Biomedical subjects

J L Hicks

Publications and source records attributed to J L Hicks.

At least 19 recordsLinked to original sources

PubMed2003

Expression of the DNA-PK binding protein E4-34K fails to confer radiation sensitivity to mammalian cells.

PURPOSE: The adenovirus E4orf6 34 kDa protein (E4-34k) is known to disrupt V(D)J recombination as a result of its interaction with the catalytic subunit of cellular DNA-dependent protein kinase (DNA-PK(cs)), a major participant in the repair of DNA double-strand breaks (DSB). Previous studies have shown that cells with disrupted DSB repair and V(D)J recombination due to attenuation of DNA-PK(cs) activity exhibit a radiation-sensitive phenotype. It is not known at present whether the E4-34k protein can also modify cellular response to ionizing radiation. In an attempt to develop a novel gene therapy strategy to modify cellular radiation response, we sought to determine if expression of the adenovirus E4-34k protein resulted in sensitization to clinically relevant doses of ionizing radiation. MATERIALS AND METHODS: In order to minimize potential bias resulting from selection procedures, we performed clonogenic survival assays on DU 145 prostate cancer cells, RKO colorectal cancer cells and 293 kidney cells following transient transfection of E4-34k- and/or E1B-55k-expressing plasmids. Western blots and immunohistochemical analyses were used to demonstrate E4-34k expression within transfected cells. FACS sorting was carried out to enrich cells transfected with a plasmid that expresses both E4-34k and enhanced green fluorescent protein. RESULTS: It is shown that E4-34k expression does not affect cellular radiosensitivity of transiently transfected populations of either DU 145 prostate or RKO colon cancer cell lines. Similarly, the radiosensitivity of human embryonic kidney 293 cells, which constitutively express the E1B-55k protein, was also unaffected. The radiosensitivity of DU 145 cells co-transfected with E4-34k- and E1-55K-expressing plasmids was unchanged, suggesting that the adenovirus E1B-55k protein does not augment any effects E4-34k might have on DNA-PK(cs) activity. CONCLUSIONS: The lack of radiosensitization by E4-34k expression is quite intriguing as it is known that E4-34k interaction with DNA-PK(cs) causes disruption of V(D)J recombination, a process dependent on DSB rejoining. These data suggest that for future studies, preferential targeting of DNA-PK(cs) DSB activity will be required to influence cellular radiosensitivity.

Adenovirus E1B Proteins↗

PubMed2001

False recognition occurs more frequently during source identification than during old-new recognition.

A number of recent reports have investigated false memories using variants of the Deese-Roediger-McDermott (DRM) paradigm. Because these false memories have been difficult to eliminate, this study investigated whether false recognition could be reduced by incorporating source-monitoring criteria into decision processes. Making claims about the manner in which items were learned should require more careful scrutiny of memories, and therefore false recognition should be minimized with source instructions as compared with old-new recognition instructions. In 3 experiments that varied the combination of sources, false recognition was increased rather than reduced by applying source-monitoring processes. The theoretical implications of these counterintuitive results are discussed in terms of the old-new detection component of source judgments.

Adult↗

PubMed2001

Output monitoring tests reveal false memories of memories that never existed.

Three experiments were conducted to assess participants' beliefs about potential false memories that might have occurred during free recall tests. An input-output monitoring test was administered that required participants to discriminate between items that were studied and recalled, studied and not recalled, or were entirely new. Critical lures from Roediger and McDermott's (1995) paradigm were inserted into this test. The results demonstrated that participants believed erroneously recalled items were both studied and recalled. The intriguing finding was that unrecalled items were believed to have been studied approximately 80% of the time, and half of those were also believed to have been recalled. This result represents a dual false memory effect in which items were believed to have been studied and also to have been recalled. The ramifications of this new procedure are discussed in terms of proposed experiments that might clarify the genesis of these false memories.

Analysis of Variance↗

PubMed2001

Infected joint replacements in HIV-positive patients with haemophilia.

