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Biomedical subjects

L Resnick

Publications and source records attributed to L Resnick.

At least 55 records · Page 3Linked to original sources
PubMed1990

Oral hairy leukoplakia.

Oral hairy leukoplakia occurs almost exclusively in human immunodeficiency virus (HIV)-infected patients and is predictive for the development of acquired immunodeficiency syndrome (AIDS). It presents as a white plaque with a rough surface, most commonly on the sides of the tongue. The eruption is frequently overlooked, and, because it is commonly mistaken for oral candidiasis, its true incidence is unknown. The leukoplakia is the result of permissive infection of epithelial cells by the Epstein-Barr virus. Antiviral therapy that inhibits Epstein-Barr virus replication can result in clinical improvement. Oral hairy leukoplakia provides a unique clinical model for investigations on the pathogenesis of Epstein-Barr virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Epstein-Barr virus small nuclear RNAs are not expressed in permissively infected cells in AIDS-associated leukoplakia.

Epstein-Barr virus (EBV) DNA structure and gene expression were analyzed in tissue specimens from oral hairy leukoplakia (HLP), a mucocutaneous lesion that develops in patients infected with human immunodeficiency virus (HIV). The structure of the terminal restriction enzyme fragments of EBV revealed that HLP is a permissive infection without a predominant, detectable population of EBV episomal DNA. In RNA preparations from this uniquely permissive infection, EBV replicative mRNAs could be identified by Northern analysis; however, the virally encoded small nuclear RNAs, the EBERs, were not detected in most HLP RNA preparations. In situ hybridization detected EBER expression in very rare cells. These data indicate that unlike other viral small nuclear RNAs, the EBERs are not expressed during viral replication and must participate in the complex maintenance of latent EBV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine.

The antiviral activity, uptake, and metabolism of 2',3'-dideoxyguanosine was investigated in human immunodeficiency virus- (HIV) infected and noninfected human cells. 2',3'-Dideoxyguanosine had anti-HIV activity (effective dose 50%: 0.1-1.0 microM) in H-9 and MT-2 cells. The addition of excess (greater than or equal to 30 microM) guanosine, deoxyguanosine, or 8-aminoguanosine had no effect on the anti-HIV activity of 2',3'-dideoxyguanosine. In [8-3H]2',3'-dideoxyguanosine-exposed cells, the intracellular radioactivity was twofold higher than the extracellular. When guanosine, deoxyguanosine, or 8-aminoguanosine was preincubated or added simultaneously to 2',3'-dideoxyguanosine, uptake of 2',3'-dideoxyguanosine was reduced by 28 to 34%, whereas addition of p-nitrobenzylmercaptopurine riboside (20 microM) had no effect. In metabolism studies using H-9 cells, dideoxyguanosine triphosphate could not be detected despite a 24-h incubation of 2',3'-dideoxyguanosine at effective anti-HIV concentrations. The addition of excess (greater than or equal to 30 microM) guanosine, deoxyguanosine, and 8-aminoguanosine, while inhibiting the catabolism of 2',3'-dideoxyguanosine, did not enhance the anabolic conversion of 2',3'-dideoxyguanosine to dideoxyguanosine triphosphate. Our failure to detect the formation of dideoxyguanosine triphosphate and the lack of reversal of antiviral effects by natural purine nucleosides raises questions on the role of this metabolite in the anti-HIV activity of 2',3'-dideoxyguanosine.

Antiviral Agents↗
PubMed1990

Anti-human immunodeficiency virus effects of dextran sulfate are strain dependent and synergistic or antagonistic when dextran sulfate is given in combination with dideoxynucleosides.

The effects of three molecular weight ranges of dextran sulfate on five different human immunodeficiency virus (HIV) isolates (from patients with acquired immunodeficiency syndrome), alone and in combination with dideoxynucleosides, were investigated in vitro. The higher the molecular weight range of dextran sulfate, the more potent the activity as assessed by a quantitative syncytium formation assay. Although all five HIV isolates had similar susceptibilities to the inhibitory effects of dideoxynucleosides, the two clinical isolates of HIV (HIV type 1 [HIV-1] TM and SP) exhibited a pattern of reduced susceptibility to dextran sulfate when compared with the two cloned isolates (HIV-1 WMF and HIV-2 ROD) and a prototype laboratory strain (HIV-1 IIIB). In combination with dideoxynucleosides, the high-molecular-weight range of dextran sulfate (500,000) resulted in an antagonistic response directed against the two clinical isolates of HIV (HIV-1 TM and SP) when the antiviral concentrations of dextran sulfate were in the ineffective range. Additive or synergistic effects were seen with the other three HIV isolates and all five HIV isolates when the low-molecular-weight range of dextran sulfate (8,000) was used. The results of these studies raise issues on the impact of drug-resistant strains on disease progression and the use of dextran sulfate in combination with nucleoside analogs for the clinical management of HIV disease.

Cells, Cultured↗
PubMed1990

Defective viral DNA in Epstein-Barr virus-associated oral hairy leukoplakia.

Defective Epstein-Barr virus (EBV) has a deleted and rearranged genome (termed het DNA) that disrupts latency and induces standard EBV to replicate in vitro. We used the polymerase chain reaction to detect, in 2 of 10 patient samples, the junction of abnormally juxtaposed EBV DNA fragments BamHI W and Z, a genomic rearrangement responsible for the biologic activity of het DNA. By sequence analysis, the junction in wild-type defective DNA appears to be similar but not identical to the recombination in the DNA of laboratory strain P3HR-1. The presence of this marker for het DNA in the epithelial lesions of two patients suggests a role for defective EBV in a human pathologic process.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The detection of HIV by in situ hybridization.

A simplified method of in situ hybridization is described for the detection of HIV targets. This standardized method can be applied to sections of formalin-fixed paraffin-embedded tissues, cell blocks, and smears of cultured cells using 3H- or 35S-labeled DNA and 35S-labeled RNA probes. In order to use elevated stringencies in the hybridization and wash steps, tissue sections and cells are covalently bonded to silanated glass slides without their subsequent loss from the slides. Routine hematoxylin and eosin or Romanovsky's stains enable the identification of the cells detected by in situ hybridization. HIV-infected neuroblastoma and lymphoid cell lines, lymph nodes, bone marrow, kidney, as well as brain tissue from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex are used to demonstrate the generality of the procedure. The standardized method described widens the ease and applicability of in situ hybridization in the investigation of pathologic tissues with the use of diverse specimens and probes.

DNA Probes↗
PubMed1990

Human immunodeficiency virus cultured from bone. Implications for transplantation.

This study demonstrates by a virologic culture method that human immunodeficiency virus (HIV) resides in bone. After freezing, some initially positive specimens no longer yielded virus, but those that continued to yield virus were not further altered by subsequent washing, which removed essentially all marrow, or by freeze-drying. The safeguards against potential transmission of HIV by a bone allograft are principally the screening and testing methods previously described, although there may be a further reduction of the remote residual risk by the freezing step in the usual technical sequence for tissue banking by sterile techniques.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Detection of a second widespread strain of Epstein-Barr virus.

The prevalence of Epstein-Barr virus (EBV) type B, which was previously found mainly in equatorial Africa, was investigated with the polymerase chain reaction in a population of healthy adults in Memphis, Tennessee. EBV was detected in the throat washings of 34 (22%) of 157 randomly selected donors, 14 (41%) of whom had type B virus and 17 (50%) type A; 3 donors (9%) had both strains. 18 additional adults with human immunodeficiency virus (HIV-1) infection and 6 severely immunocompromised children were also investigated. Results indicated that type B EBV is widespread in nature and may be reactivated by immunodeficiency.

Adult↗
PubMed1989

Comparison of the efficacy of surgery and acyclovir therapy in oral hairy leukoplakia.

To compare the therapeutic effects of surgical excision and orally administered acyclovir therapy on symptomatic oral hairy leukoplakia, 45 homosexual men who were seropositive for human immunodeficiency virus participated in a 3-month open-label study. In the 14 patients who had surgical excision, pain resolved in four symptomatic patients and the leukoplakia did not recur in the areas of excision. New foci of leukoplakia, however, appeared in 10 patients after 3 months. Of the 16 patients who received acyclovir therapy, 12 had a clinical regression, although recurrences were noted in all patients after 3 months. Three patients had resolution of pain while taking acyclovir; in two the pain recurred after acyclovir was discontinued. No spontaneous remissions of the leukoplakia occurred in the 15 patients who refused therapy. We conclude that surgical excision is effective in patients with symptomatic oral hairy leukoplakia.

Acyclovir↗
PubMed1989

Uptake of 2',3'-dideoxyadenosine in human immunodeficiency virus-infected and noninfected human cells.

The uptake of 2',3'-dideoxyadenosine was examined in a human immunodeficiency virus (HIV) infected and uninfected T cell line (H9 cells), a B cell line (Namalwa), and in normal peripheral blood mononuclear cells. After a 10-minute incubation at ambient temperature, the intracellular 2',3'-dideoxyadenosine-derived radioactivity was 8- to 16-fold higher than the extracellular radioactivity. In metabolically inactive cells (0 degrees C), the intracellular and extracellular 2',3'-dideoxyadenosine-derived radioactivities were nearly equal. In infected and noninfected H9 cells, a large excess of p-nitrobenzylmercaptopurine riboside or pyrimidine nucleosides weakly inhibited the uptake of 2',3'-dideoxyadenosine (7-30%), whereas deoxycoformycin was a stronger inhibitor (50-80%). Purine nucleosides minimally enhanced the uptake (10-20%). The cellular uptake was not associated with the accumulation of dideoxyadenosine triphosphate. In normal peripheral blood mononuclear cells, the uptake of 2',3'-dideoxyadenosine was inhibited by all agents except 2'-deoxyadenosine (15% enhancement). In contrast to H9 cells, the formation and accumulation of dideoxyadenosine triphosphate paralleled the uptake of dideoxyadenosine. The results of these studies suggest that the major route of transport of 2',3'-dideoxyadenosine into cells is by simple diffusion and that different metabolic patterns exist among cell lines and normal peripheral blood mononuclear cells. An understanding of these cellular differences could aid in the development of therapeutic strategies directed against HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Giant cell fibroblastoma. A report of a case and review of the literature.

