mean scores declined less for the zidovudine group than for the placebo group during the blinded trial (p less than 0.03) and during 1 year (p less than 0.002). However, because the QWB incorporates death into its score, these results largely reflected differences in mortality. When data from those who died were excluded, Karnofsky scores were higher for the zidovudine group at the end of the blinded trial (p less than 0.02), but at 1 year no significant differences were observed between groups. The QWB and other quality-of-life measures may contribute to more comprehensive evaluation of AIDS treatments, and may detect treatment effects earlier. Whether existing measures can detect real differences among survivors will require testing in patients with less advanced disease.

AIDS-Related Complex↗
PubMed1989

Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus.

Uncertainty has existed as to whether a T-cell deficiency exists in human immunodeficiency virus (HIV) infection different from that inherent in the reduced T-cell numbers characteristic of the disease. Heretofore, methods for measuring T-cell responses in patients have been carried out with systems requiring monocytes as accessory cells. In the presence of high concentrations of interleukin-2, however, highly purified T cells respond in a monocyte-independent fashion to antibody reactive with the CD3 component of the antigen receptor complex Ti/CD3. Highly purified T cells of HIV-infected patients responded subnormally in this anti-CD3/IL-2 system, even in the case of patients who were asymptomatic or had only lymphadenopathy. The defective T-cell responses occurred over a wide range of concentrations of the anti-CD3. Neither poor IL-2 receptor function as reflected by responses to limiting dilutions of IL-2 nor IL-1 receptor function as defined by incremental proliferation when IL-1 is added accounted for this defect, which also correlated poorly with T4 and T8 numbers. These results suggested that the T-cell abnormality was closely related to Ti/CD3 function, was not specifically or restrictively associated with T4 cells, and was not due to defective IL-2- or IL-1-receptor functions. The amount of HIV RNA in 10(5) T lymphocytes from the patients amounted to less than that found in one cell of a standard HIV infected laboratory cell line (CEM), using slot-blot hybridization. Thus the T-cell deficiency we have observed was not likely to be due directly to cell killing by HIV resident in the T4 cells. Other factors may be important in inducing the immunodeficiency, some of which are discussed.

AIDS-Related Complex↗
PubMed1989

The antiviral effect of zidovudine and ribavirin in clinical trials and the use of p24 antigen levels as a virologic marker.

The inhibition of viremia and p24 core antigenemia in patients infected with human immunodeficiency virus (HIV) was evaluated in separate multicenter, double-blind, placebo-controlled trials of zidovudine and ribavirin. Of 29 patients (14 with AIDS and 15 with AIDS-related complex [ARC]) enrolled in the zidovudine study, 16 received 250 mg of zidovudine every 4 h and 13 received placebo. No difference in HIV isolation from peripheral blood was observed at 20 w in treated versus placebo groups (79% vs. 82%). In patients tolerating zidovudine, mean p24 antigen levels dropped to 8.2% +/- 8.1% of their baseline values, whereas in placebo recipients mean p24 antigen levels declined to 61.3% +/- 40.8% of their baseline values (P less than .005). In the ribavirin study, patients with ARC treated with either 800 mg or 600 mg ribavirin daily or with placebo showed no consistent reduction in p24 antigenemia or decrease in HIV isolation. These data indicate that decline in p24 antigenemia can be a useful virologic marker in evaluation of new antiretroviral drugs.

AIDS-Related Complex↗
PubMed1989

Human immunodeficiency virus inhibition is prolonged by 3'-azido-3'-deoxythymidine alternating with 2',3'-dideoxycytidine compared with 3'-azido-3'-deoxythymidine alone.

The inhibition of the lymphadenopathy-associated virus strain of human immunodeficiency virus (HIV) by alternating regimens of two dideoxynucleosides, 3'-azido-3'-deoxythymidine (AZT) (zidovudine) and 2',3'-dideoxycytidine (ddC), was determined in CEM cells. Cultures infected with virus for 2 h were treated with clinically achievable concentrations of AZT, ddC, or a 3-day-alternating regimen of AZT and ddC. Media were completely changed every 3 days and replaced with antiviral agent, and virus production was assayed by p24 antigen and virus-specific DNA. Cells treated with no antiviral agent exhibited breakthrough infection by day 6 in culture, whereas cells treated with 0.1, 1.0, or 3.0 microM AZT had a prolonged time to viral breakthrough. For each regimen of AZT alternating with 0.05 or 0.1 microM ddC, there was consistently prolonged HIV inhibition compared with continuous treatment with AZT alone. The viral suppression achieved with the alternating combinations required AZT as well as ddC and was superior to 3 days of treatment with ddC alternating with 3 days of no antiretroviral treatment. Levels of unintegrated HIV DNA paralleled the detection of p24 antigen, with the most prolonged inhibition of virus-specific DNA occurring with AZT alternating with ddC (compared with all regimens except continuous treatment with ddC). These data suggest that alternating regimens of AZT and ddC not only might decrease toxicity associated with the two drugs but may prove to be more efficacious than AZT alone.

