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Biomedical subjects

C C Miller

Publications and source records attributed to C C Miller.

At least 73 records · Page 4Linked to original sources
PubMed1998

Spinal cord protection in descending thoracic and thoracoabdominal aortic aneurysm repair.

During aneurysm repair of the descending thoracic or thoracoabdominal aorta, the likelihood of neurological complications increases greatly after only 30 minutes of spinal cord ischemia. However, the manifestation of paraplegia or paraparesis relates not only to aortic cross-clamping time, but to multiple factors that may include aortic dissection, previous aortic surgery, advanced age, preoperative renal insufficiency, rupture, and most significantly, aneurysm extent. At greatest risk is the patient with type II thoracoabdominal aortic aneurysm. For this patient the simple cross-clamp technique, which uses no protective surgical adjuncts, heightens the threat of neurological deficit. With the surgical adjuncts of cerebrospinal fluid drainage and distal aortic perfusion, the probability of neurological deficit is appreciably lowered.

Aortic Aneurysm, Abdominal↗
PubMed1998

Nitric oxide effects on force-velocity characteristics of the rat diaphragm.

The present experiments tested nitric oxide (NO) effects on shortening velocity and power production in maximally activated rat diaphragm at 37 degrees C. Diaphragm fiber bundles (n = 10/group) were incubated at 37 degrees C in Krebs-Ringer solution containing no added drug (control), the NO synthase inhibitor Nomega-nitro-L-arginine (L-NNA; 10 mM), the NO donor sodium nitroprusside (SNP; 1 mM), or a combination (L-NNA + SNP). Loaded shortening velocity was measured via the load-clamp technique over a range of afterloads. Unloaded shortening velocity (Vo) was measured in control and L-NNA-treated bundles (n = 12/group) by using the slack test. Force-velocity data fitted to the Hill equation determined a Vmax of 13.7+/-0.4 lengths/s, contradicting the notion that rat diaphragm Vmax declines at temperatures > 35 degrees C. In contrast, L-NNA decreased Vmax (P < 0.05), loaded shortening velocity (P < 0.001), and power production (P < 0.001), but did not change Vo or maximal isometric force. All L-NNA effects were prevented by coincubating fiber bundles with L-NNA + SNP. SNP alone had no effect on any variable. These data indicate that endogenous NO is essential for optimal myofilament function during active shortening.

Animals↗
PubMed1998

Cyclin D2 interacts with cdk-5 and modulates cellular cdk-5/p35 activity.

Cyclin-dependent kinase-5 (cdk-5) is a serine/threonine kinase that displays neurone-specific activity. Experimental manipulation of cdk-5 expression in neurones has shown that cdk-5 is essential for proper development of the nervous system and, in particular, for outgrowth of neurites. Such observations suggest that cdk-5 activity must be tightly controlled during development of the nervous system. To identify possible regulators of cdk-5, we used the yeast two-hybrid system to search for proteins that interact with cdk-5. In two independent yeast transformation events, cyclin D2 interacted with cdk-5. Immunoprecipitation experiments confirmed that cyclin D2 and cdk-5 interact in mammalian cells. Cyclin D2 did not activate cdk-5 as assayed using three different substrates, which was in contrast to a known cdk-5 activator, p35. However, cyclin D2 expression led to a decrease in cdk-5/p35 activity in transfected cells. As cyclin D2 and cdk-5 are known to share overlapping patterns of expression during development of the CNS, the results presented here suggest a role for cyclin D2 in modulating cdk-5 activity in postmitotic developing neurones.

Animals↗
PubMed1998

Neuropathological abnormalities in transgenic mice harbouring a phosphorylation mutant neurofilament transgene.

Ser55 within the head domain of neurofilament light chain (NF-L) is a target for phosphorylation by protein kinase A. To understand further the physiological role(s) of NF-L Ser55 phosphorylation, we generated transgenic mice with a mutant NF-L transgene in which Ser55 was mutated to Asp so as to mimic permanent phosphorylation. Two lines of NF-L(Asp) mice were created and these animals express the transgene in many neurones of the central and peripheral nervous systems. Both transgenic lines display identical, early onset, and robust pathological changes in the brain. These involve the formation of NF-L(Asp)-containing perikaryal neurofilament inclusion bodies and the development of swollen Purkinje cell axons. Development of these pathologies was rapid and fully established in mice as young as 4 weeks of age. The two transgenic lines show no elevation of NF-L, neurofilament middle chain (NF-M), or neurofilament heavy chain (NF-H), and transgenic NF-L(Asp) represents only a minor proportion of total NF-L protein. Because other published transgenic lines expressing higher levels of wild-type NF-L do not exhibit phenotypic changes that in any way resemble those in the NF-L(Asp) mice and because the two different NF-L(Asp) transgenic lines display identical neuropathological changes, it is likely that the pathological alterations observed in the NF-L(Asp) mice are the result of properties of the mutant NF-L. These results support the notion that phosphorylation of Ser55 is a mechanism for regulating neurofilament organisation in vivo.

