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Biomedical subjects

F Dick

Publications and source records attributed to F Dick.

At least 19 recordsLinked to original sources

Auditory semantic networks for words and natural sounds.

Does lexical processing rely on a specialized semantic network in the brain, or does it draw on more general semantic resources? The primary goal of this study was to compare behavioral and electrophysiological responses evoked during the processing of words, environmental sounds, and non-meaningful sounds in semantically matching or mismatching visual contexts. A secondary goal was to characterize the dynamic relationship between the behavioral and neural activities related to semantic integration using a novel analysis technique, ERP imaging. In matching trials, meaningful-sound ERPs were characterized by an extended positivity (200-600 ms) that in mismatching trials partly overlapped with centro-parietal N400 and frontal N600 negativities. The mismatch word-N400 peaked later than the environmental sound-N400 and was only slightly more posterior in scalp distribution. Single-trial ERP imaging revealed that for meaningful stimuli, the match-positivity consisted of a sensory P2 (200 ms), a semantic positivity (PS, 300 ms), and a parietal response-related positivity (PR, 500-800 ms). The magnitudes (but not the timing) of the N400 and PS activities correlated with subjects' reaction times, whereas both the latency and magnitude of the PR was correlated with subjects' reaction times. These results suggest that largely overlapping neural networks process verbal and non-verbal semantic information. In addition, it appears that semantic integration operates across different time scales: earlier processes (indexed by the PS and N400) utilize the established meaningful, but not necessarily lexical, semantic representations, whereas later processes (indexed by the PR and N600) are involved in the explicit interpretation of stimulus semantics and possibly of the required response.

Acoustic Stimulation↗

Endovascular stenting of a renal transplant vein.

We describe successful endovascular stenting of a high-grade stenosis of a renal transplant vein in a 53-year old patient. Kidney transplantation had been performed due to IgA nephropathy and the patient had become symptomatic two months after uneventful recovery from operation.

Angioplasty, Balloon↗

Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty.

OBJECTIVES: Aim of this study is to correlate distribution pattern of lower limb atherosclerosis with cardiovascular risk factor profile of patients with peripheral arterial occlusive disease (PAD). PATIENTS AND METHODS: Analysis is based on a consecutive series of 2659 patients (1583 men, 1076 women, 70+/-11 years) with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower extremity arteries. Pattern of atherosclerosis was grouped into iliac (n=1166), femoropopliteal (n=2151) and infrageniculate (n=888) disease defined according to target lesions treated. A multivariable multinomial logistic regression analysis was performed to assess relation with age, gender and classical cardiovascular risk factors (diabetes mellitus, arterial hypertension, hypercholesterolemia, cigarette smoking) using femoropopliteal disease as reference. RESULTS: Iliac disease was associated with younger age (RRR 0.95 per year of age, 95%-CI 0.94-0.96, p<0.001), male gender (RRR 1.32, 95%-CI 1.09-1.59, p=0.004) and cigarette smoking (RRR 2.02, 95%-CI 1.68-2.42, p<0.001). Infrageniculate disease was associated with higher age (RRR 1.02, 95%-CI 1.01-1.02, p<0.001), male gender (RRR 1.23, 95%-CI 1.06-1.41, p=0.005) and diabetes mellitus (RRR 1.68, 95%-CI 1.47-1.92, p<0.001). Hypercholesterolemia was less prevalent in patients with lesions below the knee (RRR 0.82, 95%-CI 0.71-0.94, p=0.006), whereas no distinct pattern was apparent related to arterial hypertension. CONCLUSION: Clinical phenotype of peripheral atherosclerosis varies with prevalence of cardiovascular risk factors suggesting differences in mechanisms involved in iliac as compared with infrageniculate lesions. Identification of molecular mechanism might have influence on future therapeutic strategies in PAD patients.

Age Factors↗

The aspartimide problem in Fmoc-based SPPS. Part III.

A newly developed Fmoc-Asp derivative, Fmoc-Asp beta-(2,3,4-trimethyl-pent-3-yl) ester, has been tried in the Fmoc-based SPPS of H-Val-Lys-Asp-Xaa-Tyr-Ile-OH, a well-established peptide model for studying base-catalysed aspartimide formation. When synthesizing the hexapeptide incorporating Gly, Arg(Pbf), Asn(Mtt), Asp(OtBu) or Cys(Acm) for Xaa, considerable amounts of aspartimide-related by-products were to be expected. The Asp(3) beta-carboxy protecting group and the duration of exposure to bases were varied. By-product formation could be reduced by incorporation of the new Asp derivative more efficiently than by introducing the less bulky Asp(OMpe). Significant improvements were observed in cases of prolonged contact with piperidine or DBU. Both beta-carboxy protecting groups were superior to the standard Asp(OtBu) which was also included in this study, but the additional stabilization gained by our new protecting group was valuable especially in syntheses of long peptides or difficult sequences.

