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Biomedical subjects

J Pollard

Publications and source records attributed to J Pollard.

At least 19 recordsLinked to original sources
PubMed2006

Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS.

OBJECTIVE: To conduct systematic long-term follow-up (LTFU) of patients in the Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study to provide up to 8 years of safety, clinical and MRI outcomes on subcutaneous (s.c.) interferon (IFN) beta-1a in relapsing-remitting multiple sclerosis (RRMS). METHODS: The original cohort of 560 patients was randomized to IFNbeta-1a, 44 or 22 microg three times weekly (TIW) or to placebo; after 2 years, patients on placebo were rerandomized to active treatment and the blinded study continued for a further 4 years. The LTFU visit was scheduled 7 to 8 years after baseline. RESULTS: LTFU was attended by 68.2% of the original PRISMS study cohort (382/560 patients). 72.0% (275/382) were still receiving IFNbeta-1a s.c. TIW. Patients originally randomized to IFNbeta-1a 44 microg s.c. TIW showed lower Expanded Disability Status Scale progression, relapse rate and T2 burden of disease up to 8 years compared with those in the late treatment group. Brain parenchymal volume did not show differences by treatment group. Overall, 19.7% of patients progressed to secondary progressive MS between baseline and LTFU (75/381). No new safety concerns were identified and treatment was generally well tolerated. CONCLUSIONS: Despite the limitations inherent in any long-term study (for example, potential differences between returning and nonreturning patients), these results indicate that patients with relapsing-remitting multiple sclerosis can experience sustained benefit over many years from early interferon beta-1a subcutaneous therapy three times weekly compared with patients whose treatment is delayed. This effect was more apparent in the patients receiving the higher dose.

Adjuvants, Immunologic↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Humans↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy.

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2-5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

Advisory Committees↗
PubMed2006

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

BACKGROUND: Paraprotein-associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence-based and consensus guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). METHODS: Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. RECOMMENDATIONS: In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti-myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side-effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato-oncology advice.

Advisory Committees↗
PubMed2003

Comparison of plasma biomarkers with dietary assessment methods for fruit and vegetable intake.

OBJECTIVE: To assess the variability and validity of plasma-based biomarkers of antioxidant vitamin, and fruit and vegetable intake. SETTING: Leeds, Wakefield, Huddersfield and Bradford, England. SUBJECTS: A total of 54 free-living, nonsmoking women recruited from participants of the UK Women's Cohort Study (UKWCS). METHODS: Two fasting blood samples were taken at two time points, 18 months apart. A 4-day food diary was completed prior to the first blood sample and a 24-h recall was conducted at the time of the second blood collection. All blood samples were analysed for ascorbic acid and four carotenoids. Associations between antioxidant vitamin intake from all food sources and supplements, as well as fruit and vegetable intake, and plasma levels of the antioxidant vitamins were assessed. RESULTS: Using the 4-day diary, positive associations were found between micronutrient intake from all food sources and plasma concentrations of ascorbic acid (P<0.01) and beta-carotene (P<0.01). No associations were seen between plasma micronutrient levels and specifically fruit and vegetable intakes. In general, associations between plasma levels and intakes assessed by the 24-h recall were less marked than those based on the 4-day diary. CONCLUSIONS: Plasma ascorbic acid and beta-carotene are good indicators of previous vitamin C and beta-carotene intake, from all food sources. However, caution is required in extrapolating these results to include individual food groups, rich in these vitamins. The results imply that the practice of using plasma biomarkers simply as a proxy measure of dietary intake is not valid and emphasise that plasma biomarkers are not simply a reflection of dietary intake, but also of a number of physiological processes. Biomarkers in nutrition epidemiological studies are however useful to measure nutrient status at the tissue level.

Adult↗
PubMed2003

Distribution of mercury in the tissues of five species of freshwater fish from Lake Mead, USA.

