Lipid islands of the stomach: an insular issue?
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Foam Cells↗
Biomedical subjects
J Lechago
Publications and source records attributed to J Lechago.
Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases.
Energy metabolism of human colon cancer in vivo relies predominantly on glucose. Although studies have revealed increased expression of Glut1 mRNA in colon cancer, Glut1 protein (Glut1) expression in the large intestine and its significance are still unknown. The objective of this work was to determine whether Glut1 is present in human colorectal neoplasms and whether that presence is of biological significance. Formalin-fixed, paraffin-embedded tissue sections of 53 colonic adenocarcinomas, 82 adenomas, 46 hyperplastic polyps, and 38 normal colon samples were immunostained with the anti-Glut1 antibody MYM. The localization was carried out using the avidin-biotin immunoperoxidase technique. No Glut1 immunoreactivity was present in normal colonic mucosa or in hyperplastic polyps, whereas 8 (10%) of 82 adenomas showed such immunoreactivity. The frequency of Glut1 expression in adenomas increased with villous morphology and with the size of the adenoma. Forty-four (83%) of 53 colorectal adenocarcinomas expressed Glut1, and, of these, tumors in which >50% of the cancer cells expressed Glut1 had a significantly higher incidence of metastasis to the lymph nodes (P = 0.0001). It is concluded that (a) Glut1 is expressed as a late event in the carcinogenesis process in human colorectal cancer, and (b) expression of Glut1 in a high proportion of cancer cells is associated with a high incidence of lymph node metastases.
Adenocarcinoma↗
Role of luminal ammonia in the development of gastropathy and hypergastrinemia in the rat.
BACKGROUND/AIMS: Chronic infection with Helicobacter pylori causes persistent elevations in gastric juice ammonia levels. Thus, we studied the effects of experimentally induced increases in gastric juice ammonia levels on gastric structure and function and gastrin homeostasis. METHODS: Rats were fed either normal chow or the diet supplemented (20 g/dL) with ammonium or sodium acetate. RESULTS: Long-term dietary ammonium loading for 2 weeks or longer resulted in a 1.5-2-fold increase in the weight and mucosal thickness of the stomach and proximal duodenum with evidence of mild gastritis and enterochromaffinlike cell hyperplasia. The ammonium-containing diet also induced a significant 2-3-fold increase in both circulating gastrin levels of fed rats and an increase in the postprandial gastrin responses over control values. Antral gastrin levels were also markedly elevated by long-term ingestion of the test diet, which was increased 3-4-fold over control values in fasted animals and less so after meal stimulation. Consistent with these findings, gastrin-specific messenger RNA was increased 2.5-3-fold in the antrum of ammonium fed rats, whereas actin-specific messenger RNA was not affected or decreased. Animals fed a diet supplemented with 20 g/dL sodium acetate sustained modest increases in mucosal thickness and serum and antral gastrin concentration, suggesting that nonspecific gastric injury and inflammation is also a factor that influences G-cell function. CONCLUSIONS: Long-term exposure of the antral mucosa to elevated levels of ammonia in the gastric juice in the presence of gastritis, conditions similar to that occurring in subjects infected with H. pylori, seem to be causative factors in the development of G-cell hyperfunction.
Acetates↗
Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon.
Mucosal hyperplasia of the appendix is a seemingly benign change of poorly understood significance, at times found in patients with colorectal malignancy. To determine the incidence of this change and its association with colonic adenocarcinoma, we have examined the appendiceal mucosa in 122 ileocolectomy specimens gathered between 1987 and 1990, and in 273 consecutive appendectomies carried out during 1990 at The Methodist Hospital in Houston, Texas. We found that 23 out of 122 ileocolectomies (18.8%) showed mucosal hyperplasia of the appendix and, of these, 17 (77%) were associated with colorectal malignancy, predominantly of the right side. Moreover, 24 of 273 appendectomies (8.8%) exhibited the presence of mucosal hyperplasia and, of these, six (25%) also were associated with adenocarcinoma of the colon. On the basis of this significant rate of association, we feel that a concomitant colorectal carcinoma should be ruled out in patients who exhibit mucosal hyperplasia of the appendix.
Adenocarcinoma↗
Collision of transitional cell carcinoma and renal cell carcinoma. An immunohistochemical study and review of the literature.
