Search PubMed⌕ Search

Biomedical subjects

J M Brown

Publications and source records attributed to J M Brown.

At least 73 records · Page 4Linked to original sources
PubMed2000

Amodal completion and localization.

In a three-line vernier acuity task, a central line was localized between two aligned line segments. Accuracy did not improve when the segments formed a unified amodally completed percept. In a two-line vernier acuity task, a line was localized below a target line placed next to a physically segmented flank stimulus. Shifts in mean points of subjective equality suggested that amodally completed segments influenced localization. Previous conflicting findings are explained by a representation that is available early to influence perceived alignment. However, position tuning is poor. This representation may be realized physiologically by interpolation responses between amodally completed segments.

Adult↗
PubMed2000

Just the right size: cell counting in Dictyostelium.

The regulation of tissue and organism size plays an essential, but poorly understood, role in multicellular development. Genes have been identified that affect body and organ size in a number of animals. Two recently identified genes, smlA and countin, are required for the proper function of a cell-counting mechanism that regulates organism size in the eukaryotic microorganism Dictyostelium discoideum. The discovery of this process now allows the study of size regulation in a simple multicellular system.

Animals↗
PubMed2000

Assessing the relative costs of standard open surgery and laparoscopic surgery in colorectal cancer in a randomised controlled trial in the United Kingdom.

The role of laparoscopic surgery for the treatment of colorectal cancer is being explored in a multi-centre, randomised clinical trial in the UK, the MRC CLASICC Trial (Conventional versus Laparoscopic-assisted Surgery in Colorectal Cancer). An important end-point of the trial is the cost-effectiveness of laparoscopic surgery compared with that of conventional open surgery. The economic evaluation of this trial has been modelled on that in a similar trial being conducted in the USA in colon cancer. The aim of this paper is to discuss the rationale for modelling the UK trial on the US trial, and to describe the adaptations necessary for the UK trial. The parallel design of the economic evaluation in both trials will provide a unique opportunity to compare the cost implications of incorporating laparoscopic surgery in the UK and the USA, and to determine any cross-cultural differences. The UK trial will also provide information about the cost-effectiveness of laparoscopic surgery in rectal cancer.

Colorectal Neoplasms↗
PubMed2000

Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies.

Human solid tumours are considerably less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy, as well as predisposing to increased tumour metastases. However, tumour hypoxia can be exploited in cancer treatment. One such strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise. The second way to exploit hypoxia is to take advantage of the selective induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) under hypoxic conditions; gene therapy strategies based on this are in development.

Anthraquinones↗
PubMed2000

From case management to court clinic: examining forensic system involvement of persons with severe mental illness.

The study examined the flow of a state mental health agency's case-managed clients into its forensic mental health court clinic systems for evaluation of competency to stand trial (CST) for a criminal offense. An analysis of merged encounter data from the case management and court clinic systems revealed that roughly 2% of the case-managed population were referred to court clinics for evaluation of CST during a 1-year period, but that these 2% represented roughly one eighth of that year's court clinic evaluees. The likelihood of this involvement was higher for males, African-Americans, and Latinos, and for persons with a history of substance abuse, and also was associated with higher levels of previous hospitalization. In addition, CST evaluees were more likely to be non-White, male, and uninsured than were case-managed evaluees. These data indicate that demographic characteristics, substance abuse, and lack of insurance are potential risk factors for forensic and, by inference, criminal justice system involvement among persons with mental illness.

Adolescent↗
PubMed2000

Contrast effects do not underlie effects of preceding liquids on stop-consonant identification by humans.

These experiments explored the claim by A. Lotto and K. Kluender (1998) that frequency contrast explains listeners' compensations for coarticulation in the case of liquid consonants coarticulating with following stops. Evidence of frequency contrast in experiments that tested for it directly was not found, but Lotto and Kluender's finding that high- and low-frequency precursor tones can produce contrastive effects on stop-consonant judgments were replicated. The effect depends on the amplitude relation of the tones to the third formant (F3) of the stops. This implies that the tones mask F3 information in the stop consonants. It is unknown whether liquids and following stops in natural speech are in an appropriate intensity relation for masking of the stop. A final experiment, exploiting the McGurk effect, showed compensation for coarticulation by listeners when neither frequency contrast nor masking can be the source of the compensations.

Humans↗
PubMed2000

Development of a hypoxia-responsive vector for tumor-specific gene therapy.

