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Biomedical subjects

J Dorfman

Publications and source records attributed to J Dorfman.

At least 19 recordsLinked to original sources

Rostrolateral prefrontal cortex involvement in relational integration during reasoning.

Patient and neuroimaging studies indicate that complex reasoning tasks are associated with the prefrontal cortex (PFC). In this study, we tested the hypothesis that the process of relational integration, or considering multiple relations simultaneously, is a component process of complex reasoning that selectively recruits PFC. We used fMRI to examine brain activation during 0-relational, 1-relational, and 2-relational problems adapted from the Raven's Progressive Matrices and hypothesized that PFC would be preferentially recruited by the 2-relational problem type. Event-related responses were modeled by convolving a canonical hemodynamic response function with the response time (RT) associated with each trial. The results across different analyses revealed the same pattern: PFC activation was specific to the comparison between 2- and 1-relational problems and was not observed in the comparison between 1- and 0-relational problems. Furthermore, the process of relational integration was specifically associated with bilateral rostrolateral PFC (RLPFC; lateral area 10) and right dorsolateral PFC (areas 9 and 46). Left RLPFC showed the greatest specificity by remaining preferentially recruited during 2-relational problems even after comparisons were restricted to trials matched for RT and accuracy. The link between RLPFC and the process of relational integration may be due to the associated process of manipulating self-generated information, a process that may characterize RLPFC function.

Adolescent↗

Primary tracheal schwannoma.

We report a case of a primary tracheal schwannoma causing symptoms of airway obstruction in a 33-year-old man. Bronchoscopy and computerized tomography demonstrated a polypoid intratracheal mass obstructing 90% of the lumen. Tracheal resection with primary anastomosis was performed. Histologic analysis revealed a benign neurogenic tumor of Schwann cell origin.

Adult↗

NK and CTL recognition of a single chain H-2Dd molecule: distinct sites of H-2Dd interact with NK and TCR.

We generated transgenic mice expressing a single-chain beta2-microglobulin (beta2m)-H-2Dd. The cell-surface beta2m-H-2Dd molecule was expressed on a beta2m-deficient background and reacted with appropriate mAbs. It was of the expected m.w. and directed the normal development of CD8+ T cells in the thymus of a broad TCR repertoire. It also presented both exogenously provided and endogenous peptide Ags to effector CD8+ T cells. In tests of NK cell education and function, it failed to reveal any interaction with NK cells, suggesting that the site of the interaction of NK receptors with H-2Dd was disrupted. Thus, the sites of TCR and NK receptor interaction with H-2Dd are distinct, an observation consistent with independent modes of TCR and NK receptor evolution and function.

Animals↗

Angiogenesis and growth factor expression in a model of transmyocardial revascularization.

BACKGROUND: The mechanism by which transmyocardial revascularization (TMR) exerts a beneficial effect remains unknown. We hypothesize that the myocardial punctures of TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors. METHODS: Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, whereas group II (n = 28) underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohistochemistry using specific antibodies was also performed for transforming growth factor-beta, basic-fibroblast growth factor, and vasoendothelial growth factor. Growth factor expression was quantitated by comparing areas of staining (in mm2) with computerized morphometric analysis. RESULTS: Mortality was similar in both groups (5/25 versus 8/28; not significant). Group II had significantly greater vascular density than group I (5.65 versus 4.06 vessels/high-power field; p < 0.001), with a peak at 1 week postoperatively (9.12 versus 5.56 vessels/high-power field; p < 0.0001) in both groups. Overall, levels of both transforming growth factor-beta and basic-fibroblast growth factor were significantly higher in the TMR group compared with the control group (0.207 versus 0.141 mm2/mm2, p < 0.05; and 0.125 versus 0.099 mm2/ mm2, p < 0.05). CONCLUSIONS: This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as transforming growth factor-beta and basic-fibroblast growth factor. With the long-term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.

Animals↗

Myocardial tissue engineering with autologous myoblast implantation.

OBJECTIVE: Implanting myoblasts derived from autologous skeletal muscle, that is, satellite cells, for myocardial replacement has many advantages when compared with implanting either fetal cardiac myocytes (ethical and donor availability issues) or established cell lines (oncogenicity). Furthermore, autologous myoblasts do not require immunosuppression. The feasibility of satellite cell differentiation into muscle fibers, after implantation into the myocardium, was confirmed by means of a unique cell-labeling technique. METHODS: Myoblasts (satellite cells) isolated from the skeletal muscle of adult rats are labeled with 4',6-diamidino-2-phenylindone, which binds to DNA and to the protein tubulin to form a fluorescent complex, and implanted into the left ventricular wall of isogenic rats. The specimens are harvested 1 to 4 weeks after myoblast implantation. Histologic sections are examined under a fluorescent microscope. RESULTS: The labeling efficiency of satellite cells with 4',6-diamidino-2-phenylindole is nearly 100%. In 4 specimens, the progressive differentiation of implanted myoblasts into fully developed striated muscle fibers can be observed. CONCLUSION: Our earlier studies of autologous myoblast implantation into the cryoinjured myocardium of dogs suggested that these cells could differentiate into cardiac myocytes. However, it had been difficult to firmly establish these findings with the use of cell markers, thereby proving that the neomyocardium had indeed been derived from the implanted myoblasts. In this study, using 4',6-diamidino-2-phenylindole as a satellite cell marker, we were able to demonstrate that the implanted satellite cells did in fact differentiate into fully developed, labeled muscle fibers. Because of the obvious advantages of using autologous donor myoblasts, the clinical application of this approach may provide a novel strategy for the future management of heart failure.

