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Biomedical subjects

M B Young

Publications and source records attributed to M B Young.

10 recordsLinked to original sources

Analysis of gene expression in carbon tetrachloride-treated rat livers using a novel bioarray technology.

The present study successfully utilizes a new ADME Rat Expression Bioarray, containing 1040 metabolism- and toxicology-linked genes, to monitor gene expression from the livers of rats treated with carbon tetrachloride (CCl(4)). Histopathological analysis, hierarchical clustering methods, and gene expression profiling are compared between the control and CCl(4)-treated animals. A total of 44 transcripts were found to be altered in response to the hepatotoxin, 19 of which were upregulated and 25 were downregulated. Some of these gene expression changes were expected and concurred with previously published data while others were novel findings.

Animals↗

Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists.

Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets.

Platelet Activation↗

Nanomolar-affinity, non-peptide oxytocin receptor antagonists.

Non-peptide antagonists of the peptide hormone oxytocin (OT) with nanomolar OT receptor affinities are described. These compounds incorporate novel amido- and amidoalkylcamphor variations to the lead structure L-366,509 (1) to achieve receptor affinity enhancements of 2-3 orders of magnitude over that compound. The new OT antagonist L-367,773 (35) is shown to be an orally bioavailable agent with good duration in vivo and to inhibit OT-stimulated uterine contractions effectively in several in vitro and in vivo models.

Animals↗

Effect of bilateral nerve injury on the migration of labelled mononuclear cells to hypoglossal nuclei.

Whether cells responding to injury in the central nervous system are of local or hematogenous origin is still a question that has not been answered unequivocally, although ample evidence in favor of a dual origin exists. In the present investigation, mononuclear blood cells were labelled with 3HT one day before left hypoglossal nerve injury. In addition to the initial injury, some of the animals received an injury of the right nerve at a later time. The fate of labelled cells responding to the initial injury when a second injury was made was studied. With two lesions the total number of labelled cells responding was twice the number present with a single lesion at the period of peak response. This was more than could be accounted for by simple migration from left to right. The data presented suggest that mitosis and migration of cells present at the initial lesion accounted for part of the increased number of cells. The possibility that some of the cells responding to the second injury were of recent hematogenous origin was not ruled out.

Animals↗

H3T-labelled blood cells in the CNS response to axotomies at various times after isotope injection.

Numerous investigators, using tritiated thymidine to label mononuclear blood cells, have proposed a hematogenous origin for some of the reactive cells responding to injury in the CNS. However, two questions have remained unanswered: recirculation of H3T at the time of injury with labelling of proliferating local cells; and local reutilization of label released from degenerating cells. In a recently reported experiment using bilateral injuries made at different times (24), a large number os labelled cells responding to the second injury resulted from mitosis of cells already reacting to injury on the contralateral side. Additionally, the possibility that some of the labelled cells could have been newly drived from blood was not ruled out. The present experiment was designed to further explore this possibility. To minimize the problems of H3T recirculation and reutilization, the isotope was injected 3 to 17 days before nerve injury in some of the animals. At sacrifice, labelled cells were found in the nucleus of the injured nerve up to 36 days after isotope injection, with the peak of the reaction occurring at 9 days. Since the isotope was injected 3 to 17 days before injury and because there was no source of reactive cells on the contralateral side, it was felt that these labelled cells were newly derived from blood.

Animals↗

Recurrent painful calf swelling associated with gout.

A 30-year-old man had a recurrent painful calf swelling associated with gout that mimicked thrombophlebitis and possibly muscle tear. This painful calf swelling occurred in the absence of a subjective history of arthritis of the knee. A constellation of clinical signs was highly suggestive that gout was the cause of the painful calf swellings. Patients with similar conditions, after careful exclusion of thrombophlebitis, might be spared unnecessary and potentially dangerous anticoagulation or surgical intervention by early diagnosis of gout.

Adult↗