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H J Freeman

Publications and source records attributed to H J Freeman.

At least 73 records · Page 4Linked to original sources

Age-related changes in sodium-dependent glucose transport in rat small intestine.

Brush-border membrane vesicles were purified from jejunoileal segments of rats ranging from 3 to 156 wk. The kinetics of sodium-dependent glucose cotransport were studied under voltage-clamped, zero trans conditions over a wide range of cis-glucose concentrations (0.005-1.5 mM). Initial glucose uptake in brush-border membrane vesicles isolated from the proximal intestinal segment (50 cm from ligament of Treitz) of rats less than 7-8 wk of age demonstrated a distinct curvilinear Hofstee plot consistent with multiple-transport mechanisms. One system possessed an apparent Vmax of 10.6 +/- 0.5 nmol X mg prot-1 X min-1 and Km of 630 +/- 18 microM. The second system was characterized by Vmax of 0.9 +/- 0.1 nmol X mg prot-1 X min-1 and Km of 12 +/- 1 microM. In contrast, the distal segment (50 cm to end of small intestine) possessed only one sodium-dependent glucose carrier system. The apparent Vmax and Km were 1.11 +/- 0.20 nmol X mg protein-1 X min-1 and 49 +/- 7 microM, respectively. Sodium-activation curves in the presence of 0.3 and 0.03 mM glucose were consistent with more than one sodium ion with both systems. In contrast, rats 12-13 wk old and older possessed both sodium-dependent transport systems in the proximal early and distal small intestine. The high-capacity system is more abundant in the proximal than the distal segment. These data suggest that, under these specific conditions, there are two sodium-dependent glucose carriers in the intestine of young rats: one located in the jejunum characterized by high capacity and low affinity, and the second located throughout the jejunoileum characterized by low capacity and high affinity. Furthermore with age there is a development of the low-affinity system in the distal segments so that both systems are found along the length of the jejunum and ileum. Accordingly, serial and parallel heterogeneity of sodium-dependent glucose transport exists along the small intestine.

Aging↗

Effects of differing purified cellulose, pectin, and hemicellulose fiber diets on fecal enzymes in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

The fecal microflora enzymes, beta-glucuronidase and beta-glucosidase, as well as fecal bacterial counts, were examined during colon carcinogenesis in rats administered parenteral 1,2-dimethylhydrazine and fed nutritionally equivalent diets free of fiber or containing one of three single sources of dietary fiber (cellulose, hemicellulose, and pectin). Whereas pectin-fed animals had increased fecal beta-glucuronidase activities, those fed cellulose and hemicellulose, two fibers protective in dimethylhydrazine colon neoplasia, had decreased activities. Although fecal bacterial counts were not significantly changed, similar differential changes in fecal beta-glucosidase activity were noted: cellulose but not pectin or hemicellulose feeding was associated with reduced activity. Although cellulose fiber may cause differing physiological effects resulting in a reduction in colonic neoplasia development in this experimental animal model, decreased bacterial metabolic enzyme activation of carcinogens or cocarcinogens may lead to diminished exposure of colonic cells to exogenous or endogenous mutagens.

Animals↗

Regulatory peptides in Barrett's oesophagus.

Barrett's epithelium refers to the presence of ectopic mucosal types in the squamous-lined oesophagus. Previous studies have documented argentaffin and argyrophil-positive cells as well as gastrin-like immunoreactivity in oesophageal tissue extracts from patients with Barrett's mucosa. In the present study, 125 oesophageal biopsies obtained under direct vision at endoscopy from 22 patients with Barrett's oesophagus were systematically studied using fluorescence and peroxidase antiperoxidase single and double-staining immunocytochemical methods employing highly specific antibodies to localize the following peptide-containing cell types in Barrett's mucosa: gastrin, somatostatin, gastric inhibitory polypeptide, motilin, neurotensin and pancreatic glucagon. In addition, EC cells were localized using a cytochemical silver staining method. The results of this study indicate that EC cells and gastrin- and somatostatin-containing endocrine cells are detectable in Barrett's epithelium.

Adolescent↗

Effect of high hemicellulose corn bran in 1,2-dimethylhydrazine-induced rat intestinal neoplasia.

The incidence, distribution, size and histopathology of colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed a chemically-defined fiber-free diet or a diet containing 4.5% refined high hemicellulose corn bran with equivalent ratios of calories derived from fat, protein and carbohydrate. At an initial sacrifice period, reduced numbers of tumors were observed; however, at a later time period, no statistical differences were present compared to the fiber-free diet group. This study indicates that a high hemicellulose fiber source is protective in this animal model of experimental colonic neoplasia but this appears to reflect only a time-dependent delay in tumor detection or appearance.