Total mercury (Hg) concentrations were determined in seven tissues (skeletal muscle, liver, blood, gonad, brain, gill, and heart) of 59 striped bass and four tissues (muscle, liver, blood, and gonad) of 69 largemouth bass, 76 channel catfish, 12 bluegill, and 22 blue tilapia collected from Lake Mead, USA. Mercury levels generally increased according to trophic level and fish length. For striped bass, mean Hg levels (ng g(-1), wet mass) were highest in the liver (531), followed by muscle (309), heart (186), gonad (136), brain (77), gill (52), and blood (36). Similarly, Hg levels in the catfish and tilapia were liver > muscle > gonad > blood. In contrast, largemouth bass and bluegill had the highest levels in muscle, followed by liver, gonad, and blood. Generally, Hg levels were strongly correlated among the tissues, especially for blood/muscle and blood/liver. As the body burden of Hg increased, the concentration in blood and organs increased relative to the concentration in muscle. The trend was most pronounced for the liver. These relationships could form the basis of a predictive model and suggest that blood and muscle (plugs) could be useful for a non-lethal measure of Hg concentration and exposure in fish. For the striped bass, elevated Hg levels in the tissues were also correlated with degree of emaciation. Liver-to-muscle ratios were similar to literature values, except for tilapia with an average ratio of approximately 1.7, which is higher than generally reported for non-piscivores. Finally, this study demonstrates the usefulness of a solid sampling approach in trace element monitoring, especially as pertaining to in vivo analysis, analysis of a large number of samples and reduction of contamination risk.

Animals↗
PubMed2001

Expression and distribution of transcription factor NF-kappaB and inhibitor IkappaB in the inflamed peripheral nervous system.

The NF-kappaB family of transcription factors is critically involved in the immune response. The activity of these proteins is under strict control of an inhibitory molecule called IkappaB. The present study investigated the expression and distribution pattern of NF-kappaB and IkappaB in sural nerve biopsies obtained from patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and various non-inflammatory neuropathies. In inflammatory demyelinating as well as non-inflammatory neuropathies, NF-kappaB was primarily expressed by macrophages, as determined by immunohistochemistry. IkappaB, however, could be localized to macrophages as well as T cells in inflammatory demyelinating neuropathies, whereas in non-inflammatory controls Schwann cells were found to be the primary cell type expressing this inhibitor. Quantitation of immunoreactivity revealed a statistically significant increase of NF-kappaB expression in inflammatory demyelinating cases compared to controls. Our results suggest an important function of the NF-kappaB pool in the genesis of inflammatory demyelination in the peripheral nervous system.

Guillain-Barre Syndrome↗
PubMed2001

Overexpression, purification, crystallization and data collection of 3-methylaspartase from Clostridium tetanomorphum.

3-Methylaspartase (E.C. 4.3.1.2) catalyses the reversible anti elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to give mesaconic acid as well as a slower syn elimination from the (2S,3R)-epimer, L-erythro-3-methylaspartic acid. The anti-elimination reaction occurs in the second step of the catabolic pathway for glutamic acid in Clostridium tetanomorphum. The reverse reaction is of particular interest because the addition of ammonia to substituted fumaric acids is highly stereoselective and gives highly functionalized amino acids. The mechanism of the transformation is unusual and of considerable interest. 3-Methylaspartase from C. tetanomorphum has been overexpressed and purified from Escherichia coli. Crystals of the enzyme have been obtained by sitting-drop vapour diffusion. Two native data sets have been collected, one in-house on a rotating-anode generator to 3.2 A and one at the European Synchrotron Radiation Facility to 2.0 A. A 2.1 A data set has been collected on a crystal of selenomethionine protein. Combining the data sets identify the space group as P2(1)2(1)2, with unit-cell parameters a = 110.3, b = 109.9, c = 67.2 A, alpha = beta = gamma = 90 degrees. The asymmetric unit contains two monomers with 42% solvent. A self-rotation function indicates the presence of a twofold axis, consistent with a biological dimer.

Ammonia-Lyases↗
PubMed2001

Lifestyle factors affecting fruit and vegetable consumption in the UK Women's Cohort Study.

