Down-regulation of cell surface CXCR6 expression during T cell activation is predominantly mediated by calcineurin.

CXCR6, the receptor for the membrane-anchored chemokine, CXCL16, is expressed on a subset of CCR5-bearing memory T cells, and may play a role in recruiting these cells to sites of inflammation. Here, we set out to determine the effect of T cell activation on CXCR6 expression. Highly purified human peripheral blood T cells were cultured for 7-8 days in presence of IL-2 (400 U/ml) to enhance CXCR6 expression.

Assessment of neuroinflammation and microglial activation in Alzheimer's disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study.

Objectives: Inflammation contributes to degeneration in Alzheimer's disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [(123)I]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, the latter being expressed on microglia (brain resident macrophages) and upregulated under inflammatory circumstances. The objectives were to assess AD inflammation by detecting [(123)I]iodo-PK11195 uptake changes and investigate how uptake values relate with perfusion SPECT and neuropsychological findings.

Regional binding index of the radiolabeled selective 5-HT2A antagonist 123I-5-I-R91150 in the normal canine brain imaged with single photon emission computed tomography.

The pattern of the specific 5-HT2A (5-hydroxytryptamine 2A receptor) antagonist 123I-5-I-R91150 was measured in 10 healthy dogs without neurologic and behavior abnormalities. Eight cortical regions (left and right fronto-, temporo-, parieto-, and occipitocortical area), one global subcortical region (including the thalamic system) were compared with a reference region lacking receptors; that is, the cerebellum. The 123I labeled radioligand was injected intravenously 100-200 minutes before acquisition.

Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors.

The synthesis and evaluation of [(11)C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [(11)C] methyl iodide afforded the title compound [(11)C]zolpidem in a yield of 19.19 +/- 3.

An EP2 receptor-selective prostaglandin E2 agonist induces bone healing.

The morbidity and mortality associated with impaired/delayed fracture healing remain high. Our objective was to identify a small nonpeptidyl molecule with the ability to promote fracture healing and prevent malunions. Prostaglandin E2 (PGE2) causes significant increases in bone mass and bone strength when administered systemically or locally to the skeleton.

Imaging of the 5-HT2A system: age-, gender-, and Alzheimer's disease-related findings.

Serotonin (5-HT) and more specifically the 5-HT(2A) receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimer's disease (AD). The objective was to assess the 5-HT(2A) binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT(2A) receptor antagonist. Twenty-six controls and nine AD patients were included.

Influence of cooling rate on Saccharomyces cerevisiae destruction during freezing: unexpected viability at ultra-rapid cooling rates.

The purpose of this work was to study cell viability as a function of cooling rate during freezing. Cooling rate strongly influences the viability of cells during cold thermal stress. One of the particularities of this study was to investigate a large range of cooling rates and particularly very rapid cooling rates (i.

Decreased 5-HT2a receptor binding in patients with anorexia nervosa.

Unlabelled: Indirect estimations of brain neurotransmitters in patients with anorexia nervosa (AN) and low weight have demonstrated a reduction in brain serotonin (5-HT) turnover in general and led to hypotheses about dysfunction in the 5-HT(2a) receptor system. It was our aim to investigate the central 5-HT(2a) receptor binding index using SPECT brain imaging.

Methods: The 5-HT(2a) receptors of low-weight patients with AN were studied by means of the highly specific radioiodinated 5-HT(2a) receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or (123)I-5-I-R91150.

Effects of mirtazapine on sleep polygraphic variables in major depression.

Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated.

Scintigraphic visualization of inflammation in neurodegenerative disorders.

In the past few decades, our understanding of the central nervous system has evolved from one of an immune-privileged site, to one where inflammation is pathognomonic for some of the most prevalent and tragic neurodegenerative diseases. Current research indicates that diseases as diverse as multiple sclerosis, stroke and Alzheimer's disease exhibit inflammatory processes that contribute to cellular dysfunction or loss. Inflammation, whether in the brain or periphery, is almost always a secondary response to a primary pathogen.

Biodistribution and displacement studies of the selective 5-HT2A receptor antagonist 123I-5-I-R91150 in the normal dog.

There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT(2A) receptors in the brain, was introduced for SPET.

CAMPATH (alemtuzumab) for the treatment of chronic lymphocytic leukemia and beyond.

CAMPATH (CAMPATH-1H, alemtuzumab, MabCAMPATH), is a lymphocyte-depleting humanized monoclonal antibody that was recently approved in the USA and Europe for the treatment of chronic lymphocytic leukemia (CLL). It targets CD52--a small glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on normal T- and B-lymphocytes and on a large proportion of lymphoid cell malignancies--but not on hematopoietic progenitor cells. CAMPATH was shown to be effective against CLL refractory to chemotherapy with an acceptable toxicity profile.