Joint replacement in HIV-positive patients remains uncommon, with most experience gained in patients with haemophilia. We analysed retrospectively the outcome of 102 replacement arthroplasties in 73 HIV-positive patients from eight specialist haemophilia centres. Of these, 91 were primary procedures. The mean age of the patients at surgery was 39 years, and the median follow-up was for five years. The overall rate of deep sepsis was 18.7% for primary procedures and 36.3% for revisions. This is a much higher rate of infection than that seen in normal populations. A total of 44% of infections resolved fully after medical and/or surgical treatment. The benefits of arthroplasty in haemophilic patients are well established but the rates of complications are high. As this large study has demonstrated, high rates of infection occur, but survivorship analysis strongly suggests that most patients already diagnosed with HIV infection at the time of surgery should derive many years of symptomatic relief after a successful joint replacement. Careful counselling and education of both patients and healthcare workers before operation are therefore essential.

Adult↗

PubMed2000

Important landmarks of the orofacial complex.

Hard-tissue and soft-tissue landmarks of the face and oral cavity are introduced. Definitions for anatomic structures are listed, and figures to aid clinical examination are provided. Relevance of these landmarks to examination, diagnosis, and function is made.

Dentition↗

PubMed2000

The properties of retention intervals and their affect on retaining prospective memories.

Five experiments were conducted to explore how the character of the retention interval affected event-based prospective memory. According to the canons of retrospective memory, prospective performance should have been worse with increasing delays between intention formation and the time it was appropriate to complete an action. That result did not occur. Rather, prospective memory was better with increasing retention intervals in Experiments 1A, 1B, and 3. In manipulating the nature of the retention interval, the authors found that there were independent contributions of retention interval length and the number of intervening activities, with more activities leading to better prospective memory (Experiments 2 and 3). The identical retention intervals did not improve retrospective memory in Experiment 4. Theoretical explanations for these dissociations between prospective and retrospective memory are considered.

Adult↗

PubMed2000

Toward specifying the attentional demands of recognition memory.

Previous studies have concluded that recognition memory is immune to disruption from divided attention and therefore is a relatively automatic process (A. Baddeley, V. Lewis, M. Eldridge, & N. Thomson, 1984; F. I. M. Craik, R. Govoni, M. Naveh-Benjamin, & N. D. Anderson, 1996). Because costs have been found on the concurrent task used to divide attention, recognition may nevertheless require some attentional resources (M. Naveh-Benjamin, F. I. M. Craik, J. Guez, & H. Dori, 1998). The present authors used attention-demanding concurrent tasks to demonstrate significant costs on both the concurrent task and recognition memory performance. Decrements in recognition accuracy were found for classes of items that were studied deeply but not for more shallowly learned materials. The present findings suggest that recognition processes can require significant attentional resources when tested under the appropriate conditions. The results are discussed in terms of the requirements both at encoding and at test that are needed to observe dual-task decrements to recognition accuracy.

Adolescent↗

PubMed1999

The credibility of a source influences the rate of unconscious plagiarism.

Three experiments were conducted to investigate the relationship between the credibility of information and later unconscious plagiarism of that information. In each experiment, ideas concerning ways to reduce traffic accidents were presented from a more credible source (traffic planners) and a less credible source (college freshmen). After a distractor task, participants were asked to generate novel ways to reduce traffic accidents. In Experiments 1 and 2, unconscious plagiarism of ideas presented from the more credible source was greater than from the less credible source. In neither experiment was explicit memory for ideas from each source different in tests of source monitoring or free recall. However, the difference in unconscious plagiarism was eliminated in Experiment 3 by having participants generate the implications of ideas at study. The results are discussed in terms of the explicit factors that affect the incidence of unconscious plagiarism.

Adult↗

PubMed1999

Class VI unconventional myosin is required for spermatogenesis in Drosophila.

