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Biomedical subjects

J A Balint

Publications and source records attributed to J A Balint.

At least 19 recordsLinked to original sources

Formation and transport of chylomicrons by enterocytes to the lymphatics.

Digestion of triglyceride in the intestine results in the production of 2-monoglyceride and fatty acid. Phosphatidylcholine is hydrolyzed in the lumen to form lysophosphatidylcholine before its absorption. These digestion products are absorbed by the enterocytes through simple diffusion. In contrast, cholesterol absorption seems specific and is energy dependent. After entry into the enterocytes, these lipid digestion products migrate to the endoplasmic reticulum. Both fatty acid-binding protein and sterol carrier protein may be involved in the intracellular transport of fatty acid and cholesterol, respectively. Through predominantly the monoglyceride pathway, monoglycerides and fatty acids are resynthesized to form triglyceride in the endoplasmic reticulum. The lipid droplets, coated with cholesterol, phospholipid, and apolipoproteins, are then further processed in the Golgi apparatus before being released by the enterocytes through exocytosis. As yet, little is known of the factors regulating the formation and release of these chylomicrons by the enterocytes. Although apolipoprotein B is a prerequisite for the formation of chylomicrons, the question of whether its supply is rate limiting for chylomicron formation remains to be demonstrated. Other factors that may play a role in chylomicron formation are luminal phospholipid supply, Ca2+, and microtubules. Chylomicrons and very low-density lipoproteins are probably produced by the enterocytes via different pathways. For example, Pluronic L-81, a hydrophobic surfactant, affects only chylomicron formation and has little effect on very low-density lipoprotein production. The movement of chylomicrons from the intercellular space through the basement membrane to the lamina propria is not fully understood. Once inside the lamina propria, the movement of chylomicrons is probably by diffusion and is greatly facilitated by interstitial hydration; thus the lymphogogic effect of fat absorption may serve an important function for the transfer of chylomicrons from the enterocytes to the lacteal.

Animals

The effects of essential fatty acid deficiency on pulmonary alveolar macrophage function.

Male rats were maintained for periods of up to 16 weeks on a fat free diet which was supplemented with either 4% tripalmitin (essential fatty acid [EFA] deficient) or with 4% safflower oil (SAFF, control). Pulmonary alveolar macrophages (PAM) were obtained by lung lavage. PAM from EFA deficient rats had reduced phagocytic activity and capacity. Intracellular killing of ingested yeast was also reduced by EFA deficiency. The activity of acid phosphatase, beta-glucuronidase and cathepsin D from PAM was not altered by dietary treatment. Transmission electron microscopy failed to show any consistent morphologic differences between PAM from EFA deficient and SAFF animals, but did confirm the decreased phagocytosis by PAM from EFA deficient rats. However, scanning electron microscopy did show loss of pseudopodia in PAM from EFA deficient rats. EFA deficiency was demonstrated by analyzing the methyl esters of the fatty aids from the total lipid extract of PAM. The arachidonate content was decreased while the eicosatrienoate content was increased in PAM derived from rats fed the EFA deficient diet. In an effort to elucidate further the mechanism of action of EFA deficiency in impairing phagocytosis by PAM, inhibitors of various reactions which lead to oxygenated derivatives of arachidonate were studied using PAM from chow fed rats. Some of these inhibitors were effective in diminishing phagocytosis. Furthermore, PAM from these preparations when fixed in suspension and examined with scanning electron microscopy showed morphological changes similar to those seen in EFA deficiency. This similarity of surface ultrastructural changes suggests that EFA deficiency may impair phagocytic function of PAM by reducing availability of an oxygenated derivative of arachidonic acid.

Acid Phosphatase

Resistant ascites in alcoholic liver cirrhosis: course and prognosis.

