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J Marshall

Publications and source records attributed to J Marshall.

At least 55 records · Page 3Linked to original sources
PubMed2001

Karyometry of secretory cell nuclei in high-grade PIN lesions.

BACKGROUND: The goal of this study was a karyometric characterization of secretory cell nuclei in high-grade prostatic intraepithelial neoplasia (PIN) lesions. Specifically, the hypothesis is tested that distinctly different subgroups of nuclei exist in these lesions. METHODS: High-resolution images of 1,713 nuclei from high-grade PIN lesions were recorded. Karyometric features were computed. Discriminant function scores against normal reference nuclei, and nuclear abnormality values were derived. Data sets were processed by a nonsupervised learning algorithm to establish the presence of subgroups of nuclei with statistically different nuclear chromatin distributions. RESULTS: Three sets of nuclei were formed, facing an intact basal cell layer, a near vanishing basal cell layer, and a gap in the basal cell layer. For each set, a nonsupervised learning algorithm formed three statistically different subgroups of approximately equal sizes. Each subgroup is found in every one of the three sampling locations. The total optical density distribution of nuclei in two subgroups suggests an aneuploid distribution, the third subgroup has a near diploid distribution. CONCLUSIONS: Secretory cell nuclei in high-grade PIN lesions are a heterogeneous population, forming statistically different subgroups. Studies aimed at characterizing the progression of such lesions should consider the inhomogeneous nature of these nuclei.

Algorithms↗
PubMed2001

Effects of systematic methyl substitution of metal (III) tris(n-methyl-8-quinolinolato) chelates on material properties for optimum electroluminescence device performance.

We relate the chemical structure of a series of methyl (Me) substituted group III metal tris(8-quinolinolato) chelates (nMeq(3)M: n = 0, 3, 4, 5; M = Al(3+), Ga(3+)) to their photoluminescence (PL), electroluminescence, and thermal properties. Methylation of the 8-quinolinol ligand at the 3 or 4 position (pyridyl ring) results in a factor of 1.4 and 3.0 enhancement of PL quantum efficiency (phi(PL)), respectively, whereas methylation at the 5 position (phenoxide ring) results in a factor of approximately 3.0 decrease in phi(PL) relative to the unsubstituted analogue. Electroluminescent quantum efficiencies of undoped organic light-emitting devices using the aluminum tris(8-quinolinolato) chelates are 1, 0.45, 1.4, and 0.80% for unsubstituted 5-, 4-, and 3-methyl-8-quinolinol ligands, respectively. Devices made with the latter two ligands have a higher operating voltage to generate the same current density. Similar trends were observed for methylation of gallium tris(8-quinolinolato) chelates. We relate these results to the thermal properties of the compounds measured by simultaneous differential scanning calorimetry and thermal gravimetric analysis. The C-4 methylated derivatives exhibit approximately 60 degrees C lower crystalline melting points than all other derivatives, indicating the weakest cohesive forces between molecules. Unlike Alq(3), both the C-4 and C-5 methylated derivatives show no recrystallization of the glassy state below 500 degrees C and exhibit approximately 20-25 degrees C higher glass transition temperatures. We infer that methylation of the 8-quinolinol ligand reduces intermolecular interactions and consequently impedes charge transport through the film.

Journal Article↗
PubMed2001

Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss.

Proteolysis-inducing factor (PIF), a novel cachectic factor, is detectable in the urine of cancer patients experiencing weight loss. We report the expression of PIF in gastrointestinal cancers, and a correlation between PIF expression in tumours, its detection in urine and weight-loss. These data provide the first direct evidence that tumours are the source of PIF in humans.

Animals↗
PubMed2001

Sensory adaptation. Tunable colour vision in a mantis shrimp.

Systems of colour vision are normally identical in all members of a species, but a single design may not be adequate for species living in a diverse range of light environments. Here we show that in the mantis shrimp Haptosquilla trispinosa, which occupies a range of depths in the ocean, long-wavelength colour receptors are individually tuned to the local light environment. The spectral sensitivity of specific classes of photoreceptor is adjusted by filters that vary between individuals.

Adaptation, Physiological↗
PubMed2001

Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP97.

