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Biomedical subjects

I M Samloff

Publications and source records attributed to I M Samloff.

At least 55 records · Page 3Linked to original sources
PubMed1988

Differential expression of pepsinogen isozymogens in a patient with Barrett esophagus.

The pepsinogen A (PGA) isozymogens in the gastric mucosa and Barrett epithelium of a female patient with Barrett esophagus were studied on different occasions during a 3-year period by electrophoretic analysis of in vivo steady-state pepsinogen in biopsies by activity staining in combination with variant specific monoclonal antibodies and of de novo synthesized pepsinogen by autoradiography. In Barrett epithelium only one (Pg3) or two (Pg3 and Pg5) primary PGA gene products were detected, whereas in gastric mucosal biopsies three (Pg3, Pg4 and Pg5) primary gene products were demonstrated on all occasions. These differences strongly suggest differential expression/activation of individual gene numbers in the PGA gene cluster in Barrett esophagus and are in line with the preneoplastic nature of this condition. The mechanism behind this deregulation is currently under investigation by cell biology and molecular genetic techniques.

Aged↗
PubMed1988

Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels.

Malabsorption of food-bound or protein-bound cobalamin with normal absorption of free cobalamin has been described in studies of patients with gastric dysfunction. We used the egg-yolk cobalamin absorption test to study 47 patients selected not because of known gastric disorders but because they had low serum cobalamin levels with normal Schilling test results. Their egg test results were significantly lower than in normal controls, while Schilling test results were normal. Twenty of the subjects had egg test excretion below 1.5%. No features distinguished them from the 27 who excreted more than 1.5% other than the presence of lower pepsinogen I:II ratios. Eight of 19 tested patients with food cobalamin malabsorption had no evidence of abnormal gastric status by blood tests and/or gastric analysis. Also noteworthy was the finding of food cobalamin malabsorption in 60% of tested patients who had neurologic, cerebral, or psychiatric abnormalities. Food cobalamin malabsorption appears to be associated frequently with otherwise unexplained low cobalamin levels. Low cobalamin levels in patients with normal Schilling test results cannot be dismissed as insignificant without also testing for food cobalamin malabsorption, whether or not the patients have known gastric dysfunction.

Adult↗
PubMed1987

Serum pepsinogens I and II and stomach cancer.

Prospective epidemiologic studies among Hawaiian Japanese men have shown that a serum pepsinogen I (PG I) level below 20 ng/ml is highly specific for extensive intestinal metaplasia of the stomach and for the intestinal type of stomach cancer. The test, however, shows a low level of sensitivity as a predictor of the intestinal type stomach cancer. Since antralization of the corpus, as encountered in Type A atrophic gastritis and late stage Type B gastritis, results in an increase of PG II relative to PG I, we examined the sensitivity and specificity of the PG I/PG II ratio as a predictor of gastric cancer. Using a cut-off point of 2.0 in the ratio to separate subjects at high and low risk for stomach cancer, we found a modest improvement in the level of sensitivity with a small decrease in specificity. Abnormally low PG I levels and PG I/PG II ratios were associated mainly with advanced stages of the intestinal type of cancer and therefore, are not useful screening tests to identify early cases of gastric cancer. The use of the PG I/PG II ratio resulted in a modest improvement in the level of sensitivity with a small decrease in specificity.

Humans↗
PubMed1987

Subcellular localization of pepsinogen II in stomach and duodenum by the immunogold technique.

We have determined the ultrastructural localization of pepsinogen II (PG II) in aldehyde-osmium fixed, resin-embedded ultrathin sections of human gastric fundic and pyloric gland mucosa and duodenum using the protein A immunogold technique and antiserum specific for PG II. Chief cells contained homogeneous, finely granular secretory granules that were uniformly PG II-positive. In contrast, mucous neck, pyloric gland, and Brunner's gland cells contained secretory granules consisting of an eccentrically placed dense core surrounded by a clear matrix; PG II immunoreactivity was concentrated over the dense core of these biphasic granules. Pyloric gland cells also contained monophasic secretory granules having the same electron density, texture, and PG II immunoreactivity as the nucleoids of biphasic granules and clear vesicular granules that were PG II-negative. Vesicular granules also were found in Brunner's gland cells. The Golgi region of pyloric gland cells contained small PG II-positive monophasic granules adjacent to small PG II-negative vesicular granules. This observation suggests that biphasic granules may form in the Golgi region of pyloric gland cells by fusion of PG II-containing monophasic granules and PG II-unreactive vesicular granules.

