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Biomedical subjects

E Mack

Publications and source records attributed to E Mack.

At least 37 records · Page 2Linked to original sources
PubMed1986

Regulation of amino acid uptake by phorbol esters and hypertonic solutions in rat thymocytes.

Growth factors, mitogens, and malignant transformation can alter the rate of amino acid uptake in mammalian cells. It has been suggested that the effects of these stimuli on proliferation are mediated by activation of Na+/H+ exchange. In lymphocytes, Na+/H+ exchange can also be activated by phorbol esters and by hypertonic media. To determine the relationship between the cation antiport and amino acid transport, we tested the effects of these agents on the uptake of alpha-aminoisobutyric acid (AIB), methyl-AIB, proline, and leucine in rat thymocytes. Both 12-O-tetradecanoylphorbol-13-acetate (TPA) and hypertonicity stimulated amino acid uptake through system A (AIB, proline, and methyl-AIB). In addition, TPA, but not hypertonicity, also elevated leucine uptake. The stimulation of the Na+ -dependent system A was not due to an increased inward electrochemical Na+ gradient. The effects of TPA and hypertonic treatment were not identical: Stimulation of AIB uptake by TPA was observed within minutes, whereas at least 1 hr was required for the effect of hypertonicity to become noticeable. Moreover, stimulation by hypertonicity but not that by TPA, was partially inhibited by cycloheximide, suggesting a role of protein synthesis. That stimulation of Na+/H+ exchange does not mediate the effects on amino acid transport is suggested by two findings: 1) the stimulation of AIB uptake was not prevented by concentrations of amiloride or of 5-(N,N-disubstituted) amiloride analogs that completely inhibit the Na+/H+ antiport and 2) conditions that mimic the effect of the antiport, namely, increasing [Na+]i or raising pHi failed to stimulate amino acid uptake. Thus, in lymphocytes, activation of Na+/H+ exchange and stimulation of amino acid transport are not casually related.

Amino Acids↗
PubMed1985

Bromo-A23187: a nonfluorescent calcium ionophore for use with fluorescent probes.

4-Bromo-A23187, a halogenated analog of the widely studied divalent cation ionophore A23187, is a nonfluorescent Ca2+ ionophore suitable for use in the calibration of cytoplasmic free Ca2+ by fluorescent probes. Br-A23187 is shown to saturate Ca2+ sites in quin-2-loaded rat thymic lymphocytes in a manner essentially identical to ionomycin.

Aminoquinolines↗
PubMed1985

Cation and anion transport pathways in volume regulatory response of human lymphocytes to hyposmotic media.

The regulatory volume decrease of osmotically swollen human peripheral blood lymphocytes can be inhibited by agents acting on volume-activated K+- or Cl--transport pathways. Quinine, cetiedil, and 3,3'-dipropylthiadicarbocyanine were found to block the volume-induced K+ transport by interaction with sites on the outside face of the membrane, perhaps by competition with external K+. Drugs known to influence calmodulin action inhibit both volume-induced K+ and Cl- transport to varying degrees. Those inhibitors, particularly of K+ transport, are correlated with their calmodulin-antagonist activity. Penetrating sulfhydryl (SH) reagents (in contrast to nonpenetrating ones) are potent inhibitors of both volume-induced K+ and Cl- movements, indicating the presence of functionally important SH groups located within the membrane or at the cytoplasmic face. A number of agents, such as dipyridamole and oligomycin C, are specific inhibitors of the volume-activated anion pathway. In all respects studied, the inhibition characteristics of the volume-activated K+ pathway of lymphocytes resemble those of the Ca2+-activated K+ channel of red cells. In contrast, the volume-induced anion permeability differs from the primary anion-transport pathway of red cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Stimulation of hexose uptake in rat thymic lymphocytes by phorbol ester. A role for Ca2+ and Na+/H+ exchange?