We are developing new gene therapy vectors whose expression is selectively activated by hypoxia, a unique feature of human solid tumors. As vascular endothelial growth factor (VEGF) is upregulated by hypoxia, such regulatory mechanisms would enable us to achieve hypoxia-inducible expression of therapeutic genes. Constructs with five copies of hypoxia-responsive elements (HREs) derived from the 5'-untranslated region (UTR) of the human VEGF showed excellent transcriptional activation at low oxygen tension relevant to tumor hypoxia. In an attempt to achieve higher responsiveness, various combinations of HREs and promoters were examined. In addition, we also investigated whether the 3' UTR of the VEGF gene would confer increased post-transcriptional mRNA stability under hypoxic conditions. However, despite increases in the hypoxic/aerobic ratio of luciferase activity, gene expression with 3' UTR was lower due to mRNA destabilization by AU-rich elements (AREs). Thus, we found no benefit from the inclusion of the 3' UTR in our vectors. Of all the vectors tested, the combination of 5HRE and a CMV minimal promoter exhibited hypoxia responsiveness (over 500-fold) to the similar level to the intact CMV promoter. We propose that this vector would be useful for tumor selective gene therapy.

5' Untranslated Regions↗
PubMed2000

Methamphetamine rapidly decreases vesicular dopamine uptake.

Vesicular sequestration is important in the regulation of cytoplasmic concentrations of monoamines such as dopamine. Moreover, recent evidence suggests that increases in cytoplasmic dopamine levels, perhaps attributable to changes in vesicular monoamine transporter function, contribute to methamphetamine-induced dopaminergic deficits. Hence, we examined whether striatal vesicular uptake is altered following methamphetamine treatment. Multiple administrations of methamphetamine rapidly (within 1 h) decreased vesicular dopamine uptake and dihydrotetrabenazine binding, an effect that (a) persisted at least 24 h, (b) was associated with dopamine and not serotonin neurons, and (c) was unrelated to residual drug introduced by the original methamphetamine treatment. These data suggest that methamphetamine rapidly decreases vesicular monoamine transporter function in dopaminergic neurons, a phenomenon that may be associated with the long-term damage caused by this stimulant.

Animals↗
PubMed2000

The cancer-associated Sm-like oncogene: a novel target for the gene therapy of pancreatic cancer.

BACKGROUND: The prognosis for pancreatic cancer (PC) remains dismal, providing a clear need for the development of novel therapies. We have previously shown that the cancer-associated Sm-like (CaSm) oncogene is overexpressed in the great majority of pancreatic tumors and is required to maintain the transformed phenotype. The purpose of this study was to determine whether the application of CaSm antisense gene therapy would generate a significant antitumor effect against PC. METHODS: An adenoviral vector (Ad-alphaCaSm) expressing a 900-base pair antisense RNA to CaSm was created. The PC cell lines AsPC-1 and Capan-1 were infected with this vector and examined for changes in in vitro proliferation by using methyl thiazol tetrazolium and soft agar assays. SCID-Bg mice bearing subcutaneous AsPC-1 tumors were treated with Ad-alphaCaSm (1 x 10(9) plaque-forming units) as a single intratumor injection with tumor growth and survival monitored. RESULTS: AsPC-1 and Capan-1 cells showed decreased in vitro proliferation (93%, P =.0041, and 70%, P =. 0038, respectively) and anchorage independent growth (55%, P =.02, and 45%, P =.03, respectively) after treatment. Ad-alphaCaSm reduced in vivo AsPC-1 tumor growth by 40% (n = 10), extending median survival time from 35 to 60 days. CONCLUSIONS: Ad-alphaCaSm demonstrates a significant antitumor effect against pancreatic cancer both in vitro and in vivo. These results support the role of CaSm as a significant gene involved in the neoplastic transformation of pancreatic tumors. Thus CaSm represents a novel gene target in PC and holds potential as a new treatment approach either alone or in combination with existing therapies.

Adenoviridae↗
PubMed2000

A phylogenetic perspective on habitat shifts and diversity in the North American Enallagma damselflies.

Community ecologists are increasingly aware that the regional history of taxon diversification can have an important influence on community structure. Likewise, systematists recognize that ecological context can have an important influence on the processes of speciation and extinction that create patterns of descent. We present a phylogenetic analysis of 33 species of a North American radiation of damselflies (Zygoptera: Coenagrionidae: Enallagma Selys), which have been well studied ecologically, to elucidate the evolutionary mechanisms that have contributed to differences in diversity between larval habitats (lakes with and without fish predators). Analysis of molecular variation in 842 bp of the mitochondrial cytochrome oxidase I and II subunit and of the intervening Leu-tRNA and 37 morphological characters resulted in three well-defined clades that are only partially congruent with previous phylogenetic hypotheses. Molecular and morphological data partitions were significantly incongruent (p < .01). Lack of haplotype monophyly within species and small amounts of sequence divergence (< 1%) between related species in three of the four clades suggest that recent, and parallel, speciation has been an important source of community diversity. Reconstruction of habitat preference over the phylogeny suggests that the greater species diversity in fish-containing lake habitats reflects the recency of shifts into the fishless lake habit, although a difference in speciation or extinction rates between the two habitats is difficult to exclude as an additional mechanism.