Amino Acid Substitution↗
PubMed1998

Aortic valve disease in Marfan syndrome.

The Marfan syndrome patient undergoes care by many different physicians for the treatment of the varied systems affected by this connective tissue disorder. The most frequent visits are to a cardiologist, with referral to a cardiovascular surgeon who attends to the problems of dilatation and dissection of the ascending aorta. Follow-up is lifelong. Although currently some surgeons prefer to resuspend rather than replace the aortic valve, composite valve graft replacement for aortic root dilatation and aortic valve insufficiency has steadily improved patient outcome. At the same time, the almost daily discoveries of genetic science show great promise in eliminating connective tissue disorders such as Marfan syndrome in the not-too-distant future.

Aortic Valve↗
PubMed1998

Pulmonary tractotomy as an abbreviated thoracotomy technique.

BACKGROUND: Operative abbreviated thoracotomy techniques in thoracic trauma include emergency center thoracotomy, ligation of major arterial branches, packing the thoracic cavity for diffuse bleeding, towel clip or Bogota bag closure of the chest, and pulmonary tractotomy. Pulmonary tractotomy with selective vascular ligation was originally described for deep through-and-through lung injuries that did not involve hilar vessels or airways. Pulmonary tractotomy has evolved into use as an abbreviated thoracotomy technique in patients with severe thoracic or multivisceral trauma. As with any operative technique in high-risk patients, specific procedure-related complications may occur and are analyzed herein. The objective of this manuscript is to review the indications, techniques, and results for pulmonary tractotomy in trauma patients requiring abbreviated thoracotomy. METHODS: Medical records were retrospectively reviewed for 30 of 32 consecutive tractotomy patients treated at Ben Taub General Hospital, during a 3-year period. By using a model for logistic regression analysis, the characteristics of each patient and their clinical course were tested for impact on mortality. RESULTS: Seventy percent of patients had at least one intraoperative parameter indicative of acidosis (pH < 7.2), coagulopathy (prothrombin time > 13.8 or partial thromboplastin time > 38.0 seconds), or hypothermia (core temperature < 34 degrees C), and 50% of patients manifested two of these three parameters. The mortality rate among the 30 patients was 17%. Three of the five patients who died were noted to be acidotic, coagulopathic, and hypothermic. Twelve of 25 patients who survived more than 1 day had at least one thoracic complication. There were no late deaths. There was one failed tractotomy and one missed injury. A second thoracotomy was not required for control of a lung injury in any patient. Logistic regression analysis showed that intraoperative blood loss was the only predictive factor for mortality. CONCLUSION: Pulmonary tractotomy is a simple and effective technique in injured patients who require an abbreviated thoracotomy and has an acceptable mortality and complication rate. This follow-up report notes that as definitive therapy, tractotomy continues to allow for direct control of bleeding and air leak and obviates the need for formal resection.

Adolescent↗
PubMed1998

Muscle fiber architecture of the dog diaphragm.

Previous measurements of muscle thickness and length ratio of costal diaphragm insertions in the dog (A. M. Boriek and J. R. Rodarte. J. Appl. Physiol. 77: 2065-2070, 1994) suggested, but did not prove, discontinuous muscle fiber architecture. We examined diaphragmatic muscle fiber architecture using morphological and histochemical methods. In 15 mongrel dogs, transverse sections along the length of the muscle fibers were analyzed morphometrically at x20, by using the BioQuant System IV software. We measured fiber diameters, cross-sectional fiber shapes, and cross-sectional area distributions of fibers. We also determined numbers of muscle fibers per cross-sectional area and ratio of connective tissue to muscle fibers along a course of the muscle from near the chest wall (CW) to near the central tendon (CT) for midcostal left and right hemidiaphragms, as well as ventral, middle, and dorsal regions of the left costal hemidiaphragm. In six other mongrel dogs, the macroscopic distribution of neuromuscular junctions (NMJ) on thoracic and abdominal diaphragm surfaces was determined by staining the intact diaphragmatic muscle for acetylcholinesterase activity. The average major diameter of muscle fibers was significantly smaller, and the number of fibers was significantly larger midspan between CT and CW than near the insertions. The ratio of connective tissues to muscle fibers was largest at CW compared with other regions along the length of the muscle. The diaphragm is transversely crossed by multiple scattered NMJ bands with fairly regular intervals offset in adjacent strips. Muscle fascicles traverse two to five NMJ, consistent with fibers that do not span the entire fascicle from CT to CW. These results suggest that the diaphragm has a discontinuous fiber architecture in which contractile forces may be transmitted among the muscle fibers through the connective tissue adjacent to the fibers.