The tumor promoter 12-0-tetradecanoyl phorbol-13-acetate (TPA) stimulates hexose uptake into rat thymocytes. This study explores two possible messengers of this stimulation: changes in cytosolic [Ca2+], and activation of the Na+/H+ antiport. The cytosolic level of Ca2+, determined by the fluorescence of quin-2, was elevated by TPA, and this rise required extracellular Ca2+. In contrast, stimulation of hexose uptake was still observed in Ca2+ -free media even when cytoplasmic [Ca2+] was buffered with quin-2. TPA also raised the cytoplasmic pH, presumably through activation of the Na+/H+ exchange. However, replacement of extracellular Na+ by N-methylglucamine+ or choline+ which prevents the cytoplasmic alkanization did not prevent stimulation of hexose uptake by TPA. Moreover, amiloride, at concentrations that inhibit Na+/H+ exchange in these cells, did not interfere with stimulation of hexose uptake by TPA. In conclusion, stimulation of hexose uptake by phorbol ester in rat thymocytes does not appear to be mediated by changes in cytosolic free Ca2+ or in the activity of the Na+/H+ antiport.

Animals↗
PubMed1984

Labelling of the human erythrocyte glucose transporter with 3H-labelled cytochalasin B occurs via protein photoactivation.

Irradiation of human erythrocyte membranes with 3H-labelled cytochalasin B results in specific photolabelling of the glucose transporter. The action spectrum of photolabelling has a maximum at approx. 280 nm, whereas the absorption spectrum of cytochalasin B is maximal at 210 nm. By irradiating with narrow-band-width light centered at 280 nm for 2 h, 8% of the transporters become covalently labelled and 47% of the remaining cytochalasin B-binding sites are obliterated. We conclude that photolabelling driven by narrow-bandwidth irradiation proceeds via photoactivation of an aromatic amino acid residue on the transporter molecule, and when compared to wide-bandwidth irradiation, permits more efficient incorporation of the label without causing additional photodamage to the remaining transporters.

Carrier Proteins↗
PubMed1984

Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. I. Distinctions between volume-activated Cl- and K+ conductance pathways.

Human peripheral blood lymphocytes (PBL), when placed into hypotonic media, first swell and then shrink back to their original volumes because of a rapid KCl leakage via volume-activated K+ and anion permeation pathways. By using gramicidin, a cation channel-forming ionophore, cation transport through the cell membrane can be shunted so that the salt fluxes and thus the volume changes are limited by the rate of the net anion movements. The "gramicidin method," supplemented with direct measurements of volume-induced ion fluxes, can be used to assess the effects of drugs and of various treatments on cation and anion permeabilities. It is demonstrated that quinine and cetiedil are much more effective blockers of volume-induced K+ transport than of Cl- transport, while dipyridamole, DIDS, and NIP-taurine inhibit only volume-induced Cl- movement. Oligomycins block both cation and anion transport pathways, oligomycin A being more effective in inhibiting K+ transport and oligomycin C preferentially blocking Cl- movement. Ca depletion of PBL abolishes volume-induced K+ transport but has no effect on Cl- transport. Repletion of cell calcium by ionophore A23187 immediately restores rapid K+ transport without significantly affecting volume-induced Cl- transport. These observations, taken together with other reported information, can be best explained by a model in which cell swelling activates independent Cl- and K+ conductance pathways, the latter being similar in properties to the Ca2+-activated K+ transport observed in various cell membranes.

Azepines↗
PubMed1984

Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. II. Volume- and time-dependent activation and inactivation of ion transport pathways.