IDEC-131. IDEC/Eisai.

IDEC, in collaboration with Eisai, is developing IDEC-131 (E6040), a humanized monoclonal antibody (mAb) against CD154, the ligand for CD40 also called CD40L or gp39, for the potential treatment of several autoimmune diseases. IDEC-131 is based on technology that IDEC licensed from Dartmouth Medical School where researchers demonstrated the biological effects of the anti-CD154 antibody in animal models of autoimmunity. In January 2001, phase II trials in psoriasis and idiopathic thrombocytopenic purpura (ITP) were initiated.

Synthesis and in vitro evaluation of N,N'-diphenyl and N-naphthyl-N'-phenylguanidines as N-methyl-D-aspartate receptor ion-channel ligands.

A series of N,N'-diphenyl and N-naphthyl-N'-phenyl guanidine derivatives was synthesized as potential N-methyl-D-aspartate (NMDA) receptor positron emission tomography (PET) ligands. The affinity of the different compounds was determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of N'-3 and N'-3,5 substitution on affinity and lipophilicity was examined.

An infected hip prosthesis in a dog diagnosed with a 99mTc-ciprofloxacin (infecton) scan.

This case report describes the use of the 99mTc-labeled radiopharmaceutical ciprofloxacin (Infecton) in a case of hip prosthesis loosening in a dog. Serial planar radiographs were not conclusive, and culture of the synovial fluid was negative. Antibiotic treatment did not result in improvement of the lameness.

Mirtazapine, but not fluvoxamine, normalizes the blunted REM sleep response to clonidine in depressed patients: implications for subsensitivity of alpha(2)-adrenergic receptors in depression.

To determine whether alpha(2)-adrenergic receptor (alpha2AR) subsensitivity is a state or a trait marker of depression, we consecutively challenged 32 drug-free depressed patients with a clonidine REM suppression test (CREST). We then treated the patients with fluvoxamine, a selective serotonin reuptake inhibitor, or mirtazapine, a selective alpha(2)-adrenergic receptor antagonist. The first 10 patients from each treatment group who recovered were given a second challenge test.

Everolimus. Novartis.

Everolimus (RAD-001, SDZ RAD, Certican), an analog of sirolimus, is an oral immunosuppressant that inhibits growth factor-induced cell proliferation, under development by Novartis as a potential treatment for transplant rejection. Phase III trials were initiated by the end of 1998 [319337] and were ongoing in February 2001 [400448]. At the end of 2000, Novartis was hoping to file for approval of the compound in 2001 [392881], with a possible launch in mild-2002 [392881], [401979].

Biodistribution and dosimetry of (99m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies.

Unlabelled: The aim of this study was to determine the human biodistribution and radiation dosimetry of (99m)Tc-RP527, a promising radioligand for the visualization of gastrin-releasing peptide (GRP) receptor-expressing human malignancies.

Methods: Whole-body scans were obtained up to 48 h after intravenous injection of 555 MBq (99m)Tc-RP527 in each of 6 subjects. Blood samples were taken at various times up to 48 h after injection.

Treatment of transplant rejection: are the traditional immunosuppressants good enough?

Due to the improvement in the understanding of the anti-allogenic immune response, the success of transplantation medicine has increased rapidly over the last two decades. The knowledge that the T-lymphocyte played an integral role in transplant rejection, brought cyclosporine A and FK-506 to the fore as therapeutic immunosuppressants. However, the current mainstays in transplant rejection are not without their problems and many drug companies are exploring the possibilities of improving the available therapies by developing drugs with reduced toxicity, improved long-term survival and efficacy against chronic rejection and improved immunosuppressive selectivity.

Alemtuzumab (Millennium/ILEX).

Alemtuzumab, a lymphocyte-depleting humanized monoclonal antibody, is being developed by Millennium Pharmaceuticals Inc and ILEX Oncology for the potential treatment of chronic lymphocytic leukemia (CLL) [274580]. The utility of the compound for treating bone marrow (BM) stem cell transplantation-associated graft-versus-host disease (GVHD) [372946] and for ex vivo purging of BM to remove malignant T-cells [244056] is also being investigated. Additional potential therapeutic areas for which clinical trials are planned or ongoing include vasculitis, multiple sclerosis [288762] and organ transplantation [338304].

Non-invasive methods for absolute cerebral blood flow measurement using 99mTc-ECD: a study in healthy volunteers.

Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis (SA). Other methods estimate CBF by means of single-point arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as potential clinical non- to minimally invasive methods for CBF determination in a large set of carefully screened healthy volunteers over the adult age range.

Biodistribution and dosimetry of 99mTc-ciprofloxacin, a promising agent for the diagnosis of bacterial infection.

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection.