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Biomedical subjects

L L Seelig

Publications and source records attributed to L L Seelig.

54 records · Page 3Linked to original sources

Water and electrolyte movement and mucosal morphology in the jejunum of patients with portal hypertension.

Intestinal secretion and intercullular space dilatation can be induced in animal models by acute elevation of intravascular volume or portal pressure. We examined whether patients with increased portal venous pressure might represent a clinical counterpart to these animal models. Portal venous pressure, determined by hepatic wedge pressure measurement, was elevated to 10-55 mmHg (mean 29 mmHg) in 8 patients with chronic liver disease without diarrhea. Intestinal transport studies utilizing a steady-state perfusion technique revealed normal absorption of a plasmalike electrolyte solution. A solution dsigned to unmask intestinal secretion demonstrated no difference from control subjects in the movement of water, electrolytes, or protein into the intestional lumen. There was no correlation of absorption of secretion with hepatic wedge pressure. Jejunal biopsy revealed a significant increase in dilatation of intercellular spaces in patients compared to controls; this increase was not correlated with hepatic wedge pressure, but was significantly inversely correlated to plasma renin and aldosterone concentration. We conclude that patients with chronic liver disease and portal hypertension absorb water and electrolytes normally, but have mild morphologic alterations in the intestinal mucosa, possibly related to intravascular volume status.

Adult↗

Concentration of calcium and other elements at a subcellular level in the lactating epithelium of rat.

Unfixed, freeze-dried and uncoated sections of lactating mammary tissue from rat were analysed for element concentration using a scanning electron microscope fitted with energy-dispersive X-ray analytical equipment. The subcellular concentration (mmol/kg dry weight) of calcium and several other elements (Na, Mg, P, S, Cl and K) was measured in: the basal-lateral cytoplasm, the nucleus, the apical cytoplasm, and the alveolar lumen in the lactating epithelium. The element concentration data was correlated to the ultrastructural features of the microprobed areas. Ca was concentrated, 4- to 5-fold, in the apical cytoplasm in comparison to other parts of the cell. The lumen contents show a 10-fold increase over the apical cytoplasm. The apical cytoplasm includes the Golgi apparatus and secretory vacuoles containing dense granules or casein micelles. The latter are numerous in the lumen. Because most of the CA in milk is known to be bound to the casein micelles, our data support the idea that Ca is sequestered in the golgi region, and transported within the secretory vacuoles to the plasma membrane for exocytosis to the lumen.

Animals↗

Morphological evaluation of opossum lower esophageal sphincter.

Studies were performed in the opossum to evaluate the morphological characteristics of the lower esophageal sphincter. The sphincter and the esophageal body were identified manometrically and fixed in situ by perfusion with aldehyde fixative. Light microscopy revealed that: (1) longitudinal muscle layers of the sphincter and the esophageal body were similar in thickness and compactness, and (2) circular muscle of the sphincter was thicker and was composed of muscle fasciculi with abundant intervening connective tissue as compared to the compact muscle fasciculi of the circular muscle of the esophageal body. Electron microscopy showed the circular muscle fibers of the sphincter to have irregular protuberances from their surfaces, whereas the circular muscle fibers of the esophageal body possessed smooth surfaces. Several types of junctional complexes between adjacent muscle fibers were observed; however, there was no difference in their distribution in the sphincter or esophageal body. The majority of the nerve varicosities contained a mixture of agranular (350 to 450 A) and large dense core vesicles (800 to 1600 A); varicosities containing small granular vesicles were not found in any area of the esophagus. When varicosities were cut along the longitudinal axis of the axon, they often showed grouping of similar vesicle types in different areas along the axon varicosities. There was no difference in the type of varicosities found in the sphincter or the esophageal body. These studies show that: (1) circular muscle of the sphincter can be morphologically distinguished from that of the esophageal body; (2) there is no difference in the morphology of the nerve terminals or the vesicle types in the two areas; and (3) classification of the varicosities based upon the predominance of the vesicle types may be artifactual because of sampling error.

Animals↗

Changes in gastric glandular cell kinetics after small bowel resection in the rat.

