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J Zacks

Publications and source records attributed to J Zacks.

14 recordsLinked to original sources
PubMed2002

Protective effects of neurokinin-1 receptor during colitis in mice: role of the epidermal growth factor receptor.

1. The role of substance P and its high affinity neurokinin-1 receptor in colitis has not been fully elucidated. We assessed the participation of neurokinin-1 receptor in colitis using the 2,4,6,-trinitrobenzensulphonic acid and dextran sulphate-induced animal models of colitis and genetically-engineered, neurokinin-1 receptor-deficient mice. 2. Clinical signs, macroscopic and histologic damage associated with 2,4,6,-trinitrobenzensulphonic acid (12 days) and dextran sulphate (5 days) colitis were more severe in neurokinin-1 deficient than in wild-type mice, while immunoreactivities for epidermal growth factor and its receptor were similar in the colon of both mice strains before and after colitis. 3. Substance P, dose-dependently induced intestinal fibroblast proliferation and enhanced epidermal growth factor-induced proliferation in intestinal fibroblasts isolated from wild-type, but not from neurokinin-1 receptor deficient mice. 4. Substance P-induced intestinal fibroblast proliferation required the presence of epidermal growth factor receptor with kinase activity. Furthermore, substance P induced epidermal growth factor tyrosine phosphorylation and activation in normal intestinal fibroblasts. 5. Our results indicate that in mice lacking the neurokinin - 1 receptor, substance P plays a protective role in prolonged experimental colitis.

Animals↗
PubMed2001

Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by Clostridium difficile toxin A.

Toxin A (TxA) of Clostridium difficile induces acute inflammation of the intestine initiated by release of substance P (SP) and activation of the neurokinin-1 receptor. However, the mechanisms that terminate this response are unknown. We determined whether the SP-degrading enzyme neutral endopeptidase (NEP, EC 3.4.24.11) terminates TxA-induced enteritis. We used both genetic deletion and pharmacological inhibition of NEP to test this hypothesis. In wild-type mice, instillation of TxA (0.5-5 microg) into ileal loops for 3 h dose dependently increased ileal fluid secretion, stimulated granulocyte transmigration determined by myeloperoxidase activity, and caused histological damage characterized by depletion of enterocytes, edema, and neutrophil accumulation. Deletion of NEP reduced the threshold secretory and inflammatory dose of TxA and exacerbated the inflammatory responses by more than twofold. This exacerbated inflammation was prevented by pretreatment with recombinant NEP. Conversely, pretreatment of wild-type mice with the NEP inhibitor phosphoramidon exacerbated enteritis. Thus NEP terminates enteritis induced by C. difficile TxA, underlying the importance of SP degradation in limiting neurogenic inflammation.

Animals↗
PubMed1999

Imagined transformations of bodies: an fMRI investigation.

A number of spatial reasoning problems can be solved by performing an imagined transformation of one's egocentric perspective. A series of experiments were carried out to characterize this process behaviorally and in terms of its brain basis, using functional magnetic resonance imaging (tMRI). In a task contrast designed to isolate egocentric perspective transformations, participants were slower to make left-right judgments about a human figure from the figure's perspective than from their own. This transformation led to increased cortical activity around the left parietal-temporal-occipital junction, as well as in other areas including left frontal cortex. In a second task contrast comparing judgments about inverted figures to judgments about upright figures (always from the figure's perspective), participants were slower to make left-right judgments about inverted figures than upright ones. This transformation led to activation in posterior areas near those active in the first experiment, but weaker in the left hemisphere and stronger in the right, and also to substantial left frontal activation. Together, the data support the specialization of areas near the parietal-temporal-occipital junction for egocentric perspective transformations. These results are also suggestive of a dissociation between egocentric perspective transformations and object-based spatial transformations such as mental rotation.

Adult↗
PubMed1999

Cathepsin B activity and protein levels in thyroid carcinoma, Graves' disease, and multinodular goiters.

