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Biomedical subjects

D C Rubin

Publications and source records attributed to D C Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Memory and learning for a novel written style.

Subjects read and recalled a series of five short stories in one of four plot and style combinations. The stories were written in one of two styles that consisted of opposing clause orders (i.e., independent-dependent vs. dependent-independent), tense forms (i.e., past vs. present), and descriptor forms (modifier modifier vs. modifier as a noun). The subjects incorporated both plot and style characteristics into their recalls. Other subjects, who, after five recalls, either generated a new story or listed the rules that had been followed by the stories read, included the marked forms of the characteristics they learned more often, except for tense. The subjects read and recalled four stories of the same plot and style and then read and recalled a fifth story of the same plot and style or of one of the other three plot/style combinations. Ability to switch style depended on both the characteristic and the markedness.

Adult↗
PubMed1997

Enterocytic gene expression is altered in experimental gastroschisis.

Gastroschisis is a congenital anomaly in which exposure of the intestines to amniotic fluid throughout fetal life results in nutrient malabsorption. To begin to understand the molecular basis underlying epithelial changes in this condition, we investigated enterocytic gene expression during fetal development. Gastroschisis was surgically created at 24 days gestation (term = 31 days) in fetal rabbits; sham-operated and unoperated fetuses served as controls. Bowel was harvested at 28 and 31 days gestation. Cellular lactase expression was detected using immunohistochemistry, and apolipoprotein A-I and cellular retinol binding protein II (CRBPII) mRNA levels were quantitated using Northern blot analysis. Despite absence of gross histological changes in the mucosa, lactase protein expression and apolipoprotein A-I and CRBPII mRNA expression were decreased in intestine from gastroschisis compared to sham-operated animals. Expression of GAPDH (a housekeeping gene) increased over the same period, suggesting that the changes in enterocytic absorptive gene expression associated with gastroschisis were relatively specific. In conclusion, a decrease in expression of a variety of genes involved in nutrient absorption and trafficking within the enterocyte may contribute to the absorptive defects seen in this gastroschisis.

Abdominal Muscles↗
PubMed1997

Distribution of important and word-cued autobiographical memories in 20-, 35-, and 70-year-old adults.

For word-cued autobiographical memories, older adults had an increase, or bump, from the ages 10 to 30. All age groups had fewer memories from childhood than from other years and a power-function retention for memories from the most recent 10 years. There were no consistent differences in reaction times and rating scale responses across decades. Concrete words cued older memories, but no property of the cues predicted which memories would come from the bump. The 5 most important memories given by 20- and 35-year-old participants were distributed similarly to their word-cued memories, but those given by 70-year-old participants came mostly from the single 20-to-30 decade. No theory fully accounts for the bump.

Adult↗
PubMed1997

Retinoic acid stimulates early cellular proliferation in the adapting remnant rat small intestine after partial resection.

Following loss of small bowel surface area, the remnant intestine undergoes a remarkable adaptive response. To define more fully the underlying molecular mechanisms, we have identified genes that are specifically induced in the adapting remnant after partial small bowel resection. Several of these, including cellular retinol binding protein II (CRBP II) and apolipoprotein (apo) AI, participate in vitamin A and lipid trafficking. The CRBP II and apo A-I promoters contain response elements for the nuclear retinoid X receptor RXR-alpha. It is well established that vitamin A is essential for normal cell growth, differentiation and maintenance of epithelial tissues and that CRBP II functions to facilitate intestinal vitamin A absorption and metabolism. On the basis of these considerations, changes in CRBP II and apo A-I mRNA levels could reflect a role for retinoids in modulating the intestinal adaptive response. To explore this hypothesis, we used a rat resection model of intestinal adaptation to examine the temporal patterns of CRBP II, apo A-I and RXR-alpha expression postresection. CRBP II and apo A-I mRNA levels were increased in the remnant intestine in distinct temporal patterns, whereas RXR-alpha expression was unchanged. To address directly the effects of vitamin A in adaptation, retinoic acid or vehicle was administered intravenously to rats immediately after 70% small bowel resection. Compared with vehicle, all-trans-retinoic acid significantly stimulated crypt cell proliferation in the adapting remnant intestine by 6 h after surgery. These data suggest that retinoic acid acts to modulate intestinal proliferation in the adapting small intestine after loss of functional small bowel surface area.

