To examine whether pulmonary dysfunction leads to episodes of cerebral hypoxia during recurrent seizures, measurements were made of arterial blood pressure, blood-gases, cerebral pO2, and relative ...changes in cytochrome a,a3 redox levels in anesthetized, paralyzed rats. Seizures were induced serially with bicuculline (BIC) or pentylenetetrazol (PTZ). During early seizures, cerebral oxygenation increased phasically. As seizures continued, a transition often occurred following which seizures were accompanied by phasic decreases in cerebral oxygenation. In addition, pulmonary edema often occurred at an unpredictable point during a series of seizures. Seizure-associated pulmonary edema was less likely to occur with pentobarbital anesthesia and PTZ seizures, than with nitrous oxide anesthesia and BIC seizures. Pulmonary edema was always accompanied by prolonged increases in blood pressure and paroxysmal electrocortical activity, and by hypoxemia, acidemia, and decreased cerebral oxygen supply. Despite the severity of these physiological changes, the transition from phasic increases to decreases in cerebral oxygenation during serial seizures occurred with virtually the same frequency in rats with and without pulmonary edema. This indicates that this transition is independent of pulmonary edema.
The small intestinal epithelium is the most rapidly proliferating tissue in the body, with a turnover time of 2 to 3 days in mice and rats, and 3 to 6 days in humans. This turnover rate is so rapid ...that cells do not normally enter the prolonged G0 phase seen in other, more slowly dividing tissues. This renewal is critical for maintenance of the functional integrity of the gut and is very tightly regulated along the crypt–villus axis through the migration of pluripotent stem cells located within the crypts of Lieberkuhn. Crypt and villus architecture is controlled, in part, by stromal and epithelial elements. The cells acquire a differentiated phenotype as they migrate toward the villus tip (absorptive enterocyte, goblet, and enteroendocrine cells), and are eventually extruded into the lumen. Paneth cells do not migrate, however, but differentiate within the base of the crypts, eventually degenerate, and are lost through phagocytosis. Thus, a steady-state equilibrium is maintained between cell production and cell loss. Villus height follows a gradient from the duodenum, where it is greatest, to the ileum, where the shortest villi are encountered. Accordingly, there is a proximal-to-distal gradient in villus height, cell number, and absorptive surface area in the small intestine. These anatomic differences depend not only on the larger amount of ingested nutrients encountered by the proximal gut, but also on an intrinsic genetic program.
Is robotic surgery better? Hodin, Richard A
Harvard health letter,
05/2011, Volume:
36, Issue:
7
Magazine Article
Hodin discusses whether robotic surgery is better than having a surgeon do the operation. Thousands of operations today are being done with the assistance of robots. It's an impressive technology, ...but, unfortunately, there's remarkably little evidence that robotic surgery helps the patient or the surgeon. More hospitals are buying these machines, not out of any real medical need or demonstrated advantage, but because of smart, skillful marketing by the companies that make them.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
A cDNA encoding a novel member of the thyroid/steroid hormone receptor superfamily, called Rev-ErbAα, has been isolated from a rat GH
3
cell library. Rev-ErbAα is an ~56-kilodalton protein most ...similar in structure to the thyroid hormone receptor (c-erbA) and the retinoic acid receptor, but it does not bind either thyroid hormone or retinoic acid. The mRNA encoding Rev-ErbAα is present in many tissues and is particularly abundant in skeletal muscle and brown fat. A genomic DNA fragment containing the entire Rev-ErbAα cDNA sequence was isolated and characterized. Remarkably, this DNA fragment also contained a portion of the c-erbAα gene. r-erbAα-1 and r-erbAα-2 are alternative splice products of the c-erbAα gene and are members of the receptor superfamily. The genes encoding Rev-ErbAα and r-erbAα-2 overlap, with their coding strands oriented opposite one another. A 269-base-pair segment of the bidirectionally transcribed region is exonic in both the Rev-ErbAα and r-erbAα-2 genes, resulting in complementary mRNAs. Thus, through alternative splicing and opposite-strand transcription, a single genomic locus codes for three different members of the thyroid/steroid hormone receptor superfamily. Potential implications of this unusual genomic arrangement are discussed.
Background: Neurotensin, an important gut hormone, binds its receptor (NTR) to stimulate proliferation of intestinal cells; the molecular mechanisms remain largely undefined. Mitogen-activated ...protein kinases (MAPKs) translocate to the nucleus and induce transcription factors (eg, c-Fos) in response to certain trophic agents. The purpose of this study was (1) to define the signaling mechanisms regulating neurotensin and (2) to determine whether the AP-1 transcription factor c-Fos is induced.
Methods: Expression of the NTR gene was determined in the human colon cancer cell lines KM12C, KML4A, and KM20 by Northern blot analysis and ribonuclease-protection experiments. To assess whether NTR was functionally coupled to the Ca
2+-signaling pathway, intracellular Ca
2+ (Ca
2+
i) mobilization was assessed by fura-2 spectrofluorometry. To determine whether the MAPK signaling pathway was activated in KM20 cells by neurotensin, Western blots for the phosphorylated forms of MAPK (p42 and p44) and in vitro kinase assays were performed. In addition, Western blots were performed to assess levels of c-Fos after neurotensin treatment.
Results: The NTR gene was expressed in the KM20 cell line but not in KM12C or KM12LA. The NTR in KM20 cells was functionally coupled to the Ca
2+-signaling pathway as noted by a rapid (30 seconds) mobilization of Ca
2+
i after addition of neurotensin; the neurotensin-mediated response was blocked by the NTR antagonist SR48692. Both p42
MAPK and p44
MAPK were stimulated by neurotensin ~3 to 6 minutes after treatment. Increased levels of c-Fos were demonstrated, with peak levels occurring 2 hours after addition of neurotensin.
Conclusions: Our results demonstrate that neurotensin binds to its endogenous NTR in KM20 cells with stimulation of the Ca
2+- and MAPK-signaling pathways and an increase in the levels of the AP-1 protein c-Fos. Delineating the signal transduction mechanisms regulating the cellular effects of neurotensin will provide important insights into the molecular pathways responsible for gut hormone–mediated proliferation. (Surgery 1998;124:239-47.)
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
