Search PubMed⌕ Search

Biomedical subjects

J Lieberman

Publications and source records attributed to J Lieberman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Small simulated polyps in pig colon: sensitivity of CT virtual colography.

PURPOSE: The authors evaluated computed tomographic (CT) virtual colography for the detection of simulated polyps under ideal conditions, as well as the effects on lesion conspicuity of (a) collimation, (b) table pitch, and (c) orientation of the colon lumen with respect to the gantry. MATERIALS AND METHODS: Pig colon was resected and cleansed, and polyps with diameters of 3, 7, and 10 mm were created. Each specimen was scanned with collimation of 5 and 7 mm and table pitch of 1.0, 1.6, and 2.0 at angles of 0 degrees, 45 degrees, and 90 degrees to the gantry. The initial two-dimensional (2D) images were reconstructed at 1-mm intervals (2D reconstructions), from which three-dimensional (3D) virtual colography images were generated. Polyp conspicuity on the initial and reconstructed 2D images and the 3D reconstructions was evaluated on a three-point scale: 0 = polyp not depicted, 1 = polyp faintly depicted, and 2 = polyp clearly depicted. RESULTS: The 10-mm-diameter polyp was clearly depicted (grade 2 conspicuity) on every initial and reconstructed 2D image and 3D reconstruction without regard to collimation, table pitch, or angle to the gantry. The 7-mm-diameter polyp was clearly depicted (grade 2 conspicuity) on every initial and reconstructed 2D image, but conspicuity on 3D reconstructions varied as the imaging parameters varied. The 3-mm-diameter polyp was faintly depicted (grade 1 conspicuity) on the initial and reconstructed 2D images and 3D reconstructions, but conspicuity varied on the 3D reconstructions as the imaging parameters varied. CONCLUSION: CT virtual colography helped detection of small mucosal polyps regardless of the angle of the colon lumen to the gantry at which they were obtained.

Animals↗
PubMed1997

Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors.

OBJECTIVE: The authors' goals were to determine whether baseline dopamine activity contributes to response to methylphenidate and to assess the pattern of metabolic responses associated with enhanced dopamine activity. METHOD: They used positron emission tomography with 2-deoxy-2[18F]fluoro-D-glucose to evaluate the effects of two sequential doses of methylphenidate on brain metabolism in 15 healthy subjects. Dopamine D2 receptor availability was measured with [11C]raclopride to evaluate its relation to methylphenidate-induced metabolic changes. RESULTS: Methylphenidate increased brain metabolism in six subjects, decreased it in two, and did not change it in seven; however, it consistently increased cerebellar metabolism. Methylphenidate significantly increased "relative" (region relative to the whole brain) metabolism in the cerebellum and decreased it in the basal ganglia. Regional metabolic changes in the cerebellum and the frontal and temporal cortices were significantly correlated with D2 availability. Frontal and temporal metabolism were increased in subjects with high D2 receptors and decreased in subjects with low D2 receptors. CONCLUSIONS: Methylphenidate induced variable changes in brain metabolism, but it consistently increased cerebellar metabolism. It also induced a significant reduction in relative metabolism in the basal ganglia. The significant association between metabolic changes in the frontal and temporal cortices and in the cerebellum and D2 receptors suggests that methylphenidate's metabolic effects in these brain regions are due in part to dopamine changes and that differences in D2 receptors may be one of the mechanisms accounting for the variability in response to methylphenidate.

Adult↗
PubMed1996

Relationship between psychostimulant-induced "high" and dopamine transporter occupancy.

The ability of cocaine to inhibit the dopamine transporter (DAT) appears to be crucial for its reinforcing properties. The potential use of drugs that produce long-lasting inhibition of the DAT as a mean of preventing the "high" and reducing drug-seeking behavior has become a major strategy in medication development. However, neither the relation between the high and DAT inhibition nor the ability to block the high by prior DAT blockade have ever been demonstrated. To evaluate if DAT could prevent the high induced by methylphenidate (MP), a drug which like cocaine inhibits the DAT, we compared the responses in eight non-drug-abusing subjects between the first and the second of two MP doses (0.375 mg/kg, i.v.) given 60 min apart. At 60 min the high from MP has returned to baseline, but 75-80% of the drug remains in brain. Positron-emission tomography and [11C]d-threo-MP were used to estimate DAT occupancies at different times after MP. DAT inhibition by MP did not block or attenuate the high from a second dose of MP given 60 min later, despite a 80% residual transporter occupancy from the first dose. Furthermore some subjects did not perceive a high after single or repeated administration despite significant DAT blockade. These results indicate that DAT occupancy is not sufficient to account for the high, and that for DAT inhibitors to be therapeutically effective, occupancies > 80% may be required.