Amino Acids↗

Is colour vision impairment associated with cognitive impairment in solvent exposed workers?

AIMS: To determine whether acquired colour vision deficits in solvent exposed individuals are associated with cognitive impairment. METHODS: A sample of 82 painters and 38 other subjects were studied. Alcohol, drug, and smoking histories were obtained. Colour vision was tested using the Lanthony D-15-d colour vision test. Cognitive impairment was measured using the Benton visual retention test, Trail making A, and Trail making B tests. Pre-morbid IQ was estimated using the National Adult Reading Test. Solvent exposure in all subjects was estimated using a previously validated, structured subjective assessment methodology. RESULTS: After exclusion of subjects with competing causes of colour vision impairment the final group of men numbered 78. There was a significant association on multiple linear regression between the mean colour confusion index (CCI) and three measures of cognitive impairment, the Benton visual retention test, Trail making A, and Trail making B tests after adjusting for the effects of age (or IQ as appropriate), alcohol, and smoking. CONCLUSION: Acquired colour vision loss is associated with cognitive impairment in solvent exposed workers. However, given the prevalence of acquired colour vision losses in the adult population, colour vision testing is unlikely to be of value as a screening test.

Adult↗

The aspartimide problem in Fmoc-based SPPS. Part I.

A variety of Asp beta-carboxy protecting groups, Hmb backbone protection and a range of Fmoc cleavage protocols have been employed in syntheses of the model hexapeptide H-VKDGYI-OH to investigate the aspartimide problem in more detail. The extent of formation of aspartimide and aspartimide-related by-products was determined by RP-HPLC. This study included three new Fmoc-Asp-OH derivatives: the beta-(4-pyridyl-diphenylmethyl) and beta-(9-phenyl-fluoren-9-yl) esters and also the orthoester Fmoc-beta-(4-methyl-2,6,7-trioxabicyclo[2.2.2]-oct-1-yl)-alanine. 3-Methylpent-3-yl protection of the Asp side chain resulted in significant improvements with respect to aspartimide formation. Complete suppression was achieved using the combination OtBu side chain protection and Hmb backbone protection for the preceding Gly residue.

Amino Acids↗

The aspartimide problem in Fmoc-based SPPS. Part II.

The sequence dependence of base-catalysed aspartmide formation during Fmoc-based SPPS was systematically studied employing the peptide models H-Val-Lys-Asp-Xaa-Tyr-Ile-OH. The extent of formation of aspartimide and related by-products was determined by RP-HPLC. Considerable amounts of by-products were formed in the case of Xaa = Asp(OtBu), Arg(Pbf), Asn(Mtt), Cys(Acm) and unprotected Thr. Aspartimide formation could be diminished by incorporation of Asp(OMpe) or by employing milder methods for Fmoc cleavage, e.g. hexamethyleneimine/N-methylpyrrolidine/HOBt/NMP/DMSO 4:50:4:71:71 (v/v/w/v/v).

Amino Acids↗

Organic solvent exposure, genes, and risk of neuropsychological impairment.

BACKGROUND: Subtle cognitive and neurological impairments have been found in some workers exposed to organic solvents. Whether these effects occur at or below current legal limits for occupational exposure is controversial. AIM: To determine whether occupational solvent exposure is associated with neuropsychological impairment and whether such risk is modified by polymorphisms in the genes for enzymes involved in detoxification. DESIGN: Retrospective case-control analysis. METHODS: We studied 78 former dockyard painters and 42 community controls. Individual respiratory and dermal exposures to solvents were estimated. Neuropsychological tests were administered, including paper and pencil tests, tests from the Neurobehavioural Evaluation System (NES2), together with a structured neurological examination and genotyping of polymorphic enzymes involved in detoxification: GSTM1, GSTT1, GSTP1, NAT1, NAT2, SOD1 and CYP1A1. RESULTS: While initial case-control analyses failed to identify any significant differences between symptomatic and asymptomatic painters, in regression analyses increasing solvent exposure was associated with increasing risk of cognitive impairment, after adjustment for IQ (or age, where appropriate), smoking and alcohol. There was also an association between exposure and reduction in grip strength. There was limited evidence of risk modification by some enzyme polymorphisms. DISCUSSION: This association between increasing intensity of solvent exposure and neuropsychological impairment may be important at current exposure levels in the UK.

Case-Control Studies↗

Expression of cyclins E1 and E2 during mouse development and in neoplasia.

Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G(1)/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in approximately 24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry.