The UK Women's Cohort Study (UKWCS) was originally set up to look at morbidity and mortality data on subjects with a wide range of dietary intakes including vegans, lacto-ovo vegetarians, non-red meat eaters and red meat eaters. The aim of the present study was to investigate factors that affect fruit and vegetable consumption within this particular cohort of women. Females of ages 35-69 years, taking part in the UK Women's Cohort Study (N=35 367), provided health and lifestyle information including a 217-item food frequency questionnaire. In multiple logistic regression, the strongest predictors of a higher reported level of fruit and vegetable consumption were being a vegetarian or vegan, taking vitamin or mineral supplements, being married, educated to A-level or degree level and belonging to a higher socio-economic group. Conversely, smokers were found to be only half as likely as non-smokers to be high fruit and vegetable consumers. These lifestyle distinctions among three levels of reported fruit and vegetable consumption are relevant to the future targeting of health promotion strategies.

Adult↗
PubMed2001

Hypospadias repair in adults: adventures and misadventures.

PURPOSE: To evaluate long-term results and complications we reviewed the records of 42 consecutive men 18 to 47 years old (mean age 22.5) who underwent hypospadias repair between 1979 and 1999. MATERIALS AND METHODS: The study population was divided into groups 1 consisting of 8 patients without previous hypospadias surgery, 2 consisting of 12 who underwent 1 or more procedures in childhood but in whom local tissue was relatively intact and 3 consisting of 22 who underwent multiple unsuccessful hypospadias repairs with various degrees of penile deformity and loss of local tissue. RESULTS: Complications were noted in 3 of 8 (37.5%), 5 of 12 (41.67%) and 14 of 22 (63.6%) patients in groups 1 to 3, including 3 (100%), 4 (80%) and 10 (71.4%), respectively, in whom secondary surgery was successful in the long term. A patient in group 2 and 2 in group 3 await further surgery, while 2 in group 3 were lost to followup. Overall primary complications developed in 22 of the 42 men (52.3%) and 5 of the 22 (22.7%) had secondary complications. There was long-term success in 37 of 42 cases (88.1%). CONCLUSIONS: The results of hypospadias repair in adulthood differ from the results of similar procedures in childhood. Although the various techniques are similar, there is clearly a difference in terms of wound healing, infection, complication rates and overall success. Adults undergoing hypospadias repair must be counseled on all of these variables to avoid unreasonable expectations.

Adult↗
PubMed1999

PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.

PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.

Animals↗
PubMed1999

Rapamycin reverses chronic graft vascular disease in a novel cardiac allograft model.

BACKGROUND: Chronic graft vascular disease (CGVD) in cardiac allografts has been defined as a slowly evolving vasculopathy unresponsive to conventional immunosuppression. We compared 4 rodent models of CGVD to evaluate the reproducibility of CGVD in heart allografts. Rapamycin (Rapa) and cyclosporine (CSA) were then used to treat CGVD. METHODS AND RESULTS: Hearts were harvested and placed heterotopically into allogenic recipients. CGVD scores of PVG allografts from ACI recipients treated with CSA on days 1 through 10 were significantly elevated on day 90 (n=16) compared with other models (immunosuppression used): (1) Lewis to F344 recipients (CSA), (2) Brown Norway to Lewis (FK506), and (3) DA to Wistar-Firth (methylprednisolone, azathioprine, CSA). Although delayed (day 60 to 90) CSA treatment had no effect (n=6), delayed Rapa (3 mg. kg-1. d-1 IP) reversed CGVD in PVG grafts (0.22+/-0.19 on day 90, n=6). ACI isografts showed no evidence of CGVD (n=6) at day 90. Immunohistochemistry of PVG grafts revealed perivascular infiltrates consisting of CD4(+) T cells and limited numbers of macrophages persisting up to day 90. Flow cytometry demonstrated increased levels of anti-donor antibody at day 90, which was significantly inhibited by Rapa treatment. CONCLUSIONS: PVG grafts developed a significant increase in CGVD without evidence of ongoing myocardial rejection. This CGVD appeared to be mediated by both cellular and humoral mechanisms, given CD4(+) perivascular infiltrates and increased levels of anti-donor antibody. The anti-CGVD effectiveness of Rapa during a period in which there was little myocardial cellular infiltrate supports a novel mechanism of effect such as smooth muscle or B-cell inhibition.

