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R Cox

Publications and source records attributed to R Cox.

At least 19 recordsLinked to original sources
PubMed1996

Mapping striate and extrastriate visual areas in human cerebral cortex.

Functional magnetic resonance imaging (fMRI) was used to identify and map the representation of the visual field in seven areas of human cerebral cortex and to identify at least two additional visually responsive regions. The cortical locations of neurons responding to stimulation along the vertical or horizontal visual field meridia were charted on three-dimensional models of the cortex and on unfolded maps of the cortical surface. These maps were used to identify the borders among areas that would be topographically homologous to areas V1, V2, V3, VP, and parts of V3A and V4 of the macaque monkey. Visually responsive areas homologous to the middle temporal/medial superior temporal area complex and unidentified parietal visual areas were also observed. The topography of the visual areas identified thus far is consistent with the organization in macaque monkeys. However, these and other findings suggest that human and simian cortical organization may begin to differ in extrastriate cortex at, or beyond, V3A and V4.

Adult↗
PubMed1996

Role of telomeric sequences in murine radiation-induced myeloid leukaemia.

A previous study indicated that a highly inbred CBA/H mouse colony contained four genotypic variants for telomere-like repeat (TLR) sequence arrays and that one variant subpopulation that constituted 20% of the colony contributed the vast majority (> 90%) of radiation-induced acute myeloid leukaemias (AMLs). Through screening of a satellite CBA/H colony and rescreening of the original colony, we show that, whereas germline telomere sequence polymorphism is frequent in CBA/H mice, there is no genetic link between a specific TLR locus variant and susceptibility to AML. Studies on telomere-hybridising fragments between 200 bp and 150 kb revealed that the germline telomere mutation frequency was highest for restriction fragments > 50 kb. The hypervariability of these high-molecular-weight fragments resulted in each CBA/H mouse from the highly inbred colony having a different genotype. Although it was not possible to ascribe a specific somatic telomere mutation to AML development, telomere rearrangements were common in induced AMLs. Some terminal telomere-hybridising restriction fragments were shortened in AML samples in comparison with normal tissue, but, insofar as the reduction in size was relatively small, it seems unlikely that telomere erosion is a major contributor to the molecular pathology of murine radiation-induced AML.

Animals↗
PubMed1996

Microsatellite analysis of recurrent chromosome 2 deletions in acute myeloid leukaemia induced by radiation in F1 hybrid mice.

Deletions and/or rearrangements involving one copy of chromosome 2 are consistent and early events in the development of murine acute myeloid leukaemia (AML) by radiation. More than 90% of AMLs induced in the CBA strain of mice express such cytogenetic alterations, with chromosome 2 breakpoints clustering in the C and F regions of the chromosome. In inbred mouse strains, the molecular resolution of these breakpoints is problematic. However, by using x-ray-induced AMLs in FI progeny of genetically divergent CBA/H x C57BI, it has been possible to show region-specific loss of heterozygosity (LOH) in genetically linked sets of chromosome 2 microsatellite alleles from one of the two parental chromosomes. In the majority of cases, an acceptable concordance was shown for AML chromosome 2 deletion, as defined by microsatellites and as revealed by G-band cytogenetics. A degree of breakpoint clustering was found, but the identification of a number of deletion types, based on the position of proximal and distal breakpoints as defined by microsatellite analysis, strongly supports a leukaemogenic mechanism involving gene deletion. No bias towards loss of CBA or C57BI alleles was observed, and the gender of AML-presenting animals did not appear to influence the parental origin of the deletions. A molecular map of chromosome 2 breakpoints has now been established in FI AMLs as a first step towards the molecular cloning of breakpoint sequences.

Acute Disease↗
PubMed1996

Chromosomal mechanisms in murine radiation acute myeloid leukaemogenesis.

Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-irradiation events in bone marrow cells in vivo and of karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2;11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore, two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal translocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis.

Acute Disease↗
PubMed1996

Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors.

OBJECTIVE: The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. METHODS: Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients), and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. RESULTS: Rolandic cortex was activated by tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electrocortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with > 2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. CONCLUSIONS: FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.

Adolescent↗
PubMed1996

Update on the management of status asthmaticus.

