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PubMed1977

The postnatal development of the alimentary canal in the opossum. III. Small intestine and colon.

The duodenum of the newborn opossum exhibits a patent lumen containing scattered elongate villi, whereas the distal segments of the small intestine are smaller in diameter and are filled with short immature villi. The muscularis externa through the small intestine consists of a single layer of myoblasts. Interposed between the intestinal lining epithelium and the muscularis externa is an extensive capillary bed that occupies a considerable proportion of the intestinal wall. Additional villi appear to form during the postnatal period as a result of evaginations of the epithelium, together with underlying connective tissue and vasculature, into the intestinal lumen. Intestinal glands are not observed until 8.5cm, and are shallow in depth even in the adult. The epithelium of the entire small intestine is modified for absorption until just prior to weaning. The principal intestinal lining cells show an extensive apical endocytic complex, large supranuclear vacuoles and numerous cytoplasmic inclusions. Intestinal epithelial cells of the colon also appear to be modified for absorption during the first two weeks after birth. Although goblet cells and Paneth cells are present during the suckling period, they do not comprise a significant population in the intestinal epithelium until after weaning. In contrast to the small intestine, goblet cells are numerous in the colon by the ninth postnatal day. The significance of macromolecular absorption and the possibility of passive immunity being transmitted in the opossum during suckling are discussed and related to similar events that occur in the slckling young of several eutherian species. The possible functional significance of two large membranes that develop in the lamina propria of the intestines after weaning also is discussed.

Animals↗
PubMed1987

Intestinal metaplasia of the stomach in Swedish and Japanese patients without ulcers or carcinoma.

A systematic analysis of the cellular components of intestinal metaplasia (i.e., goblet cells with or without brush border cells and Paneth cells) was performed in endoscopic gastric biopsies from 984 patients without gastric ulcer or carcinoma; 359 Swedish and 625 Japanese patients. The Japanese patients, matched for age and sex, had twice as much intestinal metaplasia as the Swedes. The frequency of goblet cells and columnar cells with brush (absorptive) border increased with increasing age in both ethnic groups. Complete intestinal metaplasia (i.e. the presence of at least two or all three cellular components) was twice as frequent in the Japanese. This may reflect differences in the environment (including food habits) of the gastric mucosa in the two populations. Structural mucosal changes (i.e. pseudo-villus formations) were found more than twice as often in the Japanese. Since pseudo-villus changes occurred as often as goblet cells and brush border cells in both groups, it is suggested that the above-mentioned mucosal structural change should be considered for inclusion among the histological criteria of intestinal metaplasia of the stomach. Incomplete intestinal metaplasia (i.e. the occurrence of goblet cells without the other cellular components) occurred in similar proportions in the two populations. The present findings support the theory that incomplete intestinal metaplasia may be a para- rather than a preneoplastic phenomenon.

Adult↗
PubMed1993

"Intestinal-type" of adenocarcinoma preferentially induced in right/caudate liver lobes of rats treated with furan.

