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J Hart

Publications and source records attributed to J Hart.

At least 55 records · Page 3Linked to original sources
PubMed2000

Differential expression of MUC2 and MUC5AC mucin genes in primary ovarian and metastatic colonic carcinoma.

Colonic adenocarcinoma, the most common tumor metastatic to the ovary, may closely mimic primary ovarian adenocarcinoma, especially that of mucinous or endometrioid histology. The differential diagnosis is important for therapeutic considerations. Mucin gene expression is relatively organ-specific and may therefore have use in distinguishing between colonic carcinomas metastatic to the ovary and primary ovarian tumors. In this study, we compared the expression of MUC2 and MUC5AC apomucins in 10 colonic adenocarcinomas metastatic with the ovary, 10 ovarian endometrioid carcinomas (4 primary, 6 metastatic), and 32 primary mucinous ovarian tumors (12 cystadenomas, 10 borderline tumors, and 10 cystadenocarcinomas). Monoclonal antibodies CCP58 and 45M1 were used for immunostains of MUC2 and MUC5AC apomucin, respectively. All but 1 of the 10 metastatic colon adenocarcinomas expressed MUC2, whereas none expressed MUC5AC. None of the 10 endometrioid carcinomas expressed MUC2, and only 2 showed weak immunoreactivity with MUC5AC. All 32 primary mucinous ovarian tumors expressed MUC5AC. The percentages of MUC2-positive immunostaining for cystadenomas, borderline tumors, and cystadenocarcinomas were 0% (0/12), 50% (5/10), and 70% (7/10) respectively. These studies show that MUC2 and MUC5AC are useful markers in the distinction between colonic carcinoma metastatic to the ovary and primary ovarian carcinoma.

Adenocarcinoma↗
PubMed2000

How many cysteine residues regulate ryanodine receptor channel activity?

RyRs contain 80-100 cysteine residues per subunit, of which approximately 25% are free for covalent modification, while the remainder are either modified or form intraprotein disulfides. Oxidizing and nitrosylating reagents have several effects on single RyR channel activity, which depend on the type of modifying reagent, the isoform of the RyR, and ligands bound to the channel. We present evidence here for four major classes of functional cysteine residues associated with RyR channels, i.e., two classes with free -SH groups that either activate or inhibit channels when covalently modified and two classes, with endogenous modification, that either inhibit or activate. Single-channel characteristics provide evidence for four discrete responses within the first activating class, two responses within the second inhibiting class and two types of response within the third endogenously modified class. All but one of these changes in channel properties depend on residues located on the cytoplasmic or membrane-associated domains of the RyR; the remaining response is confined to the luminal domain. If it is assumed that each type of response depends on a separate subclass of cysteine residue and that each subclass contains a minimum of one cysteine per subunit, our results suggest that there are at least nine cysteine residues per subunit with functional connections to the gating mechanism of RyR channels. These cysteine residues may be selectively modified under physiological and pathological conditions to regulate Ca2+ release from the sarcoplasmic reticulum and contraction.

Animals↗
PubMed2000

Transcortical sensory aphasia: revisited and revised.

Transcortical sensory aphasia (TSA) is characterized by impaired auditory comprehension with intact repetition and fluent speech. We induced TSA transiently by electrical interference during routine cortical function mapping in six adult seizure patients. For each patient, TSA was associated with multiple posterior cortical sites, including the posterior superior and middle temporal gyri, in classical Wernicke's area. A number of TSA sites were immediately adjacent to sites where Wernicke's aphasia was elicited in the same patients. Phonological decoding of speech sounds was assessed by auditory syllable discrimination and found to be intact at all sites where TSA was induced. At a subset of electrode sites where the pattern of language deficits otherwise resembled TSA, naming and word reading remained intact. Language lateralization testing by intracarotid amobarbital injection showed no evidence of independent right hemisphere language. These results suggest that TSA may result from a one-way disruption between left hemisphere phonology and lexical-semantic processing.

Adult↗
PubMed2000

Uptake and retranslocation of leaf-applied cadmium (109Cd) in diploid, tetraploid and hexaploid wheats.

