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Biomedical subjects

M Hamosh

Publications and source records attributed to M Hamosh.

At least 91 records · Page 5Linked to original sources
PubMed1984

In vitro characteristics of the lipid-filled interstitial cell associated with postnatal lung growth: evidence for fibroblast heterogeneity.

This study explores the in vitro modulation of the lipid-filled phenotype of the lipid interstitial cell (LIC) isolated from the developing rat lung. Isolated LIC lose their cytoplasmic lipid droplets when cultured in fetal bovine serum (FBS) but retain their potential for lipid storage, since they rapidly reaccumulate lipid when subcultured in neonatal rat serum (NRS) and to a lesser extent in adult rat serum (ARS). The return of LIC to a lipid-filled state may not represent cell differentiation, since it occurs in the presence of bromodeoxyuridine. NRS contains twice the free fatty acids (FFA) of FBS and ARS, and doubling the FFA concentration of FBS and ARS increases LIC storage lipids. Serum triglyceride (TG) is 10 times higher in ARS and 23 times higher in NRS than in FBS. Since LIC lipoprotein lipase (LPL) activity is in the range of 3T3-L1 adipocytes (0.56 vs. 1.72 units/mg DNA), the LIC has the potential of incorporating serum lipoprotein-triglyceride. The LPL activity of LIC is 9-12 times that of fetal and adult rat lung fibroblasts and 50 times that of human lung, trachea, or skin fibroblasts; LIC are probably a source of endothelial LPL in the developing lung. The response of LIC and ARLF cyclic-AMP to hormones known to influence lipid synthesis or degradation showed that: only LIC responded to glucagon; prostaglandin E1 was a more potent stimulus to LIC; isoproterenol was a more potent stimulus to ARLF; and neither cell responded to ACTH. The unique nature of LIC tends to support further the concept of fibroblast heterogeneity within tissues.

Animals↗
PubMed1984

Comparison of the phospholipid composition of breast milk from mothers of term and preterm infants during lactation.

Phospholipids were determined in milk on postpartum day 3 (colostrum) and days 7, 21, 42, and 84 from mothers of 18 very premature (26 to 30 wk gestation age), 28 premature (31 to 36 wk), and 6 term (37 to 40 wk) infants. Lipids were analyzed by thin-layer and gas-liquid chromatography. Total fat content increased during lactation whereas phospholipids and cholesterol declined. Phospholipids were separated from neutral lipids by column chromatography and distributed by preparative thin-layer chromatography into classes, sphingomyelin, phosphatidyl choline, serine, inositol, and ethanolamine for fatty acid analysis. Phospholipids exhibited a remarkable constancy in class percentages in milks from mothers giving birth prematurely or at term. Changes were observed in fatty acid composition within each of the phospholipid classes as secretion progressed from colostrum (3d) to transitional (7d) to mature milk (21, 42, 84d). These changes in phospholipid fatty acid composition occurred only during the first 3 wk of lactation. Mature milk was found to be relatively constant in phospholipid composition.

Colostrum↗
PubMed1984

Lingual lipase in cystic fibrosis. Quantitation of enzyme activity in the upper small intestine of patients with exocrine pancreatic insufficiency.

We have measured the level of lingual lipase activity in gastric and duodenal aspirates of five patients with cystic fibrosis (CF) and pancreatic insufficiency. Lingual lipase activity (measured in vitro by the hydrolysis of long-chain triglyceride, tri-[3H]olein, at pH 4.2 and expressed in nanomoles FFA released per milliliter aspirate per minute) and pH in gastric and duodenal aspirates were measured at 10-min intervals during a a 30-min basal period and at 15-min intervals during a 2-h period after the ingestion of a test meal. In gastric aspirates, lingual lipase activity decreased from basal levels of 200 +/- 34 nmol FFA released per milliliter per minute (similar to values reported previously in normal subjects (Hamosh M., H. L. Klaeveman, R. O. Wolf, and R. O. Scow, 1975, J. Clin. Invest., 55:908-913) to 79 +/- 15 nmol FFA/ml per min during the first postprandial hour and returned to basal levels during the second postprandial hour, (206 +/- 39 nmol FFA/ml per min). Duodenal aspirates, obtained during basal conditions, had lingual lipase activity similar to that in the stomach, 178 +/- 63 nmol FFA/ml per min. Enzyme activity levels were 56 +/- 14 and 113 +/- 29 during the first and second postprandial hours. Measurements of total lipase activity delivered to the ligament of Treitz showed that lingual lipase amounted to 91.22 +/- 4.06% of the total lipase activity in the upper small intestine during the 150-min study period. The basal and postprandial gastric pH levels in the five CF patients studied (3.2 +/- 0.44, 4.0 +/- 0.16, and 4.4 +/- 0.4 for basal and first and second postprandial hours, respectively) did not differ from previously reported values for normal subjects. The pH of duodenal aspirates was however significantly lower (P less than 0.001) in CF patients, both under basal conditions (5.0 +/- 0.26) and during the first and second postprandial hours (4.9 +/- 0.13 and 4.4 +/- 0.36, respectively), than in normal subjects. The low postprandial duodenal pH enables lingual lipase to act not only in the stomach but to continue the hydrolysis of dietary fat in the upper small intestine of CF patients. The data presented show that lingual lipase remains fully active in CF and accounts for greater than 90% of total lipase activity in the upper small intestine. We suggest that, because of low intestinal pH in CF, enzyme replacement therapy containing lingual lipase could improve fat absorption in CF patients to a greater extent than the pancreatic preparations now in use.