Antiviral Agents↗
PubMed1989

Enzymatic amplification of human cytomegalovirus sequences by polymerase chain reaction.

Polymerase chain reaction (PCR) amplification was used to detect human cytomegalovirus (HCMV) sequences. The fragments selected for amplification were fragments of 130 and 152 base pairs (bp) located at two opposite ends of HCMV strain AD169 EcoRI fragment D. Amplification of the 152-bp DNA was consistently greater than that of the 130-bp DNA. At the optimal Mg2+ concentration of 5 mM, specific PCR amplification of 152-bp DNA with Taq polymerase was sensitive; only one AD169-infected fibroblast cell or 0.01 pg of AD169 fragment D DNA was needed for detection. This specific amplification was also found with various clinical HCMV isolates and peripheral blood cells and urine from patients. In 37 urine samples analyzed simultaneously by PCR and by virus cultivation, identical results were found in 35 samples, while 2 scored positive only by PCR. This suggests that specific amplification of 152-bp DNA is sensitive and can be used for rapid detection of HCMV infections.

Base Sequence↗
PubMed1989

Use of molecular probes to detect human cytomegalovirus and human immunodeficiency virus.

Human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV) cause severe disease. The identification of these viruses in clinical specimens and understanding the progression of infection and diseases relating to HCMV and HIV are essential to develop effective means for treatment and prevention. Here we describe the application of molecular probes to the diagnosis and pathogenesis of HCMV and HIV. In situ hybridization and the amplification procedure of polymerase chain reaction are used to detect both viruses; these techniques have provided important information regarding the pathogenesis of HCMV and HIV. A new technique, target cycling, may also prove useful for the detection of viruses by enriching for target sequences. The continued application of molecular probes to pathogenetic studies of HCMV and HIV promises to further our knowledge of these viruses, and of their interaction.

Cytomegalovirus↗
PubMed1988

Generation of human cytomegalovirus-specific cytotoxic T-lymphocytes in a short-term culture.

A method to generate human cytomegalovirus (HCMV)-specific CTL (cytotoxic T lymphocytes) from human peripheral blood mononuclear cells is described. This assay is unique in comparison with other methods reported to date, because it only requires a short-term (6 days) coculture of PBM and autologous infected fibroblasts without the addition of exogenous IL-2 (interleukin-2) and nevertheless is sensitive enough to determine HCMV-specific killing in a short (6 h) 51Cr-release assay using autologous HCMV-infected fibroblasts as targets. The virus-specific killing is mediated by CTL of the CD8 phenotype and it can be inhibited by a HLA class I monoclonal antibody. The sensitivity of the assay can be significantly enhanced by pretreating the targets with interferon-gamma (IFN-gamma) prior to infection with HCMV. HCMV-specific 51Cr-release is more than doubled when the IFN-gamma pretreated targets are used. This increase is mostly due to enhanced sensitivity of the fibroblasts to killing mediated by CD8-positive CTL, but some killing can be attributed to CTL of the CD4 phenotype.

Antibodies, Monoclonal↗
PubMed1988

Prevalence of psychiatric disorders among men infected with human immunodeficiency virus. A controlled study.

We used structured diagnostic interviews and rating scales to assess lifetime prevalence of psychiatric disorders, by DSM-III criteria, among an unselected sample of 56 ambulatory homosexual men in four groups: men with acquired immunodeficiency syndrome (AIDS), men with AIDS-related complex (ARC), men asymptomatic or mildly symptomatic but seropositive for antibody to human immunodeficiency virus (HIV), and HIV-seronegative men. An age- and demographically matched comparison group of 22 healthy, heterosexual controls was also studied. The homosexual men had lifetime rates of alcohol or nonopiate drug abuse (22/56 [39.3%]), generalized anxiety disorder (22/56 [39.3%]), and major depression (17/56 [30.3%]) that often preceded diagnosed medical illness or knowledge of HIV status. The six-month point prevalence of these disorders in homosexual men was also high, especially alcohol abuse in patients with AIDS-related complex, and the occurrence of a DSM-III disorder within the previous six months significantly exceeded that in heterosexual controls. The data suggest that there may be a higher prevalence of anxiety disorder and major depressive illness in homosexual men when compared with sociodemographically matched heterosexual men and that the psychiatric morbidity may have preceded the onset of the AIDS epidemic. These findings indicate that awareness of psychiatric history is necessary to comprehensive medical care of men at high risk for AIDS, even among relatively healthy outpatients.

AIDS-Related Complex↗
PubMed1988

Treatment of bacterial meningitis with once daily ceftriaxone therapy.