A case characterized by a rare synchronous occurrence of transitional cell carcinoma (TCC) of the renal pelvis and renal cell carcinoma (RCC) in the same kidney is presented. A retrospective analysis of 23 similar cases reported in the English literature over the last 71 years demonstrated a male-to-female ratio of 2:1, an average age of 64.5 years, and a left-to-right-side ratio of 3.2:1. The three most common findings at initial examination were hematuria (90%), flank pain (19%), and flank mass (14%). Moreover, 24% of patients had tumor metastases even at initial examination. Thirty-four percent of patients had bladder neoplasms, and 24% of them had a history of cigarette smoking. There is no tendency toward higher grade of malignancy or specific histologic pattern for TCC and RCC when they occur together in the same kidney. Immunohistochemical studies were used to examine TCC and RCC, with special attention paid to the site of their collision, which displayed multifocal lymphatic permeation. Both TCC and RCC were positive for epithelial membrane antigen (EMA) and cytokeratins identified by monoclonal antibodies CAM-5.2, AE1/AE3, and MAK-6. TCC was focally positive for keratin, detectable by antibody 34 beta E12, but RCC was not. The tumor tissue infiltrating the lymphatics, which seemed to be RCC, demonstrated positive staining for EMA and keratins CAM-5.2, AE1/AE3, and MAK-6 and negative staining for keratin 34 beta E12. Interestingly, the tumor in lymphatics displayed strong staining for carcinoembryonic antigen (CEA) but both TCC and RCC in the vicinity were negative. These findings suggest that keratin 34 beta E12 may play a role in the differential diagnosis between TCC and RCC and that tumor-invading lymphatics may change phenotype, including the neoexpression of CEA.
Aged↗
Gastrointestinal neuroendocrine cell proliferations.
The gastrointestinal neuroendocrine cell proliferations are comprised of a few hyperplasias and various neoplasias. The better characterized hyperplasias include G-cell hyperplasia, either primary or secondary, enterochromaffin-like (ECL)-cell hyperplasias, generally secondary to hypergastrinemia, and EC-cell hyperplasias. The neoplasias include carcinoid tumors, demonstrating low malignancy and divided into foregut, midgut, and hindgut varieties, poorly differentiated neuroendocrine carcinomas resembling their pulmonary counterparts the "oat cell" carcinomas both in histological pattern and in their highly malignant behavior mixed endo-exocrine tumors, which in turn can be divided into composite tumors formed by a population of endocrine cells and a population of exocrine cells, and amphicrine tumors formed by a uniform population of cells with a mixture of endocrine and exocrine phenotypic traits. Although some of these mixed tumors show a degree of malignancy intermediate between the classical carcinoid and an adenocarcinoma, more information must be gathered to establish firm prognostic parameters for these relatively new entities.
Carcinoid Tumor↗
Tenascin is an important component of the glomerular extracellular matrix in normal and pathologic conditions.
Tenascin (TN), a large oligomeric glycoprotein, is a recently described component of the extracellular matrix (ECM). Previous reports focusing largely on the role of TN in nephrogenesis have documented the strong expression of TN in embryonic kidney tissue and implied an important role for TN in nephrogenesis. However, the expression of TN in normal and pathologic kidneys in adults has not been systematically evaluated. In this study immunohistochemical staining for TN was applied to 184 renal specimens diagnosed as: normal kidney (23 cases); minimal change disease and its variants (8); mesangial proliferative glomerulonephritis (GN) including IgA nephropathy and mesangial proliferative lupus nephritis (9); endocapillary proliferative GN including membranoproliferative GN, lupus nephritis, and post-infectious GN (25); crescentic GN (11); membranous GN (19); focal segmental sclerosis (15); thrombotic microangiopathy (8); amyloidosis (5); diabetic nephropathy (9); primary tubulointerstitial nephritis (14); transplant rejection (14); and ischemia (24). It was found that: (a) there was unequivocal global diffuse staining limited to the mesangium in normal kidney; (b) regardless of the etiologies and the morphologic types of glomerular disease, whenever there was expansion of the ECM, whether in the mesangial, endocapillary, or extracapillary spaces, there was a concomitant and proportional in situ increase in the TN staining; (c) globally sclerotic glomeruli, regardless of causes, showed diffuse, strong staining, especially in the subcapsular fibrous deposition seen in ischemic sclerosis; (d) non-sclerotic glomeruli showing early ischemic change uniformly displayed a marked decrease or complete loss of staining; (e) in cases of thrombotic microangiopathy, there was segmental or global staining of the capillary wall, probably corresponding to the enlarged lamina rara interna; (f) all nodular lesions in diabetic glomerulosclerosis showed strong staining, but in several of them this staining was much more pronounced in the periphery than in the center of the lesion. Our study proves that TN is probably a component of the normal mesangial matrix, that TN is an ubiquitous component of the expanded glomerular ECM in pathologic conditions regardless of morphologic subtypes, and that further studies on the cell types and mechanisms responsible for TN synthesis may provide a new venue for the understanding of the process of glomerular sclerosis.
