Showing papers by "University of Texas Southwestern Medical Center published in 1975"

A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias

Abstract: A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (less than 0.11 mg per milligram of urinary creatnine). Urinary calcium was high (greater than or equal to 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (greater than 4.60 mu moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (greater than 6.86 mu moles per gram of creatinine) or high-normal fasting urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria.

Elevated plasma and tissue levels of vasoactive intestinal polypeptide in the watery-diarrhea syndrome due to pancreatic, bronchogenic and other tumors.

Abstract: The actions of the vasoactive intestinal polypeptide make it a potential candidate for mediating certain manifestations of the watery-diarrhea syndrome. Peptide levels were measured by radioimmunoassay in 25 controls and 30 patients with chronic watery diarrhea. Plasma levels were too low to measure ( < 200 pg per milliliter) in 22 of the controls, averaging 79 ± 64 pg per milliliter (S.D.). Levels were elevated in 26 of 28 plasma samples (5.1 ± 2.5 ng per milliliter), and ineach of 13 tissue extracts (5.1 ± 10.9 μg per gram); in all, 28 patients had elevated levels in plasma or tissue or both. Thirteen patients had pancreatic islet-cell adenoma, four islet-cell hyperplasia, five bronchogenic carcinoma, and one each pheochromocytoma and ganglioneuroblastoma.The findings indicate that the peptide is a probable mediator of the watery-diarrhea syndrome, that the syndrome may result from a variety of non-pancreatic tumors, and that this or a related peptide may also be secreted by these tumors. (N En...

Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.

Abstract: The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90 percent decrease in the cellular content of cholesteryl esters and a 30 percent decrease in the free cholesterol content. When these lipoprotein-deprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximal effect in elevating cellular sterol content (30 mug/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesteryl esters in normal cells. Furthermore, in fibroblasts from patients with the homozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 mug sterol/ml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Moreover, when considered in light of current concepts of LDL metabolism in intact mammals, the present data suggest that a major function of plasma LDL may be to transport cholesterol from its site of synthesis in liver and intestine to its site of uptake in peripheral tissues.

Cytoplasmic type 80S ribosomes associated with yeast mitochondria. IV. Attachment of ribosomes to the outer membrane of isolated mitochondria.

Abstract: Growing yeast spheroplasts were shown to have, on the average, four times the number of cytoplasmic ribosomes in contact with the outer mitochondrial membrane compared to starved spheroplasts. Ribosomes in contact with mitochondria in the growing spheroplast preparation, like free cytoplasmic ribosomes, exist primarily as polysome structures. In the starved spheroplast preparation, both mitochondria-bound and free cytoplasmic ribosomes exist primarily as monosomes. Mitochondria isolated from growing spheroplasts in a medium containing lmM Mg++ have cytoplasmic ribosomes bound directly to the outer membrane. These ribosomes can be quantitatively removed by washing the mitochondria with 2 mM EDTA. Mitochondria from starved spheroplasts are capable of accepting either free cytoplasmic polysomes or cytoplasmic polysomes extracted from mitochondria. However, the extent of polysome binding to mitochondria was shown to be a direct function of the Mg++ concentration; a smaller percentage of the input polysomes bind as the Mg++ concentration is lowered. At 1 mM Mg++, neither free cytoplasmic nor mitochondria-bound polysomes bind to mitochondria. Nevertheless, when growing spheroplasts are broken and mitochondria isolated in medium containing 1 mM Mg++, the mitochondria are seen to have cytoplasmic ribosomes firmly attached to the outer membrane. This result, in addition to our earlier data (Kellems, R. E., and R. A. Butow. 1974. J. Biol. Chem. 249:3304-3310), support the view that cytoplasmic ribosomes attached to the outer membrane of purified mitochondria were attached in vivo. In preparations of mitochondria isolated from growing spheroplasts, ribosomes appear to be found to specific regions of the outer membrane, namely those regions which are in close association or in contact with the inner mitochondrial membrane. This is particularly evident with mitochondria in a condensed configuration. This finding suggests a mechanism whereby cytoplasmically synthesized mitochondrial protein could be transferred by a process of vectorial translation across both membranes of the organelle.

Neisseria gonorrhoeae and neisseria meningitidis: extracellular enzyme cleaves human immunoglobulin A.