Brunner Glands↗
PubMed1987

Immunochemical, electrophoretic, and genetic heterogeneity of pepsinogen I. Characterization with monoclonal antibodies.

Two immunologic subclasses of human pepsinogen I alpha-PG I and beta-PG I, have been identified based on their reactivity toward a murine monoclonal antibody that recognizes an epitope on the alpha-PG I isozymogens. The antibody was used to purify the major alpha- and beta-isozymogens from gastric mucosa and to determine their contributions to the previously described genetic polymorphism of PG I. The alpha-epitope was localized to the pepsin region of the molecules. The two major alpha-PG I isozymogens (Pg 3 alpha and Pg 5 alpha) and the major beta-PG I isozymogen (Pg 4 beta) were demonstrated to contain net charge differences located in the respective pepsin and activation peptide regions. We propose that the alpha- and beta-subclasses contain net charge amino acid substitutions encoded by the corresponding pepsinogen genes: PGA3, PGA4, and PGA5.

Amino Acid Sequence↗
PubMed1987

Atrophic gastritis and vitamin C status in two towns with different stomach cancer death-rates.

A survey was conducted of 513 men aged 65 74 years living in two British towns with high and low stomach cancer death-rates. The prevalence of severe atrophic gastritis (defined as a serum pepsinogen I less than 20 micrograms l-1) was significantly higher in the high-risk than in the low-risk town (14.5% and 7.7% respectively); it also tended to be higher in the manual workers, who are known to have a greater risk of stomach cancer than non-manual workers. The manual workers in the high-risk town were particularly likely to have had a partial gastrectomy. Plasma ascorbate concentration and fruit intake were lower in the high-risk area and lower social classes, suggesting a poorer vitamin C status. There was, however, no direct relationship between ascorbate concentration and the presence of severe atrophic gastritis. These findings are consistent with the hypothesis that risk of stomach cancer is determined in two stages--a long-term effect, producing atrophic gastritis; and a short-term effect in which vitamin C is protective.

Aged↗
PubMed1987

Pepsinogens, pepsins, and peptic ulcer.

The role of pepsin in the pathogenesis of peptic ulcer has been the subject of intense study and debate for many years. Two difficulties inherent in distinguishing between the role of acid alone vs acid and pepsin are that a) acid-containing gastric juice always contains pepsin, and, b) that hydrogen ion concentration (pH) is a major determinant of the activity of pepsin. However, studies in animal models of peptic ulcer indicate clearly that pepsin, in combination with acid, produces much more severe and more extensive mucosal damage than acid alone. Recent interest in pepsin and its precursor, pepsinogen, has stemmed from the finding that each is remarkably heterogeneous, and that the heterogeneity has a genetic basis. Results of studies using radioimmunoassays specific for the 2 major forms of pepsinogen, pepsinogen I and pepsinogen II, have shown that serum levels of pepsinogen I and pepsinogen II, and the ratio of pepsinogen I to pepsinogen II, can be used as noninvasive probes of gastric mucosal structure and function, indicators of the genetics and heterogeneity of duodenal ulcer, and as markers of increased risk for duodenal ulcer and gastric ulcer.

Duodenal Ulcer↗
PubMed1987

Slow moving proteinase. Isolation, characterization, and immunohistochemical localization in gastric mucosa.