A group of 29 patients with decompensated cirrhosis of the liver who retained a large amount of ascites under a hospital regimen during two months or longer was identified. The prognosis for this selected group of patients, while grave [during continuous hospitalization 11 out of 29 patients (= 38%) died], is not without hope: 18 patients (62%) improved and could be discharged from the hospital. Their further course was influenced by resumption of alcohol usage. Five of 11 (45.4%) who resumed drinking died due to hepatic causes within 10 months. Of the remaining six only one lost his ascites. Those who abstained (7 patients) remained alive for an average follow-up of 33 months and all lost their ascites. Alcohol resumption significantly decreased both survival (P less than 0.05) and ascites resorption (P less than 0.0015). Continued abstinence from alcohol may thus obviate the need for surgical measures to relieve ascites in these patients.

Alcohol Drinking

The relationship of fatty acid composition and surface activity of lung extracts.

Male weanling rats were fed fat-free diets supplemented with 4% (w/w) safflower oil (control) or 4% tripalmitin (essential fatty acid (EFA) deficient) for 14 weeks. Whereas the amount of lecithin in lung lavage material remained unchanged, lung lavage lecithin from EFA-deficient rats contained significantly less palmitic acid (61.4 +/- 2.0% vs. 77.4 +/- 5.8%, P less than 0.01) than that from controls. Surface tension vs. area hysteresis loops were obtained for total lipid extracts (TLE) of lung lavage fluid, intra- and extra-cellular lipoprotein fractions (IBI and IBE) and lipid extracts of those lipoprotein fractions (LBI and LBE). A significant increase in minimal surface tension (gammamin) was found for all samples obtained from EFA-deficient rats as compared to controls. Refeeding of diets containing safflower oil for 7-14 days reversed these changes. Air pressure-volume curves on degassed, excised lungs indicated that greater pressure is required to maintain a given lung volume in EFA-deficient rats. These results support the hypothesis that the fatty acid composition of pulmonary surfactant lecithins is a major determinant of the surface activity of lung extracts.

Animals

Surfactant lecithin fatty acid composition and its relationship to the infantile respiratory distress syndrome.

In order to evaluate the role of surfactant lecithin composition in the development of the infantile respiratory distress syndrome (IRDS) we have examined lecithin fatty acid composition from gastric aspirates obtained at the time of delivery from 14 full term healthy infants, 9 control premature infants without respiratory distress, and 16 premature infants who developed IRDS. The latter had significantly reduced concentrations of palmitic acid (48.4 +/- 1.8% vs. 65.3 +/- 1.5% in fullterm and 59.5 +/- 0.8% in control premature infants, P less than 0.001). None of the infants in whom palmitic acid was more than 60% of total lecithin fatty acids developed IRDS, whereas 10 of 11 infants with values below 50% did develop this complication. Lecithin from gastric aspirate was shown to be similar in fatty acid composition to lecithins from tracheal washings and amniotic fluid. Palmitic acid concentrations in lecithins of serial tracheal washings paralleled the clinical course of eight infants with IRDS.

Fatty Acids

Role of biliary lecithin in lymphatic transport of fat.

This study was undertaken to asses the role of luminal lecithin in the lymphatic transportation of fat as chylomicrons. Two doses of fat, the low and high dose, were fed to two different groups of rats, control and bile fistula. At low dose, infusing at 35 mumoles of total fatty acid per hr of a mixture of oleic acid and monoolein, molar ratio 2:1, solubilized in 55 mumoles of sodium taurocholate, there was no difference in the lymphatic output of absorbed fat during steady state (7th and 8th hour) absorption. Infusing at a high dose, 173 mumoles of total fatty acid per hr of a mixture of oleic acid and monoolein, molar ratio 2:1, solubilized in 55 mumoles of sodium taurocholate, the bile fistula rats had lower triglyceride and phospholipid output, with a higher proportion of oleic acid in lymph lecithin than did control rats. These alterations in bile fistula rats returned to normal by addding 10 mumoles per hr of biliary lecithin to the infusate. We conclude that intraluminal biliary lecithin plays a significant role in the translocation of high doses of absorbed fat into lymph and in the amount and type of lecithin synthesized.

Animals

Alterations in phosphatidylcholine species and their reversal in pulmonary surfactant during essential fatty-acid deficiency.