Adaptation, Physiological↗
PubMed1997

Properties of word cues for autobiographical memory.

A sample of 124 words were used to cue autobiographical memories in 120 adults varying in age from 20 to 73 years. Individual words reliably cued autobiographical memories of different ages with different speeds. For all age groups, words rated high in imagery produced older memories and faster reaction times.

Adult↗
PubMed1997

The distribution of autobiographical memories across the lifespan.

Words were used to cue autobiographical memories from 20- and 70-year-old subjects. Both groups showed a decrease in memories from the childhood years and a power-function retention function for their most recent 10 years. Older subjects also had an increase in the number of memories from the ages 10 to 30. These results held for individual subjects as well as grouped data and held when either 124 or 921 memories were cued. Reaction times to produce memories were constant across decades except for childhood where they were longer.

Adult↗
PubMed1996

Regulation of sucrase-isomaltase gene expression in human intestinal epithelial cells by inflammatory cytokines.

Using metabolic labeling techniques in human intestinal epithelial cell lines in tissue culture and in situ hybridization techniques in normal and inflamed (Crohn's) intestine, recent studies have shown that there is synthesis of acute phase proteins in enterocytes. Moreover, these studies have shown that acute phase protein biosynthesis in enterocytes is regulated by inflammatory cytokines in a manner characteristic of the physiologic acute phase response. In the course of these studies it was noticed that one inflammatory cytokine, interleukin-6 (IL-6), mediated selective down-regulation of the enterocyte-specific, differentiation-dependent integral membrane protein sucrase-isomaltase (SI) in the Caco2 intestinal epithelial cell line. In the current study we examined the effect of several other inflammatory cytokines interleukin-1 (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) on synthesis of SI in Caco2 cells, examined the possibility that inflammatory cytokines affect the synthesis of other enterocyte integral membrane proteins using lactase as a prototype, and examined the possibility that SI gene expression was down-regulated in villous enterocytes in vivo during the local inflammatory response of Crohn's disease. The results show that IL-6 and IFN gamma each mediate a decrease and TNF alpha mediates an increase in synthesis of SI in Caco2 cells. The magnitude of down-regulation by IL-6 and IFN gamma is significantly greater than the up-regulation by TNF alpha. IL-1 beta has no effect on synthesis of SI. Synthesis of lactase is not affected by any of the cytokines. There is a marked specific decrease in SI gene expression in villous enterocytes in acutely inflamed Crohn's ileum as compared to adjacent uninflamed ileum and normal ileum. Taken together, these data show that inflammatory cytokines have specific and selective effects on the expression of the brush border hydrolase SI in tissue culture and in vivo and provide evidence for a previously unrecognized mechanism for disaccharidase deficiency in intestinal inflammation.

Cell Line↗
PubMed1996

Spatial imagery preserves temporal order.

Line drawings were presented in either a spatial or a nonspatial format. Subjects recalled each of four sets of 24 items in serial order. Amount recalled in the correct serial order and sequencing errors were scored. In Experiment 1 items appeared either in consecutive locations of a matrix or in one central location. Subjects who saw the items in different locations made fewer sequencing errors than those who saw each item in a central location, but serial recall levels for these two conditions did not differ. When items appeared in nonconsecutive locations in Experiment 2, the advantage of the spatial presentation on sequencing errors disappeared. Experiment 3 included conditions in which both the consecutive and nonconsecutive spatial formats were paired with retrieval cues that either did or did not indicate the sequence of locations in which the items had appeared. Spatial imagery aided sequencing when, and only when, the order of locations in which the stimuli appeared could be reconstructed at retrieval.

