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S Mishkin

Publications and source records attributed to S Mishkin.

12 recordsLinked to original sources
PubMed1979

Increased survival of rats bearing Morris hepatoma 7800 after induction of hypothyroidism.

The survival of Buffalo rats brearing Morris Hepatoma 7800 was increased significantly (23 to 31%) after induction of hypothyroidism by propylthiouracil (PTU) (0.1% in Purina rat chow) or 131I. The concentration of PTU used was in the optimal range as 0.03% PTU was less effective than 0.1%, while 0.4% PTU appeared to be toxic. Exogenous thyroxine (8 microgram/kg body weight) reversed the effects of PTU and actually shortened survival. Because food consumption and body weights of hypothyroid rats were decreased, the survival of pair-fed controls was studied and found to be the same as in untreated controls. We conclude that the hypothyroid state increases the survival of rats bearing Morris Hepatoma 7800. We have not yet been able to define any anatomical or biochemical parameters which may be responsible for this effect.

Animals↗
PubMed1979

Inhibition of the growth of Morris hepatoma No. 44 in rats after induction of hypothyroidism: evidence that Morris hepatomas are thyroid dependent.

The growth rate of Morris Hepatoma No. 44 (generation time, 6 mo) was inhibited after the induction of hypothyroidism by Propylthiouracil (PTU) (0.1% in Purina Chow), I131 (1 mCi/100 g body wt i.p.), or surgical thyroidectomy. After 11 wk of treatment, hepatoma weight was 66%, 87%, and 75% (after correction for total body wt) relative to controls in PTU-fed, I131 injected, and thyroidectomized rats, respectively. In each case, exogenous thyroxine (T4) (8 microgram/kg body wt i.p.) reversed these inhibitory effects, while T4 administered to euthyroid rats stimulated hepatoma growth. The degree of growth-inhibition achieved with PTU was not observed in pair-fed rats. In addition, after correction for differences in body weight, the sex of the tumor-bearing rats did not influence the response to PTU. Pretreatment with PTU for 2 wk before implantation did not give any added advantage over the effects of PTU administered approximately 10 days after implantation. Serum levels of triiodothyronine (T3) and T4, as well as the concentration of various biochemic parameters, were determined at the time of death. These results suggest that the growth rate of Morris Hepatoma No. 44 is thyroid hormone dependent.

Animals↗
PubMed1978

Uptake of labeled palmitate by the intact liver: role of intracellular binding sites.

The multiple-indicator dilution technique was utilized to examine the hepatic uptake of albumin-bound labeled palmitate from the portal vein blood of the pentobarbital-anesthetized dog, in a fasted state and after infusion of a variety of compounds that were expected to bind to Z protein, the cellular cytosolic protein binding free fatty acids, and their acyl-CoA derivatives. Analysis of the data indicates that after infusion of alpha-bromopalmitate, 16-bromo-9-hexadecenoate, and sulfobromophthalein sodium (which also bind to albumin), the palmitate label influx, efflux, and metabolic sequestration (removal of label from the pool of free fatty acids able to leave the cell) all increase and that, after infusion of flavaspidic acid, label efflux and metabolic sequestration increase. In vitro competitive binding studies carried out on the cellular cytosol indicat that the basis for the increase in efflux and metabolic sequestration is displacement of labeled palmitate from high affinity sites on the intracellular Z protein (which are presumably in equilibrium with and may be taken to be representative of other intracellular binding sites). These studies also suggest that increased uptake is due to similar displacement from high affinity sites on serum albumin.

Animals↗
PubMed1978

Elevated serum amylase activity in the absence of clinical pancreatic or salivary gland disease: possible role of acute hypoxemia.

Elevated serum amylase activity, in the absence of clinically apparent pancreatic or salivary gland disease, has been observed in many seemingly unrelated conditions. In a search for common etiological factors to account for hyperamylasemia in these conditions, a retrospective analysis was performed. Eighty-four episodes of hyperamylasemia (greater than 300 I.U./l. Phadebas method) occurring in 75 patients over a one-year period ending in June, 1975 were assigned to one of two groups. Group 1 consisted of 56 (67%) episodes of hyperamylasemia with clinical pancreatitis. Group 2 consisted of 28 (33%) episodes of hyperamylasemia in the absence of clinical pancreatitis. Hypoxemia (pO2 less than 75 mm. Hg.) was found in 9/15 patients in Group 2 who had arterial blood gases measured. To assess the possible relationship between acute hypoxemia and amylase activity, a prospective study was initiated. Patients with known causes of pancreatitis or renal failure were eliminated. Hyperamylasemia was found in 3/8 hypoxemic patients. This raises the possibility that acute hypoxemia alone or in combination with other factors may raise serum amylase activity, possibly through ischemic injury to the pancreas or salivary glands or other amylase containing tissues.