Animals↗
PubMed2000

Mycobacterium septicum sp. nov., a new rapidly growing species associated with catheter-related bacteraemia.

Rapidly growing mycobacteria are capable of causing several clinical diseases in both immunosuppressed and immunocompetent individuals. A previously unidentified, rapidly growing mycobacterium was determined to be the causative agent of central line sepsis in a child with underlying metastatic hepatoblastoma. Four isolates of this mycobacterium, three from blood and one from the central venous catheter tip, were studied. Phenotypic characterization, HPLC and genetic analysis revealed that while this organism most closely resembled members of the Mycobacterium fortuitum complex and Mycobacterium senegalense, it differed from all previously described species. Phenotypic tests useful in differentiating this species from similar rapidly growing mycobacteria included: growth at 42 degrees C, hydrolysis of acetamide, utilization of citrate, production of arylsulfatase (3-d), acidification of D-mannitol and i-myo-inositol, and susceptibility to erythromycin, vancomycin and tobramycin. The name Mycobacterium septicum is proposed for this new species. The type strain has been deposited in Deutsche Sammlung von Mikroorganismen und Zellkulturen as DSM 44393T and in the American Type Culture Collection as strain ATCC 700731T.

Bacteremia↗
PubMed2000

Swelling and cyanosis of the tongue associated with use of a laryngeal mask airway.

We present a case report of a patient who developed acute swelling of the tongue during anaesthesia using the laryngeal mask airway. The swelling was thought to be due to obstruction of the venous drainage of the tongue. This was associated with isolated cyanosis of the tongue and paraesthesia. The swelling and cyanosis of the tongue resolved rapidly after removal of the laryngeal mask airway. The patient suffered paraesthesia of the tip of the tongue that lasted for two weeks.

Adult↗
PubMed2000

Influences of occlusion, color, and luminance on the perception of fragmented pictures.

The contribution of the magnocellular (M) pathway to perceptual completion and depth processing was examined by comparing performance under black-and-white conditions with isoluminant color and diffuse red background conditions expected to suppress M pathway activity. Participants identified the repeated figure in pictures where only fragments of the figures were visible. The fragments were presented either alone (unoccluded) or with an occluder (occluded) filling the space between them. Identification with an occluder involved amodally completing the fragments behind it, i.e., depth processing. All unoccluded versions were easy to identify indicating perceptual completion of the fragments was not influenced by suppressing M pathway activity. Black-and-white occluded versions were also easy to identify. The significantly longer identification times for occluded versions under isoluminant and diffuse red background conditions indicates amodal completion of the fragments was hindered when M pathway activity was reduced, supporting the importance of M pathway activity for depth processing.

Color Perception↗
PubMed2000

Fundus pigmentation and equiluminant moving phantoms.

Visual phantoms are a perceptual completion illusion wherein contours and surfaces are seen where none physically exist. The visibility of moving phantoms was measured with equiluminant and near equiluminant chromatic inducing gratings for observers having a fundus classified as either darkly or lightly pigmented. Phantom visibility was greatest for observers with a lightly compared to a darkly pigmented fundus with the two groups showing differences in visibility as a function of background luminance. The results are discussed relative to equiluminant stationary phantom findings and a proposed relationship between phantom visibility and magnocellular pathway activity.

Color Perception↗
PubMed2000

Perceptual parsing of acoustic consequences of velum lowering from information for vowels.

Three experiments were designed to investigate how listeners to coarticulated speech use the acoustic speech signal during a vowel to extract information about a forthcoming oral or nasal consonant. A first experiment showed that listeners use evidence of nasalization in a vowel as information for a forthcoming nasal consonant. A second and third experiment attempted to distinguish two accounts of their ability to do so. According to one account, listeners hear nasalization in the vowel as such and use it to predict that a forthcoming nasal consonant is nasal. According to a second, they perceive speech gestures and hear nasalization in the acoustic domain of a vowel as the onset of a nasal consonant. Therefore, they parse nasal information from a vowel and hear the vowel as oral. In Experiment 2, evidence in favor of the parsing hypothesis was found. Experiment 3 showed, however, that parsing is incomplete.

Female↗