Abstract: The gonococcus and meningococcus, which infect human mucosal surfaces, elaborate a highly specific proteolytic enzyme which cleaves the immunoglobulin A1 subclass of the principal mucosal antibody, immunoglobulin A (IgA). The susceptible Pro-Thr bond lies in a unique region of the IgA heavy chain; the IgA2 subclass, lacking this peptide bond, is enzyme resistant.

Role of carnitine in hepatic ketogenesis.

Abstract: The enhancement of long-chain fatty acid oxidation and ketogenesis in the perfused rat liver, whether induced acutely by treatment of fed animals with anti-insulin serum or glucagon, or over the longer term by starvation or the induction of alloxan diabetes, was found to ba accompanied by a proportional elevation in the tissue carnitine content. Moreover, when added to the medium perfusing livers from fed rats, carnitine stimulated ketogenesis from oleic acid. The findings suggest that the increased fatty acid flux through the carnitine acyltransferase (carnitine palmitoyl-transferase; palmitoyl-CoA:L-carnitine O-palmitoyltransferase; EC 2.3.1.21) reaction brought about by glucagon excess, with or without insulin deficiency, is mediated, at least in part, by elevation in the liver carnitine concentration.

Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia.

Abstract: The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt. The results were compared with those of similar studies simultaneously performed in untreated patients with the heterozygous form of FH and with the results of earlier studies performed on normolipidemic subjects. Before shunt surgery, the rate of synthesis of LDL in the FH homozygote (mg/kg per day) was fourfold higher than in normolipidemic subjects and twofold higher than in her heterozygous mother. The fractional catabolic rate for LDL in the homozygote was decreased to 33% of normal control values. The rate of cholesterol synthesis, estimated by chemical sterol balance, was higher in the FH homozygote than in two FH heterozygotes of similar age studied simultaneously. When considered in relation to the markedly elevated level of plasma cholesterol, the observed rate of cholesterol synthesis in the FH homozygote was inappropriately elevated. Bile acid production was normal in all three children. 5 mo after shunt surgery, the rate of LDL synthesis in the homozygote had declined by 48% as compared with the preoperative value, and this caused a 39% drop in the plasma LDL cholesterol level despite a 17% reduction in the fractional catabolic rate of the lipoprotein. The rate of cholesterol synthesis fell by 62% as compared with the preoperative value. The findings of an inappropriately elevated rate of production of both cholesterol and LDL as well as a reduced fractional catabolic rate for the lipoprotein in the untreated FH homozygote are consistent with results of studies in cultured fibroblasts indicating that the primary genetic defect in FH involves a deficiency in a cell-surface receptor for LDL that regulates both cholesterol synthesis and LDL degradation. Although the mechanism for the decline in production of cholesterol and LDL after portacaval shunt surgery is unknown, it was observed that these changes were associated with marked increases in the plasma concentrations of bile acids and glucagon.

Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon.

Abstract: The enhanced capacity for long-chain fatty acid oxidation and ketogenesis that develops in the rat liver between 6 and 9 h after the onset of starvation was shown to be inducible much more rapidly by administration of anti-insulin serum or glucagon to fed rats. After only 1 h of treatment with either agent, the liver had clearly switched from a "nonketogenic" to a "ketogenic" profile, as determined by rates of acetoacetate and b-hydroxybutyrate production on perfusion with oleic acid. As was the case after starvation, the administration of insulin antibodies or glucagon resulted in depletion of hepatic glycogen stores and a proportional increase in the ability of the liver to oxidize long-chain fatty acids and (-)-octanoylcarnitine, suggesting that all three treatment schedules activated the carnitine acyltransferase system of enzymes. In contrast to anti-insulin serum, which produced marked elevations in plasma glucose, free fatty acid, and ketone body concentrations, glucagon treatment had little effect on any of these parameters, presumably due to enhanced insulin secretion after the initial stimulation of glycogenolysis. Thus, after treatment with glucagon alone, it was possible to obtain a "ketogenic" liver from a nonketotic animal. The results are consistent with the possibility that the activity of carnitine acyltransferase, and thus ketogenic capacity, is subject to bihormonal control through the relative blood concentrations of insulin and glucagon, as also appears to be the case with hepatic carbohydrate metabolism.

Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology.

Abstract: Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with "unstable angina pectoris", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with "unstable angina" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.

