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J Hodgson

Publications and source records attributed to J Hodgson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Molecular evaluation of enteroviruses in the pathogenesis of idiopathic dilated cardiomyopathy.

BACKGROUND: There is great disparity in the literature as to the presence and relevance of enterovirus in heart tissue from patients with dilated cardiomyopathy (DCM). Published estimates of enteroviral positive tissue in DCM range from 0 to 50%. Very little sequence information is so far available on those samples which are positive. HYPOTHESIS: Re-examination of fresh biopsy material from patients previously tested, plus 13 new cases of DCM, and sequencing the products would yield information on the validity of the technique and on the type of virus being detected. METHODS: RNA from biopsy or explant tissue was tested for the presence of enterovirus using reverse transcriptase polymerase chain reaction (PCR). The nucleotide sequences of all positive PCR products were determined by direct sequencing. RESULTS: Positive PCR signals were found in 10% of samples from patients with DCM and in 16% of control tissues. Two DCM and 12 control samples gave the same nucleotide sequence, which was different from the CB3 used as a positive control. The other 4 DCM samples all produced multiple bands on sequencing. CONCLUSION: The results do not support a major role for enterovirus in DCM. There is need for some caution, however, as a review of the literature shows that studies using single biopsies, such as this one, produce consistently lower estimates for enterovirus than do those wherein multiple biopsies are examined.

Adolescent↗
PubMed1997

Effect of the in vivo priming regimen for peripheral blood stem cells (PBSC) mobilization on in vitro generation of cytotoxic effectors by IL-2 activation of PBSC in a murine model.

Priming of patients with different PBSC mobilizing regimens leads to an increase by several fold in circulating hematopoietic progenitors in peripheral blood. However, the effect of these mobilizing regimens on lymphoid cells contained within the harvested PBSC population is not well understood. We have studied the effect of CY and/or G-CSF +/- IL-2 containing regimens on lymphoid cells, and their capacity to give rise to cytotoxic effectors on subsequent in vitro IL-2 activation in a murine model of PBSC mobilization. C57B1/6 mice were given CY 100 or 200 mg/kg on day 0 followed 48 h later by G-CSF 125 micrograms/kg twice a day and/or IL-2 60000 i.u. twice a day in different schedules. Mice were sacrificed on day 4, 6, 8 and 10 following CY and the number of hematopoietic progenitors mobilized to the spleens of these mice was assessed by CFC assay and cytotoxicity was evaluated by 4 h 51Cr release assay against both NK-sensitive (Yak-1), and NK-resistant (B16, C1498) cell lines after 24 h in vitro IL-2 activation in the presence of 6000 i.u./ml of IL-2. Peak numbers of CFC in the splenic PBSC population were seen on day 6 following CY. Administration of CY 200 mg/kg + GCSF, the most potent regimen for CFC mobilization, led to a marked decrease in proportion of CD3+ cells in day 6 PBSC as compared to controls (17.7% vs 3.9%) and was associated with a significant decrease in generation of cytotoxic cells after IL-2 activation. Combining IL-2 to CY + G-CSF prevented the marked loss in cytotoxicity associated with this regimen without any decrease in number of CFC mobilized. When IL-2 was combined with CY without G-CSF, the number of CFC mobilized was comparable to that seen with CY + G-CSF and these CY + IL-2 mobilized PBSC generated potent cytotoxic effectors after in vitro IL-2 activation. Thus our results indicate that combining IL-2 with a PBSC mobilizing regimen can avert a decrease in the cytotoxic potential of mobilized cells without compromising the number of hematopoietic progenitors.

Animals↗
PubMed1996

Use of a dipeptide chemical library in the development of non-peptide tachykinin NK3 receptor selective antagonists.

The use of a dipeptide library as the source of a micromolar chemical lead compound for the human tachykinin NK3 receptor is described. The screening of a dipeptide library through a cloned human NK3 receptor binding assay resulted in the identification of Boc(S)Phe(S)PheNH2 (1), which has subsequently been developed, following a 'peptoid' design strategy, into a series of high-affinity NK3 receptor selective antagonists. The structure-activity relationship of the C-terminal portion of this dipeptide lead was first explored and led to the identification of the urea derivative Boc(S)Phe(R)alphaMePheNH(CH2)7NHCONH2 (41, PD157672). This modified dipeptide has a Ke of 7 nM in blocking senktide-induced increases in intracellular calcium levels in human NK3 receptors stably expressed in CHO cells. Subsequent optimization of the N-terminal BocPhe group and the alphaMePhe residue side chain of 41 led to the identification of [S-(R*,S*)]-[2-(2,3-difluorophenyl)-1-methyl-1-[(7-ureidoheptyl)ca r bamoyl]ethyl]carbamic acid 2-methyl-1-phenylpropyl ester (60, PD161182), a non-peptide NK3 receptor selective antagonist. Compound 60 blocks the senktide-evoked increases in intracellular calcium levels in cloned human NK3 receptors stably expressed in CHO cells with Ke of 0.9 nM.

Amino Acid Sequence↗