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Biomedical subjects

C Carter

Publications and source records attributed to C Carter.

At least 145 records · Page 8Linked to original sources
PubMed1993

Use of interleukin-7, interleukin-2, and interferon-gamma to propagate CD4+ T cells in culture with maintained antigen specificity.

In contrast to CD8+ T cells, it has been difficult to establish consistently satisfactory conditions for the bulk culture of antitumor CD4+ T cells in either mice or humans. This difficulty is not limited to tumor antigen, since similar problems are encountered growing CD4+ T cells that recognize alloantigen, tetanus, or candida. Four basic findings are reviewed in this article, stemming from work with identical results in both human and mouse. (a) Although CD4+ T cells initially proliferate after exposure to appropriate antigen-presenting cells (APCs), such proliferation is not sustained; however, expansion of CD4+ T cells can be achieved with the addition of recombinant interleukin-2 (rIL2) or rIL-7. (b) Specific CD4+ responses to antigens are often better sustained with exogenous IL-7 than with exogenous IL-2. (c) Adding rIL-7 or rIL-2 permits sustained CD4+ T-cell proliferation, but subsequent culture restimulation is complicated by high background reactivity to APCs whether APCs are antigen pulsed or not; this problem can be overcome by addition of exogenous interferon-gamma (IFN-gamma) to the CD4+ cultures. (d) In certain instances proliferation is paradoxically impaired by reexposure to specific antigen, possibly reflecting apoptosis; this problem is also overcome by addition of rIFN-gamma to culture. We conclude that combinations of exogenous IL-7, IL-2, and IFN-gamma with APC restimulation can be used to sustain antigen-specific CD4+ T cells in culture. Using these techniques, antitumor CD4+ T cells were propagated from the peripheral blood of two tumor-bearing patients.

Animals↗
PubMed1993

Ouabain releases striatal polyamines in vivo independently of N-methyl-D-aspartate receptor activation.

Intrastriatally infused ouabain (200 or 1,000 microM) markedly increased the extracellular levels of striatal spermidine and spermine in dialysis experiments in halothane-anesthetized rats. The effects of ouabain (1 mM) on spermidine release were rapid and unaffected by local infusion of the competitive N-methyl-D-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 100 microM) or by systemically administered MK-801 (0.3 mg/kg i.p.), both of which treatments markedly inhibit the effects of intrastriatally administered NMDA. The peak effects of ouabain (1 mM) on spermine release were delayed with respect to those on spermidine release, or to the effects of NMDA, and were also insensitive to locally administered CPP (100 microM). However, systemically administered MK-801 (0.3 mg/kg i.p., 30 min before the striatal infusion of drugs), which totally inhibits the effects of NMDA, or CPP (10 mg/kg i.p.; 30 min before the striatal infusion of drugs) partially inhibited the effects of ouabain on spermine release, suggesting partial mediation of the delayed effects of ouabain on spermine release by indirect NMDA-receptor activation. Despite partial sensitivity of ouabain-induced spermine release to systemically administered NMDA antagonists, both spermidine and spermine can be released in vivo by sodium-pump inhibition, independently of NMDA-receptor activation.

Animals↗
PubMed1993

Measuring persistence and personality characteristics of adolescents.

The concept of persistence (to hold firmly and steadfastly to some purpose or task) has been reportedly related to personality development, motivation, and locus of control. However, there is a dearth of research on persistence primarily because a widely accepted and validated measure of persistence is lacking. A 1987 measure, the Persistence Scale for Children by Lufi and Cohen, has been the subject of validation and reliability studies. The present paper is a description of its use with 50 adolescents and the correlations between persistence and the adolescents' personality characteristics, based on Cattell's High School Personality Questionnaire. Correlations between persistence and HSPQ personality characteristics were significant. Replication with a larger sample and continued use in the study of persistence is discussed as well as persistence in relation to adolescent development.

Adolescent↗
PubMed1993

A phase I trial of carboplatin and etoposide given as continuous infusions to adults with leukemia.

Thirty-two adult patients with acute leukemia were treated with continuous infusion carboplatin and etoposide at eight different dose levels. Dose limiting toxicity was encountered at doses of carboplatin of 310 mg/m2 per day for 5 days (total 1550 mg/m2 per course) and etoposide 150 mg/m2 per day for 5 days (total dose 750 mg/m2 per course) and consisted primarily of gastrointestinal toxicity. Of the five courses given at the highest dose level, three were complicated by grade 4 gastrointestinal toxicity. The recommended dose for further phase II evaluations in acute leukemia is carboplatin 250 mg/m2 per day for 5 days by continuous infusion and etoposide 150 mg/m2 per day for 5 days given by continuous infusion. The response to treatment was notable for a single complete remission achieved in a patient with acute undifferentiated leukemia. None of the patients with chronic myeloid leukemia in blast crisis (n = 12) or with acute lymphocytic leukemia (n = 4) or acute myeloid leukemia (AML) (n = 15) achieved complete remission (CR), although all patients with AML entered on this trial had prior complete remissions that were less than 1 year in duration, and many were refractory, either to primary therapy or to the most recent attempt to obtain CR.

Acute Disease↗
PubMed1992

Neurotoxic effects of the intrastriatal injection of spermine and spermidine: lack of involvement of NMDA receptors.

The injection into the rat striatum of the polyamines spermine and spermidine (30-300 nmol) produced, 1 week after injection, a dose related loss of the neuronal markers glutamate decarboxylase and choline acetyltransferase and a decrease in the density of N-methyl-D-aspartate (NMDA) receptors (as labelled with [3H]TCP). In parallel, an increase in peripheral type benzodiazepine (p) binding site density (a marker of the associated glial reaction and macrophage invasion) was observed. Intrastriatal injection of putrescine (300 nmol) did not significantly alter any of these markers. The effect of spermine on these neuronal and glial markers was maximal 3 days after injection, and tended towards control levels at 16 days post injection. The neurotoxic effects of spermine were confirmed by histological analysis demonstrating a massive neuronal loss around the injection site and an accumulation of astrocytes and phagocytes. The neurotoxic effects of spermine (250 nmol) were not antagonised by the previous administration of the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.). Thus polyamine neurotoxicity in vivo does not seem to involve NMDA receptor activation, although it may possibly be related to the multiple effects of these compounds on diverse calcium channels and processes regulating calcium homoeostasis.

Animals↗
PubMed1992

Panic disorder and chest pain in the coronary care unit.

Consecutive admissions to a university hospital coronary intensive care unit were prospectively evaluated using a modified version of the Structured Clinical Interview for DSM-III-R by interviewers blind to the patient's cardiac status. Panic disorder was present in almost one-third of the patients. Four (21%) of the 19 patients with panic disorder also had positive cardiac findings, including 2 who had myocardial infarctions. Of the 27 patients with negative cardiac findings, 15 (55.5%) had panic disorder. Whereas panic disorder and coronary heart disease may coexist in patients with acute chest pain, there appears to be a very high prevalence of panic disorder among patients in whom cardiac disease has been excluded.

Adult↗
PubMed1992

Implication of the polyamines in the neurotoxic effects of N-methyl-D-aspartate.

N-Methyl-D-aspartate (NMDA) receptor activation selectively releases the polyamines spermine and spermidine from the rat striatum in vivo. The intrastriatal injection of spermine or spermidine is neurotoxic, but this toxicity is not blocked by MK-801 and unlikely to be mediated via the NMDA receptor. The neurotoxic effects of intrastriatally injected NMDA can, however, be reduced by polyamine synthesis inhibition with difluoromethylornithine. Alterations in polyamine metabolism in the ischaemic brain, although perhaps induced by NMDA receptor activation, may contribute to ischaemic cell loss via NMDA-independent mechanisms, possibly related to the diverse effects of polyamines on calcium homoeostasis and channel function.

Animals↗
PubMed1992

Inactivation of the human immunodeficiency virus by hypericin: evidence for photochemical alterations of p24 and a block in uncoating.

Following attachment and entry of human immunodeficiency virus (HIV) into a host cell, the HIV genomic RNA is reverse transcribed to cDNA. This step may be inhibited by hypericin, a compound that induces alterations of the retroviral capsid. Incubation of HIV with hypericin rendered the virus noninfectious. The replication of HIV was blocked early; HIV cDNA could not be detected in cells challenged with hypericin-treated HIV. Hypericin did not inhibit the binding of recombinant gp120 to CD4+ cells, nor did hypericin inhibit syncytium formation. However, reverse transcriptase activity could not be released from hypericin-treated virions. Western blot analysis revealed altered mobility of the HIV major capsid protein (p24) following hypericin treatment. Hypericin-treated recombinant HIV p24 exhibited similar altered mobility. The inactivation of HIV infectivity and the alterations in p24 mobility required hypericin incubations in the presence of visible light. Collectively, these data suggest that photochemical alterations of the HIV capsid may contribute to the hypericin-mediated inactivation of HIV. Such alterations may inhibit the release of RT activity from treated HIV, and prevent uncoating and subsequent reverse transcription of the HIV genome within a target cell.

Anthracenes↗
PubMed1992

The endothelial heparan sulfate-antithrombin III natural anticoagulant pathway in normal and transplanted human kidneys.

This is the first study of the antithrombin III-heparan sulfate natural anticoagulant pathway in human kidneys. Immunocytochemical experiments were done to demonstrate the pathway on normal renal endothelial cells. Enzymatic studies were done to show that the antithrombin III was anchored to endothelium by molecules of heparan sulfate. Displacement studies were done with glycosaminoglycans to show that the antithrombin III was bound to its glycosaminoglycan anchor via a heparinlike binding site, and replacement studies showed that antithrombin III could be returned to the same endothelial cells from which it was displaced. Immunocytochemical studies of biopsies showed that normally functioning renal allografts manifested the endothelial antithrombin III-heparan sulfate anticoagulant pathway. The pathway was compromised or absent from the microcirculation of biopsies from rejecting or rejected renal allografts, and the diminishment of endothelial ATIII was associated with the presence of fibrin deposition. It is concluded that compromise of the antithrombin III-heparan sulfate natural anticoagulant pathway results in compromised renal function in transplanted kidneys.

Adolescent↗
PubMed1992

Tissue factor in normal and transplanted human kidneys.

Tissue factor (TF) plays a central role in the initiation of blood coagulation that frequently is enhanced in renal allografts. The identification and localization of TF was studied immunocytochemically in biopsies from normal and transplanted human kidneys and classified according to its distribution. The clinical status of each allograft was then correlated with the TF classifications. From these correlations, four distributional types of TF were identified. In normal kidneys, TF was localized to glomerular epithelium and basement membranes. Glomerular TF expression did not colocalize with mesangial or endothelial HLA-DR reactivity as determined by double antibody techniques. Tissue factor in donor kidneys also was identified in the renal capsule and in the adventitia of large arteries. These structures were not reactive in long-term transplanted grafts. Some cadaver kidneys prepared for transplantation had depleted glomerular TF, and exhibited TF reactivity within stromal tissues. Long-term allografts with progressive loss of renal function and kidneys with advanced rejection exhibited diminished TF reactivity of glomerular epithelium and basement membranes. This was frequently associated with fibrin deposition within the glomeruli and in the intertubular microcirculation. These findings indicate that the evaluation of TF in transplanted kidneys is related to the prognosis of graft survival.

Adult↗
PubMed1992

Novel immunohistochemical markers of human renal allograft dysfunction--antithrombin III, Thy-1, urokinase, and alpha-smooth muscle actin.