Animals↗
PubMed1998

Peritonitis causes diaphragm weakness in rats.

Respiratory failure is a common and often lethal complication of severe peritonitis. Because this inflammatory process develops in the abdomen, adjacent to the diaphragm, we hypothesized that peritonitis might directly compromise diaphragm function. We tested this hypothesis using male Sprague-Dawley rats. We injected oyster glycogen into the rats' peritoneum, and 16 h later the peritoneum was lavaged for leukocyte analysis and muscle samples were excised. Contractile properties of diaphragm fiber bundles were measured in vitro. We found that neutrophils and macrophages were concentrated in peritoneal lavage fluid of experimental animals (p < 0.01) and were adherent to the abdominal surface of the diaphragm. Immunohistochemistry showed increases in inducible nitric oxide synthase in microvessels of the diaphragm and limb skeletal muscles but not in heart or spleen. Peritonitis decreased maximal force production by the diaphragm (23.6+/-0.6 versus 21.2+/-0.6 N/cm2; p < 0.05) and decreased the absolute forces developed at physiologic stimulus frequencies (> 30 Hz; p < 0.01), depressing the overall force-frequency relationship (p < 0.001). Peritonitis had little effect on acute muscular fatigue. These data demonstrate that peritonitis weakens the diaphragm in rats and suggest that humans with peritonitis may be predisposed to respiratory muscle dysfunction.

Animals↗
PubMed1998

Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes.

Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that exists as two isoforms, alpha and beta, encoded by separate genes. Phosphorylation targets include a variety of cytoplasmic and nuclear proteins. Recent studies found that neurofilaments, amyloid precursor protein, and tau proteins are substrates of GSK-3 and that aberrant phosphorylation of these proteins is implicated in pathologies of the nervous system. To analyse the organisation of these two genes, a YAC library was screened by polymerase chain reaction, using primers specific for human GSK-3 alpha and GSK-3 beta cDNA. Two clones, 220 and 285 kb in size, containing the complete GSK-3 alpha coding sequence, and two clones, 365 and 285 kb in size, containing the 5' coding sequence of GSK-3 beta, were isolated. By somatic cell hybrid panel DNA amplification and radiation hybrid mapping, GSK-3 alpha was found to be located at 19q13.2. On the other hand, by somatic cell hybrid panel DNA amplification and fluorescence in situ hybridisation using the 285-kb YAC clone, GSK-3 beta was mapped to 3q13.3.

Animals↗
PubMed1997

Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3beta transgenes.

In order to investigate the effect on tau of manipulating glycogen synthase kinase (GSK)-3beta activity in the brain, we created transgenic mice harbouring wild-type GSK-3beta genes or a mutant GSK-3beta that is predicted to be more active. Transgene-derived mRNAs were detected in the brains of a number of the transgenic mouse lines and several of these transgenic lines displayed transgenic GSK-3beta activity. Western blot analyses of the two lines with the highest levels of transgenic GSK-3beta activity revealed that the phosphorylation status of tau was elevated at the AT8 epitope. These observations strongly suggest that GSK-3beta is an in vivo tau kinase in the brain. Only low levels of expression of GSK-3beta were obtained and it is possible that high levels of GSK-3beta activity are lethal.

Animals↗
PubMed1997

End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest.

BACKGROUND: Survival after cardiac arrest occurring outside the hospital averages less than 3 percent. Unfortunately, the outcome of prolonged resuscitative attempts cannot be predicted. End-tidal carbon dioxide levels reflect cardiac output during cardiopulmonary resuscitation. We prospectively determined whether death could be predicted by monitoring end-tidal carbon dioxide during resuscitation after cardiac arrest. METHODS: We performed a prospective observational study in 150 consecutive victims of cardiac arrest outside the hospital who had electrical activity but no pulse. The patients were intubated and evaluated by mainstream end-tidal carbon dioxide monitoring. Our hypothesis was that an end-tidal carbon dioxide level of 10 mm Hg or less after 20 minutes of standard advanced cardiac life support would predict death. RESULTS: There was no difference in the mean age or initial end-tidal carbon dioxide level between patients who survived to hospital admission (survivors) and those who did not (nonsurvivors). After 20 minutes of advanced cardiac life support, end-tidal carbon dioxide (+/-SD) averaged 4.4+/-2.9 mm Hg in nonsurvivors and 32.8+/-7.4 mm Hg in survivors (P< 0.001). A 20-minute end-tidal carbon dioxide value of 10 mm Hg or less successfully discriminated between the 35 patients who survived to hospital admission and the 115 nonsurvivors. When a 20-minute end-tidal carbon dioxide value of 10 mm Hg or less was used as a screening test to predict death, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100 percent. CONCLUSIONS: An end-tidal carbon dioxide level of 10 mm Hg or less measured 20 minutes after the initiation of advanced cardiac life support accurately predicts death in patients with cardiac arrest associated with electrical activity but no pulse. Cardiopulmonary resuscitation may reasonably be terminated in such patients.