Acute Disease↗
PubMed1977

Reduced concentrations of Z protein in Morris hepatomas. Possible role in abnormal regulation of lipid metabolism.

The cytoplasmic concentration of Z protein (Mr approximately 12,000) was significantly reduced in a series of implanted Morris hepatomas with varying degrees of differentiation. Approximately half of the [14C]palmitoyl-CoA added to cytosol fractions from control or host livers was bound to the Z protein region whereas a much smaller proportion was bound to this region in the cytosol of nine Morris hepatomas studied. The possible implications of these findings are discussed in relation to the abnormal regulation of lipid metabolism in hepatomas.

Animals↗
PubMed1976

Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis.

Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with "routine acute pancreatitis" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins.

Acute Disease↗
PubMed1976

Effect of fasting on hepatic ligandin, Z protein, and organic anion transfer from plasma in rats.

The effect of fasting on the rate of disappearance from plasma of bromsulphthalein (BSP) and dibromsulphthalein (DBSP), the hepatic content of BSP, and the concentration of ligandin and Z protein, two hepatic organic anion-binding proteins, was studied in the rat. Fasting for 48 h decreased the plasma disappearance of BSP and DBSP and the hepatic content of BSP as well as the amount of ligandin and Z protein. Phenobarbital given prior to fasting partially prevented these changes. A method of quantitation of Z by radioimmunoassay is described. Discrepancies in Z quantiation by dye binding and immunological methods in fasted but not control rats suggest the presence of competitors for organic anion binding to Z in fasting as well as after phenobarbital administration. Results of studies of ligandin turnover during fasting suggest decreased synthesis and increased degradation of the protein. Similar events may be of pathogenetic importance in nonhemolytic unconjugated hyperbilirubinemia observed during fasting in man, horses, and other animals.

Animals↗
PubMed1975

Uptake and compartmental distribution of fatty acid by rat small intestine in vivo.

The uptake and esterification of micellar [3-H]oleate and [14-C] palmitate were uniform along the entire length of the small intestine in vivo. Fatty acids (FA) radioactivity taken up by the small intestine could be described in terms of four functionally distinct compartments analogous to those described in vitro. The KRP-extractable compartment (KEC) and albumin-extractable compartment (AEC) contained reversibly adherent unesterified FA radioactivity, while the tissue free and esterified FA compartments contained irreversibly bound radioactivity. Wheras 27% and 63% of FA uptake were reversibly bound in the KEC and AEC by the most proximal and most distal regions of the small intestine in vitro (15), less than 10% was contained in these compartments in vivo, independent of location. Linear inverse relationships were found betweeen tissue FA esterification and proportion of FA radioactivity present in the KEC,AEC, and the tissue free FA compartment in vivo. These observations allow for the possibility that FA molecules pass through these compartments prior to esterification.

Animals↗
PubMed1975

Z protein in hepatic uptake and esterification of long-chain fatty acids.

Fatty acids radioactivity was bound to Z protein in liver after administration of['3H]oleate to rats or to a perfused rat liver preparation. Pretreatment withflavaspidic acid (340 mumol/kg), a potent inhibitor of fatty acid binding to hepatic Zprotein in vitri, effectively reduced oleate radioactivity bound to Z by 90.2 plusor minus 4.3% and 85.0 plus or minus 6.2% in the intact rat and perfused liver, respectively. In spite of this effect, pretreatment of rats with flavaspidic acid did notalter plasma clearance, hepatic uptake, and esterification of ['3H]oleate. In contrast, in the perfused liver preparation, infusion of flavaspidic acid (340 mumol/kg)or bromosulphalein (360 mumol/kg) increased uptake of ['3H]oleate at least twofold,and oleate esterification was decreased by 15-30%. These results suggest that the binding of long-chain fatty acids to Z protein is not an obligatory step in their uptakeby the liver and that Z protein may be involved in fatty acid esterification.

Animals↗