Receptor dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein

Abstract: Selective radioactive labeling of the cholesteryl esters contained within human plasma low density lipoprotein has allowed the study of the metabolism of these molecules in monolayers and extracts of cultured human fibroblasts. In monolayers of normal cells, binding of low density lipoprotein to its cell surface receptor was followed by rapid hydrolysis of the [3H]cholesteryl linoleate contained within the lipoprotein and accumulation of the liberated [3H]cholesterol within the cell. The stoichiometry of the degradative process suggested that the protein and cholesteryl ester components of the lipoprotein were hydrolyzed in parallel. Incubation of intact fibroblasts with chloroquine, a known inhibitor of lysosomal degradative processes, inhibited the hydrolysis of the lipoprotein-bound cholesteryl esters. Fibroblasts from subjects with the homozygous form of familial hypercholesterolemia, which lack functional low density lipoprotein receptors and thus are unable to take up this lipoprotein when it is present in the culture medium at low concentrations, were therefore unable to hydrolyze the lipoprotein-bound [3H]cholesteryl linoleate. However, cell-free extracts from these mutant cells were capable of hydrolyzing the lipoprotein-bound [3H]cholesteryl linoleate at the same rapid rate as normal cells when incubated at acid pH. These data illustrate the essential role of the low density lipoprotein receptor and of lysosomal acid hydrolases in the metabolic utilization of low density lipoproteins by cultured human fibroblasts.

Cell surface immunoglobulin. XI. The appearance of an IgD-like molecule on murine lymphoid cells during ontogeny.

Abstract: An Ig molecule containing L chains and H chains similar to human delta-chains has been detected on the surface of radioiodinated murine lymphoid cells. Newborn mice have only IgM on their splenocytes. Between 10 and 15 days, the IgD-like molecule appears and increases in amount until 3 mo of age, when it is the predominant cell surface Ig in terms of radioactivity. IgD is found only in peripheral lymphoid tissues and is present in larger amounts on peripheral lymph node cells (approximately 85% of surface Ig) than on splenocytes (approximately 50%). IgD is also present in comparable amounts on cells from both nu/nu and germfree mice, indicating that its expression may be independent of both thymic influence and antigenic stimulation. These studies suggest that there is a switch from cell surface IgM to IgD that occurs during differentiation of virgin B lymphocytes in the spleen.

Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues.

Abstract: Ninety-three patients with a variety of joint diseases were studied for evidence of immune complexes in articular collagenous tissues. Frozen sections of freshly obtained biopsies of hyaline articular cartilage and menisci were stained with fluoresceinated monospecific antisera for evidence of human immunoglobulins (IgG, IgM, IgA) and the β1c component of complement. The criterion for the presence of complexes was the staining of two or more immunoglobulins and β1c in an identical location of sequentially cut sections. Of the 42 patients with rheumatoid arthritis (RA) 83% were positive by this criterion. In those with classic RA the incidence was 92%. Sixteen patients with fresh joint trauma or nonarthritic disease had negative findings. Among 26 patients with noninflammatory disease, 4 of 8 with polyarthritis whose features suggested primary degeneration, 1 of 11 patients with secondary degenerative arthritis, and a single case of synovial osteochondromatosis had positive findings. Among 9 patients with miscellaneous inflammatory arthritides, all of 3 with psoriatic arthritis were negative; however 2 of 6 with other inflammatory arthritides were positive. The findings in classic RA suggest that immune complexes are deposited in the articular collagenous tissues. The persistence of these complexes may play a significant role in the chronicity of the synovitis.

Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor.

Abstract: Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylgultaryl-CoA reductase (NADPH) [mevalonate:NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the 125-I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous defects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipoprotein receptor.

Electron microscopic studies of the cartilage-pannus junction in rheumatoid arthritis.

Abstract: The junction between pannus and cartilage was examined in the rheumatoid joint. Three types of cartilage-pannus junction were observed. In one, proliferating small blood vessels, surrounded by highly cellular infiltrates, penetrated deeply into the cartilage. Degeneration of the cartilage was observed around the cellular accumulations. In the second, phagocytic and fibroblastic cells invaded the cartilage. In the third, fibrous pannus overlay the cartilage. Lysis of cartilage by infiltrating cells appeared to be a major cause of cartilage erosion in rheumatoid arthritis.

Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.