Recent studies have demonstrated that kainate receptors are associated with members of the SAP90/PSD-95 family (synapse-associated proteins (SAPs)) in neurons and that SAP90 can cluster and modify the electrophysiological properties of GluR6/KA2 kainate receptors when co-expressed in transfected cells. In vivo, SAP90 tightly binds kainate receptor subunits, while SAP97 is only weakly associated, suggesting that this glutamate receptor differentially associates with SAP90/PSD-95 family members. Here, green fluorescent protein (GFP)-tagged chimeras and deletion mutants of SAP97 and SAP90 were employed to define the molecular mechanism underlying their differential association with kainate receptors. Our results show that a weak interaction between GluR6 and the PDZ1 domain of SAP97 can account for the weak association of GluR6 with the full-length SAP97 observed in vivo. Expression studies in HEK293 cells and in vitro binding studies further show that although the individual Src homology 3 and guanylate kinase domains in SAP97 can interact with the C-terminal tail of KA2 subunit, specific intramolecular interactions in SAP97 (e.g. the SAP97 N terminus (S97N) binding to the Src homology 3 domain) interfere with KA2 binding to the full-length molecule. Because receptor subunits are known to segregate to different parts of the neuron, our results imply that differential association of kainate receptors with SAP family proteins may be one mechanism of subcellular localization.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2.

PURPOSE: Hodgkin's disease patients who receive mantle irradiation have an age-dependent increased risk of developing breast cancer. To determine if genetic factors predispose these patients to develop breast cancer, we evaluated breast cancer specimens for loss of heterozygosity (LOH) at regions where BRCA1 and BRCA2, two breast cancer tumor suppressor genes, are located. We also evaluated whether breast cancers in patients who were previously treated with radiation have a more aggressive phenotype, and whether the clinical course differed from a sporadic group of breast cancer patients. METHODS AND MATERIALS: All females with Hodgkin's disease who were subsequently diagnosed with breast cancer and for whom tissue blocks were available were included. Using a case-control design, case patients (previously treated with radiation therapy) were matched with sporadic control breast cancer patients for age, breast cancer stage, and date of breast cancer diagnosis. After microdissection of tumor and normal tissue from paraffin-embedded tissue blocks, DNA was extracted and samples were examined for LOH at chromosomal segments encompassing BRCA1 and BRCA2. Breast cancer specimens were also evaluated in a blinded fashion for tumor grade and immunoreactivity to estrogen and progesterone receptors, p53, her2-neu, and topoisomerase II alpha. Comparisons were made between the case and control populations using chi2 analysis, and a paired Student's t test. Survival differences were evaluated using a log-rank test. RESULTS: From January 1960 to December 1983, 917 patients were diagnosed with Hodgkin's disease. Twelve patients were subsequently diagnosed with breast cancer and tissue blocks were available on 10 cases. No statistical difference was observed between the case and control populations for LOH at BRCA1 or BRCA2. In the Hodgkin's disease group, LOH was observed in 30% of tumors at BRCA1 and 10% of tumors at BRCA2 vs. 10% and 0% of tumors in the control group at BRCA1 and BRCA2, respectively. Breast tumors from patients who received radiation therapy for Hodgkin's disease displayed greater nuclear pleomorphism (p < 0.02), and an increase in topoisomerase II alpha expression (p < 0.05) vs. the control population. Five of 10 patients were pregnant at the time of their Hodgkin's treatment, and those patients had a shorter time interval to the development of breast cancer compared with the patients who were not pregnant (12.4 years compared with 18.6 years). There was no significant difference in disease-free survival; however, overall survival was inferior in the population previously treated with radiation therapy for Hodgkin's disease (p = 0.01). 80% of patients with a previous Hodgkin's diagnosis died of breast cancer or treatment related effects vs. 30% in the control group. CONCLUSION: We were unable to find statistical evidence for LOH at BRCA1 and BRCA2 in breast cancers from patients previously irradiated for Hodgkin's disease. Breast cancer diagnosed after mantle irradiation may be more biologically aggressive based on the greater nuclear pleomorphism and increase in topoisomerase II alpha staining. This did not translate into a statistical difference in breast cancer disease-free survival; however, overall survival was significantly inferior in the Hodgkin's disease patients.

Adolescent↗
PubMed2001

Calcium inhibits willardiine-induced responses in kainate receptor GluR6(Q)/KA-2.

