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Biomedical subjects

J Lieberman

Publications and source records attributed to J Lieberman.

At least 91 records · Page 5Linked to original sources
PubMed1995

A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees.

Cytotoxic T lymphocytes (CTL) play an important role in the immune response to viral infection by recognizing and destroying infected cells. HIV-1 elicits an unusually strong CTL response in infected individuals and clearance of the viremia of acute infection coincides with the development of HIV-specific CTL. Because HIV-specific CTL may provide protection against de novo viral infection, we compared the CTL response in seronegative volunteers treated with two vaccination approaches. Seven volunteers were immunized with a live recombinant vaccinia virus expressing the HIV envelope protein gp160LAI (HIVAC-1e) and boosted with 640 micrograms recombinant baculovirus-expressed gp160LAI in alum 1-13 months later. In a second study, three volunteers underwent four successive immunizations with 640 micrograms subunit gp160LAI in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a liver vector would be expected to generate gp160-specific CTL, while for the second, using only whole-protein subunit, the generation of specific CTL would be unlikely. Predominantly CD8+ T-cell lines generated from PBMC by nonspecific stimulation with PHA and IL-2 were screened after three to four weeks of culture for cytolytic activity against autologous targets infected with vaccinia vectors encoding envLAI, RT, gag, and lacZ control. A strong gp 160-specific CTL response was detected in two vaccines in the recombinant vaccinia plus subunit boost study. Modest responses were seen in four of the other five live vector-primed vaccinees. No significant gp160-specific CTL were observed in three volunteers given only subunit rgp160 or in five control subjects.

AIDS Vaccines↗
PubMed1995

CD43 diminishes susceptibility to T lymphocyte-mediated cytolysis.

CD43 is a major membrane sialoglycoprotein expressed by cells of hematopoietic origin. One property of CD43 is its ability to interfere with heterotypic and homotypic cellular adhesion. To determine whether CD43 expression can affect cell functions requiring intercellular adhesion, we compared a CD43-positive human T cell line (CEM) and its CD43-negative counterpart derived by gene targeting for susceptibility to cell-mediated lysis. CD43-negative CEM cells were more susceptible than CD43-positive cells to lysis by allospecific T cell lines derived from several donors. Induction of CD43 expression on transfected HeLa cells also imparted resistance to lectin-mediated lysis by a CD8+ T cell clone. The effect of CD43 expression on reducing susceptibility to lysis was more pronounced in short-term cytotoxicity assays and tended to disappear as the time of contact between the effector cell and its target increased. The enhanced susceptibility of CD43-negative cells to lysis was not associated with increased expression of adhesion molecules known to mediate antigen-independent cellular adhesion. Sialic acid residues on CD43 contributed to the CD43 protective effect. These results suggest that either diminished CD43 expression or incomplete sialylation may render hematopoietic cells more susceptible to T lymphocyte-mediated cytolysis.

Antigens, CD↗
PubMed1995

Enhanced susceptibility to human immunodeficiency virus infection in CD4+ T lymphocytes genetically deficient in CD43.

CD43 is a cell surface sialoglycoprotein expressed by most cells of hematopoietic origin, including all T lymphocytes. Elimination of CD43 expression by gene targeting in the CEM T cell line results in its increased homotypic adhesion and binding to HIV-1 gp120. Here we report that the CD43-negative CEM cells show increased susceptibility to HIV-1 infection and increased viral replication compared with the parental CD43+ CEM cell line. Increased HIV-1 replication also was observed in CEM cells with diminished CD43 expression secondary to functional inactivation of a single CD43 allele. The CD43- CEM cells were more susceptible to HIV-1-induced cytopathicity than their CD43+ counterparts. HIV-1 replication also was increased in the CD43- CEM cells after transfection with the infectious HIV molecular clone pNL4-3. These data suggest that factors that diminish CD43 expression on T lymphocytes may enhance their susceptibility to HIV-1 infection.

Antigens, CD↗
PubMed1995

Ex vivo expansion of HIV type 1-specific cytolytic T cells from HIV type 1-seropositive subjects.

Cytotoxic T lymphocytes that specifically lyse HIV-1-infected cells occur at uncommonly high frequency in the blood of infected individuals. The CTL response is dominated by the recognition of a small number of peptides encoded by HIV-1 structural and regulatory genes. These two facts have enabled us to develop potent HIV-specific CTL lines from the blood of infected patients without AIDS opportunistic infections by ex vivo culture of nonspecifically stimulated T cell lines with autologous antigen-presenting cells (APCs) preincubated with immunodominant HIV-1 peptides. After one selection, HIV-specific cytotoxicity is enhanced 1.4- to sixfold. Frequency analysis of the T cell line from 1 patient revealed that after exposure to peptide-incubated autologous B-LCLs, the frequency of CTLs specific for the gp160-expressing APCs was enhanced 6-fold and, after a second exposure, 11-fold compared to the nonselected T cell line. Because the APCs used for the frequency analysis were EBV-transformed B-LCLs, some of the specific CTLs in the culture recognized the EBV-expressing APCs. HIV-specific cytotoxicity is enhanced without augmentation of EBV-specific cytotoxicity when PBMCs are used as APCs. Because T cell lines enhanced for HIV-1 specificity are highly cytotoxic and can be expanded to approximately 10(9)-10(10) cells/ml of blood, they may be useful for laboratory research or for immunotherapy.

