Biomedical subjects

Michael D Johnson

Publications and source records attributed to Michael D Johnson.

39 records · Page 3Linked to original sources

PubMed2002

Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.

PURPOSE: Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN: We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. RESULTS: Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS: Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.

Female↗

PubMedDate not supplied

Synaptic integration in motoneurons with hyper-excitable dendrites.

Motoneurons have extensive dendritic trees that receive the numerous inputs required to produce movement. These dendrites are highly active, containing voltage-sensitive channels that generate persistent inward currents (PICs) that can enhance synaptic input 5-fold or more. However, this enhancement is proportional to the level of activity of monoaminergic inputs from the brainstem that release serotonin and noradrenalin. The higher this activity, the larger the dendritic PIC and the higher the firing rate evoked by a given amount of excitatory synaptic input. This brainstem control of motoneuron input-output gain translates directly into control of system gain of a motor pool and its muscle. Because large dendritic PICs are probably necessary for motoneurons to have sufficient gain to generate large forces, it is possible that descending monoaminergic inputs scale in proportion to voluntary force. Inhibition from sensory inputs has a strong suppressive effect on dendritic PICs: the stronger the inhibition, the smaller the PIC. Thus, local inhibitory inputs within the cord may oppose the descending monoaminergic control of PICs. Most motor behaviors evoke a mixture of excitation and inhibition (e.g., the reciprocal inhibition between antagonists). Therefore, normal joint movements may involve constant adjustment of PIC amplitude.

Animals↗

PubMedDate not supplied

Explant-cell culture of primary mammary tumors from MMTV-c-Myc transgenic mice.

We have established an explant-cell culture system for mammary gland tumors from c-myc oncogene-expressing transgenic mice and potentially other transgenic strains. By coating culture dish surfaces with fetal bovine serum and using culture media supplemented with low serum and growth factors, the mammary tumor specimens could be maintained in culture for over 3 mo. Throughout the culture period, the explants produced abundant outgrowths of epithelial cells. As the outgrowths of epithelial cells filled the dishes, the explants were serially transferred from one dish to another-a process that could be repeated at least six times, thus providing a continuous supply of primary tumor cells. This culture system provides a useful tool for studying the biology of mouse mammary gland tumors and possibly tumors from other organ sites.

Animals↗