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Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 235 records · Page 13Linked to original sources

Triglyceride kinetics: effects of dietary glucose, sucrose, or fructose alone or with hyperinsulinemia.

The effects of different dietary sugars, with or without exogenously induced hyperinsulinemia, on rat plasma triglyceride kinetics have been studied. Glucose, sucrose, or fructose were supplied as 10% drinking solutions. The sugar-supplemented groups were each divided into subgroups, one receiving 6 U of insulin per day for 2 wk from intraperitoneally implanted minipumps and the other receiving none. The same degree of hyperglycemia and of endogenous hyperinsulinemia was seen in each sugar-supplemented group. Infusing exogenous insulin restored normoglycemia and produced more pronounced but equal hyperinsulinemia in each subgroup. In those rats that received no exogenous insulin, triglyceride production increased 18% in the sucrose-supplemented group and 20% in the fructose supplemented subgroups, but not at all in the glucose-supplemented subgroup. This 20% increase in triglyceride production in the fructose-supplemented subgroup was accompanied by a six times greater (120%) increase in triglyceride concentration. This suggested that dietary fructose not only increased triglyceride production, but also impaired triglyceride removal. Exogenously induced hyperinsulinemia further increased triglyceride production in those rats receiving dietary fructose, either as the monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. As exogenous insulin returned the triglyceride concentrations to normal in the fructose-supplemented rats, it also appeared to overcome any fructose-associated impairment of triglyceride removal.

Animals↗

[Disk hernia of the lumbar spine. Radiologic study with special reference to the technic and value of nuclear magnetic resonance tomography].

Degenerations of the spinal disc especially in the lumbar region are the most frequent degenerative diseases in orthopedics. As diagnostic proceedings to discover disc herniation myelography and computerized tomography have been proven to be very usefull. Each of those methods show a high sensitivity and accuracy. Computerized tomography seems to be the first procedure because of the lac of any risk. Myelography has been reserved for the second approach, if there is any doupt in diagnosis. This paper will especially discuss advantages and disadvantages of MRI-tomography for the diagnosis of disc herniation. In MRI-tomography we have no radiation, there is no risk for the patient and we have the possibility of slices in different orientations with the sagittal orientation having priority in diagnosis of disc herniation. A more pronounced contrast in MRI relatively to the computerized tomography with nearly the same spatial resolution is an other important fact in favour for MRI. The value of MRI diagnosis of the spine depends however mainly on the use of special surface coils and on the use of high magnetic fields which provides a good signal to noise relation and which would permit us to use a thin-slice technique.

Humans↗

[A simple method for imaging disorders of cardiac wall contraction using MRT].

By means of ECG triggering, it is possible to demonstrate various phases of cardiac action. It is then possible to derive a measure for cardiac function. The disadvantage of the method consists of the long measurement period required and the creation of movement artifacts. A method is discussed which would permit the demonstration of normal cardiac movement during a short time span and which reduces artifacts. In order to obtain optimum results, a new sequence of measurements is suggested. This is based on spin-echo sequences and can readily be used with any type of MRT apparatus.

Adult↗

Milk and plasma lipid composition in a lactating patient with type I hyperlipoproteinemia.

This report describes studies on the plasma and milk lipid composition of a patient with primary Type I hyperlipoproteinemia who had been followed through her second pregnancy. Post-partum she lactated, supplying milk for assay. It was abnormal in the low content of its total lipid and in the bizarre composition of its fatty acids. The proportion of long chain fatty acids was unusually low, and that of medium chain fatty acids unusually high. Furthermore, the fatty acids of the patient's milk differed greatly from those of her plasma triglycerides. This was in marked contrast to normal nursing mothers' milk, in which the fatty acid composition is comparable to that of plasma triglycerides. The patient's milk fatty acids were shorter in chain length and deficient in essential fatty acids. During the time of lactation, the patient remained hyperlipidemic and her post-heparin plasma had no lipolytic activity. These data and the differences between the plasma and milk fatty acids suggested that in the patient the circulating triglyceride fatty acids did not enter the mammary gland. Without preformed fatty acids entering it from plasma or adipose tissue, the lactating breast apparently synthesized fatty acids de novo. These newly synthesized fatty acids were of medium, rather than long chain length. This accounted for the abundance of medium chain length triglycerides in the patient's milk. The studies suggested that the deficit of lipoprotein lipase in Type I hyperlipoproteinemia extended to the mammary gland.