Abstract: Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordi) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and modified the reduction in the reflow phenomenon to the subendocardial portion of the ischemic area. Thus, both an increase in coronary vascular resistance and a significant reduction in reflow to the subendocardial portion of the ischemic area occur in the canine heart after 120 minutes of myocardial ischemia. Moreover, the increase in coronary vascular resistance can be prevented and the reduction in reflow to the subendocardial portion of the ischemic area can be modified by the administration of hypertonic mannitol.

Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs.

Abstract: To obtain insight into the mechanism(s) responsible for the direct visualization of acute myocardial infarcts by myocardial scintigraphy with technetium-99m stannous pyrophosphate (99mTc-PYP), scintigraphic and morphologic studies were performed in 22 dogs subjected to occlusion of the proximal left anterior descending coronary artery (LAD). Grossly visible myocardial infarcts occurred in ten of 11 dogs with LAD occlusion for one day, five with LAD occlusion for two days, two with LAD occlusion for seven days and two with LAD occlusion for 13 days. Rare, microscopic foci of necrosis were observed in one dog with LAD occlusion for one day, and no lesions were present in two dogs subjected to temporary LAD occlusion for eight minutes and reflow for 24 hours. In the latter three dogs, 99mTc-PYP myocardial scintigrams were negative. In the 19 dogs with gross infarcts, 99mTc-PYP myocardial scintigrams were strongly positive at one and two days after LAD occlusion, much less positive at seven days and faintly positive at 13 days after occlusion. Positive myocardial scintigrams in most showed "doughnut" patterns, with marked peripheral concentration of radioactivity around central zones of much lower activity. On histologic examination, the one and two-day-old infarcts exhibited subendocardially located central zones and surrounding peripheral zones, both of which showed distinctive histopathological and histochemical features, including the selective occurrence in the peripheral zones of calcified muscle cells with ultrastructurally demonstrable apatite-like crystals in mitochondria. Selective occurrence of high tissue levels of 99mTc-PYP radioactivity also was demonstrated in the peripheral zones of four infarcts. Hearts with older infarcts (seven and 13 days) showed progressive replacement of necrotic myocardium by granulation tissue and progressive reduction in calcium deposits in the areas of damage. The data obtained in this study establish a temporal and topographical relationship between calcium accumulation in acute myocardial infarcts and 99mTc-PYP uptake responsible for scintigraphic detection of the lesions with this radionuclide in dogs subjected to proximal LAD occlusion.

Acute subendocardial myocardial infarction in patients. Its detection by Technetium 99-m stannous pyrophosphate myocardial scintigrams.

Abstract: Eighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannour pyrophosphate (99m-Tc-PYP). Seventeen of these patients had ECG and enzymatic evidence suggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were postivie demonstrating increased 99m-Tc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence of acute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus 99m-Tc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial infarction in patients. The absolute frequency with shich subendocardial myocardial infarction can be recognized utilizing this technique will have to be established in a larger number of patients in the future.

Lymphokines in the rheumatoid joint.

Abstract: Joint fluids and culture supernatants of synovial tissue were examined for the presence of two lymphokines. Migration inhibitory activity was found in 16 of 22 rheumatoid fluids (73%), in 3 of 15 osteoarthritis fluids (20%), and in 3 of 11 fluids from patients with various inflammatory arthritides (27%). Blastogenic activity was present in 14 of 15 rheumatoid fluids and in 1 of 7 nonrheumatoid effusions. The active materials eluted with the third peak from Sephadex G-200 and were therefore smaller than immunoglobulin or immune complexes. These findings suggest that lymphokine-like substances were present in effusions and synovial tissue of most patients with rheumatoid arthritis and some patients with other forms of chronic synovitis.

Heterogeneous Nucleation of Calcium Oxalate by Seeds of Monosodium Urate

Abstract: SummarySeeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria.This work was supported by a Grant from the USPHS (R01-AM16061) and by a Grant from Burroughs-Wellcome Co.

Aromatization of androstenedione by isolated human hairs.

Abstract: The formation of [3H]estrone has been demonstrated in human anagen scalp hair roots incubated with [1,2,6,7-3H]androstenedione, and approximate rates of formation of 0.2 pmol of estrone/mg DNA/h were observed. Thus, hair is a potential site for the extraglandular formation of estrogen in man.

On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets.