Adult↗
PubMed1984

Fat digestion in the stomach: stability of lingual lipase in the gastric environment.

Digestion of dietary fat starts in the stomach, where lingual lipase hydrolyzes triglycerides to free fatty acids and partial glycerides at pH 3.0-6.0. Lingual lipase is secreted continuously from lingual serous glands and accumulates in the stomach between meals, when gastric pH is less than 3.0. We have, therefore, examined the resistance of lingual lipase to low pH and its possible protection by dietary components present in the stomach contents. Partially purified rat lingual lipase (7-15 micrograms enzyme protein) was preincubated at 37 degrees C for 10-60 min at pH 1.0-6.0 before incubation for assay of lipolytic activity, hydrolysis of tri-[3H]olein at pH 5.4. The data show that partially purified rat lingual lipase preparations are stable at 37 degrees C in the pH range of 2.5-6.0. Enzyme activity, however, is rapidly and irreversibly lost during preincubation at pH 1.0-2.4 for 10-30 min. Protein (gelatin 1% or albumin 1% or 2.5%) cannot prevent the inactivation of lingual lipase at low pH. The large molecular species (molecular weight greater than 500,000) of lingual lipase (thought to be an aggregate of enzyme with lipids) is slightly more resistant to inactivation than the 46,000 dalton preparation, suggesting that lipids might protect the enzyme from inactivation. Indeed, about 60% of the initial lipase activity is preserved during incubation at pH 2.0 in the presence of 50 mM lecithin or 10 mM triolein. The data indicate that triglycerides which are hydrolyzed by this enzyme as well as phospholipids that are not hydrolyzed can prevent the inactivation of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Fat digestion by lingual lipase: mechanism of lipolysis in the stomach and upper small intestine.

Ten to 30% of dietary fat is hydrolyzed in the stomach by lingual lipase, an enzyme secreted from lingual serous glands. We investigated the substrate specificity of this enzyme as well as the potential of lingual lipase to act in the upper small intestine i.e., in the presence of bile salts and lecithin. The data presented show that partially purified preparations of rat lingual lipase and the lipase in gastric aspirates of newborn infants have identical substrate specificity: medium-chain triglycerides were hydrolyzed at rates 5-8-fold higher than long-chain triglycerides; the rat and human enzymes do not hydrolyze the ester bond of lecithin or cholesteryl-ester. In contrast to pancreatic lipase, the hydrolysis of triglycerides by lingual lipase is not inhibited by lecithin. But, similar to pancreatic lipase the activity of lingual lipase is inhibited by bile salts, the extent of inhibition varying with its nature and concentration. This inactivation is not prevented by colipase but is partially averted by lipids and protein, suggesting that lingual lipase can remain active in the duodenum. The pH optimum of the enzyme (2.2-6.5 in the rat and 3.5-6.0 in human gastric aspirates) is compatible with continued activity in the upper small intestine, especially during the neonatal period, when the luminal pH is under 6.5. The marked variation in lipase activity levels in gastric aspirates of newborn infants is probably due to individual variations in enzyme amounts. The characteristics of the lipase are however identical in infants with low, intermediate or high activity levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1984

Lipases and lipids in human milk: effect of freeze-thawing and storage.

Frozen storage is often used by milk banks to preserve expressed human milk for later use. Optimal storage and handling conditions which ensure minimum alteration of lipid composition have not been well defined. Therefore we investigated the effect of rapid freeze-thawing and storage conditions (-20 and -70 degrees C) on the free fatty acid (FFA) levels and on the activities of lipoprotein lipase (LPL) and bile salt-stimulated lipase (BSSL) in human milk. Since during mechanical expression leakage of serum components into milk may occur, we also investigated the effect of the presence of serum on human milk LPL during storage. Lipase activity levels were unaffected by rapid freeze-thawing (x3) followed by storage for 1 month at -20 or -70 degrees C. LPL activity (nmol FFA released/ml milk/min) was 414 +/- 128, 451 +/- 37, and 351 +/- 20 and BSSL activity (mumol FFA/ml milk/min) was 5.7 +/- 0.7, 5.5 +/- 0.8, and 5.7 +/- 0.2 in fresh, freeze-thawed, and stored milk, respectively. FFA levels (% of total lipid) were 3.01 +/- 1.05 and 10.3 +/- 1.6 in fresh-frozen milk stored at -70 and -20 degrees C for 5 months, and 3.78 +/- 1.08 and 13.60 +/- 1.25 in specimens of freeze-thawed (x3) before storage at -70 or -20 degrees C. Addition of serum had no effect on milk LPL at either temperature. We conclude that LPL and BSSL remain fully active during frozen storage of human milk and that milk fat is hydrolyzed at -20 degrees C but not at -70 degrees C. We suggest that banked human milk be stored routinely at -70 degrees C.

