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Biomedical subjects

G Horwitz

Publications and source records attributed to G Horwitz.

7 recordsLinked to original sources

Transforming events in thyroid tumorigenesis and their association with follicular lesions.

Thyroid tumors comprise a broad spectrum of neoplastic phenotypes, and distinct molecular events have been implicated in their pathogenesis. Pituitary tumor transforming gene, originally isolated from GH(4) pituitary cells, is tumorigenic in vivo, regulates basic fibroblast growth factor secretion, and is homologous to a securin inhibitor of chromatid separation. Pituitary tumor transforming gene 1 is expressed at low levels in several normal human tissues and is abundantly expressed in neoplasms, including colorectal carcinoma, where pituitary tumor transforming gene expression correlated highly with tumor invasiveness. As pituitary tumor transforming gene is regulated by E and as thyroid cancer shows a strong female preponderance, we examined pituitary tumor transforming gene 1 expression and action in human thyroid tumors and in normal human and rat thyroid cells. Increased pituitary tumor transforming gene 1 expression was evident early in thyroid tumors and was most abundantly expressed in a subset of thyroid hyperplasia, follicular adenomas, and follicular carcinomas (1.8-fold; P < 0.0001). Pituitary tumor transforming gene 1 overexpression in rat FRTL5 thyroid cells and in primary human thyroid cell cultures causes in vitro transformation and produces a dedifferentiated neoplastic phenotype. As pituitary tumor transforming gene 1 was abundantly overexpressed in follicular adenoma and follicular carcinoma, we propose that pituitary tumor transforming gene overexpression may play a role in the early molecular events leading to divergent development of follicular and papillary carcinoma.

Adult↗

Two types of image generation: evidence for left and right hemisphere processes.

The results from seven experiments provide evidence that visual mental images can be generated by either the left or right cerebral hemisphere, but in different ways. Subjects were cued to form images within a grid or within a set of four corner brackets; a single X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark was enclosed within each stimulus, and the subjects were to determine whether the X mark would have fallen on an imaged pattern. When subjects memorized descriptions of how parts were arranged, they could later form images of the composite pattern when cued in the right visual field (left hemisphere) more accurately than when they were cued in the left visual field (right hemisphere). In contrast, when subjects memorized individual segments on a screen, and 'mentally glued' them into a single pattern, they later could form images more accurately, at least in some circumstances, when cued in the left visual field. These results were predicted by the theory that images are built up by arranging parts, and that two different processes can be used to arrange them. One process uses stored descriptions to arrange parts, and is more effective in the left cerebral hemisphere; the other process uses stored memories of metric positions to arrange parts, and is more effective in the right cerebral hemisphere. Convergent evidence was obtained by having subjects memorize letters in grids (which are easily encoded using descriptions of the positions of segments) or within a space delineated by four brackets (which require memorizing the precise positions of the segments). Subjects were relatively more accurate when cued in the left visual field with bracket stimuli, but tended to be relatively more accurate when cued in the right visual field with grids stimuli. Control experiments showed that this finding was not due to hemispheric differences in the ease of forming images at different sizes or differences in the ease of perceptually encoding the probes.

Adolescent↗

Modulation of associative memory function in a biophysical simulation of rat piriform cortex.

1. Associative memory function was analyzed in a realistic biophysical simulation of rat piriform (olfactory) cortex containing 240 pyramidal cells and 58 each of two types of inhibitory interneurons. Pyramidal cell simulations incorporated six different intrinsic currents and three different synaptic currents. We investigated the hypothesis that acetylcholine sets the appropriate dynamics for learning within the network, whereas removal of cholinergic modulation sets the appropriate dynamics for recall. The associative memory function of the network was tested during recall after simulation of the cholinergic suppression of intrinsic fiber synaptic transmission and the cholinergic suppression of neuronal adaptation during learning. 2. Hebbian modification of excitatory synaptic connections between pyramidal cells during learning of patterns of afferent activity allowed the model to show the basic associative memory property of completion during recall in response to degraded versions of those patterns, as evaluated by a performance measure based on normalized dot products. 3. During learning of multiple overlapping patterns of afferent activity, recall of previously learned patterns interfered with the learning of new patterns. As more patterns were stored this interference could lead to the exponential growth of a large number of excitatory synaptic connections within the network. This runaway synaptic modification during learning led to excessive excitatory activity during recall, preventing the accurate recall of individual patterns. 4. Runaway synaptic modification of excitatory intrinsic connections could be prevented by selective suppression of synaptic transmission at these synapses during learning. This allowed effective recall of single learned afferent patterns in response to degraded versions of those patterns, without interference from other learned patterns. 5. During learning, cholinergic suppression of neuronal adaptation enhanced the activity of cortical pyramidal cells in response to afferent input, compensating for decreased activity due to suppression of intrinsic fiber synaptic transmission. This modulation of adaptation led to more rapid learning of afferent input patterns, as demonstrated by higher values of the performance measure. 6. During recall, when suppression of excitatory intrinsic synaptic transmission was removed, continued cholinergic suppression of neuronal adaptation led to the spread of excessive activity. More stable activity patterns during recall could be obtained when the cholinergic suppression of neuronal adaptation was removed at the same time as the cholinergic suppression of synaptic transmission. 7. A realistic biophysical simulation of the effects of acetylcholine on synaptic transmission and neuronal adaptation in the piriform cortex shows that these effects act together to set the appropriate dynamics for learning, whereas removal of both effects sets the appropriate dynamics for recall.

Acetylcholine↗

Test offering, not additional information, may increase HIV testing uptake in a knowledgeable population.

OBJECTIVES: To evaluate patient HIV knowledge and testing experience and assess the effect of an HIV informational handout on HIV testing propensity. DESIGN: Cross sectional, descriptive techniques were employed to assess demographics, HIV knowledge and HIV testing experience. A randomized controlled trial was performed to determine if an HIV/AIDS information sheet influenced testing propensity. SETTING: Blantyre Adventist Hospital Outpatient Clinic. SUBJECTS: Non-emergency patients over 18 years old attending during consulting hours. INTERVENTIONS: All subjects answered a questionnaire. For the randomized controlled trial component, half received an HIV information handout. MAIN OUTCOME MEASURES: Proportions were calculated to evaluate testing experience. Logistic regression was used to assess impact of written information and demographics on HIV testing propensity. RESULTS: 490 participants were recruited, of whom 57% had never been tested for HIV. Of the untested, 88% had never been offered an HIV test. Of those that had never been offered a test, 46% desired one. The sample was highly knowledgeable about HIV. Reading an information sheet had no impact on HIV knowledge (p=0.736 to 0.788) or desire for testing (p=0.387). However, age (OR=0.97, 95%CI (0.95,0.99)) and gender (OR=1.85, 95%CI (1.06, 3.23)) significantly correlated with testing propensity. CONCLUSIONS: A large percentage of patients who have never been offered HIV testing desire testing. More frequent HIV test offering by clinicians could improve testing rates. Clinician education programmes should be developed to increase test offering. Furthermore, written health information in a setting of high HIV/AIDS knowledge may not change behaviour. Alternative methods should be employed to encourage HIV testing uptake.

AIDS Serodiagnosis↗