Absorption↗
HAM56 antibody: a tool in the differential diagnosis between colorectal and gynecological malignancy.
HAM56, a monoclonal antibody first used to identify macrophages and endothelial cells, also stains many carcinomas (except those arising in the digestive tract). This property is useful in the differentiation between primary ovarian and metastatic colonic carcinomas in the ovary, or between gynecological (ovarian and endometrial) and colonic implants and lymph node metastases. This distinction is important as the prognoses of colorectal and gynecological malignancies differ significantly. Sixteen primary ovarian carcinomas (10 with peritoneal implants and 3 with lymph node metastases), eight cases of primary colonic carcinomas (four metastatic to ovary, four with peritoneal implants, and four with lymph node metastases), and three primary endometrial carcinomas, all with metastases to the ovary, were immunostained with the HAM56 antibody using the ABC immunoperoxidase technique. Linear membranous immunostaining was considered positive, whereas staining of mucin and debris was regarded as negative. Using these parameters, 15/16 ovarian primaries, 9/10 ovarian implants, 3/3 ovarian lymph node metastases, and 3/3 endometrial primaries and their ovarian metastases were positive. Colonic primaries, their ovarian metastases, peritoneal implants, and lymph node metastases were all negative. It is concluded that the HAM56 antibody is a useful tool in the distinction between colorectal and ovarian malignancies in those cases where the routine histological appearance may be ambiguous.
Adenocarcinoma↗
The value of the preoperative mucosal biopsy in the diagnosis of colorectal mucinous adenocarcinoma.
BACKGROUND: As a rule, mucinous colorectal adenocarcinomas tend to be at a more advanced stage at the time of discovery than their nonmucinous counterparts. This study assesses the potential value of the preoperative biopsy in the diagnosis of such mucinous adenocarcinomas. METHODS: The preoperative biopsy specimens and the corresponding resection specimens of 189 patients with colorectal carcinomas were examined and compared by conventional light microscopic study. The stage of the tumor, using the modified Dukes classification of Astler and Coller, was correlated with the percentage of mucinous component (MC) in the resection specimens. The MC in the preoperative biopsy was assessed by the presence of: (1) malignant-appearing glands disrupted by the presence of abundant extruded intraluminal mucin; (2) pools of mucin in the connective stroma of the adenocarcinoma; and (3) superficial pools of mucin containing ribbons or clusters of neoplastic epithelial cells. RESULTS: The presence of a significant (more than 25%) MC in the resection specimen correlated well with an advanced stage of the tumor; 82% of tumors with more than 25% MC were at the B2 or higher stage, compared with 64% of tumors with less than 25% MC (P < 0.05). Finding MC in the preoperative biopsy correlated well with a similar finding in the resection specimen and with a B2 or higher stage of the tumor in such specimens; 83% of MC-positive biopsy specimens exhibited more than 25% MC in the corresponding resection specimen, whereas only 10% of MC-negative biopsy specimens were associated with a surgical specimen containing more than 25% MC (P < 0.001). Similarly, 83% of such MC-positive biopsy specimens revealed a carcinoma at the B2 or higher stage upon resection, compared with 63% of the MC-negative biopsy specimens (P < 0.02). CONCLUSIONS: Colorectal adenocarcinomas showing MC in the preoperative biopsy are significantly more likely to reveal a high mucin content and to be at an advanced stage at resection. Thus, such preoperative findings should be recorded and made available on a prospective basis to the treating physicians.
Adenocarcinoma, Mucinous↗
Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic alpha cells. Evidence for two high affinity sulfonylurea receptors.