Human gastric mucosa contains three immunochemically distinguishable aspartic proteinases, pepsinogen I (pepsinogen A), pepsinogen II (pepsinogen C, progastricsin), and a nonpepsinogen proteinase also termed slow moving proteinase (SMP). The properties of SMP, and in particular its relationship to another aspartic proteinase, cathepsin D, were examined in this study. Slow moving proteinase and cathepsin D were isolated, respectively, from gastric mucosa and human spleen. Antiserum specific to each proteinase was prepared in rabbits. Rabbit anti-SMP did not recognize cathepsin D, and conversely, anticathepsin D did not react with SMP. Immunohistochemical studies localized SMP to surface epithelial cells in both the fundic and pyloric gland areas of the stomach. In contrast, cathepsin D was found mainly in mononuclear cells in the lamina propria and in parietal cells. Slow moving proteinase exhibited considerably lower Km values for its interaction with two chromogenic substrates than did cathepsin D. An even greater distinction between the two enzymes was found with the protein inhibitor from Ascaris lumbricoides; the activity of SMP was inhibited very strongly, whereas that of cathepsin D was not affected. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions, SMP consisted of two subunits with apparent molecular weights of 42,500 and 41,000. The last two properties characterize a less-well-known aspartic proteinase, cathepsin E. We conclude that SMP is not cathepsin D, but that it may be cathepsin E.

Cathepsin D↗
PubMed1986

Folic acid malabsorption in atrophic gastritis. Possible compensation by bacterial folate synthesis.

Folic acid absorption was studied in 12 elderly subjects with atrophic gastritis and 10 elderly normal controls using tritium-labeled pteroylmonoglutamic acid. Two folic acid absorption tests were carried out on each subject with 120 ml of either water or 0.1 N HCl. Folic acid absorption was significantly lower in subjects with atrophic gastritis than in normal controls (31% vs. 51%, respectively; p less than 0.01). In subjects with atrophic gastritis, folic acid absorption rose significantly to 54% (p less than 0.001) when administered with acid, but did not change in normal controls (50%). Serum folate levels were normal in all subjects. Proximal small intestinal pH was higher in atrophic gastritis subjects than in normal controls (7.1 vs. 6.7, respectively; p less than 0.05), as were bacterial counts of small intestinal fluid (p less than 0.01). Bacteria cultured from the aspirates of subjects with atrophic gastritis were able to synthesize folate in vitro when incubated in a folate-free medium. Atrophic gastritis results in folic acid malabsorption but not in folate deficiency, possibly due to increased bacterial synthesis of folate in the small intestine.

Aged↗
PubMed1986

Elevated serum pepsinogen I and II levels differ as risk factors for duodenal ulcer and gastric ulcer.

We investigated the possibility that serum pepsinogen I (PG I) and pepsinogen II (PG II) levels might differ as risk factors for duodenal ulcer and gastric ulcer. From 1967 to 1970, serum was obtained from 7498 Japanese men in Hawaii, and the cohort was followed up to 1981 for the development of peptic ulcer disease. Pepsinogen I and PG II levels in stored serum were significantly higher in the subjects who developed duodenal ulcer (n = 43) or gastric ulcer (n = 115) than in 212 control subjects. The linear trend in risk of each type of ulcer was highly significant for both PG I and PG II. An elevated serum PG I level (greater than or equal to 130 micrograms/L), however, was associated with about a threefold higher odds ratio for duodenal ulcer than for gastric ulcer (8.37 vs. 2.83), whereas an elevated PG II level (greater than or equal to 30 micrograms/L) was associated with about a threefold higher odds ratio for gastric ulcer than for duodenal ulcer (18.21 vs. 6.49). In contrast, the PG I/PG II ratio was significantly lower in the gastric ulcer than in the control and duodenal ulcer cases, and showed a significant linear trend in risk only for gastric ulcer. In addition, a PG I/PG II ratio of less than 4.0, which has been shown previously to be indicative of chronic gastritis, was associated with an almost 10-fold higher odds ratio for gastric ulcer than for duodenal ulcer (7.35 vs. 0.79). The results indicate that an elevated serum PG I level is a major risk factor for duodenal ulcer, whereas an elevated serum PG II level and a low PG I/PG II ratio are major risk factors for gastric ulcer.

