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Biomedical subjects

D A Ross

Publications and source records attributed to D A Ross.

At least 19 recordsLinked to original sources

Catfish Oct2 binding affinity and functional preference for octamer motifs, and interaction with OBF-1.

The DNA-binding (POU) domain of the catfish Oct2 transcription factor was shown, by electromobility shift assays and surface plasmon resonance techniques, to have an affinity for the consensus octamer motif (ATGCAAAT) that was slightly higher than its affinity for a variant motif (ATGtAAAT). This observation is consistent with the transcriptional activation potentials of catfish Oct2 alpha and Oct2 beta, which were shown to activate transcription in catfish B and T cell lines to an equivalent extent from both the consensus and variant octamer motifs. When tested in a mouse plasmacytoma cell line, catfish Oct2 alpha and Oct2 beta, as well as mouse Oct2, showed higher transcriptional activation with the variant, as compared to the consensus, octamer motif. Catfish Oct2 was shown to function synergistically with the mammalian co-activator, OBF-1, activating octamer-dependent transcription in catfish T cells. The strong transcriptional activity of OBF-1 in catfish cells was dependent on the presence of octamer motif(s) at the proximal (promoter) rather than the distal (enhancer) position.

Animals

Critical pathways in anterior cranial base surgery.

New advances in anterior cranial base surgery have dictated the need for a comprehensive, multidisciplinary approach in the treatment of lesions of this area, necessitating multiple modes of diagnostic and surgical techniques. Traditional consideration of the complex problems presented by neoplastic involvement of the anterior cranial base predicated on isolated syndrome analysis is no longer sufficient to adequately assess tumor pathology. To address these complex problems, we discuss a method of localization of pathology based on anatomic structure and function as well as the corresponding surgical approach to the anterior cranial base.

Cavernous Sinus

Subcranial approach to tumors of the anterior cranial base: analysis of current and traditional surgical techniques.

Tumors of the anterior cranial base have previously required a craniofacial resection to allow adequate tumor extirpation. An analysis of current and traditional techniques demonstrates a significant reduction in operative time, complication rate, and intensive care unit and total hospital length of stay with the use of the subcranial approach as compared with the traditional frontal craniotomy and lateral rhinotomy approach. The subcranial approach is both cost and time efficient and provides comparable morbidity and mortality rates.

Blood Loss, Surgical

Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress.

Two experiments were conducted to determine the protection and the underlying mechanisms of cellular glutathione peroxidase (GPX1) against lethal, acute oxidative stress induced by an intraperitoneal injection of 24 mg diquat/kg body weight. In experiment 1, mortality and survival times were compared among selenium (Se)-adequate or deficient GPX1 knockout mice [GPX1(-/-)] and wild-type mice (WT). In experiment 2, mice from these four groups were euthanized at 0, 1, 2, and 3 h after the injection of diquat to elucidate the time course of oxidative events. The stress produced 100% mortality in all of the groups except for the Se-adequate WT, which were euthanized on day 7 for analysis. The Se-deficient WT and the Se-adequate GPX1(-/-) had similar survival times (4.1 and 3.9 h), which were longer (p < .05) than that of the Se-deficient GPX1(-/-) (2.4 h). However, these three GPX1-deficient groups had higher levels (p < .05) of hepatic F2-isoprostanes and carbonyl contents and/or plasma alanine aminotransferase activities than those of the Se-adequate WT. The diquat-induced formations of hepatic F2-isoprostanes in these animals peaked at 1 h and preceded the rise of plasma alanine aminotransferase in the Se-adequate GPX1(-/-). Responses of hepatic superoxide dismutase activities to the diquat treatment were affected by the GPX1 level. In conclusion, GPX1 is the major selenoprotein to protect mice against the lethal oxidative stress induced by diquat.

Alanine Transaminase

The treatment planning of segmental, conformal stereotactic radiosurgery utilizing a standard multileaf collimator.