Cognition↗
PubMed1996

Enterocytic gene expression in intestinal adaptation: evidence for a specific cellular response.

After massive small bowel resection, the remnant gut epithelium undergoes an adaptive response marked by an increase in villus height, crypt depth, and crypt cell production rate. Although morphological features of gut adaptation have been well characterized, the differentiation status and response of epithelial cells populating the adaptive villus is unclear. To address these issues, cell-specific and spatial patterns of expression of a set of enterocytic genes were characterized in rats after 70% small bowel resection. The liver and intestinal (I) fatty acid binding protein (FABP) and apolipoprotein A-I (apo A-I) and apo A-IV genes were studied because they exhibit unique regional and cell-specific patterns of expression in the developing and adult gut. At 48 h after surgery, apo A-IV and I-FABP mRNA levels were increased up to 3.5-fold in adaptive remnant ileum compared with sham-operated or sham-resected control ileum. In situ hybridization and immunohistochemical analyses revealed a marked increase in enterocytic apo A-IV mRNA and protein expression in the adaptive ileum, from villus base to tip but not in crypts. By 1 wk after resection, apo A-IV, but not I-FABP, mRNA levels remained elevated in remnant ileum, although duodenal I-FABP mRNA levels were still increased. In contrast, apo A-I mRNA levels were not significantly induced. These results indicate that the enterocyte can respond acutely to loss of small bowel surface area by increasing expression of several genes. This compensatory enterocytic response is spatially (from duodenum to ileum) and temporally regulated. These results suggest initiation of the adaptive response occurs by way of a complex set of molecular pathways involving villus and crypt cells.

Adaptation, Physiological↗
PubMed1996

Analysis of cloned cDNAs differentially expressed in adapting remnant small intestine after partial resection.

After partial resection, the remnant small intestine undergoes an adaptive response. Little is known about the molecular and cellular basis of intestinal adaptation. To identify genes transcriptionally regulated in response to loss of functional bowel surface area, we have isolated cDNAs differentially expressed in the adaptive ileum 48 h after 70% proximal small intestinal resection. A cDNA library constructed from the remnant ileum of rats subjected to resection was screened using subtractive hybridization techniques. Several groups of cDNA clones that were induced during intestinal adaptation were isolated. The first included liver fatty acid binding protein, apolipoprotein A-IV, cellular retinol binding protein II, and ileal lipid binding protein. These all encode proteins involved in the absorption, metabolism, and trafficking of nutrients. A second group included the catalytic subunit of protein phosphatase 1 delta, a 78-kDa glucose-regulated protein (grp 78; a glucose-regulated member of the 70-kDa heat-shock protein family), and several pancreatitis-associated proteins. A third group of induced genes contained novel cDNAs. To better characterize the adaptive response, the temporal, spatial, and cellular patterns of expression of several of these genes were analyzed with the use of immunohistochemical and in situ hybridization techniques. These studies indicate that during early adaptation, genes involved in nutrient trafficking, protein processing, and cell cycle regulation are transcriptionally regulated in the residual small intestine in distinct temporal and regional patterns consistent with a complex multifaceted response to intestinal resection.

Acute-Phase Proteins↗
PubMed1995

Ontogenic regulation of spatial differentiation in the crypt-villus axis of normal and isografted small intestine.