We have studied the expression of alpha-smooth muscle actin (alpha sm-1) by mesangial cells, and the expression of Thy-1 glycoprotein, antithrombin III (ATIII), and urokinase by tubular epithelial cells in normal kidneys and dysfunctional renal allografts. Kidney biopsies were studied immunocytochemically for changes in each of these markers and the findings were classified into two groups and compared with creatinine plasma levels at the time the biopsies were taken. In dysfunctional grafts, mesangial alpha sm-1 and tubular epithelial Thy-1 reactivities were greatly diminished, and urokinase and ATIII were missing from proximal renal tubular epithelial cells. Urokinase, which was absent from normal renal glomeruli, appeared in glomeruli of some dysfunctional allografts. The possible usefulness of these markers in patient evaluations was supported by our finding that the distribution of vinculin, fibronectin, myosin, actin B4, desmin, glomerular HLA-DR, and the tubular expression of CD15 remained unchanged. These data prompt us to suggest that the immunocytochemical localization and evaluation of alpha sm-1, Thy-1, ATIII, and urokinase in kidney allografts may be useful adjuncts in the assessment of function in renal allografts.

Actins↗
PubMed1992

HLA-DRw52-associated DRB1 alleles: identification using polymerase chain reaction-amplified DNA, sequence-specific oligonucleotide probes, and a chemiluminescent detection system.

Polymerase chain reaction (PCR) primers were designed to specifically amplify exon 2 of the DRw52-associated DRB1 alleles for subsequent typing by sequence-specific oligonucleotide probe (SSOP) hybridization and chemiluminescent detection. The DRw52 DRB1 group, encoding 22 of the 44 W.H.O. designated DRB1 allelic products, was divided by differential PCR with two polymorphism-directed forward primers. Based on a polymorphism at codon 13, these forward primers separate the DRw52-associated alleles into subsets; one comprised of the alleles of DR3/DRw11/DRw6 and the other of DRw8/DRw12/DRB1*1404. The DRB1 alleles in the latter subset were then defined by SSOP hybridization to the amplified DNA. The preferential amplification also resulted in SSOP definition of 15 alleles in the DR3/DRw11/DRw6 subset but some DRw11/DRw13 heterozygous allelic combinations were still unresolved. Two reverse PCR primers specific for the polymorphism at codon 86 were used to obtain amplified material to which SSOP reactivity provided definitive identification of the ambiguous heterozygotes.

Adult↗
PubMed1992

Selective release of spermine and spermidine from the rat striatum by N-methyl-D-aspartate receptor activation in vivo.

The intrastriatal infusion of N-methyl-D-aspartate (NMDA; 250-1,000 microM) via a dialysis cannula in anesthetized rats resulted in a marked and rapid increase in the concentrations of spermine and spermidine recovered in the dialysate. Extracellular concentrations of NMDA-released spermine and spermidine were calculated to be in the low micromolar range. Putrescine levels were not significantly affected by NMDA. The effects of NMDA (500 microM) were blocked by the previous systemic injection of MK-801 (3 mg/kg, i.p.) but were insensitive to the intrastriatal infusion of tetrodotoxin (1 microM). Intrastriatally infused kainate or quisqualate (1,000 microM) did not increase polyamine levels in the dialysate. Spermine and spermidine dialysate levels were also significantly increased by the infusion of high concentrations of K+ (greater than 100 mM), although the effects of K+ were considerably less marked than those of NMDA. Striatal polyamines are released into the extracellular space specifically by NMDA receptor activation. Because of their multiple effects on receptor- and voltage-operated cation channels, polyamines that are released by NMDA receptor activation may play an important role in phenomena already attributed to NMDA receptor stimulation, such as long-term potentiation, synaptic plasticity, and neurotoxicity.

Animals↗
PubMed1992

Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.

We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.

Adenosine↗