We tested for the presence of sulfonylurea receptors in pancreatic alpha cells. Two high affinity sulfonylurea receptors were identified in clonal pancreatic alpha cells (alpha TC-6): a 140-kDa species observed previously in clonal pancreatic beta cells (HIT) and a second 150-kDa protein. The dissociation constant (Kd) for both receptors is approximately 3.5 nM for an iodinated glyburide analog, 5-iodo-2-hydroxyglyburide. The estimated number of receptors (Bmax) increases approximately 2-fold, from 3.1 to 6.8 pmol/mg of membrane protein as the pH of the binding buffer is reduced from 7.5 to 6. Consistent with the notion that high affinity sulfonylurea receptors are integral components of the ATP-sensitive K+ channel, we demonstrated the presence of ATP-sensitive K+ channels in inside-out patches of alpha TC-6 cells. Whole cell K+ currents that activated with time showed inward rectification at positive potentials (above 0 mV) and were almost completely suppressed by 5 nM glyburide. Likewise, glyburide blocked 86Rb+ efflux from ATP-depleted alpha TC-6 cells, an effect that was reversed by 400 microM diazoxide. The presence of sulfonylurea receptors provides a mechanism by which sulfonylureas can directly modulate alpha cell function. The properties of the 150-kDa receptor and the role of ATP-sensitive K+ channels in alpha cells remain to be elucidated, but as in beta cells, ATP-sensitive K+ channels may be involved in metabolic regulation of alpha cells by glucose.
ATP-Binding Cassette Transporters↗
Prolonged achlorhydria and gastric neoplasia: is there a causal relationship?
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Achlorhydria↗
Antral G-cell and D-cell numbers in Helicobacter pylori infection: effect of H. pylori eradication.
BACKGROUND: It has recently been recognized that Helicobacter pylori infection is associated with abnormalities in the regulation of gastrin secretion. We investigated whether there was a relationship between H. pylori infection and G-cell and D-cell numbers. METHODS: The numbers of antral G cells and D cells were compared between 20 patients with duodenal ulcer and 24 volunteers, 12 with and 12 without H. pylori infection. The effect of eradication of H. pylori infection on G-cell number was also evaluated. Antral mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of gastrin and somatostatin. RESULTS: The number of G cells was significantly (P < 0.02) less in patients with duodenal ulcer than in either infected or uninfected controls (3.7 +/- 0.3 vs. 6.2 +/- 0.6 and 5.3 +/- 0.5 G cells per gland for infected and uninfected controls, respectively). The ratio of G-cells to D-cells was similar in duodenal ulcer patients (2.2) and uninfected controls (2.0). It was found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, it is not associated with a change in the numbers of antral G cells or D cells in patients with duodenal ulcer. CONCLUSIONS: It is concluded that H. pylori infection-associated increase in gastrin secretion appear to be related to local factors regulating G-cell function.
Cell Count↗
p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a follow-up study.
BACKGROUND: There is a significant interobserver and intraobserver variation in grading dysplasia in Barrett's metaplasia. New markers are needed to optimize the assessment of potential risk of cancer development in these patients. The aim of this study is to explore the use of p53 as a marker of neoplastic progression in Barrett's metaplasia. METHODS: Immunohistochemistry was used to study p53 protein accumulation in 114 specimens from 54 patients with Barrett's metaplasia. RESULTS: Positive staining was found in 0% of the cases negative for dysplasia, 9% of those with low-grade dysplasia, 55% of those with high-grade dysplasia, and 87% of those with adenocarcinoma. Follow-up was available on 24 patients. Two patients who showed low-grade dysplasia and who were positive for p53 on biopsy showed high-grade dysplasia in follow-up biopsies. Of 21 patients who had biopsy specimens negative of p53, only one showed high-grade dysplasia on subsequent biopsy specimens. CONCLUSIONS: Our data support the hypothesis that p53 plays an important role in the progression of Barrett's metaplasia to adenocarcinoma. The follow-up study indicates that positive immunostaining for p53 may be an objective marker of neoplastic progression in Barrett's metaplasia.
Adenocarcinoma↗
Tissue-specific expression of kallikrein family transgenes in mice and rats.
