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T Moore

Publications and source records attributed to T Moore.

At least 109 records · Page 6Linked to original sources
PubMed1996

Greater residual vision in monkeys after striate cortex damage in infancy.

1. Monkeys with large unilateral surgical ablations of striate cortex, sustained either in adulthood or at 5-6 wk of age, were trained on an oculomotor detection and localization task and tested with visual stimuli in the hemifields ipsilateral and contralateral to the lesion 2-5 yr after surgery. 2. Monkeys with lesions sustained in adulthood were largely unable to detect stimuli in the hemifield contralateral to the lesion, with only one monkey showing recovery toward the end of testing. Monkeys with lesions of striate cortex made in infancy, however, each showed residual detection capacity at the beginning of testing and improved to near normal by the end of testing. 3. Each of the monkeys showing a residual ability to detect within the contralateral hemifield was also able to localize visual targets with eye movements. 4. These findings demonstrate that the vision surviving striate cortex damage in primates is more robust after early damage as has been shown to be the case for primary somatosensory, motor, and association cortex.

Animals↗
PubMed1996

Genetic conflict in early development: parental imprinting in normal and abnormal growth.

Parental (genomic) imprinting is the process by which the differential expression of maternal and paternal alleles at certain genetic loci in mammalian embryos occurs. Such loci are implicated in the control of fetal, placental and neonatal growth, and, more generally, in diverse aspects of fetal nutrient acquisition and maternal-fetal interactions. Not surprisingly, the aberrant expression of imprinted genes is implicated in a range of embryonic and fetal abnormalities. We outline how an evolutionary theory, based on classic parent-offspring conflict theory, relates to certain fetal growth abnormalities. In particular, we suggest that growth abnormalities resulting from the manipulation of preimplantation mammalian embryos in vitro (for example large calf syndrome) may reflect the occurrence of genetic conflict over the fetal growth programme in the early preimplantation period.

Cell Nucleus↗
PubMed1996

Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.

Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (ARP), accounting for approximately 25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This "bimodal expressivity" contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus.

Chromosome Mapping↗
PubMed1995

Localization of visual stimuli after striate cortex damage in monkeys: parallels with human blindsight.

Blindsight is a phenomenon in which human patients with damage to striate cortex deny any visual sensation in the resultant visual field defect but can nonetheless detect and localize stimuli when persuaded to guess. Although monkeys with striate lesions have also been shown to exhibit some residual vision, it is not yet clear to what extent the residual capacities in monkeys parallel the phenomenon of human blindsight. To clarify this issue, we trained two monkeys with unilateral lesions of striate cortex to make saccadic eye movements to visual targets in both hemifields under two conditions. In the condition analogous to clinical perimetry, they failed to initiate saccades to targets presented in the contralateral hemifield and thus appeared "blind." Only in the condition where the fixation point was turned off simultaneously with the onset of the target--signaling the animal to respond at the appropriate time--were monkeys able to localize targets contralateral to the striate lesion. These results indicate that the conditions under which residual vision is demonstrable are similar for monkeys with striate cortex damage and humans with blindsight.

Animals↗
PubMed1995

Transplantable NK cell progenitors in murine bone marrow.

Differentiation of NK cells from pluripotent hematopoietic stem cells is a poorly understood process. Although it is known that NK cells are bone marrow derived and dependent upon an intact bone marrow microenvironment for complete maturation, it is not known if they arise from an intermediate lymphoid stem cell or from progenitors exclusively committed to the NK lineage. To determine whether phenotypically distinct committed NK progenitor cells exist in murine bone marrow, we sorted cells capable of repopulating recipient mice with mature NK cells upon i.v. transfer. We identified a rare population of bone marrow cells with the phenotype Ly6+ Lin- c-kit+ CD43high Fall-3high TSA-1- AA4.1low Rh123high that is highly enriched for the ability to generate NK cells after transplantation. Although these cells are relatively depleted of Rh123low pluripotent stem cells, they are highly enriched for both lymphoid and myeloid repopulating ability. Thus, we have found no evidence to support the existence of a phenotypically distinct transplantable progenitor population in mouse bone marrow that is either exclusively committed to the NK cell lineage or exhibits the functional characteristics of a common lymphoid stem cell.