Short-term chronic exposures of rats to furan were recently found by us to preferentially induce a unique liver lobe pattern of development of small intestinal metaplasia and subsequent cholangiofibrosis, being essentially localized to the caudate and right liver lobes (L. W. Elmore, and A. E. Sirica, Cancer Res., 51: 5752-5759, 1991). We now demonstrate the preferential development of primary hepatic adenocarcinomas exhibiting small intestine mucosal cell differentiation, which have arisen at 70 to 90% incidences from the right/caudate liver lobes of Fischer 344 adult male rats by 16 months after their receiving furan by gavage at a daily dose of 30 mg/kg of body weight, five times a week, for 9, 12, and 13 weeks, respectively. In contrast, the incidences of primary hepatocellular carcinomas that developed in the furan-treated rats ranged from 0 to 20%, with the two hepatocellular carcinomas observed to be originating from the median/left liver lobes. Twenty-six of 27 hepatic adenocarcinomas analyzed exhibited glands containing on average 30.2% goblet cells, 2.1% Paneth cells, and 0.5% serotonin-positive neuroendocrine cells. Phenotypically, the glandular epithelial cells of the furan-induced intestinal-type adenocarcinomas were immunohistochemically positive for cytokeratin 19, but exhibited a heterogeneous pattern of immunohistochemical staining for gamma-glutamyl transpeptidase and showed no detectable immunostaining for transforming growth factor alpha. In addition, many of the glandular structures within these primary hepatic adenocarcinomas showed evidence of basement membrane disruption, as demonstrated by both electron microscopy and immunohistochemical staining for basement membrane laminin. While these intestinal-type adenocarcinomas appeared to have spread intrahepatically, none showed evidence of extrahepatic metastases. However, six of eight randomly selected adenocarcinomas grew progressively and retained their intestinal pattern of differentiation following serial transplantation into the fat pads of young adult Fischer 344 recipient rats. In this study, we also observed one primary hepatic cholangiocarcinoma that was characterized by a more native biliary rather than intestinal-type of differentiation. Interestingly, this was the only primary liver cancer observed by us to exhibit extrahepatic metastasis. In conclusion, our current findings clearly indicate that the small intestinal metaplasia and subsequent cholangiofibrosis developing early in the right/caudate liver lobes of furan-treated rats do not simply reflect reactive changes, but strongly correlate with the high incidences of intestinal-type of primary hepatic adenocarcinoma that occurs in the right/caudate liver lobes of rats after long-term exposures to furan.

Adenocarcinoma↗
PubMed1994

Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum. A histochemical and immunohistochemical study.

An unusual case of multicentric ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum was studied, with special attention given to the histogenesis of these neoplasms. A total of six ileal carcinoids, the largest of which was located in the wall of Meckel's diverticulum, were macroscopically and microscopically confirmed to be multicentric and revealed no visceral metastases. The histochemical and immunohistochemical profiles of the ileal carcinoids and the appendiceal carcinoma differed considerably: the former resembled subepithelial neuroendocrine cells and the latter resembled epithelial nonmucous cells and Paneth cells. The appendiceal carcinoma exhibited signs of endocrine differentiation, expressing somatostatin and vasoactive intestinal polypeptide, and secreted mucus. The tumor had metastasized to various organs. The carcinoids exhibited signs of neuroendocrine and glandular differentiation, expressing neuron-specific enolase, serotonin, chromogranin A, and endocrine granule constituent, and secreted little mucus. The data suggest different tumor cell origins or different grades of differentiation of the two types of intestinal endocrine cell tumor.

Aged↗
PubMed2002

Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis.

Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer. We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty. Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis +/- crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for and ). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients. Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.

Colitis↗
PubMed1975

Direct quantitative estimation of Paneth and total cell populations in the jejunal glands of Lieberkühn.

Direct morphometric estimation of the number of intestinal crypts per 10 mm length of jejunum, the total number of cells per crypt, and the number of Paneth cells per crypt was performed using Zenker-fixed, serially sectioned small intestines from adult BALB/c mice. The mean volume of a crypt cell was estimated to be in the order of 6.6 plus or minus 0.1 times 10-4 mm-3, while the total volume of all cells in a single crypt was 1.833 plus or minus 0.02 times 10-1 mm-3. The cell population per crypt was 278 plus or minus 7 cells, of which 44 plus or minus 10 were Paneth cells. It was estimated further that 265 plus or minus 30 crypts per 10 mm length of jejunum contained 7.4 plus or minus 0.1 times 10-4 cells, including 1.2 plus or minus 0.24 times 10-3 Paneth cells. The volume of all crypt and Paneth cells per 10 mm length of jejunum was in the order of 49 plus or minus 1.2 and 8 plus or minus 1.8 mm-3, respectively. The volume of the tunica muscularis and the surface area of the crypt's lumina were estimated to be 33.5 plus or minus 2.2 mm-3 and 118 plus or minus 19 mm-2, respectively.

Animals↗
PubMed2002

Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB.

In the small intestine, the progeny of stem cells migrate in precise patterns. Absorptive, enteroendocrine, and goblet cells migrate toward the villus while Paneth cells occupy the bottom of the crypts. We show here that beta-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 in colorectal cancer and along the crypt-villus axis. Disruption of EphB2 and EphB3 genes reveals that their gene products restrict cell intermingling and allocate cell populations within the intestinal epithelium. In EphB2/EphB3 null mice, the proliferative and differentiated populations intermingle. In adult EphB3(-/-) mice, Paneth cells do not follow their downward migratory path, but scatter along crypt and villus. We conclude that in the intestinal epithelium beta-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system.