Despite rapid proliferation, the mammalian intestinal epithelium maintains precise spatial differentiation from crypt to villus tip and from duodenum to colon. During perinatal life, the rodent gut undergoes a dramatic morphogenesis, resulting in formation of the crypt-villus and duodenal-colonic axes. The ontogeny of regional differences in gene expression in the emerging vertical axis has not been well described. We used the liver fatty acid binding protein (L-FABP) and apolipoprotein (apo) AIV genes as markers of neonatal enterocytic differentiation. In situ hybridization analyses revealed that both genes exhibit unique spatial patterns of expression along the jejunal crypt-villus axis during ontogeny, characterized by increased cellular mRNA levels in villus base enterocytes. To examine the requirement for a normal luminal environment to generate these precise patterns of cellular gene expression, we employed intestinal isograft techniques. Fetal intestines were implanted as early as embryonic day 12. Appropriate expression of the apo AIV and L-FABP genes was recapitulated during villus morphogenesis in fetal life. However, spatial patterns of gene expression in the isografted postnatal cryptvillus axis were altered. The preferential accumulation of L-FABP and apo AIV mRNA in villus base enterocytes was never observed in isografts. These results suggest that a "basal" differentiation program is encoded in fetal endoderm and mesenchyme, yet extracellular substances contained in the lumen or extrinsic to the intestine play an important modulatory role in generating spatial differentiation during ontogeny.

Aging↗
PubMed1995

Pulmonary hypertension decreases the predictive accuracy of echocardiographic clues for cardiac tamponade.

A number of echocardiographic clues of pericardial tamponade have been described, but their accuracy in patients with pulmonary hypertension has not been well elucidated. Four echocardiographic clues of pericardial tamponade, namely, right atrial collapse (RAC), right ventricular diastolic collapse (RVDC), marked (> 40%) respiratory variation in transmitral Doppler flow velocity ("flow velocity paradoxus [FVP]"), and inferior vena cava plethora (IVCP) were prospectively evaluated in 32 patients with large pericardial effusions. Of 12 patients with pulmonary hypertension, 6 had invasively determined evidence of tamponade and 6 did not; of 20 patients without pulmonary hypertension, 11 had tamponade and 9 did not. These echocardiographic clues were evaluated in a blinded fashion. Predictive accuracies for RAC, RVDC, FVP, and IVCP were 75%, 80%, 90%, and 95%, respectively, for the patients without pulmonary hypertension and 67%, 58%, 58%, and 83%, respectively, for the patients with pulmonary hypertension. Although all predictive accuracies were lower in patients with pulmonary hypertension, statistically significant decreased predictive accuracy was found only with FVP (p < 0.05). Interestingly, IVCP had the best predictive accuracy among patients with pulmonary hypertension. Our findings suggest that despite somewhat decreased accuracy in patients with pulmonary hypertension, traditional echocardiographic clues for pericardial tamponade may be useful.

Aged↗
PubMed1994

Use of isografts to study proliferation and differentiation programs of mouse stomach epithelia.

A new model system has been developed for studying the factors that regulate the proliferation and differentiation programs of the principal cell lineages present in the mouse stomach epithelium. When embryonic day 14 (E14) stomachs from C57Bl/6 mice are implanted under the subcutaneous fascia of young adult male CBY/B6 nude mouse recipients, they are rapidly vascularized and begin to grow at rates comparable to the intact stomach of a similarly aged animal. Single- and multilabel immunohistochemical studies, conducted in the intact stomach of E14 to postnatal day 42 (P42) C57Bl/6 mice and in P7, P14, P28, and P42 C57Bl/6 isografts, suggest that the apparently undifferentiated glandular epithelium of E14 stomach already has encoded positional information that permits it to establish regional differences in cell populations even in the absence of exposure to normal luminal contents. Regional differentiation is manifested by the establishment of distinct zones, each composed of gastric units with zone-specific cell lineages. This axial patterning evolves at a rate similar to that of the intact stomach, even though the E14 isograft is placed in the hormonal environment of an adult host and therefore cannot be programmed by normal developmental changes in endocrine status. Moreover, patterning is maintained in isografts despite continuous renewal of its epithelial cell lineages. Although isografts apparently possess autonomously functioning temporal and spatial programs, perturbations were noted in the proliferation and/or differentiation programs of certain lineages, e.g., the rate of accumulation of endocrine cell subpopulations is reduced in these grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium.