We have identified partial loss of function mutations in class VI unconventional myosin, 95F myosin, which results in male sterility. During spermatogenesis the germ line precursor cells undergo mitosis and meiosis to form a bundle of 64 spermatids. The spermatids remain interconnected by cytoplasmic bridges until individualization. The process of individualization involves the formation of a complex of cytoskeletal proteins and membrane, the individualization complex (IC), around the spermatid nuclei. This complex traverses the length of each spermatid resolving the shared membrane into a single membrane enclosing each spermatid. We have determined that 95F myosin is a component of the IC whose function is essential for individualization. In wild-type testes, 95F myosin localizes to the leading edge of the IC. Two independent mutations in 95F myosin reduce the amount of 95F myosin in only a subset of tissues, including the testes. This reduction of 95F myosin causes male sterility as a result of defects in spermatid individualization. Germ line transformation with the 95F myosin heavy chain cDNA rescues the male sterility phenotype. IC movement is aberrant in these 95F myosin mutants, indicating a critical role for 95F myosin in IC movement. This report is the first identification of a component of the IC other than actin. We propose that 95F myosin is a motor that participates in membrane reorganization during individualization.

Actins↗

PubMed1999

Remember-know judgments can depend on how memory is tested.

Remember-know judgments reflect the subjective state of awareness that accompanies episodic memory retrieval. We tested an old-new recognition condition, an old-new recognition followed by remember-know judgment condition, and a simultaneous remember-know-new judgment condition. These three conditions were tested for both a short (1-sec) and a long (4.5-sec) study duration. Reassuringly, results from the first two conditions did not differ from each other. Results from the third condition, however, differed from those in the first two conditions at both long and short study durations. Simultaneous consideration of all three alternatives resulted in a markedly liberal response bias, both in recognition detection and in the ascriptions of remember and know judgments. Discussion of the results is framed in terms of the single-process signal detection models that have been proposed to account for these subjective states of awareness.

Humans↗

PubMed1999

The activation of unrelated and canceled intentions.

The intention superiority effect is the finding that intentions to perform an activity are stored in a heightened state of activation. The effect has also been generalized to the finding that once an intention is fulfilled, it is inhibited relative to more neutral material about which no intentionality has been formed. In two experiments, we tested some ecological and naturally occurring situations taken from the literature on prospective memory and demonstrated that they have consistent consequences for the activation level of an intention. In Experiment 1, a constellation of unrelated activities displayed heightened activation prior to completion and displayed inhibition after completion. In Experiment 2, canceling the intention resulted in inhibition just as completing the intention does in this paradigm. The results are discussed in terms of their practical and theoretical importance to theories of prospective memory.

Humans↗

PubMed1999

Conceptual priming in a generative problem-solving task.

Three experiments explored how participants solved a very open-ended generative problem-solving task. Previous research has shown that when participants are shown examples, novel creations will tend to conform to features shared across those examples (Smith, Ward, & Schumacher, 1993). We made the shared features of the examples conceptually related to one another. We found that when the features were related to the concept of hostility, participants' creations contained hostile features that were not part of any of the examples. These results suggest that participants will design novel entities to be consistent with emergent properties of examples shown to them. We also found that a mild hostility prime from unscrambling sentences had a similar conceptual effect. Together, the two effects suggest that conceptual priming of generative cognitive tasks will influence the cognitive aspects of the creative process.

Analysis of Variance↗

PubMed1998

Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor.

A class of high-affinity inhibitors is disclosed that selectively target and irreversibly inactivate the epidermal growth factor receptor tyrosine kinase through specific, covalent modification of a cysteine residue present in the ATP binding pocket. A series of experiments employing MS, molecular modeling, site-directed mutagenesis, and 14C-labeling studies in viable cells unequivocally demonstrate that these compounds selectively bind to the catalytic domain of the epidermal growth factor receptor with a 1:1 stoichiometry and alkylate Cys-773. While the compounds are essentially nonreactive in solution, they are subject to rapid nucleophilic attack by this particular amino acid when bound in the ATP pocket. The molecular orientation and positioning of the acrylamide group in these inhibitors in relation to Cys-773 entirely support these results as determined from docking experiments in a homology-built molecular model of the ATP site. Evidence is also presented to indicate that the compounds interact in an analogous fashion with erbB2 but have no activity against the other receptor tyrosine kinases or intracellular tyrosine kinases that were tested in this study. Finally, a direct comparison between 6-acrylamido-4-anilinoquinazoline and an equally potent but reversible analog shows that the irreversible inhibitor has far superior in vivo antitumor activity in a human epidermoid carcinoma xenograft model with no overt toxicity at therapeutically active doses. The activity profile for this compound is prototypical of a generation of tyrosine kinase inhibitors with great promise for therapeutic significance in the treatment of proliferative disease.