Animals↗
PubMed1998

Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts.

OBJECTIVE: We hypothesized that ex vivo hyperbaric transfection of antisense oligodeoxynucleotides for blockade of intercellular adhesion molecule-1, an important mediator of cell adhesion and T-cell co-stimulation, would reduce chronic graft vascular disease in cardiac allografts. METHODS: PVG hearts underwent ex vivo transfection with antisense, reverse antisense intercellular adhesion molecule-1 oligodeoxynucleotide (80 micromol/L), or saline solution at 3 atm pressure for 45 minutes at 4 degrees C and were transplanted heterotopically into ACI recipients with or without treatment with intercellular adhesion molecule-1 (1A29) or leukocyte function associated antigen-1 (WT.1) monoclonal antibodies. Transfection efficiency was confirmed with fluorescein isothiocyanate-labeled oligodeoxynucleotides and fluorescent microscopy. Efficacy of intracellular adhesion molecule-1 blockade was assessed with the use of immunohistochemistry. Graft reperfusion injury was evaluated at 6 to 24 hours by neutrophil infiltration (myeloperoxidase [MPO]), cardiac edema (%wt/wt), and histologic injury (percent contraction band necrosis). Grafts from recipients treated with cyclosporine A (5 mg/kg per day, days 0 to 9) were scored for chronic graft vascular disease on postoperative day 90 ranging from 0 (no involvement) to 4 (>50% vascular occlusion). RESULTS: Transfection was highly efficient (fluorescein isothiocyanate-labeled oligodeoxynucleotides in 48%+/-5% of total myocardial nuclei) and effective at blocking intracellular adhesion molecule-1 expression (positive area in allografts taken on postoperative day 3 was reduced from 100%+/-0% to 52%+/-14%, n=4). Blockade with antisense oligodeoxynucleotides versus monoclonal antibodies was less effective at preventing reperfusion injury while more effective at reducing chronic graft vascular disease (score 0.98+/-0.48, p < 0.05). Reverse antisense oligodeoxynucleotides and vector control (antisense oligodeoxynucleotide infusion without pressure) groups failed to demonstrate this beneficial effect. CONCLUSION: Hyperbaric transfection of antisense oligodeoxynucleotides proved highly efficient, effective at blockade of intracellular adhesion molecule-1, and demonstrated a sequence-specific reduction in chronic graft vascular disease. This highly targeted alteration of donor organ immunogenicity may have an important future role in clinical immunosuppressive strategies.

Animals↗
PubMed1998

Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE).

The optic nerve of rats with EAE was examined at various times to determine the integrity of the blood-brain barrier (BBB) and to assess monocyte-macrophage, T cell, and microglial responses. In naive control animals, leakage of horseradish peroxidase (HRP) and the presence of cells expressing major histocompatibility complex (MHC) class II antigen were evident in the meninges of the retrobulbar optic nerve. In rats with EAE, microglia in the region of the lamina cribrosa and in the regions adjacent to the meninges became activated from day 7 to 8 postinduction (pi). HRP leakage was also evident in the region of the lamina cribrosa from day 7 to 8 pi. On day 8 pi, infiltration of inflammatory cells and Monastral blue leakage were apparent in the myelinated region of the optic nerve. The intensity of these cellular and vascular changes peaked at day 12 pi, when signs of clinical disease became manifest. Monocytes-macrophages expressing MHC class II and the ED1 antigen, together with lymphocytes expressing the alphabetaT cell receptor, constituted the major proportion of cells associated with inflammatory lesions. Thus: (i) the inherent weakness of the BBB as well as the presence of both antigen (myelin) and MHC class II+ cells in the retrobulbar optic nerve are likely susceptibility factors for the frequent involvement of this region in EAE and multiple sclerosis; and (ii) activation of microglia occurs early in the pathogenesis of experimental optic neuritis.

Animals↗
PubMed1998

Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE).