Uptake and retranslocation of leaf-applied radiolabeled cadmium (109Cd) was studied in three diploid (Triticum monococcum, AA), four tetraploid (Triticum turgidum, BBAA) and two hexaploid (Triticum aestivum, BBAADD) wheat genotypes grown for 9 d under controlled environmental conditions in nutrient solution. Among the tetraploid wheats, two genotypes were primitive (ssp. dicoccum) and two genotypes modern wheats (ssp. durum). Radiolabelled Cd was applied by immersing the tips (3 cm) of mature leaf into a 109Cd radiolabelled solution. There was a substantial variation in the uptake and export of 109Cd among and within wheat species. On average, diploid wheats (AA) absorbed and translocated more 109Cd than other wheats. The largest variation in 109Cd uptake was found within tetraploid wheats (BBAA). Primitive tetraploid wheats (ssp. dicoccum) had a greater uptake capacity for 109Cd than modern tetraploid wheats (ssp. durum). In all wheats studied, the amount of the 109Cd exported from the treated leaf into the roots and the remainder of the shoots was poorly related to the total absorption. For example, bread wheat cultivars were more or less similar in total absorption, but differed greatly in the amount of 109Cd retranslocated. The diploid wheat genotype 'FAL-43' absorbed the lowest amount of 109Cd, but retranslocated the greatest amount of 109Cd in roots and remainder of shoots. The results indicate the existence of substantial genotypic variation in the uptake and retranslocation of leaf-applied 109Cd. This variation is discussed in terms of potential genotypic differences in binding of Cd to cell walls and the composition of phloem sap ligands possibly affecting Cd transport into sink organs.

Biological Transport↗
PubMed2000

Side-to-side isoperistaltic strictureplasty in extensive Crohn's disease: a prospective longitudinal study.

OBJECTIVE: To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease. METHODS: Between January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn's disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. RESULTS: The indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn's disease. CONCLUSIONS: SSIS is a safe and effective procedure in patients with extensive Crohn's disease. The authors' results provide radiographic, endoscopic, and histopathologic evidence that active Crohn's disease regresses at the site of the SSIS.

Adult↗
PubMed2000

Fulminant hepatic failure from heat stroke requiring liver transplantation.

A 16-year-old man developed heat stroke during football practice when the temperature was 33.8 degrees C (heat index, 44.4 degrees C). Resuscitation with ice water lavage, external cooling, and intravenous fluids was initially successful, but the patient again became obtunded. Liver chemistry tests and the prothrombin time and serum ammonia increased markedly, and rhabdomyolysis and renal failure became evident, necessitating hemodialysis. He underwent liver transplantation for fulminant hepatic failure approximately 72 hours after admission. Rhabdomyolysis with renal failure and severe electrolyte disturbances continued despite aggressive hemodialysis and the patient had a cardiopulmonary arrest and died 10 days after transplantation. This case shows that liver transplantation cannot always overcome the generalized toxic effects of heat stroke. More aggressive hemodialysis or combined liver/kidney transplantation might result in a positive outcome in selected cases.

Adolescent↗
PubMed2000

Colon signet ring cell adenocarcinoma: immunohistochemical characterization and comparison with gastric and typical colon adenocarcinomas.

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an identical immunophenotype as the cells forming their glandular counterpart.

Adenocarcinoma↗
PubMed2000

Induction of interleukin-8 release by lung epithelium with cystic fibrosis epithelial lining fluid is marginally affected by inhibitors of interleukin-1beta.

Interleukin-1beta (IL-1beta) and neutrophil elastase (NE) are present in the epithelial lining fluid (ELF) of patients with cystic fibrosis (CF). Both factors activate surrounding cells including lung epithelial cells, causing release of IL-8, a potent chemoattractant for neutrophils. Previous studies showed up-regulation of IL-8 release by lung epithelial cells as a function of NE in CF; however, few studies addressed the relationship between IL-1beta and activation of lung epithelial cells in CF lungs. Confluent layers of A549 cells, a type II-like human lung epithelial cell line, were incubated overnight with IL-1beta (0-5 ng/ml) or NE (100 nM), and supernatants were analyzed for IL-8 by enzyme-linked immunosorbent assay (ELISA). Both IL-1beta and NE led to a significant increase in IL-8: 12.8 +/- 2.8 ng/ml and 0.8 +/- 0.3 ng/ml, respectively. Next, bronchoalveolar lavage (BAL) samples were obtained from one healthy adult volunteer and six patients with CF and measured for IL-8 and IL-1beta concentrations by ELISA. Both IL-8 (range 169.00 +/- 56.57 to 1742.04 +/- 338.98 pg/ml) and IL-1beta (range 0-24.26 +/- 0.52 pg/ml) were detected in CF specimens, whereas neither was detected in the volunteer's specimen. Normal and CF BALs then were incubated overnight at a 1:10 dilution with confluent A549 cells. Analysis by ELISA of cell-free supernatants revealed increased IL-8 production from cells stimulated with CF BALs only. Similar experiments were performed with BAL supernatants that had been incubated with soluble IL-1 type II receptor, soluble IL-1 receptor antagonist, or a peptide inhibitor of NE. Addition of IL-1 inhibitors had a marginal effect on the amount of IL-8 release after incubation with CF BAL samples, whereas inhibition of NE had no effect. Our results indicate that other factors present in ELF in CF account for IL-8 release from lung epithelial cells.

