Biomedical subjects

D Benjamin

Publications and source records attributed to D Benjamin.

At least 235 records · Page 13Linked to original sources

PubMed1989

Maternal drug use and risk of childhood nonlymphoblastic leukemia among offspring. An epidemiologic investigation implicating marijuana (a report from the Childrens Cancer Study Group).

The Childrens Cancer Study Group conducted a case-control study designed to assess in utero and postnatal exposures in children with acute nonlymphoblastic leukemia (ANLL). Analyses were performed for reported maternal use of medications and drugs in the year preceding and during the index pregnancy of the 204 case-control pairs. An 11-fold risk (P = 0.003) was found for maternal use of mind-altering drugs just prior to or during the index pregnancy. Compared with ANLL cases not exposed to marijuana, exposed cases were significantly younger at diagnosis of ANLL (P less than 0.01) and were more often of the myelomonocytic and monocytic subtypes (P less than 0.01). Use of antinausea medication for more than 11 weeks was also associated with a significantly elevated relative risk of 2.81 and a dose-response relationship was noted (P = 0.05 for trend). These results suggest that maternal drug use of marijuana may have an etiologic role in childhood ANLL and may be specific for morphologically defined subgroups.

Adolescent↗

PubMed1989

Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression.

The Ta1 (CDw26) Ag distinguishes a subset of circulating T lymphocytes that is the major population proliferating to recall Ag challenge. Unlike receptors for growth factors such as IL-2 and transferrin, the Ta1 Ag is present on T cell lines and clones irrespective of cell cycle. The appearance of Ta1 on T cells that respond to recall Ag allowed us to investigate activation requirements that may be associated with T cell immune memory. Ta1+ peripheral blood T cells were induced to proliferate by mAb recognizing either the invariant chains of the TCR, or by pairs of mitogenic antibodies directed to the CD2 molecule. In contrast, Ta1- cells were not stimulated by these antibodies. In addition, Ta1-cells did not proliferate maximally after addition of the phorbol ester PMA in combination with the calcium ionophore Ionomycin, suggesting that the intracellular targets of these agents may not be fully active. Anti-CD3-induced elevation of intracellular calcium levels was equivalent in the two subpopulations, suggesting that calcium mobilization mechanisms were intact. In contrast, PMA-induced phosphorylation of TCR CD3 chains was significantly greater in Ta1+ cells as compared to Ta1- T cells. Taken together, our results indicate that Ta1 expression, which is associated with T cell activation and memory, may be causally related to TCR and CD2-mediated activation mechanisms. The PMA inducible TCR phosphorylation in Ta1+ memory cells associated with their increased ability to proliferate after CD3/TCR or CD2 stimulation suggests that intracellular phosphorylation events may be causally associated with T cell immune memory.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Human B cell lines can be triggered to secrete an interleukin 2-like molecule.

To determine whether human B cells can be triggered to secrete interleukin 2 (IL-2), 19 tumor cell lines derived from patients with undifferentiated lymphomas of Burkitt's and non-Burkitt's types and 6 normal lymphoblastoid cell lines were tested. Cells were grown in the presence or absence of the new tumor promoter teleocidin, and culture supernatants were assayed for IL-2 activity using the standard CTLL-2 assay. Teleocidin (10 ng/ml) triggered IL-2 secretion in 7/8 (87%) EBV-negative lymphoma cell lines of American origin and in 6/6 (100%) normal lymphoblastoid cell lines, but in only 1/6 (16%) EBV-positive tumor cell lines of American origin. Teleocidin had no effect on 5/5 (0%) African Burkitt's cell lines. IL-2 secretion was not detected in control supernatants. IL-2 secretion correlated with the induction of IgM secretion and was linked to both EBV status and karyotype. The following similarities in the functional biological characteristics of T cell and B cell IL-2 suggest that B cell IL-2 is not a factor which mimics IL-2 activity in the CTLL-2 assay: (i) neutralization of IL-2 by anti-IL-2 monoclonal antibody (DMS-1); (ii) elution of IL-2 following its adsorption to CTLL-2 cells; (iii) determination of the MW of IL-2 by SDS-PAGE and Western blot analysis; and (iv) ability of B cell IL-2 to support T cell proliferation and blocking of this activity by anti-tac monoclonal antibody. cDNA probes for T cell IL-2, however, did not detect IL-2 mRNA in B cells. The cell lines were also found to constitutively express IL-2 receptors detected by anti-tac monoclonal antibody, and to secrete soluble IL-2 receptors measured by ELISA. Our results imply that under certain circumstances, B cells can be triggered to secrete IL-2 or an IL-2-like molecule and thus influence T cell activation and proliferation.