Ceftriaxone, a cephalosporin with an extended half-life and excellent antibacterial activity was used to treat bacterial meningitis, given as a single daily intravenous dose of 100 mg/kg on day one, followed by 80 mg/kg daily. A total of 22 patients were treated, of whom 14 had Haemophilus influenzae type b, five had Streptococcus pneumoniae and three Neisseria meningitidis isolated from their CSF. The CSF of all patients became sterile within 24-48 h. The CSF ceftriaxone concentrations 24 h after dosing were 10 to 100-fold higher than the MIC of the pathogenic bacteria early in therapy, and five to 50-fold higher at the end of therapy. Side effects encountered included mild diarrhoea (32%), thrombocytosis (77%) and neutropenia (9%), but none caused therapy to be stopped. Ceftriaxone is a safe and effective antibiotic for the treatment of bacterial meningitis when administered once daily.

Adolescent↗
PubMed1988

Human immunodeficiency virus-associated neurobehavioural disorder.

AIDS, ARC, and other HIV-associated diseases were originally conceptualised exclusively in terms of defects in cell-mediated immunity and its consequences. But it is now becoming clear that HIV disease can also be a primary neuropsychiatric disorder, although the precise mechanism by which the retrovirus causes impairment in brain function and, ultimately, structural brain damage, remains obscure. The work presented here indicates another shift in our thinking concerning HIV infection. Until recently it was believed that neurological and neuropsychiatric phenomena tended to occur in the late stages of HIV disease. While that might be true for the more severe form of symptomatology that has been termed the AIDS dementia complex, we believe there is at least preliminary evidence that cognitive change can occur earlier in the course of illness, perhaps even in some medically asymptomatic HIV+ individuals. Other investigators have also noted increased neuropsychological abnormality in patients before they developed AIDS or ARC. For example, Janssen et al. found that about half their patients with lymphadenopathy syndrome (LAS) had some neuropsychological test deficits. Durara et al. recently reported on cerebral metabolic rates for glucose in seven HIV+ asymptomatic individuals, compared to 10 HIV- controls. Four of the HIV+ individuals had abnormal asymmetry in frontal and temporal regions suggesting focal reduction in cerebral glucose metabolism. Further indirect evidence that virus can enter the central nervous system early in the course of HIV disease comes from the work of McArthur and associates.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cytomegalovirus infection and bronchopulmonary dysplasia in premature infants.

During a five-year period, 32 preterm infants weighing less than 2000 g were diagnosed as having postnatally acquired cytomegalovirus (CMV) infection in a neonatal intensive care unit. These CMV-infected infants were matched with 32 uninfected controls for gestational age, birth weight, and birth date; the two groups did not differ in Apgar scores or the incidence of respiratory distress syndrome and patent ductus arteriosus. Roentgenographic evidence of bronchopulmonary dysplasia (BPD) developed in 24 (75%) of 32 CMV-infected infants, an incidence significantly greater than that observed in control infants (12/32; 38%). Infants with acquired CMV infection required more respiratory support and longer hospitalization than uninfected controls. This association between acquired CMV infection in premature infants and the development of chronic lung disease provides further evidence that vigorous efforts to prevent CMV infection in hospitalized neonates is warranted.

Bronchopulmonary Dysplasia↗
PubMed1987

Ganciclovir for the treatment and suppression of serious infections caused by cytomegalovirus.

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Nosocomial cytomegalovirus infections within two hospitals caring for infants and children.

Using serology, virology, and molecular epidemiology, we investigated nosocomial transmission of cytomegalovirus (CMV) over a two-year period in two contrasting environments: a crowded, busy pediatric chronic care unit (337 patients, 43 nurses, and 76 therapists; average prevalence of CMV excretion in patients, 16%) and a small neonatal unit (293 patients and 69 nurses; average prevalence, 0.7%). In the chronic care unit no nurse or therapist acquired CMV, but two pairs of infants were infected with homologous strains of CMV, and patient-to-patient transmission was proven in one pair. In the neonatal unit no patients acquired CMV in the hospital, but two nurses seroconverted, with a nonoccupational source proven for one. Transmission from CMV-infected caretaker to patient did not occur in either environment. CMV was isolated from diapers as well as hands of patients and personnel but not from other environmental surfaces.

Adult↗
PubMed1987

Detecting human immunodeficiency virus RNA in peripheral blood mononuclear cells by nucleic acid hybridization.

We have developed a nucleic acid hybridization assay for detecting human immunodeficiency virus (HIV) RNA in peripheral blood mononuclear cells. This assay can detect HIV RNA in 10(2) cultured lymphoblastoid cells infected with HIV; it only weakly crossreacts with the RNA of HTLV-I or HTLV-II. For 39 (80%) of 49 seropositive subjects, we detected HIV sequences in the RNA from 10(6) peripheral blood mononuclear cells. In contrast, we could not detect HIV DNA in samples of DNA from the same number of cells from any of 39 seropositive individuals tested. Three of 33 seronegative individuals had false-positive results. Nevertheless, because we found an excellent correlation between results from our assay and culture of HIV from peripheral blood mononuclear cells of seropositive subjects, it is unlikely that positive cultures of HIV from these cells reflect latent infection. Nucleic acid hybridization offers a more rapid, simple, and inexpensive alternative to culture for detecting HIV-infected peripheral blood mononuclear cells.

Antibodies, Viral↗