To define the regulatory strategy for the transcriptional control of the kallikrein multigene family, we analyzed the expression of several kallikrein/SV40 T-antigen (TAg) fusion genes in transgenic mice and rats. Kallikrein family members are normally expressed at a high level in the submandibular gland and are expressed in a wide range of tissues that vary among individual family members. A total of 1.7 kb of proximal 5'-flanking DNA from the tissue kallikrein gene (rKlk1) was sufficient to confer much of the correct tissue-specific pattern on a TAg reporter gene. TAg mRNA was detectable in tissues that normally express rKlk1 and TAg-induced tumors arose in brain and pancreas. However, absolute levels of transgene mRNA were very low relative to the expression of the normal endogenous tissue kallikrein gene. In particular, expression in the salivary glands, normally very high for endogenous rKlk1, was either low or absent. An intact rKlk1 transgene with extensive flanking DNA (4.5 kb 5' and 4.7 kb 3') and complete intragenic (4 kb) sequences was expressed similarly to the fusion transgene, demonstrating that regulatory elements necessary for comprehensively correct expression are not contained within these additional gene regions. Two additional kallikrein/SV40 fusion transgenes were derived from other family members, one from the rKlk2 gene, which encodes tonin, and another from the rKlk8 gene, which encodes a prostate kallikrein. Whereas the endogenous rKlk2 and rKlk8 genes normally are expressed at high levels in rat salivary glands, they were not expressed in the salivary glands as transgenes. The results for these transgenes of three different family members indicate that control elements that direct the particular nonsalivary gland expression pattern characteristic of each family member may be present within the proximal 5'-flanking region of each gene, whereas regulatory sequences necessary for normal levels of expression in these tissues and for maximal salivary gland expression are not. We propose that the gene-associated regulatory sequences are complemented by a dominant control region that imposes salivary gland expression on the extended kallikrein family locus.
Animals↗
Anatomic contribution to differences in rabbit colonic muscle contraction.
The aim of this study was to determine if differences in the force of contraction in different regions of the rabbit colon are associated with variations in the histology of the corresponding muscle tissues. Circular and longitudinal muscles were isolated from strips of proximal and distal colonic muscle. Muscle strips stretched to L0 were either stimulated to contract or were processed for electron microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a larger perimeter (P less than 0.001) and were surrounded by increased extracellular matrix (28% of the standardized box) compared with the muscle cells from the other sites in the colon (7%-13%) (P less than 0.001). Cross-sections of the proximal circular muscle cells had a smaller perimeter and were present in a greater number than the cells from other areas of the colon. The distal circular muscle generated a larger force than the other muscles after stimulation with bethanechol or K+ (P less than 0.05). The taenia developed less force than the other muscles (P less than 0.05). Bethanechol was a less potent stimulant for the longitudinal muscles than for the circular muscles (P less than 0.05). This study suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the taenia coli is caused in part by the smaller number of cells that are available to contract and (2) the increased efficacy for the stimulation of the distal circular muscle compared with the proximal circular muscle is unrelated to the mass of muscle and seems to be related to an inherent property of the muscle.
Animals↗
Cytokeratin immunohistochemistry as a diagnostic tool for distinguishing malignant from benign epithelial lesions of the prostate.
The basal cell layer (BCL) is believed to be absent in malignant but present in nonmalignant epithelial lesions of the prostate. Using the avidin-biotin-peroxidase complex (ABC) immunoperoxidase method, we examined the value of the monoclonal antibody cocktail MA-903, which stains selectively the prostatic BCL layer, in the distinction between benign and malignant epithelial lesions of the prostate. We immunostained histologic sections of 63 prostates, containing 235 morphologic appearances: normal prostate glands, 43; benign prostate hyperplasia (BPH), 59; basal cell hyperplasia (BCH), 24; adenosis, seven; prostatic intraductal neoplasia (PIN 1), 21; PIN 2, 25; PIN 3, 16; and cancer, 40. Some degree (continuous, continuous with focal disruption, and disrupted patterns) of basal cell staining was demonstrable in all normal and BPH, BCH, and PIN 1 lesions, but was absent in 39 of 40 cancers. However, not every gland in benign lesions stained positively. Further, two of 25 PIN 2 and six of 16 PIN 3 lesions failed to reveal BCL. Our results suggest that the presence or absence of BCL, predicated on cytokeratin MA-903 immunoreactivity, may be a useful indicator in the distinction between benign and malignant epithelial lesions of the prostate.
Antibodies, Monoclonal↗
Neuroendocrine cells of the gut and their disorders.
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Digestive System↗
Immunohistochemical localization of relaxin in human prostate.
We identified relaxin in human male prostate by use of an anti-human relaxin analogue polyclonal antibody and the avidin-biotin-immunoperoxidase method. The antibody was obtained by immunizing a rabbit with a synthetic human relaxin analogue which has 95% sequence homology with native human relaxin. Human prostate tissues incubated with the anti-human relaxin analogue exhibited positive immunostaining up to an antibody dilution of 1:3200. Inhibition of immunostaining with this antibody by excess relaxin analogue demonstrated specificity of the antibody. The exact role of relaxin in human male reproductive physiology remains to be fully elucidated.
Humans↗