Antibodies, Monoclonal↗

PubMed1988

Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.

We have investigated the T cell populations in the cerebrospinal fluid (CSF) of chronic progressive multiple sclerosis (MS) patients. Individual T cells from the CSF and blood were cloned before expansion and their clonotypes were defined by analysis of rearranged T cell receptor beta chain and gamma chain genes. 87 T cell clones from blood and CSF of two patients with chronic progressive MS were examined for common TCR gene rearrangement patterns. In one patient, 18 of 28 CSF-derived T cell clones demonstrated common TCR gene rearrangements indicating oligoclonal T cell populations; in the blood, two patterns were found twice among 26 T cell clones. In another patient, 5 of 27 CSF-derived clones had common TCR gene rearrangement patterns. In contrast, no common beta chain rearrangement pattern was found among 67 T cell clones derived from the blood or CSF of a patient with subacute sclerosing panencephalitis, among 20 clones from the CSF of a patient with herpes zoster meningoencephalitis, or among 66 clones from a normal subject. A subject with atypical, fatal MS of 8-mo duration was also studied and did not have oligoclonal T cells in the CSF or blood. These results demonstrate that distinct oligoclonal T cell populations can be found in the CSF immune compartment of subjects with nonmalignant inflammatory disease and they can create a new avenue for the investigation of the specificity of the T cell response within the central nervous system.

Cerebrospinal Fluid↗

PubMed1988

Bacillus species pseudomeningitis.

A cluster of cerebrospinal fluid Gram's stains showing gram-positive bacilli and of cerebrospinal fluid cultures growing Bacillus species in a large community teaching hospital prompted an epidemiologic and microbiologic investigation. Pseudomeningitis was suspected and confirmed when cultures of uninoculated commercial trypticase soy broth with 5% Fildes enrichment grew Bacillus species. Secondary contamination of the pipettes used for inoculation accounted for the positive cerebrospinal fluid Gram's stains. The costs of this pseudo-outbreak included unnecessary antibiotic therapy, lumbar punctures, and hospitalization. Such adverse effects can be minimized by increased physician awareness of pseudoinfections and by prompt investigation of such occurrences.

Adolescent↗

PubMed1988

Abdominal x-ray and pathological findings in distal unishunt obstruction.

A new x-ray finding suggesting distal obstruction of the Unishunt is described. Fusiform swelling of the distal slit valve ("pantaloon sign") seen on an abdominal x-ray film was associated with surgically proven distal shunt obstruction in 8 of 10 patients. No patient with a normally functioning (n = 67) or proximally malfunctioning shunt (n = 6) displayed this abnormality. This finding in association with clinical and computed tomographic evidence of shunt malfunction can direct surgical revision to the appropriate site. The pathology of distal shunt malfunction is also reviewed.

Cerebrospinal Fluid Shunts↗

PubMed1988

Characterization of a pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal.

Rats were trained with food reinforcement to discriminate the anxiogenic drug pentylenetetrazol (PTZ, 20 mg/kg) from saline in a two-lever-choice task. In Experiment 1, ethanol, 8.25% w/v was given by gavage (7/day) for 4 days, with doses titrated to maintain moderate intoxication. After termination of ethanol, the rats exhibited mild overt signs of withdrawal and, in discrimination tests with saline as the test substance, they selected the PTZ lever, an effect reversed by ethanol, 2 g/kg, and by diazepam, 5 mg/kg. In Experiment 2, rats drank a nutritionally complete liquid diet containing ethanol, 4.5% w/v, for 1 week. They became tolerant to the intoxicating effect of ethanol, and blood ethanol concentration mounted with continued dosing. On termination of chronic ethanol, rats selected the PTZ lever before the onset of overt physical signs of withdrawal, and both measures returned to base line within 3 days. In Experiment 3 the percentage of rats selecting the PTZ lever after termination of ethanol depended upon the dose (up to 12.5 g/kg) and duration (up to a ceiling effect by 3 days) of ethanol administered chronically. These results indicate that a PTZ-like stimulus produced interoceptively can be demonstrated in the rat as an objective measure of ethanol withdrawal. This paradigm may provide insight into the symptom of anxiety associated with ethanol withdrawal.

Animals↗

PubMed1987

Functional gamma chain-associated T cell receptors on cerebrospinal fluid-derived natural killer-like T cell clones.