Actins↗
PubMed2006

The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota.

The intestinal tract is a complex ecosystem that combines resident microbiota and the cells of various phenotypes with complex metabolic activities that line the epithelial wall. The intestinal cells that make up the epithelium provide physical and chemical barriers that protect the host against the unwanted intrusion of microorganisms that hijack the cellular molecules and signaling pathways of the host and become pathogenic. Some of the organisms making up the intestinal microbiota also have microbicidal effects that contribute to the barrier against enteric pathogens. This review describes the two cell lineages present in the intestinal epithelium: the goblet cells and the Paneth cells, both of which play a pivotal role in the first line of enteric defense by producing mucus and antimicrobial peptides, respectively. We also analyze recent insights into the intestinal microbiota and the mechanisms by which some resident species act as a barrier to enteric pathogens. Moreover, this review examines whether the cells producing mucins or antimicrobial peptides and the resident microbiota act in partnership and whether they function individually and/or synergistically to provide the host with an effective front line of defense against harmful enteric pathogens.

Animals↗
PubMed1981

The stem-cell zone of the small intestinal epithelium. III. Evidence from columnar, enteroendocrine, and mucous cells in the adult mouse.

In the first two articles of this series we demonstrated restriction of Paneth cell formation to positions 5 and above. Restriction was independent of the Paneth cell population-density gradient in the crypt base. We concluded that our results were consistent with the presence in the adult of a stem-cell zone in positions 1-4 in which stem cells received no inducement to differentiate. To further test the stem-cell zone hypothesis we determined the site of stem-cell differentiation along mucous, enteroendocrine, and columnar cell lines using radioautography with 3H-thymidine as a label. One hour after injection of 3H-thymidine, labeled mucous cells were not observed below position 5. Only later did they appear in lower positions and not until 4 days after injection were they observed in position 1. Labeled enteroendocrine cells first appeared above, and then were seen in the top of, and finally in the middle and bottom of the Paneth cell distribution. Thirty hours after injection there were two populations of labeled columnar cells in the crypt base, a heavily labeled population and a lightly labeled one. At this time interval the heavily labeled columnar cells were only observed in positions 5 and above, but they appeared in positions 1-4 by 66 hours after injection. The above evidence led us to conclude that all differentiated offspring of the common epithelial stem cell originate in positions 5 and above. Most columnar, mucous, and enteroendocrine cells originating in positions 5 and above migrate upward. However some of these cells migrate down. All differentiated cells found in positions 1-4 migrated down from their origin in position 5 or above. We also found that only stem cells proliferate in positions 1-4. We concluded that in the adult, there is a stem-cell zone in positions 1-4 where stem cells are not induced to differentiate and persist as stem cells throughout life.

Animals↗
PubMed1997

Cryptdin gene expression in developing mouse small intestine.

In rodents, the four intestinal epithelial cell lineages differentiate and become morphologically distinct during the first 2-3 postnatal wk. In studies reported here, reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays detected Paneth cell defensin mRNAs in intestinal RNA from 1-day-old (P1) mice before crypt formation and maturation of the epithelium. Analysis of these defensin-coding RT-PCR products from P1 mice showed that 69% of clones sequenced coded for cryptdin-6, suggesting that it is the most abundant enteric defensin mRNA in the newborn. Paneth cell mRNAs, including cryptdins-4 and -5, lysozyme, matrilysin, and defensin-related sequences, also were detected in RNA from P1 mouse intestine. Unlike adult mice, where only Paneth cells are immunopositive for cryptdin, cryptdin-containing cells were distributed throughout the newborn intestinal epithelium and not in association with rudimentary crypts. Cryptdin immunoreactivity in the P1 mouse intestine was specific for intracellular granule contents, and immunofluorescent detection of cryptdins on mucosal surfaces suggested that the peptides are released into the intestinal lumen in P1 mice Defensin secretion may contribute to innate immunity of the neonatal intestine before the presence of distinguishable Paneth cells.