Over a period of approximately 3 years, our institution has implemented and refined a system of Stereotactic Radiosurgery (SRS) which utilizes the standard multi leaf collimator (MLC) of the Scanditronix MM50 Racetrack Microtron and treats in an arrangement of segmental "pseudo-arcs." This system employs a commercial BRW based stereotactic frame which is mounted to the treatment table. With the exception of the table-mounted frame hardware there have been no modifications to the treatment machine to accommodate these treatments. By use of standard evaluation parameters (e.g., treatment time, planning time, dose conformance and dose heterogeneity ratios) this system compares quite favorably with reported data from institutions treating SRS with either a GammaKnife or a standard linear accelerator with tertiary collimators.

Brain

Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein.

Since our prior work indicated that Se-dependent cellular glutathione peroxidase (GPX1) was necessary for protection against paraquat lethality, the present studies were to elucidate the biochemical mechanisms related to that protection. Four groups of mice [Se-deficient or -adequate GPX1 knockout and wild-type (WT)] were injected (i.p.) with 50 mg paraquat/kg body weight and tissues were collected 0, 0.5, 1, 2, 3, or 4 h after the injection. Whereas the ratios of NADPH/NADP and NADH/NAD in lung were reduced by 50-70% only 0.5 h after the injection in all groups, these two ratios in liver of the Se-adequate WT were significantly higher than those of the three GPX1 knockout or deficient groups 2-4 h after the injection. The paraquat-induced pulmonary lipid peroxidation and hepatic protein oxidation, measured as F(2)-isoprostanes and carbonyl contents, respectively, peaked at 1 h in these three groups. No such oxidative events were shown in any tissue of the Se-adequate WT throughout the time course. Whereas the F(2)-isoprostane formation was accelerated by both GPX1 knockout and Se deficiency in liver, it was not significantly elevated by the paraquat treatment in brain of any group. The paraquat injection also resulted in temporal changes in lung GPX activity and GPX1 protein in the Se-adequate WT, and significant reductions in lung total SOD activity in the GPX1 knockout or deficient groups. In conclusion, GPX1 plays a critical role in maintaining the redox status of mice under acute oxidative stress, and protects against paraquat-induced oxidative destruction of lipids and protein in vivo. These protections of GPX1 seem to be inducible and coordinated with those of other antioxidant enzymes.

Animals

Use of hydroxyapatite bone cement to prevent cerebrospinal fluid leakage through the frontal sinus: technical report.

OBJECTIVE: To test the efficacy of a simple technique of frontal sinus obliteration during low frontal craniotomy using hydroxyapatite cement instead of more traditional methods, such as pericranial flaps, free muscle or adipose grafts, lumbar drainage, or fibrin glue. METHODS: Eight patients undergoing low frontal craniotomy for intradural surgery had the frontal sinus obliterated by careful removal of mucosa followed by filling of the sinus with hydroxyapatite bone cement. No other adjuncts for preventing cerebrospinal fluid leakage through the sinus were used. RESULTS: At an average follow-up of 9 months, there were no cerebrospinal fluid leaks, infections, instances of resorption, or cosmetic deformities. CONCLUSION: Hydroxyapatite bone cement seems to be a simple and effective method for frontal sinus obliteration and prevention of cerebrospinal fluid leakage.

Aged

Muscarinic receptor loss and preservation of presynaptic cholinergic terminals in hippocampal sclerosis.