The microvascular and cellular responses in the retina during acute EAE were characterized using whole-mount preparations. The earliest detectable event was the accumulation of monocytes and T cells within veins on day 7 postinduction (pi). Mild breakdown of the blood-retinal barrier (BRB), activation of microglia and infiltration of monocytes and T cells into the retinal parenchyma were first evident on days 7 to 8 pi. Monocyte adhesion to the vessel wall and breakdown of the BRB were colocalized in the same vessel segments and occurred predominantly in veins. The marked difference in response observed in the retina versus the myelinated region of the optic nerve suggests that two types of inflammatory cascades are initiated. A mild response, characterised by very low numbers of T cells and monocytes and an absence of expression of MHC class II by resident microglia, is initiated when only small amounts of the encephalitogenic antigen are present in the perivascular space or associated with perivascular antigen-presenting cells. A full blown inflammatory reaction, as observed in the optic nerve, is initiated in the presence of substantial amounts of encephalitogenic antigen. This severe response is characterised by the infiltration of large numbers of CD4+, CD8+ T cells and ED1+ monocytes, and by abundant MHC class II expression by resident microglia as well as other cell types. Thus, MHC class II expression by resident microglia may be a possible effective amplifier mechanism if the encephalitogenic antigen is encountered in the tissue parenchyma.

Animals↗
PubMed1997

Effects of increased ICAM-1 on reperfusion injury and chronic graft vascular disease.

BACKGROUND: The purpose of this study was to assess the impact of increased donor cardiac intercellular adhesion molecule (ICAM-1) expression on both reperfusion injury and chronic graft vascular disease after transplantation. METHODS: Hearts were harvested from donor rats before and after pretreatment with lipopolysaccharide at -24 hours, underwent 45 minutes of cold ischemia, and were transplanted into ACI recipients with or without anti-ICAM-1 monoclonal antibody treatment. Grafts were procured early for analysis of ICAM-1 expression and reperfusion injury or the recipients were treated with cyclosporin A (to allow long-term graft acceptance) for postoperative days 0 through 9 with procurement on postoperative day 90 to histologically score for chronic graft vascular disease. RESULTS: Lipopolysaccharide-pretreated PVG heart grafts showed increased ICAM-1 expression by Northern blot and immunohistochemical analysis leading to increased reperfusion injury as assessed by neutrophil infiltration (myeloperoxidase), cardiac edema (percentage wet weight), and histologic injury (percentage area of contraction band necrosis), which was reversed by recipient treatment with anti-ICAM-1 monoclonal antibody. After administration of cyclosporin A, 5 mg/kg for 10 days, lipopolysaccharide-treated grafts had significantly worse chronic graft vascular disease scores (2.56 +/- 0.57 versus 1.84 +/- 0.75; p < 0.05 by Mann-Whitney U test). CONCLUSIONS: The induction donor inflammatory state before harvest leading to increased cardiac ICAM-1 expression promotes reperfusion injury and chronic graft vascular disease after transplantation in this rodent heterotopic heart model.

Animals↗
PubMed1997

T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease.

This study describes a novel method of inhibiting T-cell function by the use of peptides rationally designed from the T-cell antigen receptor (TCR) alpha-chain transmembrane sequence involved with TCR receptor assembly. The most effective peptide (core peptide, CP) modulating in vitro and in vivo T-cell function contained nine amino acids two of which, lysine and arginine, were hydrophilic and separated by four hydrophobic amino acids. CP without chemical modification or conjugation was able to enter non-T and T cells. Conjugation of CP at the carboxyl terminus with palmitic acid resulted in a greater inhibition of T-cell interleukin-2 (IL-2) production in vitro than peptide alone. When examined for effects in vivo, CP reduced clinical signs of inflammation in three T cell-mediated disease models including adjuvant-induced arthritis, experimental allergic neuritis, and cyclophosphamide-induced diabetes in NOD/Lt(F) mice. This peptide or its analogues has potential as a therapeutic agent in human inflammatory and autoimmune disorders.

Amino Acid Sequence↗