Adult↗
PubMed1996

No evidence for association of dopamine D2 receptor variant (Ser311/Cys311) with major psychosis.

We investigated a variant of the dopamine D2 receptor gene (Ser311/Cys311 substitution) in Caucasian patients with schizophrenia (n = 273), delusional disorder (n = 62), bipolar I affective disorder (n = 63), and controls (n = 255). No evidence for association between the receptor variant and any of the diseases was found, even when patients with younger age-of-onset (< 25 years) were compared with controls. Furthermore, in a subgroup of schizophrenia patients whom we assessed for negative symptoms, those with the Cys allele did not differ from the remainder of the group. Also, the bipolar affective disorder patients with psychotic features did not show evidence for association with the receptor variant. Thus, our results do not provide evidence for an association between this D2 receptor variant and schizophrenia, or delusional disorder, or bipolar affective disorder.

Adult↗
PubMed1996

The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients.

Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present in KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present in the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected in the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population.

Base Sequence↗
PubMed1996

Successfully treated invasive pulmonary aspergillosis associated with smoking marijuana in a renal transplant recipient.

Invasive pulmonary aspergillosis (IPA) is often a lethal entity in transplant recipients (up to 90%). We report the successful treatment of a case of IPA in a renal transplant recipient whose only risk for exposure was habitual marijuana smoking. Although marijuana smoking has been linked to the development of IPA in patients immunosuppressed for a variety of reasons, this case is the first report involving a solid organ transplant recipient. The patient's clinical course and treatment are described and the literature is reviewed with respect to environmental and patient risk factors. In this case, IPA was associated with the patient's heavy usage of marijuana during the immediate posttransplant period. Treatment was successful and included the experimental amphotericin product amphotericin B colloidal dispersion. Contemporaneous exposure to a large amount of inocula of Aspergillus within 30 days of receiving high doses of steroids appeared to be the most important factor that predisposed this patient to IPA. Transplant recipients should be specifically proscribed from marijuana use during periods of high steroid administration.

Antifungal Agents↗
PubMed1996

Effect of interleukin 12 on in vitro HIV type 1 replication depends on clinical stage.

CD8-depleted PBMCs from 20 HIV-1-seropositive donors were incubated in the presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2 or rIL-12 in five of seven asymptomatic subjects and was not induced by either cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced increased p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only in cell lines from 5 symptomatic subjects and then only marginally. In IL-2 containing cultures from subjects with minor symptoms of HIV infection, the mean p24 Ag was 320 +/- 217 pg/ml versus 27 +/- 6 in IL-12-containing cultures (p = 0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold compared to cultures from this group incubated with only rIL-2 (p = 0.03). Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from subjects who had had a major AIDS infection, although the number of CD4 cells in four of six of those cultures was markedly reduced. IL-4, IFN-gamma, and IL-10 production induced by exposure to IL-2 and/or IL-12 were also measured. In CD8-depleted cultures from all infected asymptomatic donors and from some symptomatic donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-gamma and IL-10 production. Cytokine-induced production of IL-4, IFN-gamma, and IL-10 was greater in cultures from asymptomatic donors than in cultures from symptomatic subjects. Our results suggest that IL-12 immunotherapy may be complicated by enhancement of viral expression in asymptomatic individuals.

Adult↗
PubMed1996

Prediction of HIV peptide epitopes by a novel algorithm.