Amino Acid Sequence↗
PubMed1995

A simple method to selectively expand HIV-1 specific cytotoxic T lymphocytes in vitro.

Cytotoxic T lymphocytes (CTL) may play a critical role in controlling the progression of HIV-1 disease. Conventional assays for demonstration of CTL against HIV-1 have used either fresh PBMC or T cell lines and clones generated by non-specific stimulation. These methods are limited in their sensitivity since without specific secondary stimulation in vitro, epitopes recognized at low frequency may not be detected. Moreover, derivation of CTL clones is labor intensive and not practical for studying a large number of patients. We have developed a simple method to enrich HIV-1 specific CTL in vitro. Autologous antigen presenting cells (APC), either adherent macrophages or EBV transformed B-lymphoblastoid cells, are infected with recombinant vaccinia virus encoding individual HIV-1 proteins and after overnight culture the vaccinia virus is inactivated by uv irradiation in the presence of psoralin. The infected APC are then cultured with patient's T cells and CTL activity determined 10-14 days later. We have used this method to stimulate patients' T cells obtained directly from PBMC and also after mitogenic stimulation. In both systems, the HIV-1 specific response could be enhanced up to five to ten fold. This enhancement is comparable to CTL selection by exposure to HIV-1 immunodominant peptide incubated APC. In some patients, viral-specific CTL could be detected after HIV-vaccinia selection even though the mitogen stimulated cultures had no demonstrable antiviral CTL activity. Selective expansion of CTL directed against multiple HIV-1 proteins (env, gag and RT) could be obtained from PBMC as well as from mitogen-stimulated lines from individual patients. As these lines are predominantly CD8+ T cells by flow cytometric analysis and are free of vaccinia virus as ascertained by the lack of cytopathic effect in culture, in vitro vaccinia selection might also be useful to generate CTL lines for adoptive immunotherapy.

Antigen-Presenting Cells↗
PubMed1994

Plasma homovanillic acid levels in first-episode schizophrenia. Psychopathology and treatment response.

OBJECTIVES: To examine plasma homovanillic acid (pHVA) levels in first-episode schizophrenia, to compare pHVA levels in patients and controls, and to assess the association of pHVA levels with psychopathology and treatment response. METHODS: Forty-one patients entered the study, and pHVA levels were measured at baseline and on a weekly basis for up to 6 weeks of open standardized neuroleptic treatment. Psychopathology was evaluated with the Schedule for Affective Disorders and Schizophrenia, the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions scale. Ten healthy controls were used for comparison of baseline pHVA levels. RESULTS: No differences were observed between patients and controls. Baseline pHVA level was not associated with psychopathology but was associated with time to reach remission. Baseline pHVA levels and week-1 pHVA levels were higher in responders than nonresponders. Regardless of responsiveness, female participants had higher pHVA levels than male participants throughout the study. The pattern of pHVA levels with treatment was similar in all patients with a short-term rise initially and then a decrease toward baseline values. CONCLUSIONS: These findings suggest that pHVA levels have prognostic significance for response and time to reach remission. Qualitative and quantitative differences between first-episode patients' pHVA levels and studies using a long-term, neuroleptic-exposed population suggest that changes occur with neuroleptic treatment or the progression of the illness.

Adult↗
PubMed1994

Mortality factors in geriatric blunt trauma patients.

OBJECTIVE: To examine various clinical factors for their ability to predict mortality in geriatric patients following blunt trauma. DESIGN: In this retrospective study, trauma registries and medical records from three trauma centers were reviewed for patients 65 years and older who had sustained blunt trauma. The following variables were extracted and examined independently and in combination for their ability to predict death: age, gender, mechanism of injury, admission blood pressure, and Glasgow Coma Scale score, respiratory status, Trauma Score, Revised Trauma Score, and Injury Severity Score. SETTING: Three urban trauma centers. PATIENTS: Geriatric trauma patients entering three trauma centers (Stanford [Calif] University Hospital, Vanderbilt University Medical Center, Nashville, Tenn, and Maryland Institute for Emergency Medical Services Systems, Baltimore) following blunt trauma during a 7-year period (1982 to 1989). RESULTS: The Injury Severity Score was the single variable that correlated most significantly with mortality. Mortality rates were higher for men than for women and were significantly higher in patients 75 years and older. Admission variables associated with the highest relative risks of death included a Trauma Score less than 7; hypotension (systolic blood pressure, < 90 mm Hg); hypoventilation (respiratory rate, < 10 breaths per minute); or a Glasgow Coma Scale score equal to 3. CONCLUSIONS: Admission variables in geriatric trauma patients can be used to predict outcome and may also be useful in making decisions about triage, quality assurance, and use of intensive care unit beds.