Previous studies (Kyriakides, E.C., Beeler, D.A. and Balint, J.A. (1974) Clin. Res. 22, 717a, and Burnell, J.M. and Balint, J.A. (1975) Fed. Proc. 34, 426) have indicated that essential fatty-acid deficiency in rats resulted in significant reduction of palmitate content of lung tissue and lavage phosphatidylcholines. Experiments were, therefore, undertaken to confirm and further characterize these changes and to examine the reversal of these alterations when essential fatty acid deficient rats were fed fat-free diets supplemented with linoleate for 1-14 days. Analysis of the fatty acid composition of liver lipids was used to confirm the presence of essential fatty-acid deficiency in rats that were fed a fat-free diet supplemented with 4% by weight of tripalmitoylglycerol for 14 weeks. Phosphatidylcholines from lung tissue and lavage fluid of essential fatty-acid deficient rats contained significantly less palmitate and significantly more palmitoleate and oleate than those rats receiving linoleate. These changes in fatty acid composition were reflected in a significant reduction of disaturated phosphatidylcholines (predominantly dipalmitoyl) in lung tissue and lavage fluid from essential fatty-acid deficient rats, while the total phosphatidylcholine content remained unchanged. On feeding the diet containing linoleate to the deficient rats, a reversal of these changes began after one day and was nearly complete by 7-14 days.

Animals

Spontaneous hepatic artery thrombosis with infarction of the liver.

Extensive infarction of the liver, initially thought to be halothane hepatitis, is described. The patient developed severe right upper quadrant abdominal pain and abnormal liver function tests after amputation of the leg. The correct diagnosis was made by percutaneous needle biopsy of the liver which demonstrated a large area of avascular necrosis. The patient recovered, indicating the remarkable ability of the liver to maintain function despite ischemic injury. The patient died later from an acute myocardial infarction, and at autopsy thrombosis of the hepatic artery and multiple hepatic infarcts were confirmed.

Aged

Colonic infusion in the management of the short bowel syndrome.

Two cases are presented of short bowel syndrome. Both had had the colon or part of the colon bypassed as part of prior surgical management in addition to having had extensive resection of the small bowel. Despite various medical regimens, both patients remained in negative fluid and electrolyte balance thus requiring intravenous fluid supplementation. In an effort to maintain positive fluid balance without intravenous therapy, colonic infusion of fluids was initiated. This modification of management proved effective in maintenance of adequate plasma volume and normal renal function. It is concluded that this type of therapy can be of great benefit in the management of patients with the short bowel syndrome.

Adult

Reversible vacuolar myopathy of type II fibers.

A 23-year-old ex-bicycle racer with vague gastrointestinal symptoms had an acute weight loss of 13.6 kg (30 lb). During the period of maximal weight loss, he experienced muscle weakness, dysphagia, bradycardia, and T wave changes on the electrocardiogram. His skeletal muscle biopsy showed a severe vacuolar myopathy devastating the atrophic type II fibers. Without treatment, he recovered completely and has remained well. This may be an exaggerated or acute form of type II atrophy not previously reported, or it may represent an acute muscular degeneration.

Adult

The absorption and subsequent utilization of lecithin by the rat jejunum.

Labeled lecithin (32P, 2-3H-glycerol, 1-14C-palmitate) was prepared for studying absorption of lecithin by rat intestine and its incorporation into microsomal and prechylomicron-chylomicron lecithin. Bile fistula rats were perfused intraduodenally with bile salts and lecithin plus a liquid diet. Intestinal samples were obtained after sacrifice and specific activities (DPM/mumol) of isotopes in lecithin were determined. Ratios of specific activities of isotopes were calculated and compared to respective ratios in the original perfusate lecithin. Radioactivity rapidly appeared in jejunal lecithin following perfusion. When specific activities of isotopes in prechylomicron-chylomicron lecithin were compared to those in microsomal lecithin, specific activities were always greater in prechylomicron-chylomicron lecithin. Analysis of ratios of specific activities of isotopes in jejunal lecithin showed that the ratios were nearly identical to those in perfusate phospholipid, indicating that the lysolecithin portion of luminal lecithin can be absorbed intact and can then be utilized for jejunal lecithin synthesis.

Animals