Adult↗

Very low density lipoprotein binding to cultured aortic endothelium.

Because of very low density lipoprotein's (VLDL) potential atherogenicity and the demonstration that VLDL can bind to other cells, we examined the interaction of human VLDL with cultured porcine aortic endothelium. The lipoprotein-cell interaction had many properties similar to those seen with the binding of a ligand to a cell surface receptor. It was time and temperature dependent, saturable, and reversible. Scatchard analysis of competition data suggested that there may be more than one class of binding site. The affinity of the low affinity site was similar to that for low density lipoprotein (LDL). Also, the capacity of endothelial cells to bind VLDL was similar to that for LDL, when related to apo B (i.e., particle) concentration. Not only was unlabelled VLDL able to compete for VLDL binding sites, but so was LDL and high density lipoprotein (HDL). The maximal competition either by LDL or by HDL was less than that by VLDL. The maximal competition by HDL was more than by LDL. The VLDL binding was dependent on Ca2+. It was not changed by the content of lipoprotein in the medium in which cells were grown prior to the binding studies. These observations suggest that VLDL binding to endothelial cells is similar in some respects, but not in all, to the binding of LDL. Comparison of the data with endothelial cells to previous data with adipocytes also indicated differences between the interaction of these two cell types with VLDL. It is possible that this binding process may be involved in the formation of atherogenic remnants of triglyceride-rich lipoproteins on the endothelial surface of large blood vessels.

Animals↗

Changes in very low density lipoprotein particle size and production in response to sucrose feeding and hyperinsulinemia.

The effects of chronic (2 weeks) hyperinsulinemia on the production of very low density lipoprotein (VLDL) triglyceride and on VLDL particle size were examined. Hyperinsulinemia was induced by a constant sc infusion of 6 U porcine insulin/day from an osmotic minipump. To avoid profound hypoglycemia, these rats received chow plus 10% sucrose in their drinking water. Therefore, two control groups were examined; one receiving chow plus the same amount of sucrose (high carbohydrate control) and the other receiving chow only (chow control). The constant infusion model was compared to a previously reported model of hyperinsulinemia. In that model, NPH insulin was injected for 2 weeks twice daily in incrementally increasing doses (final dose, 6 U/day) into rats that were also fed chow and given 10% sucrose drinking water. Results with the injection model were similar to those previously reported: an increase in triglyceride production in face of a decrease in FFA, a minimal decrease in serum triglyceride, and some decrease in serum glucose. The infusion model produced the same increase in triglyceride production and decrease in fatty acid concentration. However, it differed in producing an increase in serum triglyceride and no change in serum glucose. The former suggested that in the infusion model triglyceride removal was not stimulated as much as in the injection model. Since there was no hypoglycemia in the infusion model, it was unlikely that VLDL changes were caused by an increase in counter regulatory hormones. VLDL particle size was increased in the high carbohydrate controls. This indicated that changes in sucrose supplementation led to the production of more triglyceride-filled VLDL particles. Hyperinsulinemia was not accompanied by any further increase in particle size. Thus, the hyperinsulinemia-induced increase in VLDL-triglyceride production was accompanied by an equivalent increase in VLDL particle production.

Animals↗

Epidermal cells as accessory cells in the generation of allo-reactive and hapten-specific cytotoxic T lymphocyte (CTL) responses.

The capacity of epidermal cells (EC) to stimulate T cell activation is a Langerhans cell (LC)-dependent phenomenon. In all in vitro assays probed, LC subserve antigen-presenting cell functions in that they display surface-bound foreign or altered-self structures and thereby activate T cell responses. In contrast, attempts to demonstrate accessory cell (ACC) function of LC-containing EC have yielded negative results, i.e., EC lacking foreign cell surface antigens were not able to restore cytotoxic T lymphocyte (CTL) responses in Ia+ adherent cell-depleted cultures. Reasoning that the ACC function of EC might be critically linked to cluster formation between LC and other cell types involved, we tested the ACC function of EC under experimental conditions that allow a close physical contact between the cell types involved (round-bottomed microtiter plates and brief centrifugation of culture plates). By using these modifications, the failure of highly purified B6 T cells to develop alloreactive CTL activity when stimulated with either highly purified, mitomycin C-treated C3H or B6CF1 T cells was restored by the addition of B6 EC. The CTL thus generated produced significant lysis of Con-A-stimulated C3H or BALB/c, but not B6, spleen cell targets. In a similar fashion, TNP- or FITC-specific CTL were generated when (in a syngeneic system) mitomycin C-treated TNP- or FITC-modified stimulator T cells and responder T cells were co-cultured in the presence, but not in the absence, of unmodified EC. The capacity of EC to restore CTL activity in a culture system depleted of Ia-bearing cells was not dependent upon their H-2 type, but was critically linked to the presence of Ia-bearing LC. We therefore conclude that LC-containing EC can subserve the ACC function in the generation of H-2-restricted CTL, provided that culture conditions are chosen that allow a close physical contact between the cell types involved.