Animals↗

Further evidence for sublexical components in implicit memory for novel words.

This study provides further evidence for the notion, proposed by Dorfman (1994), that activation of sublexical components plays an important role in implicit memory for novel words. Priming in an identification task was observed consistently when nonwords were formed out of morphemes; weaker, more variable effects were observed when nonwords were composed of syllables or pseudosyllables. Priming was insensitive to changes in the surface features (type case) of the stimuli and was disrupted by rearrangement of the stimulus components. Results are interpreted in terms of the activation and integration of preexisting sublexical representations and as evidence against the role of newly established episodic or perceptual representations. It is concluded that findings of priming for novel information should not be taken as evidence against an activation view.

Adult↗

Inhibitory effects of class I molecules on murine NK cells: speculations on function, specificity and self-tolerance.

This review addresses the physiological role of class I-mediated inhibition of NK cell lysis. It is suggested that several distinct activating receptors can stimulate NK lysis, all of which can be inhibited by class I molecules on the target cell. Evidence that most or all peptides that bind a class I molecule can cause inhibition is discussed, supporting a model in which NK cells detect loss of class I molecules, rather than loss of specific peptide/class I complexes. Finally, the acquisition of self-tolerance among NK cells is addressed with respect to data suggesting that autoaggressive NK cells are not deleted but rather exhibit altered characteristics which may render them unable to lyse autologous cells.

Animals↗

Sublexical components in implicit memory for novel words.

Five experiments investigated the role of sublexical components in implicit memory for novel words. Priming on an implicit word judgement task occurred consistently for nonwords formed out of familiar linguistic components (morphemes and syllables) but minimally for nonwords formed out of unfamiliar pseudosyllabic components. This effect was dissociable from explicit memory and insensitive to changes in the surface features of the stimuli. Moreover, it depended on unitization of stimulus components as opposed to priming of individual components. Results are interpreted in terms of the activation and integration of prior linguistic knowledge and as evidence against the role of new (perceptual or episodic) representations in implicit memory for new information.

Humans↗

Implicit and explicit forgetting: when is gist remembered?

Recognition (YES/NO) and stem completion (cued: complete with a word from the list; and uncued: complete with the first word that comes to mind) were tested following either semantic or non-semantic processing of a categorized input list. Item/instance information was tested by contrasting target items from the input list with new items that were categorically related to them; gist/categorical information was tested by comparing target items semantically related to the input items with unrelated new items. For both recognition and stem completion, regardless of initial processing condition, item information decayed rapidly over a period of one week. Gist information was maintained over the same period when initial processing was semantic but only in the cued condition for completion. These results are discussed in terms of dual process theory, which postulates activation/integration of a representation as primarily relevant to implicit item information and elaboration of a representation as mainly relevant to semantic (i.e. categorical) information.

Cues↗

Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2.

We have used long-range physical mapping and restriction fragment length polymorphisms between two mouse species to determine the chromosomal organization and location of the genes encoding three distinct isoforms of the alpha-subunit of the brain sodium channel. Physical mapping by pulsed-field gel electrophoresis has established that Scn2a and Scn3a (genes encoding type II and type III sodium channel alpha-subunit isoforms) are physically linked and are separated by a maximum distance of 600 kb. The segregation of restriction fragment length variations in backcross progeny of a Mus musculus and Mus spretus mating indicates that Scn 1 a (gene encoding the type I sodium channel alpha subunit) and Scn2a are tightly linked and are separated by a distance of 0.7 cM. Linkage analysis in backcross and recombinant inbred (BXD and AKXD) strains of mice localized the three sodium channel genes to the proximal segment of mouse chromosome 2 and suggested the probable gene order centromere-Hc-Neb-Pmv7-Scn2a/Scn3a-Scn1a-Mpmv 14. These results indicate that the three isoforms of the brain sodium channel alpha-subunit are encoded by three distinct genes that share a common ancestral origin.

Abnormalities, Multiple↗

Cloning of the H,K-ATPase beta subunit. Tissue-specific expression, chromosomal assignment, and relationship to Na,K-ATPase beta subunits.

We have isolated cDNA clones encoding the bovine and rat gastric H,K-ATPase beta subunit. A bovine abomasum lambda gt11 cDNA library was screened with a monoclonal antibody raised against the rabbit H,K-ATPase beta subunit. A single positive phage clone containing an approximately 900-base pair cDNA insert was identified as reactive with the antibody. The identity of the cDNA was established by comparing the deduced amino acid sequence with sequences of cyanogen bromide fragments of the porcine H,K-ATPase beta subunit. Polymerase chain reaction and rapid amplification of cDNA ends were used to generate a cDNA fragment encoding the carboxyl-terminal portion of the rat gastric H,K-ATPase beta subunit. A rat stomach cDNA library was screened with the polymerase chain reaction product, and several full-length beta subunit cDNA clones were identified. The open reading frame predicts a protein of 294 amino acids with a molecular weight of 33,689. The rat H,K-ATPase beta subunit shows 41% amino acid sequence identity to the rat Na,K-ATPase beta 2 subunit and shares a number of structural similarities with Na,K-ATPase beta subunit isoforms. By analyzing the segregation of restriction fragment length polymorphisms among recombinant inbred strains of mice, we localized the H,K-ATPase beta subunit gene to murine chromosome 8. Northern and Western blot analysis reveals that this gene is expressed exclusively in stomach. Our results suggest that the H,K-ATPase and Na,K-ATPase beta subunits evolved from a common ancestral gene and may play similar functional roles in enzyme activity.

Adenosine Triphosphatases↗