Cathepsin B (CB) is involved in the hydrolysis of thyroglobulin (Tg) and thought to be regulated by thyroid stimulating hormone (TSH) in the normal thyroid. Our analyses of 91 thyroid tissues from 71 patients with Graves' disease (GD), multinodular goiter (MNG), papillary carcinoma (PC), or follicular carcinoma (FC), demonstrated a 2-fold increase in expression of CB in GD and an average increase of 1.5-fold in MNG (varying from 10-fold below normal to 6-fold above normal in MNG nodules), as might be predicted by the altered functional status of thyroid follicular cells in those diseases. However, CB activity was not downregulated in conjunction with the known "blocking effect" of malignancy on many thyroid functions, but rather increased on average 9-fold in papillary carcinomas (n = 33), and also showed a marked increase in 2 follicular carcinomas. Activity measurements were confirmed by CB protein detection on Western blot with moderately increased CB protein levels demonstrated in GD, variable expression in nodules of MNG, and markedly increased protein expression in carcinomas. In all diseased states, increased protein was detected primarily as overexpression of the 27 kd heavy chain of 2-chain mature CB and less frequently as overexpression of 31 kd single-chain mature CB. However, an additional 35 kd protein form was noted in 3 of 9 PCs, 1 of 2 FCs, and 1 of 4 GD cases but in none of 10 MNG cases. In conjunction with elevated CB activity plus additional protein bands on Western blots, altered patterns of CB immunohistochemical staining were observed, irrespective of the type of thyroid disease, suggesting certain common changes in CB expression, posttranslational processing, and vesicular trafficking. In summary, GD and MNG thyroid tissues demonstrated altered CB expression in keeping with predicted functional changes in thyroid follicular cells, while increased CB expression in carcinomas indicated a more pathological role for CB in thyroid cancers, possibly related to the processes of invasion or metastasis.

Blotting, Western↗
PubMed1999

Bars and lines: a study of graphic communication.

Interpretations of graphs seem to be rooted in principles of cognitive naturalness and information processing rather than arbitrary correspondences. These predict that people should more readily associate bars with discrete comparisons between data points because bars are discrete entities and facilitate point estimates. They should more readily associate lines with trends because lines connect discrete entities and directly represent slope. The predictions were supported in three experiments--two examining comprehension and one production. The correspondence does not seem to depend on explicit knowledge of rules. Instead, it may reflect the influence of the communicative situation as well as the perceptual properties of graphs.

Adult↗
PubMed1998

Somatotopy of the human arm using fMRI.

We describe a technique for mapping out human somatosensory cortex using functional magnetic resonance imaging (fMRI). To produce cortical activation, a pneumatic apparatus presented subjects with a periodic series of air puffs in which a sliding window of five locations moved along the ventral surface of the left arm in a proximal-to-distal or distal-to-proximal direction. This approach, in which the phase-delay of the stimulus can be used to produce somatotopic maps of somatosensory cortex, is based on a method used to generate retinotopic maps of visual cortex. Functional images were acquired using an echoplanar 1.5T scanner and a T2*-weighted spiral acquisition pulse sequence. The periodic series of air puffs created phase-related activation in two cortical regions of the contralateral parietal lobe, the posterior bank of the central sulcus and a more posterior and lateral region.

Adult↗
PubMed1992

Crossreacting human lymphoma idiotypes.