Bile Acids and Salts↗
PubMed1984

Effect of heparin on serum and tissue lipases in the developing rat.

The frequent inclusion of heparin in fluids used for total parenteral nutrition in infants, prompted an investigation of the ability of heparin to release lipoprotein lipase (LPL) and hepatic lipase (HL) from the endothelial surface into the circulation, and of the effect of heparin on tissue stores of lipase in the postnatal period. In rat pups, plasma postheparin lipolytic activity (PHLA) released by IP administration of heparin (0.5 unit/g body wt) was 15% of adult values at birth and increased rapidly to reach 60% on day 10. Repeated doses of heparin (in adult rats, given 0.1 unit/g IV) at 1 and 4 h after the initial dose did not affect the maximal response to heparin. In all age groups 80% of PHLA was inhibited by 0.5 M NaCl, suggesting a mostly nonhepatic origin for the released enzyme. Heart, lung, and liver lipase activities of rat pups were not significantly different from controls not given heparin. The pattern of change in tissue enzyme content was similar for heart and lung, but different from hepatic lipase. LPL activity in the former increased from 10 and 30% to 60 and 100% of adult values between birth and 10 days while in the latter enzyme activity exceeded adult levels at birth and decreased to 50% of adult values during the latter half of the suckling period (days 10-21). Our results demonstrate that heparin does not cause depletion of tissue lipases in the postnatal period. The parallel increases in LPL content of peripheral tissues and PHLA suggest that in all age groups heparin-induced release of LPL into the circulation is proportional to tissue lipolytic activity.

Age Factors↗
PubMed1983

Gastric lipolysis in the developing rat. Ontogeny of the lipases active in the stomach.

The first step in fat digestion occurs in the stomach, where 10-30% of dietary triacylglycerols are hydrolyzed to partial (di- and mono-) acylglycerols and free fatty acids. Preduodenal fat digestion is an important compensatory mechanism in the newborn because of immature pancreatic (lipase) and hepatic (bile acid synthesis) function. Since hydrolysis of fat in the stomach can be catalyzed by enzymes of lingual (Hamosh, M. (1979) Pediatr. Res. 13, 615-622) and possibly gastric origin, we have studied the developmental pattern and quantitative contribution of these two enzymes to intragastric fat digestion by measuring lipase activity in homogenates of lingual glands and gastric mucosa of rats from birth until 60 days of age. Total lipolytic activity in rat gastric mucosa was only 2-10% of that in the lingual glands throughout the entire period studied. Lingual lipase activity increased steadily from birth until day 50, whereas the activity in the gastric mucosa reached peak levels at 17-20 days and declined sharply after weaning. Throughout the period of study--suckling, weaning, and young adulthood--lingual and gastric lipase had very similar characteristics: pH optimum in the range of 5.0-6.0 and 2.5-5.0-fold higher activity on medium-chain (tri[14C]octanoin) than long-chain (tri[3H]olein) triacylglycerols. In the lingual glands, lipase activity was higher during fasting, probably because of accumulation of enzyme (without depletion during meals), whereas in the gastric mucosa lipase levels were higher after feeding, suggesting adsorption of lingual lipase (which reaches the stomach with the ingested food) onto the gastric mucosa. From birth to weaning, there was rapid and extensive hydrolysis of triacylglycerol in the stomach (decrease from 98 mol% in rat milk to 33.6-48.9 mol% in the stomach contents half an hour after feeding). The intragastric lipolysis remained almost constant from birth until day 20, in spite of a marked increase in food consumption, probably because of the continued rise of lingual lipase levels. The direct relationship between high intragastric lipolysis and high lingual lipase activity suggests that lingual lipase is the major digestive enzyme in the newborn.

Aging↗
PubMed1983

Comparison of the lipid composition of breast milk from mothers of term and preterm infants.

