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Biomedical subjects

H Metzger

Publications and source records attributed to H Metzger.

At least 91 records · Page 5Linked to original sources
PubMed1986

The receptor for immunoglobulin E: examination for kinase activity and as a substrate for kinases.

Purified receptor-immunoglobulin E (IgE) complexes incubated with [gamma-32P]-ATP incorporated phosphorus into tyrosines on the beta and gamma chains of the receptor. The activity had the typical characteristics of a tyrosine kinase. Immunoprecipitation of the complexes with anti-IgE left the activity in the supernatant, demonstrating that the receptor itself was not the kinase. The receptor was also phosphorylated when membranes or intact cells were incubated with radioactive ATP or phosphate, respectively, but in each case the subunits or amino acid residues that were modified were distinctive.

Animals↗
PubMed1986

[Value of rapid sequential computed tomography for the diagnosis of liver cirrhosis].

Thirty-eight patients with cirrhosis of the liver and thirty-seven controls were examined by dynamic computer tomography in a prospective study. Time-density difference curves for the liver, spleen, portal vein, aorta and vena cava were treated mathematically ('gamma fit'). Comparison of the values of the difference curves of liver, spleen and portal vein showed significantly lower and delayed peaks in patients with cirrhosis than in normal people. The time-density difference curves of the liver showed a highly significant shallow decline in the presence of cirrhosis. Discriminant analysis of the curve parameters using the spleen showed differentiation between normals and cirrhosis patients of 90.2%, and using the liver curve a separation of 83%. Combining these parameters of liver and spleen curves improved the separation between cirrhotic patients and normals to 94%.

Female↗
PubMed1986

Interaction between proteins localized in membranes.

We present a conceptual framework for evaluating the effect on the self-association of proteins in membranes due to the presence of other proteins at high concentrations (excluded volume effect) and the high concentration and preoriented state of the reactive species. We have calculated the magnitude of such effects using plausible values for the concentrations of proteins in membranes, for the degree to which proteins may tilt and move vertically, and for their dimensions. Compared to the association of monomers tumbling freely in an experimentally realistic volume, we calculate that these factors alone can increase the likelihood of forming dimers 10(6)-fold and of forming trimers and higher oligomers many orders of magnitude greater. We discuss the implications of our calculations for experimental manipulations of membrane proteins, for biosynthetic assembly of multisubunit membrane proteins and formation of membrane lesions by assemblies of exogenous proteins, and for the activation of cellular events induced by the interaction of membrane receptors with themselves or with other membrane proteins.

Cholesterol↗
PubMed1986

The receptor for immunoglobulin E as a membrane protein.

Mast cells and related cells have a surface glycoprotein that avidly binds monomeric immunoglobulin E (IgE). This protein is more complex than originally thought, its analysis having been complicated by its lability in mild detergents. The properties of this receptor, especially with respect to its interaction with lipids and detergents, is reviewed and the implications for the study of other membrane protein systems are discussed.

Detergents↗
PubMed1986

Humoral and blood pressure effects of the angiotensin converting enzyme inhibitor ramipril in essential hypertension.

The humoral and antihypertensive activities of the angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylic acid (ramipril, Hoe 498) were investigated in 10 patients with essential hypertension (WHO stage I or II). After a 7-day placebo period, the patients were treated with 5 mg ramipril orally once daily for 14 days. Peak serum concentrations of the active metabolite M1 (dicarboxylic acid) of 5.4-62.0 ng/ml were observed 2-6 h after the first oral dose. The maximum ACE inhibition of 95% was reached 2-4 h after the first oral dose, inhibition exceeded 70% 24 h after dosing. The maximum drop in the systolic and diastolic blood pressure (random zero sphygmomanometer) was measured 4 h after ramipril (p less than 0.02, p less than 0.01), but blood pressure on days 7 and 14 of the treatment period was not different from pretreatment values. Automatically recorded blood pressure results showed a marked reduction of both systolic and diastolic blood pressure during treatment compared to placebo. No side effects occurred. From the present data it is concluded that ramipril is a potent ACE inhibitor in hypertensive patients and that further controlled studies are required for the evaluation of the antihypertensive effect of 5 mg ramipril in essential hypertension.

Adult↗
PubMed1985

Noncovalently and covalently bound lipid on the receptor for immunoglobulin E.

We describe experiments which indicate that lipids interact with the receptor for immunoglobulin E (IgE) in several ways. Evidence for loosely bound lipid comes from observations on the special conditions that are required in order to oxidatively iodinate the alpha chain of the receptor in IgE-receptor complexes. Evidence for tightly, but still noncovalently, bound lipids comes from studies on the lipids required to inhibit dissociation of the subunits of the receptor in micellar detergent. Finally, biosynthetic studies indicate that the subunits of the receptor contain ester-linked fatty acids. The latter modification appears to take place on receptors that have already been inserted into the plasma membrane.