We have examined an unselected series of 72 lymphomas of diverse histologies with a panel of mouse monoclonal antibodies specific for human B-lymphoma-derived Ig idiotypes (anti-ids) to determine the nature and extent of id/anti-id crossreactivity. The anti-id antibodies were prepared from Ig isolated from seven follicular center cell lymphomas by heterohybridoma technique. Thirty-six of 75 individual anti-ids obtained in this manner were further selected based on their reactivity with highly restricted or private idiotypic determinants. Twelve of the 72 (17%) lymphoma biopsies reacted with one or more of the 36 anti-ids that detect private determinants. A pool consisting of five individual antibodies would have detected 11 of the 12 crossreacting tumors. Staining of tumor cell populations was homogeneous in the positive cases, suggesting uniform idiotype expression. If there was a segregated staining pattern, it was generally related to the presence of CD3+ T cells in the section. These follicular center cell-derived anti-ids cross-reacted with follicular center cell tumors of all histologic grades with frequencies ranging from 13% to 50%. The structural basis for the crossreactivity of our lymphoma-derived private anti-ids is as yet not known. However, the reactivity of certain anti-ids with both kappa- and lambda-expressing tumors suggests a biased use of V gene segments in these crossreactive clones that is probably related to the VH gene. These data suggest the possibility that lymphoma may develop in a highly restricted pool of normal differentiated B cells or in B-cell subsets that express a limited repertoire of unmutated VH gene segments.

Animals↗
PubMed1992

Inferring articulation and recognizing gestures from acoustics with a neural network trained on x-ray microbeam data.

This paper describes a method for inferring articulatory parameters from acoustics with a neural network trained on paired acoustic and articulatory data. An x-ray microbeam recorded the vertical movements of the lower lip, tongue tip, and tongue dorsum of three speakers saying the English stop consonants in repeated Ce syllables. A neural network was then trained to map from simultaneously recorded acoustic data to the articulatory data. To evaluate learning, acoustics from the training set were passed through the neural network. To evaluate generalization, acoustics from speakers or consonants excluded from the training set were passed through the network. The articulatory trajectories thus inferred were a good fit to the actual movements in both the learning and generalization conditions, as judged by root-mean-square error and correlation. Inferred trajectories were also matched to templates of lower lip, tongue tip, and tongue dorsum release gestures extracted from the original data. This technique correctly recognized from 94.4% to 98.9% of all gestures in the learning and cross-speaker generalization conditions, and 75% of gestures underlying consonants excluded from the training set. In addition, greater regularity was observed for movements of articulators that were critical in the formation of each consonant.

Adult↗
PubMed1990

Clonal diversity in human B cell lymphoma. I. Idiotypic and genetic analysis of lymphoma heterohybrids.

Secretory heterohybrid clones from seven pristine human B cell lymphomas of diverse histologic types were established to investigate the question of tumor clonal diversity. We found that in six tumors, heterohybrid-derived Ig showed similar band patterns in IEF; families of anti-Id prepared from tumor Ig reacted uniformly with individual heterohybrids and original tumor; and the V gene loci displayed little variation on Southern analysis. In one patient who was followed with serial multiple site biopsies over a 14-mo period, clonal Id was preserved until the final stage of his disease, in spite of cytotoxic treatment. In a single follicular tumor (J.M.), each of the anti-Id reacted uniformly with the parent tumor and the individual heterohybrids, except that three of six clones failed to react with a single anti-Id family member. A Southern analysis of the VH gene locus revealed an identical gene rearrangement that was shared by the parent tumor and each heterohybrid. However, there was considerable heterogeneity of J.M. heterohybrid Ig in IEF gels, and we demonstrated the production of variant lambda L chains by the heterohybrid clones. One type of lambda L chain had a normal mobility in SDS-PAGE gels but larger lambda variants were produced by four of six heterohybrids. A Southern analysis of the VL gene displayed considerable variation in the type of lambda rearrangement present in the various heterohybrids, suggesting extensive diversity at the VL gene locus. In a second tumor (S.C.) that exhibited uniform anti-Id tumor reactivity we were also able to demonstrate the presence of a second minor tumor cell population (a biclonal tumor). Our data suggest that intraclonal VH variation may vary considerably with lymphoma subtype and mutagenic exposure and that an additional mechanism for generating spontaneous intraclonal heterogeneity is genetic variation at the VL locus.

Antibodies, Anti-Idiotypic↗