Adult↗
PubMed1997

Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells.

Tau is a neuronal microtubule-associated protein whose function is modulated by phosphorylation. GSK-3beta is a tau kinase. GSK-3beta is part of the wingless signalling pathway and stimulation by wingless is predicted to down-regulate GSK-3beta activity. In Drosophila imaginal disc cells, overexpression of dishevelled, a component of the wingless pathway, mimics the wingless signal. We have therefore studied the effect that overexpression of the murine dishevelled-1 protein has on GSK-3beta-mediated phosphorylation of tau in transfected CHO cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3beta-mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease and the possible relevance of these findings to Alzheimer's disease pathogenesis are discussed.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Surgical treatment of a septic dentigerous cyst in a goat.

A slowly growing lesion of the rostral mandible of a goat was diagnosed to be a septic dentigerous cyst. The lesion was treated surgically to remove one displaced tooth and debride the cystic cavity, and systemic antibiotic therapy was applied. Thirty-four weeks later the goat was clinically and radiographically improved and the problem had not recurred.

Animals↗
PubMed1997

Phosphorylation of tau by glycogen synthase kinase 3beta affects the ability of tau to promote microtubule self-assembly.

To study the effects of phosphorylation by glycogen synthase kinase-3beta (GSK-3beta) on the ability of the microtubule-associated protein tau to promote microtubule self-assembly, tau isoform 1 (foetal tau) and three mutant forms of this tau isoform were investigated. The three mutant forms of tau had the following serine residues, known to be phosphorylated by GSK-3, replaced with alanine residues so as to preclude their phosphorylation: (1) Ser-199 and Ser-202 (Ser-199/202-->Ala), (2) Ser-235 (Ser-235-->Ala) and (3) Ser-396 and Ser-404 (Ser-396/404-->Ala). Wild-type tau and the mutant forms of tau were phosphorylated with GSK-3beta, and their ability to promote microtubule self-assembly was compared with the corresponding non-phosphorylated tau species. In the non-phosphorylated form, wild-type tau and all of the mutants affected the mean microtubule length and number concentrations of assembled microtubules in a manner consistant with enhanced microtubule nucleation. Phosphorylation of these tau species with GSK-3beta consistently reduced the ability of a given tau species to promote microtubule self-assembly, although the affinity of the tau for the microtubules was not greatly affected by phosphorylation since the tau species remained largely associated with the microtubules. This suggests that the regulation of microtubule assembly can be controlled by phosphorylation of tau at sites accessible to GSK-3beta by a mechanism that does not necessarily involve the dissociation of tau from the microtubules.

Alzheimer Disease↗
PubMed1997

Lactation associated with acidophilic pituitary adenoma, pheochromocytoma, and cystic endometrial hyperplasia in two goats.

Two unbred adult female goats were examined for persistent, inappropriate lactation. Prostaglandin F2 alpha treatment was ineffective in relieving the condition. Over 5 months, 1 goat developed evidence of CNS disease; this same goat had persistently high serum prolactin concentrations. At necropsy, both goats had an acidophilic adenoma of the pars distalis, a condition that, to our knowledge, has not previously been reported in goats. In addition, both goats had pheochromocytomas and cystic endometrial hyperplasia, conditions that are rarely reported in small ruminants. The inciting cause of inappropriate lactation in goats can be difficult to determine. Pituitary adenomas should be suspected when treatment with prostaglandins is unsuccessful, signs of CNS disease develop, or persistently high serum prolactin concentrations are detected.

Adenoma, Acidophil↗
PubMed1997

Tau phosphorylation in cells transfected with wild-type or an Alzheimer's disease mutant Presenilin 1.

We have studied the effect of overexpressing either wild-type or an Alzheimer's disease mutant Presenilin 1 (PS1) on tau phosphorylation in transfected Chinese hamster ovary (CHO) and COS cells. Tau transfected into these cells is predominantly non-phosphorylated at many PHF-tau sites but co-transfection with the tau kinase glycogen synthase kinase-3 beta (GSK-3 beta) induces phosphorylation that generates epitopes for several phosphorylation-dependent antibodies. Co-transfection of tau with either wild-type or mutant PS1 did not alter tau phosphorylation as detected by five different antibodies. Likewise, co-transfection of the PS1s did not influence GSK-3 beta-mediated tau phosphorylation. The implications of these results for the pathogenesis of Alzheimer's disease are discussed.

Alzheimer Disease↗