A number of studies have demonstrated that willardiine [(S)-1-(2-amino-2-carboxyethyl) pyrimidine-2,4-dione] is a useful agonist for the activation of AMPA/kainate receptors. Here we examine the effect of extracellular calcium on currents evoked by willardiine in HEK 293 cells expressing the GluR6(Q)/KA-2 kainate receptor subunits. At a concentration of 1.8 mM, Ca2+ inhibited the currents induced by 100 microM willardiine by approximately 50%. When extracellular Na+ ions were replaced with Ca2+ ions there were no measurable inward currents. We conclude that Ca2+ inhibition of the willardiine-induced response is concentration dependent.

Alanine↗
PubMed2001

Kainate receptor activation induces mixed lineage kinase-mediated cellular signaling cascades via post-synaptic density protein 95.

Kainate receptor glutamate receptor 6 (GluR6) subunit-deficient and c-Jun N-terminal kinase 3 (JNK3)-null mice share similar phenotypes including resistance to kainite-induced epileptic seizures and neuronal toxicity (Yang, D. D., Kuan, C-Y., Whitmarsh, A. J., Rincon, M., Zheng, T. S., Davis, R. J., Rakis, P., and Flavell, R. (1997) Nature 389, 865-869; Mulle, C., Seiler, A., Perez-Otano, I., Dickinson-Anson, H., Castillo, P. E., Bureau, I., Maron, C., Gage, F. H., Mann, J. R., Bettler, B., and Heinemmann, S. F. (1998) Nature 392, 601-605). This suggests that JNK activation may be involved in GluR6-mediated excitotoxicity. We provide evidence that post-synaptic density protein (PSD-95) links GluR6 to JNK activation by anchoring mixed lineage kinase (MLK) 2 or MLK3, upstream activators of JNKs, to the receptor complex. Association of MLK2 and MLK3 with PSD-95 in HN33 cells and rat brain preparations is dependent upon the SH3 domain of PSD-95, and expression of GluR6 in HN33 cells activated JNKs and induced neuronal apoptosis. Deletion of the PSD-95-binding site of GluR6 reduced both JNK activation and neuronal toxicity. Co-expression of dominant negative MLK2, MLK3, or mitogen-activated kinase kinase (MKK) 4 and MKK7 also significantly attenuated JNK activation and neuronal toxicity mediated by GluR6, and co-expression of PSD-95 with a deficient Src homology 3 domain also inhibited GluR6-induced JNK activation and neuronal toxicity. Our results suggest that PSD-95 plays a critical role in GluR6-mediated JNK activation and excitotoxicity by anchoring MLK to the receptor complex.

Animals↗
PubMed2001

Hydraulic conductivity of fixed retinal tissue after sequential excimer laser ablation: barriers limiting fluid distribution and implications for cystoid macular edema.

OBJECTIVES: To measure the hydraulic conductivity (HC) of human retina and to determine the presence and location of high-resistance barriers to fluid movement through the retina. METHODS: Forty-one pairs of human eyes were investigated using an HC chamber. Once baseline HC had been determined, the effect of ablating through varying thickness of retina from the vitreous or photoreceptor surface using an excimer laser (193 nm) was investigated. Tissue samples were then processed for histological investigation. RESULTS: The HC of fixed intact human retina was 2.54 x 10(-10) m/s per pascal at 539 Pa (range, 0.6 x 10(-10) to 3.3 x 10(-10) m/s per pascal; SD, 0.6 x 10(-10) m/s per pascal [1 mm Hg equals 133 Pa]). Ablation from either surface resulted in little change in HC until a critical depth was reached, at which point there was an order of magnitude increase. The critical depth was approximately 170 microm from the inner limiting membrane when ablating from the vitreous surface and 70 microm from the inner limiting membrane when ablating from the photoreceptor surface. Histological specimens showed that these barriers were the synaptic portion of the outer plexiform layer, and the inner plexiform layer, respectively. CONCLUSIONS: The 2 high-resistance barriers to fluid flow through the retina are the synaptic portion of the outer plexiform layer, and the inner plexiform layer. CLINICAL RELEVANCE: These observations help to explain the distribution of cystoid macular edema seen in histological studies and with optical coherence tomography.