Asthma is a common and debilitating problem in children. Its many costs to society include morbidity, hospitalization and treatment expenses, and a rising mortality rate. This paper examines recent trends in therapy for status asthmaticus. Oxygen, inhaled beta-adrenergic agonists, and corticosteroids remain the cornerstones of therapy for the child with a severe exacerbation of asthma. Ipratropium bromide provides additional bronchodilatation in the patient who does not respond to standard therapy. Theophylline may have a role in chronic outpatient management of asthma, but the data supporting the addition of this medication in acute therapy for status asthmaticus are inconclusive. Antibiotics are only indicated in children with asthma complicated by infection, such as sinusitis or pneumonia. Magnesium sulfate and heliox may have a role in helping the asthmatic child who is critically ill and for whom other interventions have failed. Mechanical ventilation has many complications. The concept of permissive hypercapnia may be important in limiting barotrauma. Prevention of exacerbations of asthma include limiting environmental exposure to allergens and tobacco, using corticosteroids, and reinforcing compliance with therapy.

Adrenal Cortex Hormones↗
PubMed1996

Ipsilateral hemisphere activation during motor and sensory tasks.

PURPOSE: To compare activation of the ipsilateral cerebral hemisphere during tactile sensory and motor tasks involving the right and left hands. METHODS: Eight volunteers had functional MR imaging to measure the extent of cerebral hemisphere activation during a motor task and sensory task involving each hand. Hemispheric indexes (left hemisphere activation minus right hemisphere activation)/(left hemisphere activation plus right hemisphere activation) were computed for each hand and each task. The indexes for two tasks and the two hands were compared. RESULTS: The left-hand motor tasks activated the ipsilateral hemisphere in right handers significantly more than did the right-hand tasks. Motor tasks produced a greater activation of the ipsilateral hemisphere than did the sensory tasks. No significant differences were found between the hemispheric indexes for the right-hand and left-hand sensory tasks. CONCLUSION: This study confirms findings of a previous study, showing that the left hemisphere is active in left-hand motor tasks. Activation of the ipsilateral hemisphere is significantly less pronounced during sensory tasks than during motor tasks.

Adolescent↗
PubMed1996

Chromosomal abnormalities in neutron-induced acute myeloid leukemias in CBA/H mice.

Acute myeloid leukemias (AMLs) induced in CBA/H mice by 1 MeV fission neutrons have been examined for chromosomal abnormalities by G-band analysis. In common with X-ray- and alpha-particle-induced AMLs in CBA/H mice, more than 90% (16/17) of the myeloid leukemias had chromosome 2 abnormalities, in this case, all interstitial deletions. Chromosome 2 breakpoints were not wholly consistent, but clustering in three specific G-band regions was observed. Very distal (H-region) breakpoints were more common in the neutron AMLs than in X-ray- or alpha-particle-induced leukemias. These data indicate that neutron-induced AMLs in CBA/H mice are not characterized by a specific chromosome deletion but that a variety of chromosome 2 deletion types are associated with the disease. Trisomy of chromosome 1(12.5% AMLs) and aneusomy of chromosomes 6 (31% AMLs) and Y (37.5% AMLs) were noted. While chromatid breakage was observed occasionally in neutron-induced AML, no clear indications of persistent chromosomal instability or high levels of stable chromosomal change were apparent.

Acute Disease↗
PubMed1996

Test-retest precision of functional MR in sensory and motor task activation.

PURPOSE: To determine the test-retest precision of functional MR maps of regions in the brain "activated" by sensory, motor, and cognitive tasks. METHODS: Echo-planar images were acquired at 1.5 T in four subjects during voluntary motor activity involving the thumb and fingers and during tactile stimulation of the palm. Each subject performed the two tasks twice. Functional images of each task were generated at three thresholds. Test-retest precision was calculated in terms of two ratios: 1) the pixels activated in both iterations of the tasks in proportion to the pixels activated by either iteration of the task, and 2) the ratio modified to include first-order neighboring pixels. The first is referred to as pixel precision, and the latter as first-order-neighbor pixel precision. RESULTS: In each subject, activation from the first and second iteration of each task was located in the same region of the same gyrus. Pixel precision was .57 for the two tasks (at a threshold of 0.50). First-order-neighbor precision was greater than .80 for the two tasks at the same threshold. CONCLUSION: High test-retest precision can be obtained in functional MR.

Adult↗
PubMed1995

Spontaneous and ionizing radiation-induced chromosomal abnormalities in p53-deficient mice.