The proliferation of gastric mucosal cells was studied in male Sprague-Dawley rats after a 50% resection involving the proximal small intestine. Two months after the operation, resected and control animals were given either a single or four successive intraperitoneal injections of 1 muCi of [3H]thymidine per g of body weight. Animals from each group were killed 1 hr after the single injection and 3, 7, 30, and 60 days after the first multiple dose injection [3H]thymidine. The number of labeled parietal, chief, and mucous cells of the gastric glands were measured. At the 3-, 30-, and 60-day periods, the percentages of labeled parietal and chief cells were significantly increased in animals with small bowel resection when compared with corresponding controls. The percentages of labeled mucous cells of the gastric glands were also increased in animals with small bowel resection at the 3- and 7-day periods. One hour after a single injection of [3H]thymidine, the percentage of labeled gastric mucosal progenitor cells in animals with small bowel resection, although increased, was not significantly different from that in controls. It is, therefore, believed that the increases in percentage labeling of gastric glandular epithelial cells at 3, 7, 30, and 60 days could not solely be explained on the basis of an increased turnover rate of gastric progenitor cells. Rather, it might be concluded that the increase in glandular epithelial cells is accomplished, in part, by increased differentiation of gastric progenitor cells.

Animals↗

Effect of small bowel resection on the gastric mucosa in the rat.

Male Sprague-Dawley rats (120 to 130 gm), unoperated, sham-operated, and those with a 50% resection of the proximal small intestine, were studied after periods of 3, 6, 9, or 12 months. Differences in body weight and in the surface area, thickness, volume, and cellular content of the gastric mucosa between these three groups of animals were compared and statistically analyzed. After an initial loss in body weight, animals with small bowel resection and sham-operated animals attained weights equivalent to unoperated controls. Comparison of the groups for mucosal surface areas of the body of the stomachs showed no significant differences at the 3-, 6-, or 9-month periods. However, 12 months after surgery, the mucosal surface area of stomachs from resected animals was significantly greater than in corresponding controls. At 3, 6, and 9 months after resection, the thickness and volume of the gastric mucosa and the epithelial cell populations (parietal and nonparietal) of the gastric glands were significantly greater than in controls. However, at 12 months, there was no significant difference in any of these parameters between the controls and the experimental animals. The DNA content of the gastric mucosa was significantly greater for animals with small bowel resection than for corresponding controls at 1 and 6 months after surgery. It is concluded that hyperplasia of the gastric glands exists for at least 9 months after proximal small bowel resection in the rat. This hyperplastic response may be responsible for the previously observed (N Engl J Med 272:509-514, 1965; Surgery 65:292-297, 1969) gastric hypersecretion associated with extensive small bowel resection.

Animals↗

Effect of protonated 2,4,6-triaminopyrimidine, a tight junction blocker, on intestinal transport in dog ileum in vivo.

Previous in vitro experiments suggest that protonated 2,4,6-triaminopyrimidine (TAP+) inhibits passive Na+ movement across tight junctions of various epithelial tissues. So far no evidence has been found that TAP+ interferes with other mucosal transport processes. Because blockage of the tight junctions would be a promising tool in studying intestinal transport physiology, the effect of TAP+ was investigated in the dog ileum in vivo. When TAP+ was added to a sodium-free mannitol solution, the transepithelial sodium diffusion potential was significantly decreased (60% inhibition with 34 mm TAP+); this would be expected if TAP+ inhibited NA+ permeation through tight junctions. However, TAP+ was also found to diminish Na+ and Cl- absorption. Furthermore, TAP+ increased unidirectional Na+ flux from plasma to lumen; this is opposite to the expected result of tight junction blockage. In addition, TAP+ reduced glucose, fructose, and xylose absorption by about 50%. In ileal loops exposed to cholera toxin, TAP+ enhanced secretion by a rate equal to the rate by which it reduced absorption in loops not exposed to cholera toxin. All changes induced by TAP+ approached normal within 4 hr of its removal from the perfusate. TAP+ did not cause nay mucosal damage that could be detected by protein leakage or by light microscopy. These studies show that TAP+ has many effects on intestinal transport processes that cannot be explained on the basis of tight junction blockage.

Animals↗

Pattern of osmium deposition in the parietal cells of the stomach.

Parietal cells of the stomach of the hamster show extensive amounts of dense material in a variety of organelles after prolonged exposure to a solution of osmium tetroxide. Conspicuous amounts of reduced osmium compounds are evident within the granular endoplasmic reticulum, perinuclear cisterna, and vesicular elements of the Golgi complex. Dense material is also apparent within cristae of the mitochondria, the surface coat of the microvilli of the intracellular canaliculus, and vesicular elements of the multivesicular bodies. Multivesicular bodies, containing numerous small osmiophilic elements, are often seen surrounding and/or in close contact with mitochondria. The proximity of the multivesicular bodies to the mitochondria appears to be related to an autophagic process involving degradation of mitochondria. The distribution and intensity of the precipitates within the organelles of the parietal cells vary in different regions of the gastric glands. The findings of this study emphasize that cell structures other than the Golgi complex may contain large concentrations of reduced osmium compounds after prolonged exposure to a solution of osmium tetroxide.

Animals↗

Second generation effects of maternal ethanol consumption on immunity to Trichinella spiralis in female rats.