Adult↗
PubMed1986

Differential distribution of pepsinogen II between the zones of the human prostate and the seminal vesicle.

Pepsinogen II (PG II) is a gastric proenzyme which has previously been found in both human seminal fluid and the prostate gland. However, no regional distribution of PG II has been noted within the prostate nor has it been found in the seminal vesicle. Bouins-fixed sections of central zone, peripheral zone and seminal vesicle, taken from 10 prostates removed at radical prostatectomy or cystectomy, were exposed to antibody against PG II and stained using the A-B-C immunoperoxidase technique. Formalin-fixed tissue from autopsy prostates of four men in the third decade, and six cases with BPH nodules, were also examined for PG II activity. In nine of 10 seminal vesicles, and seven of 10 central zone samples, more than 50 per cent of the cells stained positive for PG II. By contrast, in nine of 10 peripheral zone samples staining was present in five per cent or less of the epithelial cells. Similarly, PG II activity in the four autopsy prostates occurred almost entirely within the central zone and ended abruptly at the boundary between the peripheral and central zones. BPH nodules contained no PG II activity. These findings provide the first evidence that the central and peripheral zones may serve different biological functions. Embryologically it is currently thought that the prostate is of endodermal origin and the seminal vesicle of mesodermal origin. The presence of large amounts of PG II in both the seminal vesicle and central zone lends support to the hypothesis of a common mesodermal origin for these two structures.

Aged↗
PubMed1986

Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators.

The ratio of pepsinogen I to pepsinogen II in the circulation decreases progressively with increasing severity of atrophic gastritis of the fundic gland mucosa. Fasting blood was obtained from 359 free-living and institutionalized elderly people (age range, 60 to 99 years). A pepsinogen I/pepsinogen II ratio less than 2.9, indicating atrophic gastritis, was found in 113 (31.5%) subjects. The prevalence of atrophic gastritis increased significantly with advancing age (P less than .05). Within the atrophic gastritis group, 84 had a pepsinogen I level greater than or equal to 20 micrograms/L, indicating mild to moderate atrophic gastritis, and 29 had a pepsinogen I level less than 20 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. A significant increase in the prevalences of elevated serum gastrin levels (P less than .005), low serum vitamin B12 levels (P less than .005), circulating intrinsic factor antibody (P less than .005), and anemia (P less than .025) was observed with stepwise increases in severity of atrophic gastritis. Subjects with atrophic gastritis exhibited a lower mean serum vitamin B12 level (P less than .05) and a higher mean folate level (P less than .05), but no difference was detected in mean hemoglobin levels or serum levels of iron, ferritin, retinol or alpha-tocopherol. It is concluded that serum pepsinogen I and pepsinogen II levels can be used to determine the prevalence and severity of atrophic gastritis, that atrophic gastritis is common in an elderly population, and that atrophic gastritis is associated with vitamin B12 deficiency and anemia. Further, higher folate levels in atrophic gastritis may be related to an accumulation of 5-methyl tetrahydrofolate in serum due to vitamin B12 deficiency and/or greater folate synthesis by the intestinal flora resulting from bacterial overgrowth secondary to hypo- or achlorhydria.

Aged↗
PubMed1986

Relationships between the human pepsinogen DNA and protein polymorphisms.

Pepsinogens (PGA) are the inactive precursors of pepsin, the major acid protease found in the stomach. The PGA gene family exhibits polymorphic variation in human populations that can either be demonstrated by electrophoretic analysis of the proteins or by analysis of the respective genes with cDNA probes. Here, we describe the interrelationships between the most common pepsinogen protein phenotypes and the corresponding pepsinogen haplotypes (A, B, and C) containing different combinations of the PGA3, PGA4, and PGA5 genes. We propose that this unusual genetic variation involving haplotypes that contain three, two, and one genes, respectively, is the result of molecular evolution by gene duplication.