Abbreviated Injury Scale↗
PubMed1994

Imaging endogenous dopamine competition with [11C]raclopride in the human brain.

This study images dopamine release in response to a neurochemically specific challenge with the psychostimulant drug methylphenidate. Changes in synaptic dopamine induced by methylphenidate were evaluated with positron emission tomography and [11C]raclopride, a D2 receptor radioligand that is sensitive to endogenous dopamine. Methylphenidate significantly decreased striatal [11C]raclopride binding. The decrease was variable and was negatively correlated with age. Mood and anxiety at baseline, were also correlated with methylphenidate-induced DA changes. This strategy provides a tool to investigate the responsiveness of the dopamine system in the normal and diseased human brain and to investigate the neurochemical correlates of behavior.

Adult↗
PubMed1994

Popliteal pseudoaneurysm as a complication of an adjacent osteochondroma.

A 19-year-old man presented to our institution with a 4-month history of a pulsatile mass in the left popliteal fossa. Evaluation including plain x-ray films, MRI, and arteriography revealed a pseudoaneurysm associated with an underlying exostosis of the distal femur. The pseudoaneurysm was repaired with a saphenous vein patch and the exostosis was excised. This case is reported in conjunction with an extensive review of the literature, which yielded only 25 similar cases reported in the English language since 1953. The majority of cases involved young men (20/26), whose ages ranged from 9 to 45 years (mean 20 years). Fifteen of the 26 cases involved isolated exostoses, and in less than half (12/26), antecedent trauma was identified as a cause of the pseudoaneurysm. The origin of exostoses and their relationship to popliteal pseudoaneurysms are discussed. Repair of the pseudoaneurysm and excision of the involved exostosis are recommended.

Adult↗
PubMed1994

Methylphenidate decreases regional cerebral blood flow in normal human subjects.

To assess the effects of methylphenidate (MP) on cerebral blood flow (CBF), 5 healthy males were studied using 15O-water and positron emission tomography before and after MP (0.5 mg/kg iv). MP significantly decreased whole brain CBF at 5-10 minutes (25 +/- 11%) and at 30 minutes (20 +/- 10%) after its administration. Decrements in CBF were homogeneous throughout the brain (regional decrements 23-30%) and probably reflect the vasoactive properties of MP. The vasoactive properties of MP should be considered when prescribing this drug chronically and/or when giving it to subjects with cerebrovascular compromise.

Adult↗
PubMed1994

Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor.

We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13-year period without antiviral treatment. She received the infected transfusion for intra- and postpartum blood loss immediately after delivery of her second child in 1981. She had no acute febrile syndrome and has never had HIV-associated clinical signs or symptoms in the 13 years since infection. She was first tested and found positive for HIV antibodies in 1985, and the infected blood donor was diagnosed with AIDS in 1986 and died of AIDS-related complications in 1989. Two other recipients of packed erythrocytes from this donor (in 1980 and 1982) also became infected and were subsequently diagnosed with AIDS. Between January 1986 and April 1994, in the setting of continuous and unambiguous Western blot HIV-specific antibodies and intermittently positive low-level HIV DNA signal after polymerase chain reaction (PCR) amplification, more than 30 separate cell cocultures performed in several independent laboratories failed to yield evidence of infectious virus, despite special efforts to induce and detect HIV replication. Immunologically, a strong in vitro proliferative response to HIV envelope proteins also distinguished this subject from other asymptomatic HIV+ individuals.

Adult↗
PubMed1994

Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.

OBJECTIVE: The aim of this study was to determine the relation between plasma fluphenazine levels and clinical response in first-episode schizophrenic patients. METHOD: Data from 36 first-episode schizophrenic or schizoaffective inpatients diagnosed according to the Research Diagnostic Criteria were evaluated. The patients received open, standardized treatment with fluphenazine, 20 mg/day, for at least 4 weeks. Psychopathology was assessed biweekly, and plasma fluphenazine levels were ascertained weekly. Patients were classified as responders or nonresponders, and correlations between their neuroleptic levels and ratings of psychopathologic and extrapyramidal symptoms were computed. RESULTS: Plasma fluphenazine levels for weeks 1 through 4 were significantly correlated with each other but were not correlated with age, gender, diagnosis, or race. Mean neuroleptic levels (weeks 3 and 4) were not different between responders and nonresponders and were not correlated with measures of psychopathology or extrapyramidal symptoms. CONCLUSIONS: These results do not indicate an association between plasma fluphenazine levels and response to treatment or extrapyramidal side effects in first-episode schizophrenia. The disparity between the results of this study and those of previous studies may be due to methodological differences or to a biologically based difference between first-episode and chronic patients.

Adolescent↗