Biomedical subjects

P C Colony

Publications and source records attributed to P C Colony.

13 recordsLinked to original sources

PubMed1991

Alterations in lectin binding in the proximal and distal colon of Sprague-Dawley rats with 1,2 dimethylhydrazine administration.

Sequential changes in rhodamine or fluorescein isothiocyanate-conjugated lectin binding of proximal and distal colonic crypts were studied during and after the administration of the 1,2 dimethylhydrazine (DMH). Five adult its unexposed to DMH or vehicle served as baseline controls. Tissue from normal appearing colon and tumor tissue was incubated with Ulex europaeus agglutinin 1 (UEA), Arachis hypogaea (PNA), Dolichos biflorus (DBA) and Griffonia simplicafolia 1 (GSA1). Distinct regional differences were noted in the baseline controls. UEA, PNA and DBA binding were absent in the distal colonic crypt cells. In the proximal colon minimal UEA and PNA binding was noted in the lower crypt whereas DBA binding was intense. GSA1 binding was diffuse in the upper and lower crypt of both regions. During carcinogenesis a progressive increase in PNA binding was noted in normal appearing colonic crypts from both regions. A progressive increase in PNA binding in proximal and distal colonic tumors was noted over time. Similar to normal tissue, DBA bound markedly to proximal colon tumors but was absent in most distal colonic tumors. UEA stained all proximal tumors intensely at all time points. In distal colonic tumors, UEA staining was diminished at 30 weeks compared to tumors analyzed at 16, 22 and 26 weeks. Mucin depletion was also a feature of tumor tissue compared to adjacent normal and hyperplastic glands. This study documents the region specific changes in lectin binding in normal and neoplastic colonic crypts induced by DMH.

1,2-Dimethylhydrazine↗

PubMed1989

Structural and enzymatic changes during colonic maturation in the fetal and suckling rat.

To assess correlations between cellular differentiation and enzymatic maturation in the developing rat colon, tissue from fetal, suckling, weanling, and adult rats was analyzed by electron microscopy and assayed for lactase, alkaline phosphatase, and sodium-potassium-stimulated adenosine triphosphatase activities. The proximal and distal colon were analyzed independently at all ages. All three enzymes were detected in the fetal colon when the cells were highly undifferentiated. Postnatally, significant regional differences in cellular ultrastructure appeared, only some of which were directly paralleled by enzymatic changes. Each enzyme had a distinct region-specific developmental pattern. Lactase and sodium-potassium-stimulated adenosine triphosphatase were significantly enhanced at birth, decreasing to adult levels by 15 days postnatal. Regional differences were present, but the patterns were similar. These patterns did not parallel the increase in microvillar height and number and basolateral interdigitations of the surface columnar cells, the structural correlates of lactase, and sodium-potassium-stimulated adenosine triphosphatase, respectively. In contrast, developmental changes in alkaline phosphatase activity paralleled structural maturation, at least in part. The activity levels in the distal colon did not change significantly with age and few major structural changes were noted. In the proximal colon, activity increased markedly after birth, and after 10 days decreased rapidly to adult levels, a pattern that coincided with the transient appearance of villi and specialized cells with apical tubules and vesicles known to have alkaline phosphatase activity. The results show age- and region-related changes in cellular ultrastructure and enzymatic activities, only some of which appear to be directly correlated.

Alkaline Phosphatase↗

PubMed1989

Central neurotensin affects rat gastric integrity, prostaglandin E2, and blood flow.