Adolescent↗
PubMed2000

Behavioral interventions for adolescents with type 1 diabetes: how effective are they?

OBJECTIVE: To evaluate the effectiveness of behavioral interventions for adolescents with type 1 diabetes based on a systematic review of the literature. RESEARCH DESIGN AND METHODS: The literature was identified by searching 11 electronic databases, hand-searching 3 journals from their start dates, and contacting individual researchers. Only articles that reported evaluations of behavioral (including educational and psychosocial) interventions for adolescents (age range 9-21 years) with type 1 diabetes that included a control group were included in the present review. Data summarizing the key features of the interventions and their effects were extracted from each article. Where possible, effect sizes for the randomized control trials (RCTs) were calculated. RESULTS: The search process identified 64 reports of empirical studies. Of these, 35 studies included a control group, and 24 were RCTs. Effect sizes could be calculated for 18 interventions. The overall mean effect size calculated across all outcomes was 0.33 (median 0.21), indicating that these interventions have a small- to medium-sized beneficial effect on diabetes management. Interventions that were theoretically based were significantly more effective than those that were not (P<0.05, 1-tailed). CONCLUSIONS: Research to date indicates that these interventions are moderately effective. Several methodological weaknesses to be avoided in future studies are noted. It is also recommended that investigators use the reach, efficacy, adoption, implementation, and maintenance (RE-AIM) framework to guide the design of future studies, which should result in more disseminable interventions. RE-AIM assesses the intervention's reach, or percent or representativeness of patients willing to participate; efficacy across a range of outcomes; adoption, or the percent and representativeness of settings willing to implement the intervention; implementation, or the consistency of the delivery of the intervention as intended; and maintenance, or the extent to which delivery of the intervention becomes a routine part of health care in the medical setting.

Adolescent↗
PubMed2000

Neural substrates of orthographic lexical access as demonstrated by functional brain imaging.

OBJECTIVE: To delineate regions involved in visual word recognition. BACKGROUND: The processes and regions involved in visual word recognition have been somewhat controversial for over 100 years. METHODS: This study used regional cerebral blood flow as assessed by functional magnetic resonance imaging to study normal subjects (N = 9) on an individual within-subject basis while they were actively engaged on-line in a visual lexical decision task. Standard analysis techniques were used for identifying regions of activation. RESULTS: Across subjects, the task activated a number of regions, including the occipital pole, lateral and basal occipitotemporal (including lingual and fusiform) regions, superior and middle temporal gyri, and supramarginal and angular gyri. Typically, these regions were activated bilaterally; when activation was unilateral, it was on the left. Some of the areas activated (e.g., inferior parietal regions) have not been previously reported to be involved in such types of processing by activation studies but have been implicated in lesion studies. CONCLUSIONS: These results broaden the areas known to be involved in visual word recognition. The bilateral activation associated with visual word recognition is in some respects analogous to the "what" system in visual recognition described in subhuman primates. In addition, the study raises several methodologic issues. The within-subject analysis showed variability in the specific regions activated when subsequently comparing across individuals, raising implications for future functional imaging studies.

Adult↗
PubMed2000

Expression of Jun family members in human colorectal adenocarcinoma.