PURPOSE: Prior single-photon emission tomography studies showed losses of muscarinic acetylcholine receptor (MAChR) binding in patients with refractory mesial temporal lobe epilepsy. Experimental animal studies demonstrated transient losses of MAChR due to electrically induced seizures originating in the amygdala. However, the relations between cholinergic synaptic markers, seizures, and underlying neuropathology in human temporal lobe epilepsy are unknown. We tested the hypotheses that human brain MAChR changes are attributable to hippocampal sclerosis (HS), and that HS resembles axon-sparing lesions in experimental animal models. METHODS: We measured MAChR binding-site density, an intrinsic neuronal marker, within the hippocampal formation (HF) in anterior temporal lobectomy specimens from 10 patients with HS and in 10 autopsy controls. Binding-site density of the presynaptic vesicular acetylcholine transporter (VAChT) was measured as a marker of extrinsic cholinergic afferent integrity. MAChR and VAChT results were compared with neuronal cell counts to assess their relations to local neuronal losses. RESULTS: Reduced MAChR binding-site density was demonstrated throughout the HF in the epilepsy specimens compared with autopsy controls and correlated in severity with reductions in cell counts in several HF regions. In contrast to MAChR, VAChT binding-site density was unchanged in the epilepsy specimens compared with autopsy controls. CONCLUSIONS: Reduction in MAChR binding in HS is attributable to intrinsic neuronal losses. Sparing of afferent septal cholinergic terminals is consistent with the hypothesis that an excitotoxic mechanism may contribute to the development of HS and refractory partial epilepsy in humans.

Adult

Characterization of Oct2 from the channel catfish: functional preference for a variant octamer motif.

The Ig heavy chain enhancer of the channel catfish (Ictalurus punctatus) has an unusual position and structure, being found in the 3' region of the mu gene and containing eight functional octamer motifs of consensus (ATGCAAAT) and variant sequences. The presence of multiple octamer motifs suggests that an Oct2 homologue may play an important role in driving expression of the Ig heavy chain locus in a teleost fish. To test this hypothesis, two catfish Oct2 cDNAs (alpha and beta) were cloned by screening a catfish B cell cDNA library. Catfish Oct2 alpha and beta isoforms are derived by alternative RNA splicing; as determined by Southern analysis, Oct2 is a single copy gene. In comparisons with mammalian Oct2, the catfish Oct2 isoforms show high sequence conservation in their N-terminal regions and POU domains, but extensive divergence in their C-terminal regions. Catfish Oct2 a and beta are tissue restricted, bind both consensus and variant octamer motifs, and activate transcription in both catfish and murine cells. In contrast, mouse Oct2 activated transcription in mouse but not catfish cells. Catfish Oct2 beta is a more potent transcriptional activator than Oct2 alpha. In transient expression assays, catfish Oct2 beta showed a marked preference for the octamer variant, ATGtAAAT, which occurs twice in the catfish enhancer. Mouse Oct2 also showed increased activity with the variant octamer when tested in mouse B cells. Gel-shift analysis competition assays indicated that catfish Oct2 binds the consensus octamer motif with an apparently higher affinity than it does the variant motif.

Alternative Splicing

Influence of head trauma on outcome following anterior temporal lobectomy.

BACKGROUND: There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. OBJECTIVE: To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.

Adult

Tracheotomy tube occlusion status and aspiration in early postsurgical head and neck cancer patients.

The purpose of the present study was to investigate tracheotomy tube occlusion status and prevalence of aspiration utilizing videofluoroscopy. A prospective study was done of 16 consecutive, early, postsurgical head and neck cancer patients with tracheotomy. Selection criteria included the ability to tolerate tracheotomy tube occlusion prior to and during the modified barium swallow procedure, oral and/or pharyngeal surgical resection, no history of neurological disease or stroke, and medical clearance to begin oral feeding. There was 100% agreement among the independent reviewers on ratings of the presence or absence of aspiration. It was found that occlusion status of the tracheotomy tube did not influence the prevalence of aspiration in the immediate postoperative period. No trends were observed when comparing bolus consistency, type of tracheotomy tube, or presence/absence of a nasogastric tube and the ratings of aspiration.

Adult

Localization of a gene for incomplete X-linked congenital stationary night blindness to the interval between DXS6849 and DXS8023 in Xp11.23.

Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by night blindness, nystagmus, myopia, a variable decrease in visual acuity, an abnormal electroretinographic response, and a disturbance in dark adaptation. Two forms of X-linked CSNB have been defined, complete CSNB in which rod function is extinguished, and incomplete CSNB in which rod function is reduced but not extinguished, as seen by electroretinography and dark adaptometry. In studying a large family of Mennonite ancestry, we have confirmed linkage between the locus (CSNB2) for incomplete CSNB and genetic markers in the Xp11 region. In particular, lod scores of 12.25 and 15.26 at zero recombination were observed between CSNB2 and the markers DXS573 and DXS255. Detailed analysis of critical recombinant chromosomes in this extended family have refined the minimal region for the CSNB2 locus to the interval between DXS6849 and DXS8023 in Xp11.23.

Adaptation, Physiological

Soft tissue reconstruction following hemipelvectomy.

BACKGROUND: Resection of primary and metastatic pelvic bone disease may result in large soft tissue deficits. Guidelines for soft tissue reconstruction following pelvic bone resection were evaluated in a retrospective study. METHODS: Over a 5-year period 21 patients (31%) required soft tissue reconstruction following pelvic bone resection. Data on these patients were retrieved from case records. RESULTS: Twelve patients underwent immediate, planned reconstruction, 1 a two-stage reconstruction, and 8 patients required a delayed procedure for complications after bone resection and primary closure. Soft tissue reconstruction was usually accomplished with muscle-based flaps; (25 flaps in 20 patients: 20 pedicled, 5 free), or with skin grafts alone (1 patient). Specific postreconstruction complications occurred in 9 patients, 5 in flaps based on the ipsilateral rectus muscle. CONCLUSION: Flap closure is indicated to achieve primary closure and eliminate deadspace. The ipsilateral rectus muscle should be used with caution and contralateral-based rectus flaps considered. Indications for free flaps include the size and location of the defect and availability of tissue from an amputated limb.

Adult

Skeletal expansion combined with soft-tissue reduction in the treatment of obstructive sleep apnea in children: physiologic results.

Twenty consecutive children, ranging in age from 6 days to 18 years, were treated with skeletal expansion, in addition to soft-tissue reduction, for medically refractory obstructive sleep apnea. The underlying diagnoses were craniofacial microsomia (n = 6), Down syndrome (n = 3), Pierre Robin syndrome (n = 3), cerebral palsy (n = 3), Nager's syndrome (n = 1), Treacher Collins syndrome (n = 1), cri du chat syndrome (n = 1), juvenile rheumatoid arthritis (n = 1), and temporomandibular joint ankylosis (n = 1). Fourteen children had severe medically refractory sleep apnea and were tracheostomy candidates; in the remaining six, tracheostomies were placed shortly after birth and could not be decannulated. Overnight, 12-channel polysomnography was obtained before and after surgery. The mean apnea index improved from 7.42 to 1.26, the mean respiratory disturbance index improved from 25.24 to 1.72, and the mean lowest apnea-related oxygen saturation improved from 68% to 88%. Of the 14 children with medically refractory obstructive sleep apnea, two required tracheostomies. Of the six patients with tracheostomies, five have been decannulated at the time of this writing. Skeletal expansion in conjunction with soft-tissue reduction in the pediatric population permits substantial increases in the volume of both the nasopharynx and oropharynx. Creative use of conventional osteotomies and the application of distraction osteogenesis have enabled surgeons to apply maxillofacial and craniofacial techniques in treating children with obstructive sleep apnea.

Adolescent

Transosseous transposition of a pedicled rectus abdominis flap to cover hip wounds.

Bone-marrow transplantation may be complicated by aseptic necrosis of the femoral head. Prolonged immunosuppression places the patient at increased risk of infection and is of particular concern if replacement arthroplasty is contemplated. Infection of a prosthesis usually requires thorough debridement and removal of the device. However, attention must also be paid to the resultant cavity and soft-tissue cover. Several flaps have been reported for this problem, though limitations of flap size may make it difficult to achieve both objectives. This report describes the use a pedicled rectus abdominis flap that was tunnelled through the acetabulum in order to gain direct access to the hip and allow adequate length both to fill the dead-space and to provide cover.

Adult

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas.

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.

Acetylcysteine