The deleterious effects of maternal ethanol consumption on neonatal immune development and early immune responses has been well documented. However, the effects of such neonatal exposure to maternally consumed ethanol on the neonates' immune responses in their adult life, especially in combination with additional ethanol exposure, has received little attention. For these experiments, female rats were fed on either 6% ethanol or pair-fed isocaloric control Lieber-DeCarli liquid diets for 30 days prior to, and during, pregnancy and lactation. One day after weaning their pups, the mothers were infected with 1000 Trichinella spiralis larvae, and maintained on diets for an additional 20 days. At this time, they were challenged with 2000 T. spiralis larvae, killed 3 days later, and their immune status determined. These animals served as the first generation alcohol animals. Their female offspring served as the experimental second generation animals. These animals received maternal ethanol during pregnancy and lactation and control diet during their juvenile period (from weaning to 90 days of age). They were then subjected to a schedule of ethanol or pairfeeding, identical to the first generation dams. Two groups of second generation animals were established: Group 1 was exposed to ethanol during their dam's pregnancy and lactation periods only, with no subsequent ethanol treatment; Group 2 received ethanol during their dam's pregnancy and lactation periods and then again throughout their adult experimental period. Our previous studies showed only minimal changes following a secondary challenge in T. spiralis-immunized rats; however, neonates born to alcohol-consuming mothers did show some depressed secondary immune responses when challenged soon after weaning. We chose to use a secondary immune challenge to assess further immune alterations in second generation adult animals. No differences between any of the ethanol and pair-fed groups were observed in intestinal worm burdens, which is similar to data previously reported for adult alcohol-consuming animals. However, second generation group 2 animals demonstrated significantly reduced proliferation responses to T. spiralis antigen and Concanavalin A (Con A) stimulation relative to the ethanol first generation and to the second generation Group 1 animals. This group also demonstrated significantly lower absorbencies in the ELISA assay for specific IgM and IgG anti-T. spiralis antibodies than the pair-fed, ethanol first and second generation Group 1 animals. The proportion of total T cells and cytotoxic T cells was significantly lower and the proportion of natural killer cells was elevated in both second generation ethanol Groups 1 and 2 relative to the ethanol first generation and pair-fed groups. In addition, Group 2 second generation animals showed significantly lower proportions of total leukocytes and T cells than Group 1 second generation animals. Although secondary immune responses to T. spiralis infection were not altered in rats exposed to ethanol only as adults, exposure to maternal ethanol does affect some specific immune responses in second generation adult life and maternal exposure may exert cumulative immune effects in concert with later consumption of ethanol by offspring born to alcoholic mothers.

Age Factors↗

Preliminary study of how alcohol consumption during pregnancy affects immune components in breast milk and blood of postpartum women.

Human milk has been shown to contain numerous immune components that can potentially protect the infant during the period before its own immune system is completely developed. Alcohol consumption in both experimental animals and humans has been associated with alterations to a number of immune parameters. We have investigated the possibility that alcohol consumption during pregnancy alters certain immune components in day 3 postpartum breast milk and peripheral blood of women. Our study group consisted of 10 alcoholic beverage drinkers (moderate to heavy, most of whom smoked a 1/2-1 pack of cigarettes per day), 15 non-drinking/non-smoking controls, and 10 non-drinking/smokers (1/2-1 pack per day) controls. The immune parameters measured in these otherwise healthy women were: (1) percentage and absolute number of the various subsets of leukocytes; (2) percentage of T cells, B cells, T helper and cytotoxic/suppressors subsets, and natural killer cells; (3) levels of the cytokines IL-6, IL-8 and TNF-alpha; (4) levels of IgA in milk and IgG in serum. Milk from the alcohol group contained an elevated amount of IL-8 as compared with milk from non-smoker controls; however, it did not differ statistically from that of the smoker controls. Blood from the alcohol group showed an increased level of IL-8 when compared with that from both smoker and non-smoker controls. The total number of leukocytes in milk was elevated in milk from the alcohol group as compared to both the smoker and non-smoker control groups. In the leukocyte component of milk, neutrophils predominate and are responsible for the elevation in total number of cells, as both lymphocyte and macrophage populations did not differ from those of the controls. For lymphocytes, B cells were also increased in blood of the smokers as compared with the alcohol and non-smokers controls. There were no statistical differences in any of the other immune parameters tested among the three groups. The present study found that alcohol consumption during pregnancy could modulate the production of IL-8 and infiltration of certain leukocytes in milk and blood of postpartum women. Some of these alterations were also evident in the smoker controls and thus could not be attributed to alcohol consumption alone.

Alcohol Drinking↗