The products of the Jun family genes, c-Jun, JunB and JunD, are essential components of the activating protein-1 transcription factor complexes that are critically important in the control of cell growth, differentiation and neoplastic transformation. Although increased c-Jun expression has been reported in human colorectal tumors, expression of JunB and JunD in these tumors has not previously been characterized. In the current study, we examined 24 cases of human colorectal adenocarcinoma by western immunoblotting analysis and immunohistochemical staining for the expression of c-Jun, JunB and JunD proteins. Normal-appearing colonic mucosa distant from the tumors in the same colectomy specimens were used as a reference for comparison. The results showed that both c-Jun and JunB proteins were undetectable or barely detectable in normal mucosa but their expression levels were significantly increased in human colorectal adenocarcinomas. In contrast, JunD protein was present at high levels in normal mucosa and only showed a minimal increase in adenocarcinomas. These observations suggest that different Jun proteins may serve different roles in regulating colonic epithelial cell growth and in colorectal tumorigenesis.

Adenocarcinoma↗
PubMed1999

Making sense out of jargon: a neurolinguistic and computational account of jargon aphasia.

OBJECTIVE: To identify the cognitive and neuroanatomic bases of neologistic jargon aphasia with spared comprehension and production of written words. METHODS: Detailed analysis of performance across experiments of naming, reading, writing, repetition, and word/picture matching by a 68-year-old woman (J.B.N.) served to identify which cognitive mechanisms underlying naming and word comprehension were impaired. J.B.N.'s impairments were then simulated by selectively "lesioning" a computer model of word production that has semantic, word form, and subword phonologic levels of representation (described by Dell in 1986). RESULTS: In comprehension experiments, J.B.N. made far more errors with spoken word input than with written word or picture input (chi-square = 40-59; df = 1; p < 0.0001) despite intact auditory discrimination. In naming experiments (with picture, definition, or tactile input), J.B.N. made far more errors in spoken output relative to written output (chi-square = 14-56; df = 1; p < 0.0001). These selective impairments of spoken word processing were simulated by reducing connection strength between word-level and subword-level phonologic units but maintaining full connection strength between word-level and semantic units in Dell's model. The simulation yielded a distribution of error types that was nearly identical to that of J.B.N., and her CT and MRI scans showed a small subarachnoid hemorrhage in the left sylvian fissure without infarct. Cerebral angiogram showed focal vasospasm in sylvian branches of the left middle cerebral artery. CONCLUSION: Focal left perisylvian dysfunction can result in a highly selective "disconnection" between word-level and subword-level phonologic representations manifest as neologistic jargon aphasia with intact understanding and production of written words.

Aged↗
PubMed1999

Cutting edge: blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells.

The effect of blocking the CD28/B7 costimulatory pathway on intestinal allograft rejection was examined in mice. Murine CTLA4Ig failed to prevent the rejection of allografts transplanted into wild-type or CD4 knockout (KO) mice but did inhibit allograft rejection by CD8 KO recipients. This effect was associated with decreased intragraft mRNA for IFN-gamma and TNF-alpha and increased mRNA for IL-4 and IL-5. This altered pattern of cytokine production was not observed in allografts from murine CTLA4Ig-treated CD4 KO mice. These data demonstrate that blockade of the CD28/B7 pathway has different effects on intestinal allograft rejection mediated by CD4+ and CD8+ T cells and suggest that these T cell subsets have different costimulatory requirements in vivo. The results also suggest that the inhibition of CD4+ T cell-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines.

Abatacept↗
PubMed1999

Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients.

Alcohol-related liver disease (ALD) is a common indication for orthotopic liver transplantation (OLT) in adults. Although return to 'heavy drinking' post-OLT is believed to be uncommon, the prevalence and severity of alcohol-related liver injury in such patients is not well characterized. We retrospectively reviewed the records of 68 adult patients who underwent OLT for ALD to determine the incidence of return to heavy drinking and to assess their clinical outcome. Follow-up ranged from 8-99 months (mean 42) post-OLT; 54 patients were followed for > or = 12 months. Ten patients (15%) had evidence of coexisting viral hepatitis (hepatitis C in 9 and hepatitis B in 1) before OLT. Six of 68 patients (8%) returned to heavy drinking post-OLT, and three of those died of alcoholic hepatitis at nine months, 2.5 and 3.5 years after OLT. In two of these three patients, premortem liver biopsy showed histologic features of alcoholic hepatitis in addition to bridging fibrosis or cirrhosis. None of the three patients who died of ALD had coexisting viral hepatitis. Of the 57 patients surviving for > or = 3 months post-OLT, 4 of 8 patients (50%) with steatosis and Mallory bodies in their native livers returned to heavy drinking compared to only 2/49 (4%) without these histologic findings (P<0.05). In conclusion, the incidence of heavy drinking post-OLT was uncommon, however, it was associated with fatal alcoholic hepatitis in 50% of patients. Rapidly progressive alcohol-related liver injury was seen even in the absence of coexisting viral hepatitis. The presence of steatosis and Mallory bodies in the native liver, which suggests recent or ongoing alcohol-related liver injury, predicted a return to heavy drinking post-OLT.