The aim of this study is to define the effect(s) of centrally administered neurotensin (NT) on gastric mucosal integrity, prostaglandin E2 (PGE2) generation, and blood flow during stress induced by cold-water restraint (CWR) in rats. Intracerebroventricular (icv) NT reduced macroscopic and microscopic damage. The former effect was dose dependent and was totally blocked by indomethacin pretreatment. Gastric mucosal PGE2 increased 27 and 30% at 30 and 60 min, respectively, in nonrestrained rats given icv NT. PGE2 generation was reduced in control rats during CWR but was maintained in CWR rats treated with icv NT. Gastric mucosal blood flow (GMBF) was significantly reduced in control rats during CWR. Mucosal blood flow was maintained at nonrestraint levels in the presence of icv NT during CWR; however, this effect was abolished by parenteral indomethacin pretreatment. Similarly, intravenous 16,16-dimethyl-PGE2 (200 micrograms.kg-1.h-1) maintained GMBF of non-CWR levels as well as preventing the macroscopic damage normally associated with CWR. These data suggest a protective role for central NT on the gastric mucosa, mediated, at least in part, by PGE2 generation and gastric mucosal blood flow.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Cellular proliferation in proximal and distal rat colon during 1,2-dimethylhydrazine-induced carcinogenesis.

Sequential changes in proliferative parameters in proximal and distal colonic crypts were studied during 1,2-dimethylhydrazine-induced carcinogenesis using [3H]thymidine autoradiography as a probe. 1,2-dimethylhydrazine (20 mg/kg) and vehicle (ethylenediaminetetraacetic acid) control rats received weekly s.c. injections for 20 wk. All animals received a pulse of [3H]thymidine before death at weeks 2, 6, 10, 16, 22, 26, or 30. In addition, 8 animals unexposed to 1,2-dimethylhydrazine or vehicle served as baseline controls. Dramatic regional differences were noted in the baseline controls. Crypt length, labeling index, and proliferative zone size were all significantly greater distally than proximally (p less than 0.05), whereas the labeling index of the proliferative zone tended to be enhanced proximally. During 1,2-dimethylhydrazine treatment the crypt length, labeling index, and proliferative zone size increased in both regions. As these parameters changed in parallel, the differences between proximal and distal colon did not change significantly during carcinogenesis. Actual tumor formation did differ, however, with tumors appearing earlier and in greater abundance in the distal colon. These findings show similar proliferative changes in both the proximal and distal colon during 1,2-dimethylhydrazine treatment and indicate that the enhanced baseline proliferative state of the distal colon compared with the proximal colon must be considered in the process of tumor formation.

1,2-Dimethylhydrazine↗

PubMed1988

The effects of chronic ethanol administration on polyamine content during dimethylhydrazine-induced colorectal carcinogenesis in the rat.

Chronic ethanol (EtOH) consumption has been implicated as a co-carcinogen, selectively promoting rectal tumor formation. We studied the effects of EtOH consumption on tumor formation and polyamine content (putrescine, spermidine and spermine) in proximal and distal colon and rectum of Sprague-Dawley rats treated with the procarcinogen 1,2-dimethylhydrazine (DMH). Sixty-four adult male rats were pair fed nutritionally complete liquid diets with 36% of calories supplied as EtOH or isocaloric carbohydrates. Both groups received 4 weeks of the liquid diet followed by 4 weeks of standard laboratory chow during which 50% of the rats in each group received DMH (30 mg/kg) or vehicle s.c. weekly. This cycle was repeated four times (32 weeks). Animals were sacrificed at the end of each 8 week cycle and normal appearing and available tumor bearing tissue from proximal and distal colon and rectum was obtained for polyamine content and histology. Five animals, unexposed to DMH or EtOH served as baseline controls. There were no consistent regional differences in putrescine, spermidine or spermine of baseline controls. A progressive decrease in tissue putrescine was seen in all three regions of the control group and was significant at 24 and 32 weeks versus baseline controls. In all three regions, chronic EtOH consumption prevented the decrease in tissue putrescine. Spermidine content was also significantly increased in the distal colon of EtOH-treated animals compared to baseline values. Consistent changes in spermine content were seen in any treatment group or region. A significant increase in putrescine content of normal appearing and tumor-bearing tissue of DMH treated animals at 32 weeks was noted. Chronic EtOH administration did not augment rectal or colonic polyamine content in DMH-treated animals. Likewise, chronic EtOH consumption did not alter the number, size or distribution of large bowel tumors of DMH treated animals.

Animals↗

PubMed1987

Endocytosis and vesicular traffic in fetal and adult colonic goblet cells.