1,2-Dimethylhydrazine↗

A quantitative study of enteric endocrine cells in celiac sprue.

A quantitative morphological investigation of eight endocrine cell types in mucosal biopsies from adults with untreated celiac sprue was undertaken. The quantitative data expressed as cells per millimeter of epithelium most accurately reflected the changes seen in celiac disease, as it takes into account changes in mucosal thickness due to the absence of villi in celiac biopsies. The results showed significant increases in the number of cholecystokinin and enterochromaffin cells, a significant decrease in somatostatin, gastric inhibitory polypeptide and secretin cells, and no change in the motilin, gastrin, and glicentin cells. Significant changes in cell size (cross-sectional area) were also demonstrated in the somatostatin and gastrin cells which were smaller in the celiac biopsies.

Adult↗

Amino acid and dipeptide absorption in rats fed chemically defined diets of differing fiber composition.

In rats chronically fed a fiber-free diet or one of the three nutritionally equivalent fiber-containing diets, in vivo jejunal absorption of L-leucine from a free amino acid mixture of L-leucine and glycine as well as equimolar solutions of the dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. In addition, total and brush border amino peptidase activities for the two dipeptide substrates were examined in small bowel segments. With two of three fiber diet groups, absorption of L-leucine from the free amino acid solution was reduced without a detectable change in peptide transport or aminopeptidase activities. This investigation provides evidence that peptide transport mechanisms are relatively spared with long-term feeding of fiber-containing diets similar to observations recorded in disease states associated with protein-energy malnutrition.

Amino Acids↗

Cytomegalovirus hepatitis: evidence for direct hepatic viral infection using monoclonal antibodies.

Cytomegalovirus-induced hepatitis presented as acute right upper quadrant pain with a cholestatic profile in a middle-aged woman. The presentation was confused by the presence of gallstones. Her course was complicated by pleuritis, atypical lymphocytosis, lymphadenopathy, and transient arthritis. Urine virus cultures grew cytomegalovirus and seroconversion of indirect immunofluorescent antibody to late cytomegalovirus antigen was demonstrated. Biopsies of the patient's liver failed to grow cytomegalovirus or to show viral inclusions. Electron micrographic studies were negative. Biopsy specimens were stained with monoclonal antibodies to cytomegalovirus by an indirect fluorescence technique. Clearly defined inclusions were specifically stained. Both nuclear and cytoplasmic inclusions were demonstrated using monoclonal antibodies CH16 and CH12, respectively. Insofar as we are aware, this is the first reported direct evidence for hepatic viral infection with this virus in a previously healthy adult.

Antibodies, Monoclonal↗

Crohn's disease: emerging pathologic and bacterial spectrum.

The evolution, in recent years, of concepts of inflammatory bowel disease in part reflect improved methods of defining disease, especially with modern microbiologic methods, endoscopy and mucosal biopsy. Although clinicians have focused on idiopathic ulcerative colitis and Crohn's disease, a host of new entities are now becoming recognized. Many of these are bacterial, such as Yersinia- or Campylobacter-associated enterocolitis. Thus, a "new" group of inflammatory bowel diseases has recently emerged, some with newly described pathologic features and others reflecting improved methods of detection with newer microbiologic methods. With evolving methods of recognition, other entities will likely be described as causes of inflammatory bowel disease.

Bacterial Infections↗

Differential effects of surgical suture materials in 1,2-dimethylhydrazine-induced rat intestinal neoplasia.

The incidence, distribution, size, and histopathology of rat small and large bowel tumors induced by sequential administration of 1,2-dimethylhydrazine followed by cecal placement of one of six differing types of suture materials were systematically examined. In addition, measurements of beta-glucuronidase activities in large bowel contents followed by fecal trace metal determinations were done. The results indicate that specific slowly absorbed and nonabsorbable suture materials in the absence of a surgical anastomosis promote tumor induction locally in the rat cecum. In addition, cecal suture material composed of multifilament stainless steel wire enhanced tumor development at a "downstream" site in the distal colon, paralleling increased fecal beta-glucuronidase activities at this site and implicating a possible luminally mediated mechanism for colon tumor development in this animal model.

Animals↗

Intestinal assimilation of a proline-containing tetrapeptide. Role of a brush border membrane postproline dipeptidyl aminopeptidase IV.