Identification of promiscuous or multideterminant T cell epitopes is essential for HIV vaccine development, however, current methods for T cell epitope identification are both cost intensive and labor intensive. We have developed a computer-driven algorithm, named EpiMer, which searches protein amino acid sequences for putative MHC class I- and/or class II-restricted T cell epitopes. This algorithm identifies peptides that contain multiple MHC-binding motifs from protein sequences. To evaluate the predictive power of EpiMer, the amino acid sequences of the HIV-1 proteins nef, gp160, gag p55, and tat were searched for regions of MHC-binding motif clustering. We assessed the algorithm's predictive power by comparing the EpiMer-predicted peptide epitopes to T cell epitopes that have been published in the literature. The EpiMer method of T cell epitope identification was compared to the standard method of synthesizing short, overlapping peptides and testing them for immunogenicity (overlapping peptide method), and to an alternate algorithm that has been used to identify putative T cell epitopes from primary structure (AMPHI). For the four HIV-1 proteins analyzed, the in vitro testing of EpiMer peptides for immunogenicity would have required the synthesis of fewer total peptides than either AMPHI or the overlapping peptide method. The EpiMer algorithm proved to be more efficient and more sensitive per amino acid than both the overlapping peptide method and AMPHI. The EpiMer predictions for these four HIV proteins are described. Since EpiMer-predicted peptides have the potential to bind to multiple MHC alleles, they are strong candidates for inclusion in a synthetic HIV vaccine.

Algorithms↗
PubMed1996

Gender differences in neuroleptic nonresponsive clozapine-treated schizophrenics.

Gender differences in neuroleptic-refractory chronic schizophrenic disorder patients were examined to determine whether a superior or equivalent antipsychotic response in women vs. men existed similar to that of the general schizophrenic population. Sixty-nine DSM-III schizophrenic patients (47 males and 22 females) were treated with clozapine using a standardized medication regime. The gender differences in these neuroleptic-nonresponsive chronic schizophrenic disorder patients differed from those previously observed in the general schizophrenic population in that an equivalent antipsychotic treatment response in females versus males was not found. These treatment-refractory women appear to be a severely ill subgroup of female schizophrenics with distinct onset of illness, course and treatment response characteristics.

Adolescent↗
PubMed1996

Temporal relationships between the pharmacokinetics of methylphenidate in the human brain and its behavioral and cardiovascular effects.

Positron emission tomography was used to compare the pharmacokinetics of [11C]methylphenidate in the human brain with the temporal course of the subjective and cardiovascular effects observed after intravenous methylphenidate (0.5 mg/kg). Four subjects were tested twice with [11C]methylphenidate, at baseline and after methylphenidate. All subjects showed almost identical uptake of 11C labeled drug in brain, as well as a very similar decrease in binding of [11C]methylphenidate in basal ganglia, after pretreatment with methylphenidate. In contrast, the magnitude of the behavioral and cardiovascular changes induced by methylphenidate varied among the subjects. The temporal course for methylphenidate effects paralleled closely the pharmacokinetics of [11C]methylphenidate in brain for the perception of "restlessness" and for changes in systolic blood pressure and heart rate. In contrast, methylphenidate induced "high", "anxiety" and changes in diastolic blood pressure decreased rapidly despite long lasting binding of the drug in brain. These results indicate that binding of methylphenidate in brain does not appear to predict individual responses to the drug and that more than one neurotransmitter and/or adaptation process are likely to be involved in the behavioral and cardiovascular effects of methylphenidate.

Adult↗
PubMed1996

Psychosis and genes with trinucleotide repeat polymorphism.

Abnormal expansion of genes with trinucleotide repeat (TNR) polymorphism has been found in a number of neuropsychiatric disorders. These disorders and the major psychoses, schizophrenia and bipolar affective disorder, appear to share an interesting phenomenon: genetic anticipation. Because TNR expansion correlates with anticipation, these unstable DNA sites are considered important candidate loci for the major psychoses. We investigated genes with TNR polymorphisms, including B1, B33, B37, and the N-cadherin gene, in unrelated Caucasian North American and Italian schizophrenics (n = 53 to 74), and matched controls. Also, unrelated Caucasian North American patients with bipolar I affective disorder were screened for the B33 and N-cadherin genes (n = 49 and 63, respectively). No unusually long alleles that would suggest abnormal expansion of the TNR were observed for any of these genes. Also, no statistically significant results were found in tests for genetic association between any of these genes and schizophrenia. For B37, a trend toward a difference in allele counts between schizophrenics and controls was observed. However, no clear evidence for a role of these TNR-containing genes in schizophrenia or bipolar affective disorders was found.