Structural and functional differences between adult and fetal colonic goblet cells have not been clearly defined. To compare the binding, uptake, and intracellular pathway of internalized apical membrane in fetal and adult goblet cells, cationic ferritin (CF) was used as a nonspecific probe. The initial distribution of membrane anionic sites was determined in segments of proximal and distal colon from fetal (18-22 days) and adult rats that were fixed prior to a 10-minute exposure to CF at 4 degrees C. Uniform binding along the apical membrane and microvilli was noted at all ages. To assess uptake and intracellular transport, segments of proximal and distal colon from fetal and adult rats were exposed to CF for 10 minutes at 4 degrees C prior to a saline wash and incubation in saline or Liebovitz L-15 medium for 3, 6, 15, 30, or 60 minutes at 37 degrees C. In addition, fetal rats between 18 and 22 days gestation (birth) were exposed to CF continuously for 10-30 minutes via an intracaecal injection. The results showed extensive uptake of CF in the fetal goblet cells and a more variable intracellular pathway than in with the adult. Within 3 minutes, numerous CF positive vesicles and tubules were present within the apical cytoplasm as well as interspersed among the secretory granules of the fetal goblet cell. Most of these vesicles were smooth surfaced, although some were coated. By 15 minutes, CF was frequently seen in multivesicular bodies, and occasionally in vacuoles in the vicinity of the Golgi. No CF was detected in Golgi cisternae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of enterally fed epidermal growth factor on the small and large intestine of the suckling rat.

Epidermal growth factor (EGF) has been shown to be present in the milk of several species, including the rat, and to have gastrointestinal effects when given parenterally or orally in pharmacologic doses. We investigated the effect of enteral EGF in physiologic doses on the small intestine and colon of suckling rats. Serum thyroxine (T4) levels were also measured. Rats were gavage-fed by hand with an artificial formula with or without added EGF every 3 h from 11 to 14 days of age. Intake was adjusted to deliver 30 kcal/100 g b.wt./day of formula and 16 micrograms/kg/day of EGF approximating the daily caloric intake, and about twice the estimated daily EGF intake for suckling rats. Weight gain did not differ between groups (fed EGF: 3.8 + 0.2 g; not fed EGF: 3.7 + 0.1 g). The protein content of the whole colon of rats fed an EGF-containing formula was significantly lower and the DNA content significantly higher, than in rats fed formula without added EGF. The protein/DNA ratio was therefore markedly higher in the animals fed formula without added EGF; these effects were most evident in the distal colon. In contrast, there was no effect of EGF on small intestinal protein and DNA content; lactase, sucrase, and maltase activities were likewise unaffected, as was serum T4. These data suggest a physiologic role for breast milk EGF in the development of the suckling rat colon.

Animals↗

PubMed1987

Lectin binding patterns in developing rat colon.

To evaluate qualitative changes in brush-border and goblet cell glycoconjugates during colonic development, rhodamine-conjugated lectins were applied to tissue from fetal (18-22 day), suckling (1-20 day), and weanling (22-26 day) rats. Tissue from the proximal and distal colon of each animal was incubated with Triticum vulgaris, Arachis hypogaea, Glycine max, or Ulex europeus agglutinin I. Formalin-fixed paraffin sections and unfixed frozen sections were coded, read blindly, and graded from negative (-) or weak (+) to intensely positive (4+). The results showed a unique developmental pattern for each lectin, although in all cases the adult binding pattern was established by weaning. Alterations in the binding pattern between paraffin and frozen sections were noted only for Arachis hypogaea and Glycine max. Minimal Glycine max binding was seen at any age in paraffin sections, although in frozen sections a weak but consistent supranuclear binding was seen in goblet cells of postnatal animals. In contrast, both the brush-border and goblet cells were intensely fluorescent after exposure to Triticum vulgaris. This fluorescence was present in both regions at all ages studied. Ulex europeus agglutinin I also labeled goblet cells in the fetal and neonatal colon, but late in the suckling period regional differences appeared. This resulted in a significant loss of labeled goblet cells distally and a restriction of Ulex europeus agglutinin I-positive cells to the base of the crypts proximally. Finally, Arachis hypogaea showed a transient brush-border binding in paraffin sections of the proximal colon before weaning, whereas frozen sections revealed a supranuclear localization in goblet cells in both regions after birth. These studies indicate significant changes in membrane-associated and goblet cell secretory glycoconjugates in the developing rat colon.