The mechanism of hydrolysis and absorption of a proline-containing tetrapeptide, Leu-Pro-Gly-Gly (10 mM) by rat intestine was examined in vivo by using jejunal perfusion methods. The peptide substrate and hydrolysis products were analyzed by use of an automated amino acid analyzer. Leucine, proline, and glycine were absorbed by the intestine at a significantly higher rate from the tetrapeptide than from an equivalent amino acid mixture. The analysis of the hydrolytic products in the lumen during in vivo perfusion of the tetrapeptide showed that two dipeptides, Leu-Pro and Gly-Gly, were the major products. These two dipeptides were also the major hydrolytic products when a purified rat intestinal brush border membrane preparation was incubated with Leu-Pro-Gly-Gly. The rate of hydrolysis of the tetrapeptide was much higher than that for several other proline-containing peptides (Leu-Pro, Pro-Leu, and Pro-Gly-Gly) that were tested. Studies using Gly-Pro-beta-naphthylamide, a specific substrate for postproline dipeptidyl aminopeptidase IV, showed that this enzyme is mainly localized to the brush border membrane and is responsible for the hydrolysis of the tetrapeptide into the two dipeptides Leu-Pro and Gly-Gly. Thus, brush border membrane dipeptidyl aminopeptidase IV very likely plays an important role at the intestinal mucosal cell surface in the final stages of digestion of proline-containing peptides.

Animals↗

Lectin histochemistry of 1,2-dimethylhydrazine-induced rat colon neoplasia.

Lectins linked to fluorescein were used as carbohydrate probes to examine the goblet cell mucin and epithelial cell surface glycoconjugate alterations in an experimental rodent model of colonic neoplasia induced with parenteral 1,2-dimethylhydrazine dihydrochloride. Lectins derived from Triticum vulgare (WGA), Ricinus communis (RCA1), and Limulus polyphemus (LPA) showed reduced labeling of goblet cell mucin in these tumors, while binding with peanut lectin from Arachis hypogaea (PNA), a lectin ordinarily failing to bind to mucin in normal colon, was positive. In addition, RCA1 and LPA showed increased cell surface labeling of neoplastic epithelial cells. Finally, alterations were observed in lectin binding to "transitional" colonic mucosa adjacent to colonic tumors from carcinogen-treated rats. These findings indicate that significant alterations in both membrane and mucin glycoconjugates occur in colonic tumors and mucosa adjacent to tumors in a chemically induced experimental animal model of human colon cancer.

1,2-Dimethylhydrazine↗

Effects of purified cellulose and pectin fiber diets on mutagenicity of feces and luminal contents of stomach, small and large bowel in rats.

The mutagenicity in extracts of fecal pellets and luminal contents obtained from specific sites along the gastrointestinal tract was examined in male Wistar rats fed a chemically-defined fiber-free diet or nutritionally and calorically equivalent diets containing different amounts of either cellulose or pectin (4.5 or 9.0%) or a mixture of cellulose and pectin (4.5% each). Mutagenicity was measured with the fluctuation test for weak mutagens using Salmonella typhimurium strains TA98 and TA1535 as test organisms. Dietary fiber reduced the mutagenicity of fecal pellets from most of the animals. However, given the number of animals studied, the reduction was only significant for the 9.0% pectin diet (TA98), the 9.0% cellulose diet (TA1535) and the mixed fiber diet (TA1535). Analysis of the contents of stomach, distal small bowel, cecum and colon after a period of 8 weeks on a fiber-free diet revealed that the distal small bowel content had a mutagen concentration that was several times that at any other site. The mutagenicity of the small bowel content of animals on diets containing either 9.0% cellulose or 9.0% pectin was significantly lower than that of animals on a fiber-free diet, as assayed by either of the test strains of S. typhimurium. A similar reduction was detected in animals on the 4.5% cellulose or 4.5% pectin diet by test strain TA1535, but a diet containing a mixture of the same fiber polymers did not reduce the mutagenicity of the small bowel content. The mutagenicity of the contents of the stomach, cecum and colon was not significantly influenced by dietary fiber.

Animals↗

Effects of small bowel transection, resection, or bypass in 1,2-dimethylhydrazine-induced rat intestinal neoplasia.

The incidence, distribution, size, and histopathology of rat small and large bowel tumors induced by sequential administration of 1,2-dimethylhydrazine followed by either small bowel resection, 50% jejunoileal resection, or 50% jejunoileal bypass were examined in addition to measurements of transit times and beta-glucuronidase activities in large bowel contents. The results indicate that even limited small bowel resection or bypass promotes intestinal neoplasia, particularly in the large bowel, and this effect seems independent of the chronic injury imposed by suture lines. Although no differences in transit times were observed, increased beta-glucuronidase activities in both cecum and distal colon of resected but not bypassed rats was detected. Moreover, an apparent subsite redistribution of small bowel tumors to ileum and large bowel tumors to more proximal colon in bypassed rats suggests that the mechanisms involved for tumor enhancement differ substantially from those in resected rats.

1,2-Dimethylhydrazine↗