Aging↗
PubMed1975

An electron microscopic study of intestinal metaplasia in human gallbladder.

Areas of intestinal metaplastic epithelium in gallbladders removed by cholecystectomies performed for gallstones were studied with the electron microscope. Three gallbladders contained areas of goblet cells and endocrine enterochromaffin-like cells and one gallbladder also Paneth cells. The goblet cells contained mucin granules of slightly variable size and shape and relatively great electron lucency. The intervening columnar epithelial cells contained various amounts of electron-lucent mucin granules. The round or oval enterochromaffin-like cells rested on the basement membrane, and in these cells the small, round, electron-opaque secretory granules were located in the infranuclear region. The supranuclear cytoplasm of the Paneth cells in the intestinalized epithelium contained typical large, round secretory granules. The fine structures of the various cells in the metaplastic epithelium bore resemblance to those of the cells in the intestinalized stomach mucosa.

Basement Membrane↗
PubMed2003

Inflammatory bowel diseases and brain-gut axis.

The influence of stress on inflammation in inflammatory bowel disease (IBD) is reviewed. In experimental forms of colitis in rats, stress reactivated the disease. A study of stable IBD patients who were followed for over five years explored the influence of stress on exacerbating the disease. Those patients with high prolonged stressful life events were found to have a 90% recurrence rate of their colitis as compared to only 40% recurrence in low stress patients. Some of the mediators of stress include VIP, TNFalpha, heat shock proteins, glucocorticoid and catecholamines. Stress was shown to increase intestinal permeability to markers such as Cr-EDTA, HRP and dextran 10,000 in rats. In addition, stress increases the permeability of intestinal M-cells. Finally, stress increased the permeability of Paneth cells to HRP. Since Paneth cells synthesize NOD2 mRNA and protein, stress may play a role in the genesis or reactivation of Crohn's disease involving the terminal ileum. Brain-gut interactions via neural, hormonal and cytokine signals can diminish the mucosal protective factors and increase the permeability of luminal antigens into the intestinal epithelial and immune cells. Stress appears to play a key role in exacerbating and accentuating the intestinal inflammation in IBD through brain-gut interactions.

Animals↗
PubMed1996

Image quantitation of intestinal metaplasia in entire gastrectomy specimens from Swedish and Japanese patients.

The aim of this work was to investigate the extension of intestinal metaplasia (IM), as well as to quantitate various components of IM (namely sialomucins, sulfomucins and Paneth cells), in entire gastrectomy specimens from Swedish and Japanese patients. The length of the gastric mucosa was assessed by morphometry. The percent of sections with IM was regarded as the extension of IM in the specimens. Histochemically labeled sialomucins, sulfomucins and Paneth cells (the 3 main findings in gastric IM) were quantified in separate sections with the aid of an image analyzer. In total, 1,321 sections corresponding to 6 gastrectomy specimens were quantified. Sialomucins and sulfomucins were more extensively distributed in the 4 specimens with carcinoma than in the 2 without carcinoma (one having a peptic ulcer and the other, hereditary gastric cancer syndrome (HGCS) without carcinoma). On the other hand, quantitative analysis in Swedish specimens indicated that the highest values for sialomucins, sulfomucins and Paneth cells were present in HGCS. When Swedish and Japanese specimens with adenocarcinoma were compared, only sulfomucins (denoting Types II and III IM) were significantly higher in those carrying an intestinal-type carcinoma (ITC) than in those with diffuse-type carcinoma (DTC). The results substantiate those obtained with gastric biopsies by other authors. On the other hand, the mucosal extension and the amount of sulfomucins are not comparable parameters (since that mucin was not equally distributed, but "concentrated" in certain areas in the mucosa). One possible conclusion is that the focal distribution of acidic mucins and of Paneth cells in the gastric mucosa may strongly influence their detection rate in gastric biopsies. Thus, haphazard biopsy of the gastric mucosa may fail to sample areas with sulfomucins in population studies aiming to detect individuals at risk. Such sampling errors in gastric biopsies may explain the conflicting results on this subject appearing in the literature.

Gastrectomy↗
PubMed2003

Detection of gastric cancer and premalignant lesions by novel marker glycoprotein 87 using monoclonal antibody Adnab-9.