Adult↗
PubMed1999

Neural pathways in tactile object recognition.

OBJECTIVE: To define further the brain regions involved in tactile object recognition using functional MRI (fMRI) techniques. BACKGROUND: The neural substrates involved in tactile object recognition (TOR) have not been elucidated. Studies of nonhuman primates and humans suggest that basic motor and somatosensory mechanisms are involved at a peripheral level; however, the mechanisms of higher order object recognition have not been determined. METHODS: The authors investigated 11 normal volunteers utilizing fMRI techniques in an attempt to determine the neural pathways involved in TOR. Each individual performed a behavioral paradigm with the activated condition involving identification of objects by touch, with identification of rough/smooth as the control. RESULTS: Data suggest that in a majority of individuals, TOR involves the calcarine and extrastriatal cortex, inferior parietal lobule, inferior frontal gyrus, and superior frontal gyrus-polar region. CONCLUSIONS: TOR may utilize visual systems to access an internal object representation. The parietal cortices and inferior frontal regions may be involved in a concomitant lexical strategy of naming the object being examined. Frontal polar activation likely serves a role in visuospatial working memory or in recognizing unusual representations of objects. Overall, these findings suggest that TOR could involve a network of cortical regions subserving somatosensory, motor, visual, and, at times, lexical processing. The primary finding suggests that in this normal study population, the visual cortices may be involved in the topographic spatial processing of TOR.

Adult↗
PubMed1999

The role of CD8 and CD4 T cells in intestinal allograft rejection: a comparison of monoclonal antibody-treated and knockout mice.

BACKGROUND: The relative contribution of CD8 and CD4 T cells to allograft rejection remains an unresolved issue. Experimental results suggest that the relative importance of these T-cell subsets may vary depending on the model used and the organ studied. We have previously shown that treatment of murine recipients of intestinal allografts with a depleting anti-CD8 or a depleting anti-CD4 monoclonal antibody (mAb) significantly inhibited allograft rejection. This study was undertaken to further examine the contribution of CD8 and CD4 T cells to the rejection of intestinal allografts. METHODS: Intestinal allografts from B6C3F1/J (C57BL/6 x C3H/HeJ) mice were transplanted into C57BL/6 recipients. Recipient groups included mice with an acquired deficiency in CD8 or CD4 T cells caused by treatment with depleting mAb or mice genetically deficient in CD8 or CD4 T cells as a result of disruption of the genes encoding major histocompatibility complex (MHC) class I, MHC class II, CD8, or CD4. In all cases, rejection was assessed histologically at predetermined time points. In some recipient groups, graft function was also assessed using a maltose absorption assay. RESULTS: Rejection, assessed between days 10 and 28 after transplantation, was significantly inhibited in mice deficient in CD8 or CD4 T cells after treatment with depleting mAb. In contrast, mice genetically deficient in either CD8 T cells (MHC class I or CD8 knockouts) or CD4 T cells (MHC class II or CD4 knockouts) rejected intestinal allografts promptly. Both histologic and functional evaluation of anti-CD8 mAb-treated mice on day 60 showed that the inhibition of rejection persisted even after the return of a substantial number of CD8 T cells. Although intestinal allografts from anti-CD8 mAb-treated mice displayed little to no evidence of rejection on day 60 after transplantation, these mice were able to reject both donor and third-party skin grafts. CONCLUSIONS: These results demonstrate that the inhibition of intestinal allograft rejection associated with mAb treatment is not attributable solely to depletion of CD8 or CD4 T cells. Furthermore, anti-CD8 mAb administration did not induce donor-specific tolerance or cause nonspecific immune suppression, as indicated by the skin-grafting experiments. Our findings suggest that at least some depleting mAbs mediate their protective effect on allograft rejection via an alternative mechanism such as the induction of a regulatory cell population(s).

Animals↗