alpha 1-Antitrypsin (alpha 1-AT) is an acute phase plasma protein predominantly derived from the liver which inhibits neutrophil elastase. Previous studies have suggested that alpha 1-AT is also expressed in human enterocytes because alpha 1-AT mRNA could be detected in human jejunum by RNA blot analysis, and alpha 1-AT synthesis could be detected in a human intestinal adenocarcinoma cell line Caco2, which spontaneously differentiates into villous-like enterocytes in tissue culture. To definitively determine that the alpha 1-AT gene is expressed in human enterocytes in vivo, we examined tissue slices of human jejunum and ileum by in situ hybridization. The results demonstrate specific hybridization to enterocytes from the bases to the tips of the villi. Although there was no hybridization to enterocytes in most of the crypt epithelium, there was intense specific hybridization in one region of the crypt. Double-label immunohistochemical studies showed that alpha 1-AT and lysozyme co-localized to this region, indicating that it represented Paneth cells. Finally, there was a marked increase in hybridization to alpha 1-AT mRNA in villous enterocytes and Paneth cells in Crohn's disease. The results of this study provide definitive evidence that alpha 1-AT is expressed in human jejunal and ileal enterocytes in vivo, and show that alpha 1-AT is also a product of Paneth cells. Together with the results of other studies, these data raise the possibility that alpha 1-AT detected in fecal alpha 1-AT clearance assays for diagnosing protein-losing enteropathies is predominantly derived from sloughed enterocytes.

Adenocarcinoma↗
PubMed1992

Use of fetal intestinal isografts from normal and transgenic mice to study the programming of positional information along the duodenal-to-colonic axis.

The four principal cellular constituents of the mouse intestinal epithelium are all derived from a multipotent stem cell functionally anchored near the base of its crypts. Differentiation of enterocytes, enteroendocrine, and goblet cells occurs during an orderly upward migration from monoclonal crypts supplied by a single active stem cell to adjacent polyclonal small intestinal villi or to their colonic homologs, the surface epithelial cuffs. Paneth cells differentiate as they descend to the base of crypts. This epithelium undergoes rapid and perpetual renewal yet is able to maintain cephalocaudal (duodenal-to-colonic) differences in the differentiation programs of its four cell types from the time of its initial cytodifferentiation in late fetal life (embryonic (E) days 16-17). Rat liver fatty acid-binding protein/human growth hormone transgenes (Fabpl/hGH) have been used as novel phenotypic markers to describe the biological properties of gut stem cells and the differentiation programs of their enterocytic and enteroendocrine lineages. To determine whether the multipotent stem cell is able to retain a "positional" address in the absence of luminal signals, we prepared isografts from the proximal small intestine or distal small intestine and colon of E15-E16 Fabpl/hGH transgenic mice and their normal littermates and implanted them into the subcutaneous tissues of young, adult male CBY/B6 nude mice. Immunocytochemical and histochemical studies indicate that appropriate position-specific differences in the differentiation programs of each of the four principal cell lineages are present along the cephalocaudal and crypt-to-villus (or crypt-to-epithelial cuff) axes of isografts harvested 4-6 weeks after implantation. This suggests that the gut stem cell can be characterized not only by its multipotency and enormous capacity for self-renewal but also by its ability to be programmed (? imprinted) with positional information. Transgene expression is reduced in a number of enteroendocrine subpopulations in small intestinal and colonic isografts compared to the intact gut. Moreover, the decision to express the Fabpl/hGH transgene appears to be coordinated between adjacent crypts as evidenced by (i) the presence of multicrypt patches of wholly reporter (hGH)-positive or reporter-negative cells in the intact colon and in colonic isografts and (ii) by the presence of coherent bands of reporter-positive or -negative cells that emanate from adjacent monophenotypic crypts and extend to the apical extrusion zone of distal small intestinal villi.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