We have derived 33 independent T cell clones from the cerebrospinal fluid (CSF) of a patient with subacute sclerosing panencephalitis using a single T cell cloning method. 6% (2 of 33) of these clones express the T cell receptor gamma (TCR-gamma) protein and are called CSF TCR-gamma clones. Phenotypic analyses of the CSF TCR-gamma clones indicate that they are WT-31-, CD3+, CD4-, and CD8-. The TCR-gamma protein exists on the cell surface as part of an 85-kD disulphide-linked dimer noncovalently associated with the CD3 polypeptides. The CSF TCR-gamma clones have NK-like activity that can be inhibited by anti-CD3 mAbs. Both CSF TCR-gamma clones proliferated in response to anti-CD3 mAbs coupled to Sepharose beads and/or IL-2. Furthermore, stimulation of one of these clones with anti-CD3 mAbs results in a rapid rise in intracellular calcium. These data suggest that T cells bearing the CD3-TCR-gamma protein complex are functional and play a role in the human immune response.

Cerebrospinal Fluid↗

PubMed1987

Modulation of the discriminative stimulus produced by pentylenetetrazol by centrally administered drugs.

Pentylenetetrazol is anxiogenic in humans and produces an interoceptive discriminative stimulus in rats which is mimicked by anxiogenic drugs and other treatments and antagonized by anxiolytic drugs. It was proposed that the discriminative stimulus of pentylenetetrazol originates centrally. This hypothesis was tested by injecting small amounts of anxiogenic or anxiolytic drugs into the brain and comparing their ability to mimic or block, respectively, the response to pentylenetetrazol, observed after systemic injection. Food-restricted rats were trained in a two-lever operant task to discriminate the interoceptive discriminative stimulus produced by pentylenetetrazol. Intraperitoneal or intracerebroventricular injection of Ro 5-3663 was substituted in a dose-dependent manner for the stimulus produced by systemically administered pentylenetetrazol. Diazepam injected systemically, blocked the pentylenetetrazol-like stimulus associated with Ro 5-3663 administered systemically or centrally. Midazolam injected intracerebroventricularly and in a dose-dependent manner, antagonized the discriminative stimulus produced by systemic injection of pentylenetetrazol. When injected into the amygdala, midazolam also antagonized in a dose-dependent manner the pentylenetetrazol-induced stimulus. Thus, these data suggest that there are sites in the CNS for both the initiation of a pentylenetetrazol-like stimulus by Ro 5-3663 and the antagonism of the stimulus produced by pentylenetetrazol by midazolam.

Amygdala↗

PubMed1987

Anxiety-like subjective effect of ethanol antagonist RO 15-4513 demonstrated in pentylenetetrazol discrimination.

Ro 15-4513, a benzodiazepine-receptor ligand which antagonizes ethanol, was tested in the pentylenetetrazol discrimination, a bioassay for anxiogenic drugs. Rats were trained with food reward to discriminate pentylenetetrazol (PTZ) from saline in a two-lever operant task. In lever-selection tests, rats selected the PTZ lever both after PTZ and after Ro 15-4513. The PTZ-like stimulus produced by Ro 15-4513 was blocked by diazepam and by the benzodiazepine receptor blocker Ro 15-1788. Substitution for the anxiogenic drug PTZ, and blockade by the anxiolytic diazepam, support the hypothesis that Ro 15-4513 is anxiogenic; blockade by Ro 15-1788 suggests that the PTZ-like stimulus produced by Ro 15-4513 occurs through its action at the benzodiazepine receptor.

Animals↗

PubMed1987

Motion aftereffects associated with pursuit eye movements.

Contrary to an earlier report [Anstis and Gregory, Q. Jl exp. Psychol. 17, 173-174 (1965)], we find that the sustained retinal motion caused by tracking a moving target over a stationary grating does not result in a motion aftereffect (MAE) which is equivalent to that resulting from comparable retinal motion caused by actual motion of a grating. The MAE associated with tracking generally occurs in elements falling on areas not previously exposed to retinal motion. It is in the same direction as the previous retinal motion in the display and is apparently an induced MAE caused by a weak, below threshold MAE in the elements stimulating areas that were previously exposed to retinal motion. Based on an analysis of eye movement records, we do not believe that the weakness of the tracking MAE is primarily a function of the poor quality of the tracking eye movements. Other possible reasons for the weakness of the MAE are suggested.

Adaptation, Ocular↗

PubMed1987

Secondary immune amplification following live poliovirus immunization in humans.