Hypotonic dilution of human peripheral blood lymphocytes (PBL) induces large conductive permeabilities for K+ and Cl-, associated with the capacity of the cells to regulate their volumes. When rapid cation leakage is assured by the addition of the ionophore gramicidin, the behavior of the anion conductance pathway can be independently examined. Using this technique it is demonstrated that the volume-induced activation of Cl- transport is triggered at a threshold of approximately 1.15 X isotonic cell volume. If the volume of a cell is increased to this level or above, the Cl- transport system is activated, whereas if the volume of a swollen cell is decreased below the threshold value, the Cl- transport is inactivated. Activation and inactivation are independent of the relative volume changes and of the actual cellular Na+, K+, or Cl- concentrations, as well as of the changes in membrane potential in PBL. When net salt movement and thus volume change are inhibited by specific blockers of K+ transport (e.g., quinine, or Ca2+ depletion), volume-induced Cl- conductance shows a time-dependent inactivation, with a half-time of 5-8 min. The Cl- conductance, when activated, appears to involve an all-or-none response. In contrast, volume-induced K+ conductance is a graded response, with the increase in K+ flux being roughly proportional to the hypotonicity-induced increase in cell volume. The data indicate that during lymphocyte volume response in hypotonic media, anion conductance increases by orders of magnitude, exceeding the K+ conductance, so that the rate of the volume decrease (KCl efflux) is determined by a graded alteration in K+ conductance. When the cell volume approaches the isotonic value, it is stabilized by the inactivation of the anion conductance pathway.

Biological Transport↗
PubMed1983

Glucagonomas. Ultrastructure and immunocytochemistry.

Pancreatic tumors harboring glucagon immunoreactive cells were found in four patients with diabetes mellitus. Alpha-cell (glucagon) granules were present in three tumors; pancreatic polypeptide (PP) immunoreactive cells were detected in two. In two patients the tumors were malignant and one of these had the glucagonoma syndrome; the other was a member of a family with MEN-type I syndrome. These cases illustrate three clinical subtypes of glucagonoma.

Adenoma, Islet Cell↗
PubMed1983

Incidental coenurosis: larval cestode presenting as an axillary mass.

This article describes the occurrence of a coenurus, the encysted larval stage of a cestode of the genus Multiceps, within the axilla of a 40-year-old Nigerian woman. The patient had a history of intraductal carcinoma of the breast two years prior to the finding of an ipsilateral axillary mass. Pathologic evaluation of the biopsy specimen yielded the diagnosis of coenurosis. Only four other cases of human Multiceps infestation have been reported in the United States with fewer than 100 validated cases worldwide. Surgical removal of the larval parasite is the only known effective therapy.

Adult↗
PubMed1983

Allotransplantation of human parathyroid tissue without immunosuppression.

Organ culture facilitates successful transplantation of endocrine tissue in allogenic and xenogenic rodent systems. The major obstacle in applying this approach to human tissue is the difficulty in keeping adult human tissue alive in organ culture for a prolonged period. For this reason we have used an in vivo culture system that allows preservation of endocrine tissue for weeks or months. C57BL/6 (H-2b) thyroid grafts transplanted beneath the kidney capsule of Balb/c (H-2d) nude mice and retransplanted 15 days later to CBA (H-2k) mice survive indefinitely without immunosuppression. We report here the use of the "interim host system" for allogenic parathyroid tissue in two patients with long-standing hypoparathyroidism after total thyroidectomy.

Adult↗
PubMed1982

Resection of gastrinoma in the Zollinger-Ellison syndrome.

Patients with the Zollinger-Ellison syndrome have been managed by total gastrectomy and more recently, by the use of H2-receptor antagonists. An alternative approach has been to identify those who might be cured by excision of a pancreatic islet-cell tumor without removal of the stomach. The course of such a patient is reported. A 40-yr-old man with massive gastric hypersecretion, acid-peptic disease, diarrhea, and elevated serum gastrin was treated by excising a pancreatic gastrinoma. Serum gastrin and gastric secretion became and have remained normal for 7 yr. Symptoms ceased and provocative tests with secretin and calcium have remained normal. Three additional patients with Zollinger-Ellison syndrome in whom pancreatic islet-cell tumor resection alone has resulted in long-term cures have been identified. All were middle-aged men with severe diarrhea. These successes, the availability of techniques that permit early identification and localization of gastrinomas, and the advent of H2-receptor antagonists that can control gastric hypersecretion without gastrectomy must be considered in managing patients with gastrinomas.