Chromosomes, Human, 6-12 and X↗
PubMed1985

Inhibition of peptic activity by sucralfate.

It is known that antacids containing aluminum hydroxide inhibit peptic activity by raising intragastric pH and by adsorbing pepsin. Since sucralfate contains aluminum hydroxide moieties, the possibility that this drug might inhibit peptic activity by these same mechanisms was examined. Sucralfate was incubated at a concentration of 10 mg/ml with samples of human gastric juice having pH values between 1.5 and 4 for 30 minutes at 37 degrees C. The proteolytic activity of the supernatant was then determined at a pH of 2.2 against a bovine hemoglobin substrate. When the initial pH of the gastric juice sample was 1.5, sucralfate was converted to a viscous gel and the pH of the incubation mixture rose to 2.9. However, there was no decrease in the peptic activity of the supernatant. In contrast, when the pH of the gastric juice sample was more than 2, the drug remained in suspension, but there was a graded rise in pH to a maximum of 4.1 and a progressive decrease in peptic activity (determined at a pH of 2.2) to a nadir of 65 percent of the control value. However, because peptic activity declines rapidly at a pH of more than 3, peptic activity at the ambient pH of the samples was reduced to only 25 percent of the control value. The results indicate that at pH values of more than 2, sucralfate inhibits peptic activity by both adsorbing pepsin and buffering hydrogen ions.

Adsorption↗
PubMed1985

Comparison of tri-potassium di-citrato bismuthate tablets with ranitidine in healing and relapse of duodenal ulcers.

120 patients were randomly allocated to receive ranitidine 150 mg twice daily or a tri-potassium di-citrato bismuthate (TDB) tablet four times a day in a trial comparing the effects of these drugs in the short-term healing and post-healing relapse rates of duodenal ulceration. At 4 weeks 81% of those on ranitidine and 90% of those on TDB had healed ulcer craters. At 8 weeks 97% of those on ranitidine and 97% of those on TDB had healed. These differences are not significant. After ulcer healing, the cumulative rates of relapse, as determined endoscopically, for symptomatic and symptomless ulcers were 74% for ranitidine and 41% for TDB at 4 months (p less than 0.001), 87% for ranitidine and 55% for TDB at 8 months (p less than 0.001), and 89% for ranitidine and 62% for TDB at 12 months (p less than 0.001). Females had significantly lower relapse rates than males. In the ranitidine group smokers had a higher rate of early relapse and failure to remain healed at 12 months than did non-smokers; no such difference occurred in the TDB-treated group.

Adult↗
PubMed1985

Serum pepsinogens I and II and gastric mucosal histology after partial gastrectomy.

We determined the effect of postgastrectomy gastritis on serum pepsinogen I and pepsinogen II concentrations in 108 subjects with subtotal gastric resection. Eleven had normal remnant mucosa, 22 had superficial gastritis, and 75 had atrophic gastritis. In the subjects with superficial gastritis, serum pepsinogen I and II concentrations were significantly higher than in those with normal remnant mucosa, but the ratio of pepsinogen I to II did not differ from normal. In atrophic gastritis, serum pepsinogen I concentrations fell with increasing severity of mucosal damage, but pepsinogen II was persistently raised. Consequently, the ratio of pepsinogen I to II in subjects with atrophic gastritis was significantly lower than in those with superficial gastritis or normal remnant mucosa. Discriminant function analysis revealed that the ratio of pepsinogen I to II, in combination with the absolute level of pepsinogen II, had a sensitivity of 80%, a specificity of 73%, and a positive predictive value of 87% for atrophic gastritis in this population. We propose that the parallel increase in serum pepsinogen I and II concentrations in postgastrectomy superficial gastritis is because of an increased rate of endocrine release of both zymogens from the fundic glands, and that the dichotomy in pepsinogen I and II concentrations in postgastrectomy atrophic gastritis results from the loss of fundic glands, which produce both zymogens, and the appearance of metaplastic pyloric glands, which produce only pepsinogen II.

Gastrectomy↗