Eight subjects inoculated orally with live attenuated poliovirus were investigated to study the effects of live virus infection on human T-cell responses. Proliferation to poliovirus and unrelated recall antigens were measured serially over a 3-week period. Five of eight subjects inoculated demonstrated a clear anamnestic response to poliovirus, but three did not. Only the five subjects demonstrating an anamnestic response to poliovirus were found to have augmented secondary immune responses to two unrelated recall antigens (tetanus toxoid and reovirus) and in the autologous mixed lymphocyte response (AMLR). No consistent changes were found in circulating T-cell surface activation antigens whether or not the subjects responded to poliovirus. These studies suggest that an asymptomatic poliovirus infection associated with immunization in humans can induce nonspecific secondary immune amplification as measured by in vitro T-cell proliferative response. This amplification pathway is a potential mechanism for immune responses against antigens other than those of the infecting virus.

Administration, Oral↗

PubMed1986

Antigen reactive memory T cells are defined by Ta1.

Ta1 is a 105,000 dalton protein that is weakly expressed on a small fraction of resting human peripheral blood T cells but strongly expressed in vitro on T cell clones and a substantial proportion of activated T cells. Unlike receptors for growth factors such as IL 2, the Ta1 antigen is present on T cell lines and clones irrespective of cell cycle. The function of Ta1 was investigated after separation of T lymphocytes into Ta1-enriched and Ta1-depleted subpopulations that were obtained from normal human subjects. Although Ta1-enriched T cells constitute only 10 to 15% of the E rosette-positive lymphocyte population, most, if not all, of the anamnestic response to the recall antigens tetanus toxoid and mumps reside in the Ta1+ population. Both Ta1-enriched and -depleted cells responded equally well to the mitogen PHA. The autologous mixed lymphocyte response was also greater in the Ta1-enriched subpopulation but not to the degree seen with soluble antigen. Increased proliferation was not due simple to increased inducer cell function within the Ta1+ subpopulations because both Ta1- and Ta1+ cells induced similar amounts of Ig synthesis in the presence of PWM. Additionally, increasing numbers of Ta1- cells did not suppress the enhanced proliferative responses of Ta1+ cells, and thus Ta1- cells do not appear to be functioning as suppressor cells. The Ta1 antigen appears to be a marker for previously activated T cells in peripheral blood, and this subpopulation appears to include T memory cells.

Antigens, Surface↗

PubMed1986

Burkitt's cells can be triggered by teleocidin to secrete interferon-gamma.

The secretion of interferon (IFN)-gamma by T lymphocytes is mediated by the synthesis of interleukin 2 (IL-2) and the availability of IL-2 receptors. Since some Burkitt's lymphoma lines express Tac antigen and can be triggered to secrete IL-2 following activation with the new tumor promoter teleocidin, we addressed the question of whether the induction of IL-2 by B lymphocytes is accompanied by the induction of IFN-gamma. IFN-gamma has not been detected in any of the 25 cell lines studied, and following stimulation with teleocidin, we triggered the synthesis of IFN-gamma in JLP(C), a pre-Burkitt's cell line. The mechanism of IFN-gamma secretion by B lymphocytes is not clear. Our findings demonstrate that the synthesis of IL-2 by B cells is not accompanied by IFN-gamma and suggest that the synthesis of IFN-gamma is not mediated by IL-2 or IL-1 or B-cell growth factor. Neutralization studies have shown that IFN-gamma secretion is not accompanied by the induction of IFN-alpha or IFN-beta. Our data imply that B cells can be triggered to secrete IFN-gamma under certain circumstances. Whether similar function occurs in vivo is not known.

Animals↗

PubMed1986

Heterogeneity of B-cell growth factor receptor reactivity in healthy donors and in patients with chronic lymphatic leukemia: relationship to B-cell-derived lymphokines.

Twenty-five long-term B-cell lines were studied for B-BCGF activity. The cell lines were cultured in the presence or absence of the new tumor promoter teleocidin, and control and teleocidin-treated derived supernatants were cocultured with purified B cells obtained from healthy donors and patients with B chronic lymphatic leukemia (B-CLL), in the presence of anti-mu. In attempt to delineate the role of other B-cell lymphokines in promoting proliferation of activated B cells, the supernatants were also studied for interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-gamma). The effect of B-cell-derived lymphokines on the proliferation of activated B cells obtained from the 14 donors was heterogeneous, and three types of response were observed: In four healthy donors there was induction of B-cell proliferation by B-cell lymphokines derived from both control cells and teleocidin-treated cells. In cells obtained from the other five healthy donors there was induction of B-cell proliferation by B-cell lymphokines derived from teleocidin-treated cells. In the five B-CLL patients, B-cell proliferative response to B-cell lymphokines derived from both control cells and teleocidin-activated cells was absent. Comparison of B-BCGF reactivity to T-BCGF reactivity demonstrated that B-CLL B lymphocytes did not respond to either B-BCGF or T-BCGF, whereas normal B cells responded to T-BCGF and may proliferate upon stimulation with B-cell-derived IL-2 and/or B-BCGF. These results suggest heterogeneity of B-BCGF receptor reactivity in B lymphocytes derived from healthy donors, and lack of both B-BCGF and T-BCGF receptor reactivities in B lymphocytes derived from B-CLL patients; B-cell-derived lymphokines influence normal B-cell response but not leukemic B cells; B-BCGF optimal effect is in large part due to other B-cell lymphokines, especially B-cell-derived IL-2; the possible existence of various B-BCGFs.