Adult↗
PubMed1981

Retained biliary tract stones. Nonsurgical treatment with capmul 8210, a new cholesterol gallstone dissolution agent.

The ability of Capmul 8210, a commercial solvent that predominantly consists of glyceryl 1-mono-octanoate, to dissolve retained common duct stones by direct infusion into the T-tube was tested in 20 patients with a total of 43 stones. Of 19 patients who completed their infusion, stone disappearance was observed in 15, giving a success rate of 79%. The dissolution time for a single stone averaged four days. A slight rise in serum alkaline phosphatase and amylase levels occurred in some patients, and rapidly returned to normal when treatment was concluded. Other side effects, such as nausea and vomiting epigastric discomfort, or diarrhea, occurred occasionally but were easily controlled medically. We believe that this agent is a useful adjunct in the management of postoperative choledocholithiasis in the patient with an indwelling T-tube.

Alkaline Phosphatase↗
PubMed1981

Metabolism and biliary excretion of 2,4,5,2',4',5'-hexachlorobiphenyl in the rhesus monkey (Macaca mulatta).

The metabolism and biliary excretion of 3H-2, 4, 5, 2', 4', 5'hexachlorobiphenyl (HCB) were studied in two rhesus monkeys (Macaca mulatta), a young, mature female and a juvenile male. This compound is a major constituent of those commercial polychlorinated biphenyl (PCB) mixtures with high chlorine content, and it is also a prevalent PCB analogue in human adipose tissue. Following cannulation of the common bile duct and duodenum, allowing collection of a known fraction of bile with return of the remaining bile into the duodenum, the animals received 3H-HCB (1 gm/kg body weight) by gastric intubation. Bile was collected daily for 3 weeks. During the 3-week period, 1.3% and 4% (from the female and male, respectively) of the administered radioactivity were excreted in the bile. As has been demonstrated for other species, the monkey apparently metabolizes and excretes HCB at a rate slower than for compounds containing two adjacent unsubstituted carbons. Approximately 2% of the bile radioactivity in the adult female and 12% in the juvenile male were extracted with organic solvents. Thin layer chromatography (TLC), using a benzene:ethyl acetate (12:1) solvent system, of the organic extracts of bile separated four major regions of radioactivity designated as I, II, II, and IV with Rf values of 0.86, 0.67, 0.58, and 0.00, respectively. Region I consisted of the parent HCB, which was identified by analysis with gas chromatography-mass spectrometry (GC-MS). Region II consisted of a metabolite identified as 2,4,5,2',4',5'-hexachloro-3-hydroxybiphenyl (OH-HCB) by analysis with GC-MS of the methylated derivative of the metabolite. Region III probably contained a more polar metabolite, which has not yet been identified. Region IV contained an even more polar material, probably including conjugates of HCB metabolites. Release of OH-HCB from the water-soluble fraction of bile in the presence of beta-glucuronidase and lack of release of OH-HCB in presence of beta-glucuronidase with saccharo-1, 4-lactone (a beta-glucuronidase inhibitor) or in the presence of aryl sulfatase with saccharo-1, 4-lactone provided evidence of water-soluble, glucuronic acid conjugates of OH-HCB in the bile. The hexachlorobiphenyl was excreted in the bile as HCB, OH-HCB, and water-soluble conjugates of HCB metabolites, probably including 2,4,5,2',4',5'-hexachloro-3-hydroxybiphenyl glucuronide. The metabolism of HCB may or may not include the formation of an arene oxide.

Animals↗
PubMed1981

Effect of truncal vagotomy and pyloroplasty on hepatic bile composition in the rhesus monkey.

Changes in gallbladder motility and alteration of bile composition have been implicated in the formation of gallstones after truncal vagotomy. Hepatic bile composition was found to be unchanged after truncal vagotomy with Heineke-Mikulicz pyloroplasty in our long-term study. . The data suggest that the alleged increase in the incidence of cholelithiasis after vagotomy and pyloroplasty can be isolated from an effect on the liver. These results may have implications for the preferred course of surgical intervention in certain patients.

Animals↗