Adolescent↗
PubMed2001

Effect of collagenase inhibitors on corneal haze after PRK.

The aim of the study was to determine whether collagenase inhibitors reduce corneal haze after photorefractive keratectomy (PRK). Inhibition of the initial removal phase of healing may limit the subsequent repair and replacement phases responsible for haze and regression. Thirty rabbits received -6.00D 5 mm right PRK. They were randomized to five treatment groups: G. cysteine, G. ethylene diamine tetra-acetic acid (EDTA), G. ascorbate, Oc. tetracycline or no drops. Dichlorotriazinyl aminofluorescein (DTAF) was applied to the wound immediately after surgery in two rabbits of each group, to delineate newly-synthesized from original tissue. Corneal haze was assessed by a video-linked frame grabber with computerized grey scale analysis. Corneas were taken for histology at 1 or 3 months post-operatively. Corneal haze was not significantly different between the treatment groups and controls. The severity of the histological changes varied between individuals. Within the ablation zone the epithelium was on average 10% thicker (3--4 micro m) than outside, and in some rabbits there were irregularities of the epithelial--stromal junction. The new subepithelial tissue had a mean depth of 7.8 micro m, and the superficial stroma was disorganized to a mean depth of 49 micro m. No particular treatment demonstrated significant benefits over controls; but of the treatments used, cysteine tended to produce the best results. Eyes treated with EDTA fared worst in most respects. The collagenase inhibitors used did not improve the outcome of PRK in rabbits. It remains to be determined whether firstly, the new more potent agents would have an effect, and secondly, whether collagenase inhibitors are of benefit in humans.

Administration, Topical↗
PubMed2001

Antitumor activity of cationic lipid complexed with immunostimulatory DNA.

We previously reported that treatment of intraperitoneal tumors with complexes of cationic lipid and noncoding plasmid DNA leads to the development of a specific, cytotoxic T-cell response correlating with the rejection of established tumor cells as well as subsequent tumor re-challenge. Here, focusing on an intraperitoneal AB12 mesothelioma model, we show that the anticancer effects of the lipid:DNA complex are associated with DNA containing immunostimulatory CpG motifs. Complexes prepared with cationic lipid and bacterial plasmid DNA, Escherichia coli genomic DNA fragments, or synthetic immunostimulatory CpG oligodeoxynucleotides provided a substantial survival benefit, whereas eukaryotic DNA and methylated bacterial DNA had little or no therapeutic activity. Alternative inflammatory stimuli such as thioglycolate, poly(I:C), and incomplete or complete Freund's adjuvant failed to reproduce the antitumor activity obtained with the lipid:DNA complex. The innate immune response triggered by lipid:DNA complexes led to the development of a systemic immune response against tumor cells that allowed animals to reject tumors not only at the intraperitoneal treatment site, but also at a distal subcutaneous site. These data demonstrate that immunostimulatory DNA complexed with cationic lipid is a potent inducer of innate and adaptive immune responses against tumor cells and represents a potentially useful tool in the immunotherapy of cancers for which tumor-associated antigens have not been identified.

Animals↗
PubMed2001

Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits.

BACKGROUND: Melanocyte-stimulating hormone (MSH) is a known anti-inflammatory agent and we investigated whether it reduces the inflammatory reaction following ocular surgery. METHODS: Rabbits received a perforating corneolimbal cut. Treatment involved topical (10(-8)M) or intramuscular (50 mg/kg/day) MSH, topical steroids or saline. The parameters studied were hyperemia, edema, aqueous protein levels and the number of inflammatory cells in the aqueous, as well as their number determined histologically in the injured cornea. Each parameter was assessed at 24 h post injury. RESULTS: Topically and systematically applied MSH reduced edema to levels 60% and 76%, respectively, of those observed in operated saline-treated eyes (P<0.001), and their efficacy was comparable to that of topical steroids. The decrease in hyperemia brought about by MSH was more pronounced than that produced by steroids. Aqueous protein levels were reduced by a similar degree in the steroid- and MSH-treated eyes as in the saline group (P<0.001 for each treatment group); In MSH- and ste-roid-treated eyes the number of inflammatory cells in the aqueous was reduced by 80% and 50%, respectively. CONCLUSION: We demonstrated that MSH reduced the clinical signs of ocular inflammation, curtailed blood-aqueous barrier (BAB) disruption, and reduced aqueous inflammatory cell number. The efficacy of MSH applied systemically or topically was similar to that of steroids in reducing clinical signs of trauma, but MSH efficacy in maintaining BAB integrity surpassed that of steroids. We suggest that the melanocortins might be a useful anti-inflammatory agents in ocular trauma.