Bipolar Disorder↗
PubMed1996

Three regions of HIV-1 gp160 contain clusters of immunodominant CTL epitopes.

HIV-1 infection stimulates a strong CTL response that coincides with resolution of viremia in acute infection and declines with development of opportunistic infections. Recognition of HIV gp160 by PBMC-derived T cell lines from 20 HIV-infected subjects is dominated by the response to a small number of peptide epitopes. Overlapping CTL epitopes restricted by multiple MHC Class I elements were identified in 3 relatively conserved regions of gp160 (amino acids 49-68, 591-600 and 844-863). CTL from five of 20 subjects recognized three overlapping immunodominant epitopes in the 49-68 a.a. region restricted by A24, B38, and B55. CTL from four subjects recognized at least three distinct epitopes in a.a 591-600 in the context of A24, B8, B14, and B27. CTL from seven subjects recognized epitopes within a.a. 844-863 restricted by A30, B7, B8 and B35.

Cell Line↗
PubMed1996

EBV-specific cytotoxic T lymphocytes protect against human EBV-associated lymphoma in scid mice.

Scid mice develop human EBV-positive B cell tumors after injection with EBV-transformed human B cells or peripheral blood lymphocytes from EBV-seropositive donors. Injection of cytotoxic T cell (CTL) lines, selectively expanded in vitro to recognize autologous EBV-transformed B cells, protected mice against developing human lymphoproliferative disease. CTL protection required a single dose of polyethylene-glycol-conjugated IL2. Mice were not protected by CTL that did not specifically recognize EBV-transformed B cells or by mitogen-activated lymphocytes.

Adoptive Transfer↗
PubMed1996

Deriving respiration from pulse wave: a new signal-processing technique.

Investigations of autonomic nervous system activity using spectral analysis of heart rate (HR) and blood pressure (BP) variability is very popular in many scientific disciplines, and yet only half of all studies involving spectral analysis control for respiration. Because respiration modulates HR and BP variability, knowledge of the respiratory rate is necessary for the proper interpretation of HR and BP power spectra. We devised and validated a new signal-processing technique to derive respiration from the blood pressure wave. This technique is based on the relationship between oscillations in the area under the dicrotic notch of the pulse wave and respiration. The results of our view signal-processing technique yielded significant correlations between protocols of the actual number of respiratory cycles and our blood pressure-derived respiratory cycles and their respective spectra for a number of standard autonomic tests (P < 0.05). Our method will allow retrospective extraction of the respiratory wave and as such afford a more precise interpretation of HR and BP spectra.

Adult↗
PubMed1995

Association study of dopamine D3 receptor gene and schizophrenia.

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied.

Alleles↗
PubMed1995

Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by using Listeria monocytogenes as a live vaccine vector.

Cytolytic T cells, acting through cytokines or by direct lysis of infected target cells, have been shown to play a significant role in the control of viral infections and may be responsible for the prolonged asymptomatic phase following infection by HIV. Accordingly, methods that can generate strong cell-mediated immune responses may be useful in the development of prophylactic and therapeutic vaccines against HIV. Listeria monocytogenes is a Gram-positive intracellular microorganism that elicits strong cell-mediated immune responses against its own secreted proteins following infection. In this study we have modified the chromosome of L. monocytogenes so that it stably expresses and secretes the p55 HIV gag gene product and examined the cell-mediated immune response of BALB/c mice to infection with this recombinant organism. Infected animals were found to mount a specific, strong, long-lasting CD8+ cytolytic T cell response against a predominant epitope contained within the p24 fragment of the HIV Gag protein. This epitope previously has been shown to be recognized by CTLs obtained from some HIV-infected humans. Our results suggest that chromosomally modified strains of L. monocytogenes may provide valuable vaccine vectors for use against HIV.

AIDS Vaccines↗