Chromosomal abnormalities have been assessed in p53-deficient mice. The in vivo frequency of spontaneous stable aberrations in bone marrow cells was elevated by approximately 20-fold in p53 nulls and 13-fold in p53 heterozygotes compared to wild-type. No excessive induction of stable aberrations by gamma-irradiation was observed, but p53 deficiency resulted in excess radiation-induced hyperploidy (> 10-fold wild-type frequency). No influence of p53 genotype on sister chromatid exchange or G2 chromatid damage was observed in mitogen-stimulated spleen cell cultures; however, a p53 effect on postirradiation mitotic entry was seen. Abnormalities in chromosome segregation and mitotic delay following irradiation in p53-deficient mice suggest a G2-M checkpoint role for p53 and are broadly consistent with data on tumorigenesis in these animals.

Aneuploidy↗
PubMed1995

Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns.

BACKGROUND: Human growth hormone is an anabolic agent that attenuates injury-induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up-regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering > 40% of total body surface area. OBJECTIVE: The authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. METHODS: Ten massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. RESULTS: Donor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. CONCLUSION: Results indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural proteins and other components needed to rebuild the junctional structures.

Adolescent↗
PubMed1995

Both cdc2 and cdk2 promote S phase initiation in Xenopus egg extracts.

Xenopus egg extracts induce S phase DNA replication in added sperm pronuclei in a highly regulated manner, similar to events in vivo. Removal of cyclin-dependant kinases (cdks) or cdk2 from these extracts using affinity matrices severely inhibits initiation of S phase. We have used p13suc1 beads to remove both cdk2 and cdc2 proteins from egg extracts and developed a method to replace either protein alone to assess their capacity to initiate DNA replication. Re-addition of either cdk2 or cdc2 proteins to depleted extracts, through translation of their respective mRNAs, restimulated replication, judged by both total synthesis and labelling index. An ATP-binding-site mutant cdk2 mRNA (cdk2.R33) failed to stimulate replication and inhibited S phase initiation in mock-depleted extracts. Both human and Xenopus cdc2 mRNAs rescued replication in this system. Human mutant mRNAs have been used to show that the stimulation induced requires cdc2 catalytic activity, though not its mitotically active form. Rescue of replication by p34cdc2 is also observed in extracts depleted of cdks with a cdk2 antibody, which still retain much of their endogenous cdc2 protein. We conclude that newly synthesised p34cdc2, but not the inherited 'old' form, can induce S phase and in this form may overlap in function with p33cdk2.

Animals↗
PubMed1995

Gallbladder disease in pregnancy.

OBJECTIVE: To evaluate management and pregnancy outcomes in pregnant women with gallbladder disease. STUDY DESIGN: We reviewed the records from three teaching hospitals in central North Carolina from 1986 to 1993 to evaluate women who were admitted with gallbladder disease during pregnancy. RESULTS: Forty-two women were admitted with symptomatic cholelithiasis; 67% were white, the average age was 26 years, and the mean gestational age at presentation was 26 weeks. Conservative management with intravenous hydration, narcotics, dietary changes and antibiotics, if needed, was the first line of treatment in all 42 cases. Conservative management was successful in 17 women, with 8 requiring more than one admission. Nineteen patients failed medical management and needed cholecystectomy; three cases were laparoscopic. The diagnosis in the surgical group included 3 women with biliary colic, 14 with cholecystitis and 2 with gallstone pancreatitis. Four cholecystectomies were performed in the first trimester, 10 in the second and 5 in the third. Thirteen of 19 patients had no postoperative complications and delivered at term. Four women had uterine contractions controlled with tocolytics and delivered at 35 weeks or more. Two of 19 delivered prematurely--one at 32.5 weeks, 15 weeks after a laparoscopic cholecystectomy, and another at 34 weeks, 10 weeks after an open cholecystectomy. Of the patients who delivered prematurely, none were within the immediate postoperative period, and it appears unlikely that the cholecystectomy was causative. No maternal or perinatal mortality was noted. CONCLUSION: This review and others indicate that surgery should be reconsidered as possible primary management in pregnant women with symptomatic gallbladder disease.

Adult↗
PubMed1994

Competitive inhibition of lipolytic enzymes. X. Further delineation of the active site of pancreatic phospholipases A2 from pig, ox and horse by comparing the inhibitory power of a number of (R)-2-acylamino phospholipid analogues.