Animals↗

Comparison of a virtual microscope laboratory to a regular microscope laboratory for teaching histology.

Emerging technology now exists to digitize a gigabyte of information from a glass slide, save it in a highly compressed file format, and deliver it over the web. By accessing these images with a standard web browser and viewer plug-in, a computer can emulate a real microscope and glass slide. Using this new technology, the immediate aims of our project were to digitize the glass slides from urinary tract, male genital, and endocrine units and implement them in the Spring 2000 Histology course at the University of Iowa, and to carry out a formative evaluation of the virtual slides of these three units in a side-by-side comparison with the regular microscope laboratory. The methods and results of this paper will describe the technology employed to create the virtual slides, and the formative evaluation carried out in the course. Anat Rec (New Anat) 265:10-14, 2001.

Computer-Assisted Instruction↗

Synthesis and application of Fmoc-His(3-Bum)-OH.

This paper presents a reevaluation of the synthesis and properties of Fmoc-His(3-Bum)-OH regarding its application in SPPS with minimal racemization of histidine residues during coupling and esterification reactions. By-product formation during the deprotection of the test peptides could be significantly reduced by scavenging the concomitantly formed HCHO, e.g. with methoxyamine.

Amino Acids↗

Linguistic and nonlinguistic priming in aphasia.

Studies of real-time processing in aphasia suggest that linguistic symptoms may be due to deficits in activation dynamics rather than loss of linguistic knowledge. To investigate the domain specificity of such processing deficits, we compared performance by Italian-speaking fluent aphasics, nonfluent aphasics, and normal controls in a linguistic priming task (grammatical gender) with their performance in a color-priming task that requires no verbal mediation. Normal or larger than normal color-priming effects were demonstrated in both aphasic groups. Gender priming did not reach significance in either group, even though the patients displayed above-chance sensitivity to gender class and gender agreement in their accuracy scores. The demonstration of spared gender knowledge despite impaired gender priming underscores the utility of on-line techniques in the study of aphasia. The demonstration of spared color priming suggests that priming deficits in aphasia are either (1) specific to speech and language or (2) specific only to those sensorimotor and attentional processes that language shares with other nonlinguistic systems.

Adult↗

The large subunit of replication factor C promotes cell survival after DNA damage in an LxCxE motif- and Rb-dependent manner.

Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We show here that the LxCxE binding site in Rb mediates both cell survival and cell-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protective effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damage in an Rb-dependent manner.

Amino Acid Motifs↗

Language deficits, localization, and grammar: evidence for a distributive model of language breakdown in aphasic patients and neurologically intact individuals.

Selective deficits in aphasic patients' grammatical production and comprehension are often cited as evidence that syntactic processing is modular and localizable in discrete areas of the brain (e.g., Y. Grodzinsky, 2000). The authors review a large body of experimental evidence suggesting that morpho-syntactic deficits can be observed in a number of aphasic and neurologically intact populations. They present new data showing that receptive agrammatism is found not only over a range of aphasic groups, but is also observed in neurologically intact individuals processing under stressful conditions. The authors suggest that these data are most compatible with a domain-general account of language, one that emphasizes the interaction of linguistic distributions with the properties of an associative processor working under normal or suboptimal conditions.

Adult↗

Exposure to organic solvents and personality.

OBJECTIVES: Although cognitive and neuropsychological changes have been found after high cumulative exposures to solvents, it is not clear whether such exposures are associated with personality characteristics. To study this two groups of British and Chinese dockyard painters who had been heavily exposed to paint solvents have been investigated. METHODS: 260 Male dockyard painters in the United Kingdom, 539 local community controls, 109 Chinese dockyard painters, and 255 dockyard controls completed the Eysenck personality questionnaire, neuroticism (N) and social conformity or dissimulation (L) scales. The non-parametric Kruskal-Wallis test was used to evaluate differences in scores of personality traits between painters and controls. Adjusted relative risks for painters having high N and L scores were calculated in a Breslow-Cox regression analysis, and exposure-response relations were examined in multivariate logistic regression analysis. Non-parametric Spearman's correlation was used to examine relations between previously determined neuropsychological symptoms and personality. RESULTS: Both British and Chinese data showed that mean neuroticism scores of painters were significantly higher than controls, whereas scores of social conformity did not differ. Relative risk of being a painter increased significantly with increasing N scores, but L scores showed no such trend. In a case-control analysis, there were significant exposure-response relations for the N score. In the United Kingdom the odds ratios (ORs) (95% confidence interval (95% CI), were 2.03 (0.79 to 5.22) for 1-4 years of exposure, 2.38 (0.82 to 6.91) for 5-9 years, 7.05 (1.27 to 39.25) for 10-14 years, and 1.76 (0.63 to 4.89) for 15-41 years. In the Chinese painters, ORs were 4.66 (1.38 to 15.75) for 2-14 years, 10.03 (2.96 to 34.04) for 15-18 years, and 13.56 (3.78 to 48.59) for 19-43 years. Neuroticism was significantly positively related to neuropsychological symptoms in all subjects. Social conformity showed no association with neuropsychological symptoms in British painters and a negative relation among the Chinese painters. CONCLUSION: Increasing symptoms suggesting neuroticism seemed to relate to the duration of painting whereas scores for social conformity and dissimulation did not. The relation between exposure time and response suggests that increased neuroticism may be caused by long term occupational exposure to organic solvents.