Administration, Topical↗
PubMed2001

When ottoman is easier than chair: an inverse frequency effect in jargon aphasia.

This paper presents evidence of an inverse frequency effect in jargon aphasia. The subject (JP) showed a pre-disposition for low frequency word production on a range of tasks, including picture naming, sentence completion and naming in categories. Her real word errors were also striking, in that these tended to be lower in frequency than the target. Reading data suggested that the inverse frequency effect was present only when production was semantically mediated. It was therefore hypothesised that the effect was at least partly due to the semantic characteristics of low frequency items. Some support for this was obtained from a comprehension task showing that JP's understanding of low frequency terms, which she often produced as errors, was superior to her understanding of high frequency terms. Possible explanations for these findings are considered.

Aged↗
PubMed2001

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study.

PURPOSE: To investigate the use of intravitreal injection of triamcinolone acetonide (TA) for the treatment of refractory uveitic cystoid macular edema (CME). DESIGN: Prospective, nonrandomized, self-controlled comparative trial. PARTICIPANTS: Six patients with chronic CME resistant to treatment with systemic steroids, orbital floor steroids, and cyclosporine A. Three patients were followed for more than 1 year, and the other three for between 3 and 9 months. INTERVENTION: Injection of 2 mg of TA into the vitreous cavity. TESTING: Optical coherence tomography scanning of the fovea before and after injection and logarithmic minimal angle of resolution visual acuity. MAIN OUTCOME MEASURES: Visual acuity, retinal thickness, cystoid space height, and intraocular pressure. RESULTS: There was complete anatomic resolution of CME in five of the six cases within 1 week after injection. Cystoid spaces began to return between 6 weeks and 3 months after injection. Two patients with longer term follow-up responded to further orbital floor steroid injection and had no CME 1 year later. One patient had raised intraocular pressure develop, requiring a trabeculectomy. Mean improvement in visual acuity after 12 months was 0.27 (range, 0.14-0.42). CONCLUSIONS: Complete anatomic and, to some extent, functional recovery can be induced by intravitreal TA despite long-term refractory inflammatory CME. Optical coherence tomography aids in the management of these cases.

Adult↗
PubMed2001

A case-control study of physical activity and non-insulin dependent diabetes mellitus (NIDDM). the San Luis Valley Diabetes Study.

PURPOSE: The purpose of this study was to examine the association between physical activity and non-insulin dependent diabetes mellitus (NIDDM). METHODS: We conducted a population-based case-control study in Hispanic and non-Hispanic white men and women, ages 20-74. A total of 167 cases with NIDDM and 1100 controls with normal glucose tolerance were included. All subjects completed an oral glucose tolerance test. RESULTS: Persons with recently diagnosed NIDDM reported significantly lower levels of physical activity than control subjects. For total metabolic units, the odds ratio for subjects in the highest tertile compared to those in the lowest tertile was 0.60 (95% confidence interval (CI) = 0.37-0.98) after adjusting for age, sex, ethnicity, and family history of diabetes. The adjusted odds ratio for persons reporting high levels of vigorous activity (at least three times per week for 20 minutes) was also less than 1, but was not statistically significant (odds ratio (OR) = 0.73, 95% CI = 0.47-1.14). Similar adjusted odds ratios were observed for high versus low levels of self-assessed work activity (OR = 0.50, 95% CI = 0.34-0.74) and leisure time physical activity (OR = 0.62, 95% CI = 0.44-0.90). Further adjustments for body mass index attenuated the strength of the association between physical activity and NIDDM. This is consistent with the hypothesis that obesity is one consequence of physical inactivity that puts individuals at increased risk for NIDDM. The association of physical activity and NIDDM was stronger in Hispanic than in non-Hispanic white subjects, although this difference was not statistically significant. CONCLUSIONS: High levels of physical activity are associated with lower odds of NIDDM and this relationship may be stronger in Hispanic subjects.

Adult↗