Animals↗

PubMed1987

Qualitative and quantitative changes in sialomucins during 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat.

Regional differences in goblet cell glycoproteins have been demonstrated qualitatively and, to a limited extent, quantitatively in the normal adult colon. In disease states, alterations in these glycoproteins, particularly the sialoglycoproteins (SGs), have been reported. The present study defined parallel qualitative and quantitative changes in SGs in three colon regions during 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]-induced carcinogenesis. SGs were assessed histochemically by use of high iron diamine-Alcian blue (pH 2.5) staining, and tissue sialic acid levels were measured by a modified Warren assay. Two groups of inbred SD rats (n = 28) were pair-fed nutritionally complete liquid diets with 36% of calories supplied as ethanol or isocaloric carbohydrates. The dietary alcohol was added to selectively enhance rectal tumors, a region of prevalent tumors in humans. Both groups received 4 weeks of liquid diet followed by 4 weeks of standard laboratory chow with weekly sc injections of DMH. This 8-week cycle was repeated four times (32 wk). Animals from each group were sacrificed at 8, 16, 24, and 32 weeks, and adjacent tissues from proximal and distal colon and rectum were prepared for histology and biochemical assay. The results showed a progressive increase in sialomucin staining in normal-appearing mucosa in distal colon and rectum in both groups but not in the proximal colon. In contrast, tissue sialic acid increased in all three regions as early as 8 weeks, and significant increases were consistently present by 32 weeks. A different pattern was observed in tissue from frank tumors. Compared with normal-appearing mucosa, both sialomucin staining and tissue sialic acid levels were reduced in tumor tissue by 32 weeks. These studies indicated that tissue sialic acid levels may provide a simple and reliable screening technique in the early diagnosis of premalignant change in all regions of the colon.

1,2-Dimethylhydrazine↗

PubMed1985

Macromolecular transport in the fetal rat intestine.

Macromolecular barrier function of the fetal rat small intestine and colon was analyzed from 16 to 22 days gestation (birth). During this period the epithelium is converted from stratified to simple columnar. To assess permeability, horseradish peroxidase (HRP) was introduced by microinjection into the lumen or into the umbilical circulation. Proximal small intestine, distal small intestine, and colon were examined after 10-20 min. Paracellular passage of HRP through occluding junctions was not observed after either intraluminal or intravascular injection. After intraluminal injection, transepithelial transport of HRP from lumen to blood occurred in all regions at all ages studied. Horseradish peroxidase was present in cytoplasmic vesicles of most cells in the primitive stratified epithelia, during epithelial conversion, and in simple columnar epithelia. After intravascular injection, HRP was present in the lamina propria and in intercellular spaces of the epithelium, but HRP did not enter tight junctions. Tracer was taken up into cytoplasmic vesicles of both stratified and simple columnar epithelial cells, but was only rarely seen in the lumen. We conclude that there is rapid transcellular, vesicle-mediated transport from lumen to blood across both stratified and simple columnar epithelia of fetal rat small intestine and colon; after intravascular injection, macromolecules may be taken up into vesicles at basolateral epithelial cell surfaces but are not rapidly transported into the lumen; paracellular passage does not occur in the fetal ages studied.

Animals↗

PubMed1985

Localization of carbonic anhydrase activity in the developing rat colon.

