Biomedical subjects

D C Montague

Publications and source records attributed to D C Montague.

4 recordsLinked to original sources

PubMed2003

Bone is a target for the antidiabetic compound rosiglitazone.

Rosiglitazone is an FDA-approved oral antidiabetic agent for the treatment of type 2 diabetes. This compound improves insulin sensitivity through the activation of the nuclear receptor, peroxisome proliferator-activated receptor-gamma (PPAR-gamma). In addition to sensitizing cells to insulin, the PPAR-gamma2 isoform appears to be critical for the regulation of osteoblast and adipocyte differentiation from common mesenchymal bone marrow progenitors. We have demonstrated previously that PPAR-gamma2 activated with rosiglitazone acts as a dominant inhibitor of osteoblastogenesis in murine bone marrow in vitro. Here, we show that in vivo, rosiglitazone administration results in significant bone loss. When rosiglitazone (20 microg/g body weight/d) was given to 6-month-old, nondiabetic C57BL/6 mice for 7 wk, a significant decrease in total body bone mineral density was observed. Analysis of bone microarchitecture, using micro-computed tomography, demonstrated a decrease in bone volume, trabecular width, and trabecular number and an increase in trabecular spacing. Histomorphometric analysis showed a decrease in bone formation rate, with a simultaneous increase in fat content in the bone marrow. Changes in bone morphology and structure were accompanied by changes in the expression of osteoblast- and adipocyte-specific marker genes; the expression of the osteoblast-specific genes Runx2/Cbfa1, Dlx5, and alpha1(I)collagen were decreased, whereas the expression of the adipocyte-specific fatty acid binding protein aP2, was increased. These in vivo data suggest that rosiglitazone therapy may pose a significant risk of adverse skeletal effects in humans.

Animals↗

PubMed2002

A rat resistance exercise regimen attenuates losses of musculoskeletal mass during hindlimb suspension.

Exposure to microgravity and/or spaceflight causes dramatic losses in both muscle and bone mass. In normal gravity, resistance exercise has been effectively used to increase muscle and bone mass. We tested a novel form of resistance exercise training using flywheel technology as a countermeasure to offset the loss of musculoskeletal mass during 4 weeks of adult rat hindlimb suspension (HS), an unloading model of microgravity. Male, Sprague-Dawley rats (6-month old) were operantly conditioned to perform resistance exercise, and then randomly assigned to groups of sedentary control (CON), HS, and HS with resistance exercise training (HSRT; 2 sets of approximately 21 repetitions, 3 days week(-1) for 4 weeks during suspension). In soleus, HS resulted in lower (P < 0.05) muscle mass to body mass ratio (approximately 50% of controls) and rates of protein synthesis. HSRT significantly attenuated the loss of muscle mass in soleus muscle, and rates of protein synthesis for soleus were similar for HSRT and controls. There were no differences among groups for mass or rates of protein synthesis in extensor digitorum longus. In cancellous regions of the distal femur, HS resulted in significant reductions of bone mineral density (BMD), but this was restored to control levels with HSRT. Cortical regions of the femur were not different among HS, HSRT or control groups. Together, these data suggest that resistance training using flywheel technology may be a promising tool to attenuate losses of the musculoskeletal system during periods of hindlimb unloading.

Animals↗

PubMed1993

Retrieval and amplification of DNA from unstained histopathological sections.

Testing of compounds for carcinogenic potential in vivo involves various experimental designs. A few of these techniques are directed to demonstrate the genotoxicity and mutagenicity of the compound by histopathology. These changes shown by histochemical means include monoclonal antibody directed cellular markers. Development of the polymerase chain reaction technique (PCR) for amplification of DNA has facilitated the investigation of molecular events related to the formation of malignant neoplasms. We describe here a method for screening tissues for mutations of the H-ras gene using monoclonal antibodies directed toward normal and mutant p21 proteins. Formalin-fixed, paraffin-embedded tissue sections are used to subsequently confirm the gene mutation by PCR amplification of the H-ras gene. The results indicated a successful application of this technique to demonstrate the presence of p21 oncoprotein in the tissues tested.

Antibodies, Monoclonal↗

PubMed1982

Methane: Interhemispheric concentration gradient and atmospheric residence time.

The ground level concentrations of methane in the atmosphere have been measured to be in the range from 1.45 to 1.62 parts per million by volume (ppmv) of dry air in remote locations between 62 degrees N and 54 degrees S latitudes during the time period from November 1977 to July 1979. The average (+/-rms) concentration for the northern hemisphere was 1.57 +/- 0.02 ppmv in January 1978 and 1.59 +/- 0.02 in July 1979. The average concentration in the southern hemisphere was lower-1.47 +/- 0.02 in January 1978 and 1.51 +/- 0.01 in July 1979. The ratio of concentrations between the two hemispheres was 1.068 +/- 0.016 in January 1978 and 1.055 +/- 0.013 in July 1979, for an average of 1.06 +/- 0.01. The higher concentrations in the northern hemisphere require either that the sources of methane lie preferentially in the northern hemisphere or that the removal processes operate more rapidly in the southern hemisphere or both. The primary removal process for CH(4) is reaction with tropospheric OH radicals and its estimated atmospheric lifetime is 10.5 +/- 1.8 yr. The observed interhemispheric gradient is consistent with this lifetime and preferential release of methane in the northern hemisphere. Measurements taken in the Amazon basin region indicate the presence of a substantial source of methane in that area.

Journal Article↗