Milk was collected from mothers of 18 very premature (26 to 30 wk gestation age), 28 premature (31 to 36 wk), and six term (37 + wk) infants on day 2 to 3 (colostrum), and at 1, 3, 6, and 12 wk postpartum. Fat content for 154 milk samples was 2.80 g/dl gravimetrically and 2.66 g/dl by quantitative thin-layer chromatography. Fat content increased during lactation, whereas phospholipids and cholesterol declined. Concentrations of medium-chain fatty acids increased from colostrum to mature milk and were highest in preterm milk. Compensatory decreases were observed in very premature and premature oleic acid. Long-chain polyunsaturated fatty acids were highest in colostrum and reduced in mature milk. Long-chain polyunsaturated fatty acids were also higher in very premature and premature milk than in term milk. These elevated levels of readily absorbed medium-chain fatty acids and long-chain polyunsaturated fatty acids in preterm milk may be of special benefit for the needs of premature infants.

Adolescent↗
PubMed1983

Respiratory distress syndrome in the newborn: relationship to serum prolactin, thyroxine, and sex.

Prolactin and thyroxine levels were measured by radioimmunoassay in cord blood of 61 premature infants of 26-36 weeks gestation. 30 of the infants subsequently developed respiratory distress syndrome (RDS). The infants who developed RDS had a mean cord prolactin level of 174.5 +/- 24.5 ng/ml and a mean cord thyroxine level of 5.9 +/- 0.4 micrograms/dl. In the 31 healthy infants, the mean cord prolactin and thyroxine levels were significantly higher (226.3 +/- 25.8 ng/ml and 7.1 +/- 0.4 micrograms/dl, respectively). The correlation coefficient between prolactin and thyroxine was r = 0.56 in infants with RDS (p less than 0.0008). Both prolactin and thyroxine correlated with gestational age in the RDS group (r = 0.71 and 0.47, respectively). Discriminant analysis shows that the correlation between prolactin and thyroxine is independent of gestational age (r2 = 0.32, p less than 0.05). There was no correlation between the levels of prolactin and thyroxine in infants without RDS. In the healthy group, the cord prolactin levels were significantly higher (p less than 0.01) in female (335.8 +/- 47.7 ng/ml) than in male infants (209 +/- 17.2 ng/ml). Premature infants who develop RDS have significantly lower thyroxine and prolactin levels in cord blood than infants who remain healthy.

Female↗
PubMed1982

Triacylglycerol hyrolysis in the isolated, perfused rat lung.

We have studied the mechanism of hydrolysis of labeled long-chain triacylglycerols in the isolated, ventilated, perfused rat lung. Hydrolysis of emulsified tri[3H]oleate or doubly labeled [3H]glyceryl, tri[14C]oleate was measured by quantitation of [3H]oleate or of [14C]oleate and [3H]glycerol released into the perfusate. Hydrolysis was directly proportional to the initial triacylglycerol concentration of the perfusate in the range of 0.30 to 2.2 mM. The release of free fatty acids was linear after an initial lag period, the length of which was inversely proportional to the triacylglycerol concentration. Studies with doubly labeled [3H]glyceryl, tri[14C]oleate showed that, during triacylglycerol hydrolysis, the molar ratio of free fatty acid to glycerol released is close to 1, suggesting that about one-third of the fatty acids hydrolyzed is released into the pulmonary circulation. The earlier appearance of free fatty acid than glycerol in the venous effluent indicates that the first step in triacylglycerol hydrolysis occurs at the endothelial surface. In order to investigate the role of lipoprotein lipase in this process, we administered heparin, which leads to immediate release of lipoprotein lipase from the endothelium to the circulation in vivo, 10 min and 4 h before isolation and perfusion of the lungs. Heparin administration 10 min prior to perfusion led to marked release of lipoprotein lipase from the lungs and completely abolished the subsequent hydrolysis of circulating triacylglycerols. Perfusions carried out 4 h after heparin administration show that in the lung, endothelial lipoprotein lipase levels did not return to normal within 4 h after heparin administration. The data show that circulating triacylglycerols are hydrolyzed by endothelial lipoprotein lipase during passage through the lung.

Animals↗
PubMed1982

Hydrolysis of triacylglycerol emulsions by lingual lipase. A microscopic study.

The effect of lingual lipase on four different triacylglycerol emulsions was observed by light microscopy at pH 5-6. The extent of hydrolysis on the microscope slide was determined with the aid of radioactive emulsions or by analyzing the products by gas-liquid chromatography. Artificial emulsions that had been stabilized with amphiphilic lipids gradually coalesced during the unstirred lipase reactions. Gum arabic-stabilized emulsions and human milk fat droplets did not stick to each other or coalesce during lingual lipase hydrolysis. No visible liquid-crystalline product phases, as are seen with pancreatic lipase (Patton, J.S. and Carey, M.C. (1979) Science 204, 145-148), were observed with lingual lipase. The products of lingual lipase activity, protonated fatty acid and diacylglycerol, appear to remain dissolved in the oil phase of the triacylglycerol particle.

Animals↗