Carbonic anhydrase activity was localized histochemically by light and electron microscopy in the proximal and distal colon of developing rats. Fixed tissue was taken for normal morphology and carbonic anhydrase localization from fetal (20-22 days gestation), suckling (1-19 days postnatal), weanling (20-25 days postnatal), and adult rats. The proximal colon had distinct villi at birth which were diminished between days 5 and 11 postnatally. The distal colon lacked villi at birth but had rudimentary crypts (ridges and furrows) which were replaced during the suckling period by a flat mucosa interspersed with true crypts. Carbonic anhydrase first appeared in both proximal and distal colonic epithelial cells on the day of birth (22 days gestation). Goblet cells were nonreactive at each developmental period. In neonatal rats, epithelial cells in the upper half of the villi of the proximal colon and on the surface and upper crypts of the distal colon were positive for carbonic anhydrase throughout the cytoplasm. Cells at the villar base (proximal colon) or in the deep crypt (distal colon) had reaction product in the intercellular spaces but not the cytoplasm. By 11 days postnatal, cytoplasmic reaction product was present in proximal colonic cells in the upper three-fourths of the crypt and was concentrated in a heavy band in the apical cytoplasm. In the distal colon, cytoplasmic positive cells did not extend as deeply into the crypts and the apical banding pattern was weak. Intercellular spaces in the deeper crypt epithelium were positive in both proximal colon and distal colon, suggesting a membrane-bound carbonic anhydrase. It was concluded that carbonic anhydrase appeared suddenly at birth and was continuously present in mid- to upper-crypt (or upper villus in early neonatal proximal colon) non-goblet cells into adulthood. This suggests a functional role for carbonic anhydrase in chloride-bicarbonate exchange across the neonatal and adult colonic mucosa.

Age Factors↗

PubMed1985

Effects of prior adrenalectomy on postpneumonectomy lung growth in the rat.

The effects of adrenalectomy, with and without subsequent glucocorticoid replacement therapy, on postpneumonectomy compensatory lung growth in the rat were investigated. Male Sprague-Dawley rats (200-230 g) were subjected to no operation (UNOP), left pneumonectomy (PNX), or PNX preceded by bilateral adrenalectomy 5 days earlier (ADX/PNX). At 14 days post-PNX, when compensatory lung growth is normally complete in 200-g rats, right lung (RL) dry weights of PNX (263 +/- 6 mg, n = 26) and ADX/PNX (334 +/- 13 mg, n = 25) rats were increased 58 and 101%, respectively, relative to UNOP controls (166 +/- 5 mg, n = 10). Increases in total DNA, RNA, and protein in the right lungs of PNX and ADX/PNX rats occurred in proportion to RL dry mass. The increase in all parameters examined in PNX and ADX/PNX rats at 7 days post-PNX was half that at 14 days, indicating linear lung growth in both treatment groups. The stimulatory effect of ADX on lung growth was blocked by hydrocortisone acetate (HCA), administered intraperitoneally in daily doses of 5 mg/kg, beginning on the day of PNX. The RL dry weights of HCA-treated ADX/PNX rats (241 +/- 7 mg, n = 10) did not differ significantly from the corresponding value in PNX rats (270 +/- 14 mg, n = 7). The lower RL weights in the HCA-treated rats resulted from an inhibition of cell division, as evidenced by the total RL DNA content, which was similar to that in PNX animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1985

Glucocorticoid receptors in isolated intestinal epithelial cells in rats.

There is evidence that glucocorticoid hormones influence a variety of epithelial cell functions in the small intestine. To exert their effect, glucocorticoids bind to cytoplasmic glucocorticoid receptors (GR), which, following translocation to the nucleus, stimulate mRNA transcription and then protein synthesis and ultimately trigger hormonal actions. To determine the distribution of GR in small intestinal villus and crypt cells, we measured GR activity in enriched villus and crypt cell fractions by use of [3H]dexamethasone. In normal rats GR activity was present in all cell fractions but was lowest in fully mature villus cells of the upper villus and greatest in immature crypt cells. In contrast, 1 wk after adrenalectomy and ovariectomy or sham operation, both of which reduced plasma corticosterone levels, GR activities were comparable in enriched villus cell and enriched crypt cell fractions. Kinetic studies indicated a single class of binding sites with comparable Kd values in villus and crypt cells of normal and steroid-depleted animals, suggesting that there are more glucocorticoid-binding sites in crypt than in villus cells of normal animals. Immature crypt cells may be more susceptible to glucocorticoid modulation than fully mature villus cells in normal rats in view of their higher GR activity.

Adrenalectomy↗