Abstract: Spleen cells cultured with syngeneic trinitrophenyl (TNP)-modified stimulator cells display a cytotoxic effect against syngeneic TNP-modified targets, but not against modified targets from unrelated H-2 haplotypes. Targets that share the K and I region of the H-2 complex with the stimulator (or effector) cell are lysed to the same extent as the specific targets, while targets that share the I region only are not. When only the D region is shared, a weak cytotoxic effect is observed. Therefore, the stimulator (or effector) and target cell must share the K or D but not the I region of the H-2 complex in order for optimal cytotoxicity to occur. Spleen cells sensitized to irradiated TNP-modified H-2-allogeneic cells are cytotoxic to these specific cells. Coculture of F1 hybrid cells with irradiated TNP-modified parental cells result in a cytotoxic effect against only those specific parental cells and not TNP-modified cells from the other parent. The cytotoxic effect of the F1 effector cells in the cell-mediated lympholysis test is blocked by the addition of unlabeled TNP-modified targets that are H-2 syngeneic with the sensitizing parental strain, but not H-2 syngeneic with the other parental strain. These data demonstrate that the specificity of the effector cell in this syngeneic cytotoxicity system is directed against altered self H-2-controlled-gene products, rather than a requirement for sharing of histocompatibility genes between effector and target cell in order for lysis to occur. The role of H-2 antigens in determining the sensitivity of a target cell to T-cell-mediated lysis is discussed.

Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and nondiabetics

Abstract: The effect of the intravenous infusion of insulin plus glucose on plasma glucagon levels was studied in hyperglycemic fasting adult-type and juvenile-type diabetics and compared with fasting nondiabetics. Adult-type diabetics were given insulin for 2 h at a rate of 0.03 U/kg-min, raising their mean insulin to between 25 and 36 muU/ml; glucagon declined from a base-line value of 71+/-2 (SEM) to 56+/-1 pg/ml at 120 min (P less than 0.001). In juvenile-type diabetics given the same insulin-glucose infusion, glucagon declined from a base-line level of 74+/-8 to 55+/-5 pg/ml at 120 min (P less than 0.05). The absolute glucagon values in the diabetic groups did not differ significantly at any point from the mean glucagon levels in nondiabetics given insulin at the same rate plus enough glucose to maintain normoglycemia. When glucagon was expressed as percent of baseline, however, the normoglycemic nondiabetics exhibited significantly lower values than adult-type diabetics at 90 and 120 min and juvenile-type diabetics at 60 min. In nondiabetics given insulin plus glucose at a rate that caused hyperglycemia averaging between 134 and 160 mg/dl, glucagon fell to 41+/-7 pg/ml at 120 min, significantly below the adult diabetics at 90 and 120 min (P less than 0.01 and less than 0.05) and the juvenile group at 60 min (P less than 0.01). The mean minimal level of 39+/-2 pg/ml was significantly below the adult (P less than 0.001) and juvenile groups (P less than 0.05). When insulin was infused in the diabetic groups at a rate of 0.4 U/kg-min together with glucose, raising mean plasma insulin to between 300 and 600 muU/ml, differences from the hyperglycemic nondiabetics were no longer statistically significant. It is concluded that, contrary to the previously reported lack of insulin effect in diabetics during carbohydrate meals, intravenous administration for 2 h of physiologic amounts of insulin plus glucose is accompanied in unfed diabetics by a substantial decline in plasma glucagon. These levels are significantly above hyperglycemic nondiabetics at certain points but differ from normoglycemic nondiabetics only when expressed as percent of the baseline. At a supraphysiologic rate of insulin infusion in diabetics, these differences disappear.

Fetal plasma prolactin levels.

Abstract: Prolactin levels were measured by radioimmunoassay in umbilical cord plasma from fetuses, in capillary plasma from neonates, and in venous plasma from adults The concentrations of prolactin in cord plasma from fetuses having gestational ages of 16 to 19 weeks, 20 to 34 weeks, and 35 to 42 weeks were 53 ± 16 (mean and SE), 233 ± 30 and 371 ± 7 ng/ml, respectively The prolactin levels decreased to 218 ± 35 ng/ml during the first neonatal week The similarity of the patterns of prolactin levels, reported gestational estrogen levels and adrenal weights, as well as the known biological properties of prolactin, estrogen, and ACTH is consistent with the view that these three factors may be involved in the growth of the fetal adrenal cortex and its involution in the newborn