Adolescent↗

Nasal, eye, and skin irritation in dockyard painters.

OBJECTIVES: To determine whether the risk of irritant symptoms in painters is related to their exposure to paint. METHODS: The prevalences of skin, eye and nasal symptoms were compared in 260 United Kingdom and 109 Chinese dockyard painters, 539 British community controls, and 255 Chinese dockyard controls, relative to their exposure to paints. RESULTS: Painters showed an excess of irritant symptoms compared with controls. Adjusted relative risks (RRs) (95% confidence interval (95% CI) were: for skin irritation 1.58 (1.19 to 2.08) in British painters and 2.68 (1.73 to 4.09) in Chinese painters; for eye irritation, 1.41 (0.98 to 2.05) and 3.01 (1.90 to 4.76); and for nasal irritation, 1.53 (1.10 to 2.14) and 6.73 (3.53 to 12.82), respectively. Exposure duration-response relations were found for these symptoms; the risks decreased with time after exposure ended. CONCLUSIONS: Irritant symptoms occur more often in dockyard painters than in controls, and this is likely to be a response to exposure to paint.

Adolescent↗

A dermal model for spray painters. Part II: estimating the deposition and uptake of solvents.

The contribution of dermal exposure to the total body burden of a given chemical is difficult to assess. However, it is possible that as regulatory pressures lead to reductions in inhalation exposure, the proportion of uptake via the dermal route will increase. This study brings together recent work in the field of dermal exposure to provide a model to estimate both exposure and uptake of solvents through the skin. Using spray painters as an example, the process of modelling exposure is described from identifying the determinants of exposure through to calculating the flux of solvent through the stratum corneum and thus the total dermal uptake. Results from a range of exposure scenarios are presented and areas requiring further research and validation are highlighted. The model should allow the estimation of combined dermal and inhalation exposure to solvents in both current work situations and retrospective epidemiological studies. Furthermore, it is envisaged that the model may provide the basis for generic assessment of dermal exposure and uptake.

Air Pollutants, Occupational↗

Blood transfusions and risk of non-Hodgkin's lymphoma subtypes and chronic lymphocytic leukemia.

Allogeneic blood transfusion has been suggested as a risk factor for non-Hodgkin's lymphoma (NHL), possibly specific to certain NHL subtypes, or chronic lymphocytic leukemia (CLL). Self-reported transfusion history and risk of NHL subtypes and CLL were examined in a cohort of 37,934 older Iowa women, using data from a questionnaire mailed in 1986. Through 1997, 229 cases of NHL and 57 cases of CLL in the cohort were identified through linkage to the Iowa Surveillance, Epidemiology and End Results Cancer REGISTRY: Women who reported ever receiving a blood transfusion were at increased risk for all NHLs [age adjusted relative risk (RR), 1.6; 95% confidence interval (CI), 1.2-2.1). On the basis of the Working Formulation classification, blood transfusion was positively associated with low-grade NHL (RR, 2.7; 95% CI, 1.7-4.5) but not with intermediate-grade NHL (RR, 1.1; 95% CI, 0.7-1.6); there were only 8 cases of high-grade NHL. Blood transfusion was positively associated with follicular (RR, 2.8; 95% CI, 1.6-5.1) and small lymphocytic (RR, 3.4; 95% CI, 1.5-7.9) NHL subtypes but not with diffuse NHL (RR, 1.0; 95% CI, 0.7-1.5). There was also a positive association with CLL (RR, 1.7; 95% CI, 1.0-3.0). Finally, transfusion was associated with nodal (RR, 1.8; 95% CI, 1.3-2.5) but not extranodal (RR, 1.2; 95% CI, 0.7-2.1) NHL. Further adjustment for marital status, farm residence, diabetes, alcohol use, smoking, and red meat and fruit consumption did not alter these associations. In conclusion, prior blood transfusion was associated with NHL and CLL, and the strongest associations were seen for low-grade NHL, particularly follicular and small lymphocytic NHL.

Aged↗