Animals↗

[Modification of the NMR-tomogram by blood flow].

Blood flow causes alterations of the NMR-Signal. Cross-sections of vessels will sometimes be imaged as dark spots, sometimes as highlighted areas. These highlightings of the lumen of vessels are often interpreted as caused by obstruction. In this paper the mechanisms of signal-intensity alterations as caused by blood flow will be described in order to prevent errors in interpreting of NMR-Images. The results of flow-measurements with the 0.35 Tesla imaging system in Berlin will also be presented. Finally, clinical examples of flow influence on images will be discussed.

Blood Flow Velocity↗

Crosslinking transfer RNA and messenger RNA at the ribosomal decoding region: identification of the site of reaction on the messenger RNA.

Wybutine (Ywye), situated next to the 3'-side of the anticodon of tRNAPhe from Saccharomyces cerevisiae, can be photo-crosslinked to mRNA when bound to Escherichia coli ribosomes. Crosslinking can be obtained with poly(U) as well as with oligonucleotides such as pAUGUUU or p(U)6. In order to identify the site of reaction on the mRNA, 5'-[32P]-labelled pAUGUUU was crosslinked by irradiation at 320 nm with Phe-tRNAPhe from yeast bound to the acceptor-site. The photoproduct was subsequently digested with P1-nuclease and analyzed by electrophoresis followed by homochromatography in the second dimension. As a result of the photoreaction the wybutine was found to be crosslinked to the U at the 5'-position of the corresponding UUU-codon.

Base Sequence↗

Milk fat structure of a patient with type 1 hyperlipidemia.

Structural analyses were performed on milk fat samples obtained 3-10 days postpartum from a lactating patient with primary Type 1 hyperlipidemia. The milk triacylglycerols contained 3-7% C10, 14-21% C12, 20-30% C14, 22-26% C16 and 20-30% C18 (largely oleic) acids. Gas liquid chromatographic (GLC) analyses of the X-1,3- and X-1,2-diacylglycerols on polar siloxane columns showed a markedly non-random association of acyl chains. Stereospecific analyses indicated that the short chain length fatty acids were confined essentially to the sn-3-position of the triacylglycerol molecule. Furthermore, these acids were largely absent from the phosphatidylcholines and the endogenous sn-1,2-diacylglycerols of the milk fat. It is concluded that the short chain fatty acids are incorporated into the milk triacylglycerols during the final stage of biosynthesis via the phosphatidic acid pathway, and that the overall fatty acid distribution is consistent with the 1-random 2-random 3-random hypothesis.

Animals↗

Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring. Therapeutic considerations.

Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Identification of a site on 23S ribosomal RNA located at the peptidyl transferase center.

3-(4'-Benzoylphenyl)propionyl[3H] Phe-tRNA bound to the peptidyl site of the ribosome is photo-crosslinked exclusively to 23S RNA on irradiation at 320 nm. The site of reaction has been identified both by hybridization and primer-extension experiments as uridine-2584 and uridine-2585, located within the central loop of domain V according to the secondary structure model of 23S RNA. The fact that the covalently crosslinked tRNA retains its ability to form a peptide bond, together with the proximity of this site to the position of several mutations leading to chloramphenicol or erythromycin resistance strongly argue that this region of the 23S-like rRNAs is an integral component of the peptidyl transferase site. On the basis of these results, and from comparative analysis of the 16 available large subunit rRNA sequences, we propose a model for the functional organization of the peptidyl transferase site involving interaction of domains II and V of 23S rRNA.

Acyltransferases↗

Hyperinsulinemia and in vivo very-low-density lipoprotein-triglyceride kinetics.