Gastric adenocarcinoma (GC), the second most frequent cancer in the world, is highly prevalent in Asia. A screening test for early-stage GC would represent a major advance in the management of this disease. Associated conditions such as chronic atrophic gastritis (CAG) with intestinal metaplasia are manifested by specialized intestinalized tissue that often includes Paneth cells. Adenoma-associated antigen glycoprotein 87 (GP87), defined by the Adnab-9 monoclonal antibody and shed into the gut, is associated with epithelial cells, some of which resemble Paneth cells. We evaluated the diagnostic value of GP87 for cancer and gastric premalignant lesions. One hundred and seven sections of normal, benign, and premalignant gastric mucosa and 79 sections of pericancerous tissue were evaluated for expression of GP87 by immunohistochemistry. Eighty-two patients with GC, 34 patients with benign chronic disease, 35 patients with premalignant conditions, and 80 normal controls were evaluated by ELISA for GP87 in feces and gastric juice. Adnab-9 immunostaining for GP87 was significantly positive in CAG and intestinal metaplasia (>77.8%), compared with 0% in normal controls (P < 0.05). Fecal GP87 was positive in 79.3% of patients with gastric cancer, including early-stage lesions, and in 84% of patients with CAG versus 10% of controls (P < 0.05). Positive proportions for each pathological group in tissue correlated with that in feces (r = 0.99; P < 0.02). GP87 is differentially expressed in premalignant gastric lesions that appear to be the origin for fecal GP87, which may be useful for early detection of GC.

Animals↗
PubMed1989

Use of transgenic mice to study the routing of secretory proteins in intestinal epithelial cells: analysis of human growth hormone compartmentalization as a function of cell type and differentiation.

The intestinal epithelium is a heterogeneous cell monolayer that undergoes continuous renewal and differentiation along the crypt-villus axis. We have used transgenic mice to examine the compartmentalization of a regulated endocrine secretory protein, human growth hormone (hGH), in the four exocrine cells of the mouse intestinal epithelium (Paneth cells, intermediate cells, typical goblet cells, and granular goblet cells), as well as in its enteroendocrine and absorptive (enterocyte) cell populations. Nucleotides -596 to +21 of the rat liver fatty acid binding protein gene, when linked to the hGH gene (beginning at nucleotide +3) direct efficient synthesis of hGH in the gastrointestinal epithelium of transgenic animals (Sweetser, D. A., D. W. McKeel, E. F. Birkenmeier, P. C. Hoppe, and J. I. Gordon. 1988. Genes & Dev. 2:1318-1332). This provides a powerful in vivo model for analyzing protein sorting in diverse, differentiating, and polarized epithelial cells. Using EM immunocytochemical techniques, we demonstrated that this foreign polypeptide hormone entered the regulated basal granules of enteroendocrine cells as well as the apical secretory granules of exocrine Paneth cells, intermediate cells, and granular goblet cells. This suggests that common signals are recognized by the "sorting mechanisms" in regulated endocrine and exocrine cells. hGH was targeted to the electron-dense cores of secretory granules in granular goblet and intermediate cells, along with endogenous cell products. Thus, this polypeptide hormone contains domains that promote its segregation within certain exocrine granules. No expression of hGH was noted in typical goblet cells, suggesting that differences exist in the regulatory environments of granular and typical goblet cells. In enterocytes, hGH accumulated in dense-core granules located near apical and lateral cell surfaces, raising the possibility that these cells, which are known to conduct constitutive vesicular transport toward both apical and basolateral surfaces, also contain a previously unrecognized regulated pathway. Together our studies indicate that transgenic mice represent a valuable system for analyzing trafficking pathways and sorting mechanisms of secretory proteins in vivo.

Animals↗
PubMed1999

Gene expression of group II phospholipase A2 in intestine in Crohn's disease.

OBJECTIVE: Phospholipase A2 (PLA2) has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases. Our aim was to identify cells that express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein levels in the intestine in Crohn's disease. METHODS: Tissue samples were obtained from the intestine of 20 patients with Crohn's disease (seven operated and 13 colonoscopied) and from eight control patients without inflammatory diseases. The samples were studied by immunohistochemistry for PLA2-II enzyme protein and in situ hybridization for PLA2-II mRNA. RESULTS: PLA2-II protein and mRNA were detected in the Paneth cells of the small intestinal mucosa in all patients and controls. PLA2-II protein and mRNA were found in the columnar epithelial cells of the small intestinal mucosa in six of eight and eight of eight patients with Crohn's ileitis, respectively. In the eight control patients PLA2-II protein and mRNA were not found in these cells (p = 0.007 and p < 0.001, respectively). Metaplastic Paneth cells, which consistently contained PLA2-II mRNA, were found in the colonic mucosa in five of six patients with Crohn's colitis and of one of eight control patients (p = 0.026). The columnar epithelial cells of the colonic mucosa contained PLA2-II protein in three of six and PLA2-II mRNA in six of six patients with Crohn's colitis, whereas the protein was found in these cells in none of eight of the controls (p = 0.055) and the mRNA in only one of eight (p = 0.005) controls. CONCLUSIONS: In Crohn's disease, Paneth cells and columnar epithelial cells of the small and large intestinal mucosa synthesize PLA2-II at the site of active inflammation.

Adolescent↗
PubMed1976

Electron microscope study of experimental enteric adenovirus infection in mice.

Using fluorescent antibody techniques (FA) and light microscopy (LM) and electron microscopy (EM), this paper describes the morphological features of the ileum in the DK1 mouse orally challenged with adenovirus K87. At the peak of infection, virus is easily identified by FA in the epithelium of the villi and crypts of the ileum. LM shows that fluorescent cells have large, bizarre, uniformly basophilic nuclei containing deoxyribonucleic acid, as indicated by histochemical tests. EM further identifies these nuclei as belonging to columnar, goblet, or Paneth cells, all epithelial cells facing the lumen with a microvillus border. The basophilic material in the nuclei consists of virus particles 75 nm in diameter arranged in crystalline arrays. When found in the cell cytoplasm, the virions do not form arrays but are scattered or form irregular aggregates, which may or may not be enclosed by single membranes. Infected columnar cells show mild cytopathic effects with no cell degeneration and necrosis, whereas the goblet and Paneth cells appear normal and maintain synthetic and secretory functions. All infected cells, however, share an abnormally accelerated extrusion rate, with columnar and goblet cells often being shed from the side rather than from the tip of the villi. The Paneth cells, which do not migrate out of the crypts, show a higher than normal rate of extrusion in the crypt lumen.

Adenoviridae↗
PubMed1969

Paneth and goblet cell renewal in mouse duodenal crypts.

Proliferation of Paneth and goblet cells of mouse duodenal crypts was studied by high resolution light microscope radioautography. In one group of mice, blood levels of thymidine-(3)H were sustained for up to 12 hr by repeated injections of isotope to facilitate identification of proliferating cells. In these animals, many goblet cell nuclei incorporated thymidine-(3)H whereas only 1 of 6261 tabulated Paneth cells was labeled. Cells intermediate in structure between undifferentiated and goblet cells and between undifferentiated and Paneth cells were identified and their light and electron microscopic features are described. A significant number of these "intermediate" cells incorporated thymidine-(3)H into their nuclei. Another group of mice received a single injection of thymidine-(3)H. These animals were killed 4 hr to 29 days after isotope administration. Goblet cells and intermediate cells with labeled nuclei were identified 4 hr after thymidine-(3)H but could not be seen after 15 days. In contrast, Paneth cells with labeled nuclei were not observed until 24 hr after thymidine-(3)H but were still present at 29 days, long after labeled undifferentiated, goblet, and intermediate cells had disappeared. We conclude that differentiated Paneth cells in mouse duodenum do not normally proliferate, but, instead, arise by differentiation from undifferentiated crypt cells or from intermediate cells. Moreover, once formed, Paneth cells persist in crypts for a prolonged period. In contrast, intermediate cells and crypt goblet cells proliferate actively and are less stable cell populations than differentiated Paneth cells. The precise function of the intermediate cells is not known, but they may represent transition forms between undifferentiated cells and the more matrure secretory cells. Damage of crypt epithelial cells, thought to be due to radiation effects, was evident in both groups of mice.

Animals↗