Animals↗
PubMed1995

Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells.

Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression.

Cell Differentiation↗
PubMed1995

Genetic conflict and evolution of mammalian X-chromosome inactivation.

The existence of parentally imprinted gene expression in the somatic tissues of mammals and plants can be explained by a theory of intragenomic genetic conflict, which is a logical extension of classical parent-offspring conflict theory. This theory unites conceptually the phenomena of autosomal imprinting and X-chromosome inactivation. We argue that recent experimental studies of X-chromosome inactivation and androgenetic development address previously published predictions of the conflict theory, and we discuss possible explanations for the occurrence of random X-inactivation in the somatic tissues of eutherians.

Animals↗
PubMed1995

Post-operative problems following anterior cruciate ligament reconstruction.

Seventy adult patients were studied during the postoperative rehabilitation period following anterior cruciate ligament reconstruction in order to investigate the role of pre-, intra-, and postoperative factors in range of motion and graft problems. A standard bone-patellar tendon-bone autograft was used for the reconstruction. Pre- and intraoperative factors such as concomitant injuries, time from injury to surgery, age, sex, and tunnel placement were recorded. Tunnel placement was recorded on intraoperative radiographs of the final guide pin placement and compared to pin placement on cadaver knees. The results indicated a significant relation between early reconstruction (< 1 month) following the injury and range of motion problems during the early rehabilitation period (P < 0.001). This relation disappeared by the end of the first postoperative year. Prolonged surgery was also associated with early motion problems (P < 0.05). Graft laxity or failure was correlated with an earlier return of range of motion (P < 0.05). We hypothesized that graft failure can have a biologic cause rather than a mechanical one since intraoperative X-rays indicated a near-anatomic tunnel placement in this patient group when compared to ideal placement in the cadaver knees.

Adolescent↗
PubMed1995

Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon.

A randomized, double-blind, placebo controlled, cross-over study was conducted to determine the clinical efficacy of and patient tolerance to sustained-release glyceryl trinitrate (GTN) patches in the treatment of Raynaud's phenomenon. The patients studied were those with primary Raynaud's disease (n = 21) and patients with Raynaud's phenomenon secondary to systemic sclerosis (n = 21). GTN patches (0.2 mg/h) were found to be effective in reducing the number (P < 0.05) and severity of Raynaud's attacks (P < 0.05) in both groups of patients. Objective assessments by infrared thermography did not show any significant improvement when the patients were on GTN patches (P > 0.05). Headaches, refractory to treatment, led to the withdrawal of eight patients from the study and occurred in approximately 80% of the remaining patients. Thus, in spite of the subjective efficacy, the frequent headaches will limit the use of GTN patches in Raynaud's phenomenon. Elucidating the mechanism of action of the beneficial and adverse effects of GTN at the molecular level may shed light on the pathogenesis of Raynaud's phenomenon and its treatment.

Administration, Cutaneous↗
PubMed1995

Comparison of PCR and standard cytological staining for detection of Pneumocystis carinii from respiratory specimens from patients with or at high risk for infection by human immunodeficiency virus.

The detection of Pneumocystis carinii DNA by PCR was compared with routine cytologic staining techniques (CYT). A total of 284 clinical respiratory specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or at high risk for human immunodeficiency virus infection were evaluated. Eighty specimens were positive by PCR, and 69 were positive by CYT. PCR was able to detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus 4 samples). Of the 19 patients whose respiratory specimens were positive for P. carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In this clinical setting in particular and in the evaluation of sputum specimens, the ability of PCR to detect a low parasitic load suggests that this technique may become an important additional tool, along with current cytological methods, for the detection of P. carinii.

Adult↗
PubMed1994

Expression of CD43 on murine and human pluripotent hematopoietic stem cells.