Antigens, Surface↗

PubMed1986

Expression of normal myeloid-associated antigens by acute leukemia cells.

Monoclonal antibodies that react with hematopoietic cells and their precursors in a stage and lineage restricted fashion were used in indirect immunofluorescence assays to examine leukemic cells from 105 pediatric age patients. The differentiative states of blasts from 42 patients with acute nonlymphocytic leukemia (ANLL) were defined by these antibodies. When these were compared to their morphologic and histochemical levels of differentiation as defined by the French-American-British (FAB) classification, no direct relationship was found. The reactivity of these antibodies with leukemic cells from 63 patients with acute lymphocytic leukemiA (ALL) was also investigated, and the usefulness of these antibodies in distinguishing leukemias of myeloid from those of lymphoid origin was demonstrated.

Acute Disease↗

PubMed1985

B-cell-derived interleukin-1 (IL-1)-like factor. II. Sources, effects, and biochemical properties.

A variety of types of human B-cell lines were evaluated for their ability to produce interleukin 1 (IL-1)-like factors. All of the eight Epstein-Barr virus (EBV)-transformed B lymphocyte lines, three of four of the EBV+ lymphoma lines, only three of seven of the EBV- lymphoma lines, and none of the three tested myeloma lines secreted some IL-1 activity. The IL-1-like factor produced by the cell lines was detected on the basis of its thymocyte comitogenic and/or fibroblast proliferative activities. Injections of partially purified IL-1-like factor from one of the EBV-transformed B-lymphocyte lines also induced the appearance of an acute phase protein (haptoglobin) in the serum of C3H/HeJ mice. These biological activities are identical with those of monocyte-derived IL-1. Thymocyte comitogenic activity and fibroblast proliferation activity from one of the EBV-B cell line-derived IL-1-like activities were not dissociable by biochemical procedures, including HPLC gel filtration and HPLC anion-exchange chromatography. However, the IL-1-like factor from one of the EBV-B lymphocyte cell lines was larger in size (25 kDa) and more acidic (pI 5.5) than monocyte-derived IL-1.

Animals↗

PubMed1985

Immunodiagnosis of childhood ALL with monoclonal antibodies to myeloid and lymphoid associated antigens.

Sixty-five cryopreserved leukemic samples from children diagnosed and treated as having acute lymphocytic leukemia (ALL) were retrospectively examined for the presence of lymphoid and myeloid associated antigens by indirect immunofluorescence using monoclonal antibodies. Expectedly, the majority of these specimens expressed antigens known to be expressed on lymphoid, and not myeloid malignancies. These included the common acute lymphoblastic leukemia antigen (CALLA), the p32 B-cell associated antigen, and T-cell associated antigens. Leukemic cells from the 8 remaining patients expressed antigens known to be present on both myeloid and lymphoid leukemias. These included HLA/DR, and the antigens identified by BA-1 and BA-2. Cells from 2 of these 8 patients reacted with antibodies that define antigens present on normal and malignant myeloid cells. Both specimens reacted with 1G10, an anti-granulocyte antibody, and one reacted with 5F1 which reacts with monocytes, nucleated red blood cells, megakaryocytes and platelets. One of these patients relapsed while receiving ALL therapy, and the morphology of her leukemic cells became characteristic of acute monocytic leukemia (AMoL). The second patient failed ALL therapy but responded to standard acute nonlymphocytic leukemia (ANLL) therapy, clearing her peripheral blasts. Thus these studies confirm that cell surface phenotyping with monoclonal antibodies can recognize ALL cells that express myeloid rather than lymphoid associated antigens and demonstrate that the malignant cells display a clinical behavior consistent with the diagnosis of ANLL.

Adolescent↗