Two series of (R)-phospholipid analogues, each containing a n-propyl group at the C-1 position and various acylamino functions at the C-2 position have been synthesized and their inhibitory properties towards three mammalian pancreatic phospholipases A2 have been determined. The members of the first series of analogues all contained the zwitter-ionic phosphocholine headgroup which in the second series was replaced by the anionic phosphoglycol function. In the saturated 2-acylamino phospholipids the length of the acyl chain ranged from 8 to 18 carbon atoms. The unsaturated 2-acylamino analogues possessed a chain length of 11 or 18 carbon atoms and contained one, two, three or four double bonds. For inhibitors with a saturated acylamino group, the phospholipases A2 from pig, ox and horse show a sharp optimum in inhibitory power Z for an acyl chain length of 10 carbon atoms. The inhibitory behaviour of the unsaturated acylamino analogues is more complex: both the zwitter-ionic and the anionic inhibitors demonstrate an increase in Z with an increasing number of cis-double bonds but the degree of improvement is dependent on the position of the double bonds. Subsequently the influence of polar groups at carbon position 12 of the dodecanoylamino phospholipids on Z was analyzed. Substitution of the terminal methyl group by an OH-function lowers the inhibitory potency of the three enzymes by a factor of 4 to 5 both in the phosphocholine and phosphoglycol series. Replacement of the methyl group by potentially charged functions (-NH2, -COOH) resulted in a complete loss of inhibitory properties. Blocking of the amino group and carboxyl function by t-butyloxycarbonylation and esterification, respectively, fully restored the inhibitory power. Finally we investigated how changes in the polar headgroup and the presence of aromatic rings at the C-1 or C-2 position influenced the inhibitory potency of the analogues.

Acylation↗
PubMed1994

Radiation therapy of pineal region tumors: 25 new cases and a review of 208 previously reported cases.

PURPOSE: Malignant pineal region tumors are rare neoplasms arising in midline structures of the brain. This report analyzes the influence of histology, tumor location, radiation dose, treatment volume, age and cerebrospinal fluid findings on freedom from relapse, freedom from spinal relapse and survival. METHODS AND MATERIALS: Patient and treatment parameters of 25 cases of pineal region tumors managed at Stanford University are presented, and an additional 208 published cases were reviewed. Univariate and multivariate analysis were performed to delineate parameters predictive of freedom from relapse, freedom from spinal relapse, and survival for all 233 patients. RESULTS: The 5- and 10-year freedom from relapse for Stanford patients was 63% and 46%, respectively. The 5- and 10-year survival for Stanford patients was 67% and 61%, respectively. The 5- and 10-year freedom from relapse for the total 233 cases was 66% and 61%, respectively. The 5- and 10-year survival for all patients was 74% and 68%, respectively. For the entire group, biopsy confirmed germinoma and non-biopsied tumors had superior freedom from relapse compared to non-germinoma germ cell tumors (p = 0.03, p = 0.005, respectively). Non-biopsied patients had improved survival compared to non-germinoma germ cell tumors (p = 0.004). Pineal parenchymal tumors had worse freedom from relapse compared to non-biopsied patients (p = 0.04). For patients with suprasellar tumors, germinomas were associated with improved freedom from relapse compared to non-germinoma germ cell tumors (p = 0.02). Simultaneous pineal and suprasellar tumors had superior survival compared to solitary tumors of pineal (p = 0.04), suprasellar (p = 0.03), or third ventricle location (p = 0.03). Twenty-two patients (9.4%) developed isolated spinal relapse. Five- and 10-year spinal relapse rates for all patients were 11% and 13%. Survival after spinal relapse was 19%. Pineal parenchymal tumors had lower freedom from spinal relapse compared to non-biopsied patients (p = 0.001). For tumors located in the pineal gland, germinomas and pineal parenchymal tumors had lower freedom from spinal relapse than did non-biopsied patients (p = 0.006, p = 0.004, respectively). Pineal germinomas had lower freedom from spinal relapse than germinomas with suprasellar location (p = 0.04). Univariate and multivariate analysis identified tumor histology as the most significant predictor of freedom from relapse, freedom from spinal relapse and survival. CONCLUSION: Histologic type had the greatest impact on outcome. Treatment recommendations should be based on assessment of histologic type and extent of disease.

Adolescent↗
PubMed1994

Molecular mechanisms of radiation oncogenesis.

Resolving the molecular mechanisms of radiation oncogenesis represents an important but daunting challenge in radiation research. This brief review outlines the principal oncogenic mechanisms that need to be considered in the context of radiation effects on the genome, how these might relate to specific gene and chromosomal changes relevant to neoplasia and the possible implications of such knowledge for the modelling of cancer risk. The long-term application of this mechanistic knowledge to the determination of tumour causality and for the assessment of individual cancer risk is also briefly discussed.

Humans↗