To understand regulation of hemopoiesis, it would be helpful to identify physiologically relevant function-associated molecules on stem cells. Here, we report the detailed examination of CD43 expression on murine and human pluripotent hemopoietic stem cells. Mouse stem cells were found within the Ly6+Lin-CD43high subpopulation of bone marrow. These cells, upon transfer into SCID mice, caused rapid repopulation of thymus, spleen, and bone marrow. Retransfer of bone marrow cells from primary SCID recipients of Ly6+Lin-CD43high cells into secondary recipients resulted in repopulation of lymphohemopoietic cells. All Ly6+Lin-CD43high cells were found to express high levels of c-kit. In contrast, Ly6+Lin-CD43-/low cells caused limited and variable thymic and splenic repopulation. These cells failed to repopulate the marrow cavity and did not contain retransplantable stem cells. These data indicate that murine pluripotent stem cells express high levels of CD43. Examination of human fetal bone marrow cells revealed a population of CD34+CD38-CD43+ cells. When single sorted cells with this phenotype were cultured in vitro, they were able to produce colonies with a dispersed growth pattern. Cells with this growth pattern have previously been shown to have myeloid and lymphoid growth potentials and extensive self-renewal capacity. Furthermore, CD34+CD38-HLA-DR+ cells, recently shown to be highly enriched in stem cell activity, expressed relatively high levels of CD43. Because CD43 has recently been shown to bind to intercellular adhesion molecule-1, these data suggest a possible role for CD43 in the regulation of hemopoiesis.

ADP-ribosyl Cyclase↗
PubMed1994

Effect of free-radical scavengers and hyperbaric oxygen on random-pattern skin flaps.

OBJECTIVE: To determine whether treatment with the combination of hyperbaric oxygen and free-radical scavengers or inhibitors would result in increased skin-flap survival. DESIGN: An animal model with male Sprague-Dawley rats was used. The flap was a cranial-based dorsal 3 x 12-cm random-pattern skin flap that included the panniculus carnosus. Rats were randomly assigned to one of 10 treatment groups. INTERVENTIONS: The radical scavengers superoxide dismutase, catalase, and alpha-tocopherol acetate and the inhibitor allopurinol were used to combat or scavenge radicals. Oxygen (100%) treatments were for 90 minutes at 2.5 atm absolute daily. MAIN OUTCOME MEASURES: At 7 days, the flaps were examined for survival by fluorescein injection. Lipid peroxidation as a measure of tissue damage was measured by thiobarbituric acid-malondialdehyde analysis. RESULTS: The combination of treatments resulted in significantly increased flap survival compared with untreated controls (P < .05) except in the group treated with allopurinol and hyperbaric oxygen. Lipid peroxidation was inhibited by the superoxide dismutase plus catalase and the alpha-tocopherol treatments but not by treatment with allopurinol. CONCLUSION: Moderate doses of radical scavengers or antioxidants coupled with a conservative hyperoxic exposure regimen can result in the increased survival of random-pattern skin flaps.

Allopurinol↗
PubMed1994

Clinical development of anticancer agents from natural products.

Recent years have seen the introduction into clinical trials of new classes of chemotherapeutic agents which are derived from natural sources and have novel mechanisms of action. Examples of some of these newer classes of agents are presented here to illustrate both the opportunities they represent with respect to cancer treatment applications and the challenges which they represent from the clinical development perspective. Cumulatively the problems encountered with the development of the agents described are representative of the spectrum of issues encountered in the development of natural products, ranging from initial characterization and purification through the difficulties encountered in obtaining sufficient quantities of material for preclinical studies and then ultimately for clinical trials. Since these agents have unique mechanisms of action and are often exquisitely dose- and schedule-dependent in pre-clinical studies, they represent significant complexities with respect to determining the optimal regimen of administration clinically. The particular agents chosen for description here represent the spectrum of natural source-derived materials as well as mechanisms of action. The taxanes are derived from tree sources and interfere with the mitotic spindle apparatus; the camptothecins, while also derived from trees, appear to exert their activity through interactions with topoisomerase I. Bryostatin, derived from a marine animal, has powerful effects on protein kinase C (PKC), and therefore affects signal transduction pathways within cells. Fumagillin analogs appear to exhibit their important antitumor activity not through a direct effect on cancer cells but rather through effects on the tumor neovasculature. Taken as a whole, the spectrum of agents and activities described here confirms the continued importance of natural products in current anticancer agent development and reflects the complexities involved in this area of clinical research.

Antineoplastic Agents, Phytogenic↗