Biomedical subjects

M Rohan

Publications and source records attributed to M Rohan.

4 recordsLinked to original sources

PubMed2006

Effects of macrophage inducible nitric oxide synthase in murine septic lung injury.

Inducible nitric oxide synthase (iNOS) contributes importantly to septic pulmonary protein leak in mice with septic acute lung injury (ALI). However, the role of alveolar macrophage (AM) iNOS in septic ALI is not known. Thus we assessed the specific effects of AM iNOS in murine septic ALI through selective AM depletion (via intratracheal instillation of clodronate liposomes) and subsequent AM reconstitution (via intratracheal instillation of donor iNOS+/+ or iNOS-/- AM). Sepsis was induced by cecal ligation and perforation, and ALI was assessed at 4 h: protein leak by the Evans blue (EB) dye method, neutrophil infiltration via myeloperoxidase (MPO) activity, and pulmonary iNOS mRNA expression via RT-PCR. In iNOS+/+ mice, AM depletion attenuated the sepsis-induced increases in pulmonary microvascular protein leak (0.3 +/- 0.1 vs. 1.4 +/- 0.1 microg EB.g lung(-1).min(-1); P < 0.05) and MPO activity (37 +/- 4 vs. 67 +/- 8 U/g lung; P < 0.05) compared with that shown in non-AM-depleted mice. In AM-depleted iNOS+/+ mice, septic pulmonary protein leak was restored by AM reconstitution with iNOS+/+ AM (0.9 +/- 0.3 microg EB.g lung(-1).min(-1)) but not with iNOS-/- donor AM. In iNOS-/- mice, sepsis did not induce pulmonary protein leak or iNOS mRNA expression, despite increased pulmonary MPO activity. However, AM depletion in iNOS-/- mice and subsequent reconstitution with iNOS+/+ donor AM resulted in significant sepsis-induced pulmonary protein leak and iNOS expression. Septic pulmonary MPO levels were similar in all AM-reconstituted groups. Thus septic pulmonary protein leak is absolutely dependent on the presence of functional AM and specifically on iNOS in AM. AM iNOS-dependent pulmonary protein leak was not mediated through changes in pulmonary neutrophil influx.

Animals↗

PubMed2004

Brain T2 relaxation times correlate with regional cerebral blood volume.

We previously reported cerebellar and putaminal transverse relaxation time (T2) differences in children with ADHD and in adults with childhood trauma. As brain T2 can be altered by deoxyhemoglobin concentration ([dHb]) and because [dHb] is proportional to regional cerebral blood volume (rCBV), at steady state we attributed those differences to rCBV changes. Studies in other species have established a correlation between T2 and rCBV; however this has yet to be demonstrated in human brain. Echo planar imaging (EPI) T2 relaxometry and dynamic susceptibility-contrast (DSC) MRI were used to measure T2 and rCBV in 11 healthy adults. Significant T2-rCBV correlations were observed in both cerebellar vermis and putamen (r = 0.759,p = 0.007;r = 0.782,p = 0.004, respectively). These correlations predict 9 +/- 3% and 10 +/- 3% rCBV changes, respectively, for each 1-msec change in T2. Consequently, brain T2 measurements may be useful for estimating steady-state rCBV.

Adolescent↗

PubMed2001

Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors.

Genetic studies have identified mutations in key regulators of the Wnt/beta-catenin pathway in a variety of cancers, most frequently in colon cancers. However, whether the pathway is activated in clinical cancer samples is not easily determined, and therefore it is useful to find markers that could be surrogates to show activation of the Wnt/beta-catenin pathway. Gene expression profiles were analyzed in SW620, a colon cancer cell line in which beta-catenin levels are stabilized as a consequence of truncated adenomatous polyposis coli and were compared with profiles of the same cells transfected with antisense oligodeoxynucleotides. Treatment of cells with beta-catenin antisense oligodeoxynucleotides resulted in a decrease in the levels of axin2 and human naked cuticle (hnkd) mRNAs. Interestingly, the proteins encoded by both of these mRNAs are known inhibitors of the beta-catenin pathway. In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/beta-catenin pathway. Further, levels of both axin2 and hnkd mRNA were also found to be elevated in about 65% of laser microdissected cells from human colon tumors compared with laser microdissected cells of normal morphology from the same patient samples. The increased expression of axin2 and hnkd correlated with truncations in adenomatous polyposis coli in the same patient samples. These results reveal that it is possible to detect activation of a carcinogenic pathway in human cancer samples with specific markers.

Axin Protein↗

PubMed2000

Pulmonary microvascular changes during sepsis: evaluation using intravital videomicroscopy.

A variety of pulmonary microvascular changes occur during sepsis. These include abnormal vascular reactivity, leukocyte sequestration, and leakage of protein into the alveoli. Based on intravital videomicroscopy we have developed a method to directly assess in vivo the changes that occur in the pulmonary microcirculation in a rat model of sepsis. Male Sprague-Dawley rats were assigned to control or sepsis groups. Sepsis was induced by cecal ligation and perforation. Twenty four hours later, rats were anesthetized, mechanically ventilated, and their lung prepared for intravital videomicroscopy. A specially designed transparent thoracic window was inserted into the chest wall. The dependent surface of the lung was superfused with saline solution and visualized with an inverted microscope. Vascular contractility, to phenylephrine, (PE) and hypoxia of small (15-25 microm in diameter) and medium (40-50 microm) arterioles was examined. Leukocyte traffic in the pulmonary microcirculation was studied after in vivo labeling of leukocytes with Rhodamine and visualized with fluorescence microscopy. Leak of albumin into the alveolar space was measured with FITC-labeled albumin and fluorescence microscopy. Both small and medium sized pulmonary arterioles in septic animals exhibited attenuated vascular contractility to phenylephrine, but only medium-sized arterioles displayed hypocontractility to hypoxia. Further, in septic animals there was an increase in both the number of stationary leukocytes in the pulmonary microcirculation and an increase in alveolar capillary protein leak. We conclude: (1) direct visualization of the pulmonary microvascular pressor response to hypoxia and PE in the rat is possible using this technique, (2) similar to previous in vitro studies with larger vessels, pulmonary arterioles have an attenuated contractile response to PE and hypoxia in sepsis, and (3) there is an increase in both the number of stationary leukocytes and protein leak into the alveolus in the lungs of septic animals.

Animals↗