Animals↗
PubMed1985

Dissociation of the receptor for immunoglobulin E in mild detergents.

We previously showed that, in the absence of phospholipids, exposure of the tetrameric receptor for immunoglobulin E to mild detergents dissociates the intact beta chain and two gamma chains from the alpha chains. Having developed a practical method for assaying the dissociation, we have now explored a variety of different detergents, detergent concentrations, temperatures, times, salts, pHs, and other factors that influence the detergent-induced dissociation. Our findings should be useful for optimizing the stability of the receptor and for future studies on recombination of the subunits. The data suggest the following: (1) The critical perturbant is micellar detergent. (2) Unlike solubilization of membranes, where a molar ratio of micellar detergent:lipid of 2 is adequate, dissociation of the receptor is incomplete even at molar ratios of micellar detergent:receptor of greater than 10(5) and may be limited by a reversible component. (3) Detergents that are best for solubilizing membranes are also best for dissociating the receptors. (4) The latter observation and other data implicate bound lipid as stabilizing the receptor. Our findings may be applicable to the study of interactions between membrane proteins in general.

Animals↗
PubMed1985

Lumbar and thoracic spinal cord oxygen tension during aortic cross-clamping.

In order to investigate the changes in tissue oxygen and the efficiency of the collateral circulation in the different regions of the spinal cord (SC) during aortic occlusion, surface PO2 (sPO2) was measured on the exposed SC in the pig in the lumbar (L3-5) as well as in the thoracic (Th6-8) parts before, during and after a 45 minute occlusion. The pigs were divided into two groups: group IA: cross-clamping of the aorta immediately below the left subclavian artery; group II: occlusion of the aorta immediately above the arteria radicularis magna anterior (ARMA). In response to occlusion, the sPO2 distal to the occlusion always decreased significantly (group IA: mean lumbar sPO2 from 42.3 mm Hg to 3.2 mm Hg, mean thoracic sPO2 from 34.9 mm Hg to 3.9 mm Hg; group II: mean lumbar sPO2 from 28.0 mm Hg to 7.9 mm Hg). Mean thoracic sPO2 in group II remained constant. No statistically significant differences between the distal regions could be established. The collateral circulation in the thoracic as well as in the lumbar region was insufficient at least during occlusion.

Animals↗
PubMed1985

Effect of hypovolemic hypotension on the cerebral oxygen supply of rats with slightly raised or lowered body temperatures.

Combination effects of hypovolemia and body cooling or warming being important for laboratory animals, accident victims, hemorrhagic patients, etc. have been investigated in the anesthetized rat brain. Combined hypovolemic hypotension (MAP +/- SD = 36 +/- 7 mm Hg) and additional cooling (32 degrees) intensified the drop of cerebral cortex PO2 (rPO2) (initial rPO2 +/- SD = 28 +/- 16 mm Hg, hypovolemic rPO2 = 16 +/- 12 mm Hg, N = 15) while slight body warming (39 degrees) improved the cerebral hypoxia (initial rPO2 +/- SD = 41 +/- 20 mm Hg, hypovolemic rPO2 = 32 +/- 21 mm Hg, N = 11) despite arterial saturation of the oxyhemoglobin was normal (N = 11).

Animals↗
PubMed1985

Coordinate synthesis and degradation of the alpha-, beta- and gamma-subunits of the receptor for immunoglobulin E.

The surface receptor for immunoglobulin E (IgE) on rat basophilic leukemia cells and their normal counterparts has been postulated to consist of four polypeptide chains: a 45-kDa alpha-chain which binds IgE, a 33-kDa beta-component and two disulfide-linked, 9-10-kDa gamma-polypeptides. The instability of this complex in mild detergents makes it possible that, in vivo also, the structure may not be stable and that there is an independent assembly or exchange of the chains. We studied this question using surface-labeling and biosynthetic labeling techniques and found that the chains turn over coordinately and do not independently exchange. The results provide further support for the proposal that the alpha beta gamma 2 complex is the unit receptor for IgE.

Animals↗
PubMed1985

[Circumscribed and diffuse skin thickening (peau d'orange) of the female breast].

Skin thickening of the breast observed by mammography should always alert the radiologist to suggest the possibility of carcinoma. The roentgenographic appearance of skin thickening, however, is nonspecific and identical in each disorder, and provides no clue to its benign or malignant origin. It is therefore important to the radiologist to be familiar with the possible etiologies, which can often be simply evaluated by obtaining an appropriate medical history, clinical inspection or a thorough physical examination of the breast. A review of the mammary skin thickening is given, and the differential diagnosis is discussed with reference to the literature.

Adenocarcinoma, Scirrhous↗
PubMed1985

Catalytic unit of adenlyate cyclase: purification and identification by affinity crosslinking.

The guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG)-activated adenylate cyclase from rabbit myocardial membranes was purified approximately equal to 60,000-fold to a specific activity of 15 mumol X mg-1 X min-1 by Lubrol PX extraction, affinity chromatography, and gel permeation HPLC. The major purification (greater than 2000-fold) was achieved by affinity chromatography on forskolin-Sepharose, a method previously developed in this laboratory. The final product appeared as two major peptides of Mr 150,000 and 42,000 and one minor peptide of Mr 45,000 when analyzed by NaDodSO4/polyacrylamide gel electrophoresis. It is suggested that the Mr 42,000 and 150,000 components represent the alpha-subunit of the stimulatory guanine nucleotide binding regulatory protein (GS) and the catalytic unit, respectively, because upon crosslinking of a reconstituted adenylate cyclase containing the [32P]ADP-ribosylated alpha-subunit of GS (Mr, 42,000), a single radiolabeled product of Mr 190,000 appeared on NaDodSO4/polyacrylamide gels. Further identification is based on the correlation of the Mr 150,000/42,000 bands with enzymatic activity when the purified enzyme was analyzed by various chromatographic procedures.

Adenylyl Cyclases↗
PubMed1985

Direct measurements of oxygen tension on the spinal cord surface of pigs after occlusion of the descending aorta.

Spinal cord injury is the most dreaded complication of operative procedures on the descending aorta. Our previous experimental study on pigs indicated that an increase in the cerebrospinal fluid pressure after aortic cross-clamping did not influence the occurrence of spinal cord injury. We therefore concluded that the cause of spinal cord injury after aortic cross-clamping is due to primary oxygen deficiency in the spinal cord distal to the occlusion site, especially in the area supplied by the artery of Adamkiewicz. The aim of the present study is to examine the primary ischemic cause of spinal cord injury after aortic cross-clamping by directly measuring the oxygen tension on the spinal cord surface in pigs. During the occlusion phase, oxygen tension decreased significantly distal to the clamping site and especially in the areas supplied by the artery of Adamkiewicz both after occlusion of the high thoracic (Group I) and the lumbar aorta (Group II). The marked decrease in oxygen tension proves that hypoxia is the primary reason for spinal cord injury. The presence of a "steal phenomenon" should be discussed.

Animals↗
PubMed1984

Phase separation of the receptor for immunoglobulin E and its subunits in Triton X-114.

Above its critical micelle concentration, Triton X-114 in solution forms two phases at room temperature: a lower phase containing supramicellar aggregates and an upper phase largely depleted of detergent. This property of the detergent is potentially useful for separating under mild conditions proteins that bind detergent from those that do not (Bordier, C. (1981) J. Biol. Chem. 256, 1604-1607). We studied the distribution of the receptor for immunoglobulin E (IgE) and its subunits in the two phases. IgE and IgE complexed either with intact receptors or with the alpha chains of the receptor alone are principally partitioned into the upper phase, whereas the unliganded receptor as well as the isolated alpha, and especially the beta and gamma chains of the receptor, preferentially partition into the lower detergent phase. Chromatography of IgE and of the subunits of the receptor on a hydrophobic support showed that the beta and gamma chains have a considerably greater hydrophobic surface than the alpha chains or IgE. These results indicate that the distribution of a protein in the two phases of phase-separated Triton X-114 is not an all-or-none effect based upon whether it binds detergent or not. Rather, it reflects the overall balance between the hydrophobic and hydrophilic properties of the protein's surface.

Animals↗
PubMed1984

Initial characterization of the calcium channel activated by the cross-linking of the receptors for immunoglobulin E.

It is currently thought that aggregation of the receptor for immunoglobulin E on mast cells, basophils, and a tumor analog, rat basophilic leukemia (RBL) cells, induces an enhanced permeability of the plasma membrane to calcium, thereby initiating degranulation of the cells. Even in the absence of calcium ions, aggregation of the receptor causes depolarization of the plasma membrane (Kanner, B. I., and Metzger, H. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 5744-5748), suggesting that other ions can traverse the putative channel. Direct evidence for this now has been obtained with measurements of increased 22Na+ fluxes in the absence of calcium ions, induced by aggregation of receptors. This reaction was optimally studied in the presence of ouabain. When aggregation of the receptor was induced by reacting the cell-bound IgE with a multivalent antigen, the sodium flux was completely inhibited by univalent hapten. The sodium flux was also completely inhibited by 2 mM calcium. Aggregation-induced 45Ca2+ fluxes were observed in the presence of millimolar concentrations of external Ca2+, but not in its absence. Depolarization of the plasma membrane potential by the addition of potassium to the medium in the presence of calcium did not itself induce degranulation. In fact, aggregation of the receptors for IgE in the presence of high external potassium resulted in a greatly diminished degranulation. These data indicate that the ion channel modulated by aggregation of receptor differs from the voltage-dependent type of calcium channels. We suggest that in the absence of calcium this channel is rather unspecific, but that calcium can modify it to become calcium selective.

Animals↗