A 15-year-old white boy with a giant cell fibroblastoma of the skin of the abdomen is described. Giant cell fibroblastoma is a rare soft tissue neoplasm that most commonly occurs in children as a small, painless mass in the dermis and subcutaneous tissue. Although local recurrences have been reported, no metastases have occurred. Giant cell fibroblastoma must be differentiated from other spindle cell neoplasms.

Abdomen↗
PubMed1989

Multiple sclerosis-like illness occurring with human immunodeficiency virus infection.

We describe seven men with a neurologic disease clinically indistinguishable from multiple sclerosis occurring in association with seropositivity for the human immunodeficiency virus, type 1 (HIV-1). Histopathology of the CNS obtained in three patients (2 by brain biopsy, 1 at autopsy) was consistent with MS. The neurologic symptoms preceded the onset of clinically evident immunosuppression in all patients. In three men, HIV-1 seropositivity was demonstrated concomitantly or within 3 months of the onset of their neurologic disease. In the others, features of MS preceded the demonstration of HIV-1 seropositivity by 41 months, 59 months, 11 years, and 18 years, respectively. Despite the superimposition of varying degrees of cellular immunodeficiency associated with HIV-1 infection, six of these men continued to experience relapsing neurologic symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Brain-reactive antibodies and the AIDS dementia complex.

To determine the role of autoantibodies in the development of the AIDS dementia complex, brain-reactive antibodies (BRAs) were assayed in 30 sera samples obtained from AIDS patients. Eighteen samples were obtained from AIDS patients with neuropsychological complications, and 12 samples were obtained from patients without any neuropsychological involvement. BRAs were analyzed using strips of nitrocellulose electroblots as a source of antigen, and were prepared from a sample of normal human parahippocampal tissue subjected to SDS-PAGE. Fourteen of 18 patients with neuropsychological complications and 4 of 12 patients without such complications were positive for BRAs to a protein with Mr of 45,000-50,000.

AIDS Dementia Complex↗
PubMed1988

Regression of oral hairy leukoplakia after orally administered acyclovir therapy.

To define the role of Epstein-Barr virus (EBV) in the pathogenesis of oral hairy leukoplakia, 13 human immunodeficiency virus-seropositive men with clinical and histologic evidence of oral hairy leukoplakia were enrolled in an open-label trial of orally administered acyclovir therapy (3.2 g/d for 20 days). Of six patients who received therapy, five exhibited clinical regression. Once therapy was discontinued, recurrences occurred in all responders. Among seven patients who refused therapy, no spontaneous remissions occurred. Before therapy, EBV replication within the leukoplakia was demonstrated by immunofluorescence tissue staining or electron microscopy in five patients who were studied. Human papillomavirus was not detected by immunocytochemistry or electron microscopy from tissue specimens of six patients. After therapy, biopsy specimens from two patients with complete responses revealed a normalization of histologic abnormalities and an inability to detect EBV in previously involved mucosa by immunofluorescence or in situ DNA hybridization assays. It was concluded that EBV replication within the epithelial cells of the tongue is necessary for the development of oral hairy leukoplakia.

Acyclovir↗
PubMed1988

Nucleotide dimers suppress HIV expression in vitro.

A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-5' adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2', 3'-dideoxy;-5'-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxy-5'-thymid ilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.

Antiviral Agents↗
PubMed1988

Early penetration of the blood-brain-barrier by HIV.

CNS dysfunction occurs frequently in patients with HIV infection. To better define the role of HIV in the pathogenesis of neurologic dysfunction, HIV isolation and antibody studies were investigated from the CSF in 52 seropositive patients, 29 with and 23 without neurologic signs and symptoms, in various stages of disease development ranging from asymptomatic to ARC to AIDS. HIV was recovered from the CSF of 5 of 29 (17%) patients with neurologic signs and symptoms and 5 of 23 (22%) neurologically asymptomatic patients. All patients with positive CSF HIV cultures had antibodies directed against HIV p24 and gp41 in serum and CSF by Western blot analysis and elevated intra-blood-brain-barrier total IgG and HIV-specific IgG synthesis rates. The frequency of CSF HIV isolation from the group of seropositive patients without AIDS, 9 of 32 (28%), exceeded that of patients with AIDS, 1 of 20 (5%) (p less than 0.05). These findings indicate that HIV infects the CNS early in the course of viral infection and prior to the development of HIV-associated neurologic abnormalities.

Adult↗