The effect of hyperinsulinemia (2 wk of twice daily NPH insulin) on the kinetics of very-low-density lipoprotein (VLDL)-triglyceride (TG) was studied in rats. To avoid profound hypoglycemia the rats were allowed sucrose ad libitum. Two control groups were needed: chow only and ad libitum sucrose-supplemented (high-CHO). The insulin-treated rats had 15 times higher IRI and 50% lower plasma glucose levels than either control group. Their TG production exceeded and their TG concentrations were less than those of either control group. This indicated that their TG removal was increased even more than their TG production. This increase in TG production occurred despite lower plasma free fatty acid (FFA) levels, suggesting that a greater proportion of TG fatty acids came from a source other than FFA. Compared with chow controls, high-CHO controls had the same peripheral IRI, a slight increase in TG production, and an increase in TG concentration. The differences between the effects of CHO supplementation alone or together with injected insulin may relate to the IRI and/or the route of access of insulin (peripheral vs. portal). The present studies indicate that hyperinsulinemia, either directly or indirectly, accelerates triglyceride turnover.

Animals↗

Long term open loop intravenous insulin infusion in type I diabetes: feasibility, problems and promise.

The response of four Type I diabetic patients to long term (1,4,4, and 8 months) intravenous insulin infusion is reported. As compared to their usual subcutaneous depot insulin treatment, glycosylated hemoglobin (HbAl) decreased from 12.2 +/- 0.7 to 8.8 +/- 0.9 (p less than 0.05). However, only 49 to 76.5% of self blood glucose monitoring results were between 60-179 mg/dl range. Although 6.3 to 15.2% of capillary blood glucose levels were less than 60 mg/dl, severe hypoglycemia occurred only on one occasion. Plasma cholesterol, triglyceride and high density lipoprotein all decreased significantly (p less than 0.005). The major motivating factors for participation in this study were: (1) the hope of preventing diabetic complications; (2) the wish for more knowledge about diabetes; (3) a sense of special purpose and (4) a general interest in science and research. Catheter obstruction as a result of insulin aggregation terminated the study in two subjects. A third subject requested the study be stopped primarily because of imposed travel restrictions. In one subject, the study was stopped because of a disrupted personal life and developing depression. Diabetic ketoacidosis or sepsis from the centrally placed intravenous catheter did not occur. Although long term intravenous insulin infusion is feasible in a clinical research setting, insulin aggregation continues to be a major limiting factor. The widespread clinical use of implantable pumps will have to await the development of a suitable insulin formulation.

Adult↗

Chronic haematogenous osteomyelitis; studies on an experimental model.

The progression of acute haematogenous osteomyelitis into a chronic infection was investigated in a group of ten dogs in which the infection was produced by injection of micropaque barium mixed with Staphylococcus aureus or Salmonella Group C-2 into the tibial nutrient artery. Antibiotics were not used. Twenty four months later the infected limb of the surviving animals exhibited clinical, histological, radiological and microbiological changes which closely resembled those found in chronic haematogenous osteomyelitis (CHO) in humans. We observed spontaneous fractures, skin fistulae, bone sequestration and active bone remodelling. The original infecting bacteria were often replaced by different microorganisms because of skin fistulae or haematogenous contamination. Although the initial mortality was high the surviving animals showed signs of local and systemic symbiosis with the infecting bacteria. In two animals the previously infected and remodelled bone failed to show histological evidence of infection. This model may be useful in the study of a variety of factors affecting the natural history of CHO, particularly those encompassing the immunological response of the host.

Animals↗

A new model of human VLDL metabolism based on simultaneous studies of its APOB and triglyceride.

Previous studies which separately examined the behavior of the B apolipoprotein and of the triglyceride of VLDL had raised the possibility that each was metabolized in a different manner. The present studies have explored this possibility by simultaneously studying each of these VLDL constituents in thirteen humans. 125I-labeled Sf 60-400 lipoproteins were injected. The fate of their apo B (a reflection of the metabolism of the lipoprotein particle) was followed in this, and in the smaller Sf 12-60 lipoproteins. In everyone, the larger particle was catabolized to the smaller one. Furthermore, the smaller particle was derived exclusively from the larger one. The behavior of the lipoproteins' triglyceride was examined by following the specific activity of 3H-triglyceride which had been endogenously labelled by injecting 2-3H-glycerol. Some of the larger lipoproteins' triglyceride appeared in the smaller particles. However, in contrast to the apo B, the triglyceride in the smaller particle was not derived exclusively from that in the larger particle. In eleven subjects, the triglyceride specific activity curves above demonstrated that some of the triglyceride entered the smaller circulating particle from a source other than the large particle.

Adult↗