Animals↗

PubMed1998

Event-based prospective memory and executive control of working memory.

In 5 experiments, the character of concurrent cognitive processing was manipulated during an event-based prospective memory task. High- and low-load conditions that differed only in the difficulty of the concurrent task were tested in each experiment. In Experiments 1 and 2, attention-demanding tasks from the literature on executive control produced decrements in prospective memory. In Experiment 3, attention was divided by different loads of articulatory suppression that did not ultimately lead to decrements in prospective memory. A high-load manipulation of a visuospatial task requiring performance monitoring resulted in worse prospective memory in Experiment 4, whereas in Experiment 5 a visuospatial task with little monitoring did not. Results are discussed in terms of executive functions, such as planning and monitoring, that appear to be critical to successful event-based prospective memory.

Adult↗

PubMed1998

An investigation of everyday prospective memory.

Prospective memory, remembering to carry out one's planned activities, was investigated using a naturalistic paradigm. Three experiments, with a total of 405 participants, were conducted. The goal was to demonstrate that the cognitive processing underlying successful everyday prospective remembering involves components other than mere "memory." Those components are probably best represented as individual differences in various cognitive capacities. More specifically, metamemory, attentional capacities, and planning processes that reprioritize intentions according to the demands of everyday life may determine how people actually accomplish the plans they establish for themselves. The results of these experiments suggest that researchers interested in the topic will have to contend with a multidimensional set of factors before any comprehensive understanding of prospective remembering can be realized.

Adult↗

PubMed1998

A decrement-to-familiarity interpretation of the revelation effect from forced-choice tests of recognition memory.

In the revelation effect, the probability of labeling a target or a lure as "old" on item recognition tests increases if just prior to their recognition judgment, participants first identify a disguised version of the test item. The same occurs with interpolated tasks that occur just prior to a recognition judgment if the task shares constituents with the test items. One explanation of this test bias is an increased feeling of familiarity that comes from the identification stage preceding the recognition judgment (e.g., D. C. LeCompte, 1995; C. R. Lou, 1993). This study's finding in 4 experiments that 2-alternative forced-choice recognition either yields no effects of revelation or an "antirevelation" effect, even when both items were studied or nonstudied, is incongruent with this explanation. The authors argue that revelation decrements familiarity, and this results in a more liberal criterion shift. They also argue that their theory is more consistent with previous empirical data.

Choice Behavior↗

PubMed1997

Processing strategies and secondary memory in very rapid forgetting.

When a memory test is unexpected, recall performance is quite poor at retention intervals as short as 2-4 seconds. Orienting tasks that change encoding conditions are known to affect forgetting in such "very rapid forgetting" paradigms where people are misled to believe that recall will not be required. We evaluated the hypothesis that differences in forgetting among orienting tasks are attributable to contributions of secondary memory during encoding in two experiments. In Experiment 1, short-term recall performance was inversely related to task demands during encoding, although long-term memory performance was not. Task demands were assessed by making the duration of stimulus presentation dependent on the time required to perform three different orienting tasks. In Experiment 2, we compared performance of that variable-length stimulus presentation to the fixed-length presentation used in most prior research. The results suggested that additional encoding or rehearsal time does not have an appreciable impact on short-term performance. Thus, differences in forgetting appeared to be a function of the contribution of secondary memory rather than a function of the time available to engage in primary memory rehearsal strategies.

Analysis of Variance↗

PubMed1997

Linking postdoctoral general dentistry programs with community-based clinical care settings.

This article presents the results of a small workgroup convened by the American Association of Dental Schools to examine experiences related to establishing and conducting dental education programs that have significant affiliations with community-based clinical care settings. The workgroup meeting is a component of the association's effort to identify and promote innovative and non-traditional methods by which the number of postdoctoral general dentistry (PGD) positions can be increased to meet current demand for PGD education. The participants identified factors and conditions believed to be critical to successful program linkages. The information should be helpful to others as they consider opportunities to establish PGD programs or increase their number of PGD training positions.

Accreditation↗