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H Metzger

Publications and source records attributed to H Metzger.

At least 109 records · Page 6Linked to original sources
PubMed1984

Reconstitution of the receptor for immunoglobulin E into liposomes. Reincorporation of purified receptors.

Mast cells and related cells have on their surface receptors that bind immunoglobulin E (IgE) with high affinity and which, when aggregated, trigger exocytosis. We recently demonstrated that when these receptors are solubilized with mild detergents, their subunits dissociate unless an appropriate lipid:detergent ratio is maintained. The conditions required to maintain the receptors' integrity appeared to parallel those previously determined as necessary to obtain adequate incorporation of unpurified IgE-receptor complexes from detergent extracts into liposomes. We now show that purified IgE-receptor complexes having the full complement of subunits become preferentially inserted into liposomes. If the receptor subunits are chemically cross-linked to each other, at least some of such receptors can be incorporated, even though lipid is omitted during their purification. The findings suggest that the IgE-binding alpha subunit of the receptor is anchored to the bilayer by means of one or both of the other subunits.

Animals↗
PubMed1984

PO2 and pH measurements within the rabbit oviduct following tubal microsurgery: reanastomosis of previously dissected tubes.

Adhesions of the fallopian tube might be a source of generalized infertility. In order to improve the mechanical and functional properties of the oviduct, microsurgical replacement of the affected tubular segments have been applied, however, with contradictory results. In order to improve the situation and gain further information about this problem, catheter microelectrodes for Po2 and pH measurements within the lumen of the fallopian tube have been developed. The validity of the measurements was tested in a series of rabbits (Dutch belt strain, n = 19, 3.5-4.5 kg bw) which have been laparatomized under pentobarbital anesthesia during the oestrus phase. From one side of the oviduct 1 cm was resected and the free ends reanastomosed while the other side served as a control. Six to eight weeks later Po2 and pH values within the oviduct were measured. After another 4-5 weeks ovulation had been induced and artificial insemination performed. 64 hours later the rabbits were sacrificed. The oviducts were isolated and the corpora lutea as well as the ova were collected and examined histologically. The mean Po2 of the oviduct was 53 (+/- 16) mm Hg (mean +/- SD) for the control side and 56 (+/- 13) mm Hg (mean +/- SD) within the anastomosed tubes. The range of values was the same in both groups (n = 8) 34-75 mm Hg. A T-test comparison of the means of the two groups gave p-values which were not significant (p greater than 0.1). Po2 fluctuations with small-fast amplitudes (1 mm Hg) and additional slow-large oscillations (about 20 mm Hg) have been observed similar to the Po2 waves described for muscle and brain. The mean pH value of the oviduct a showed slight, statistically significant pH differences (7.75 reanastomosed side, 7.94 control side) whereby the degree of adhesions was correlated with luminal pH value. In three rabbits the relationship between corpora lutea and fertilized ova was 1:6, 2:9, 3:6 for the reanastomosed side while the control side showed balanced quotients of 4:4, 4:4, 6:6. In two rabbits unfertilized ova have been observed within the reanastomosed tubes where the typical outside layer of mucoproteids was absent while the control side was normal. Nevertheless, within both oviducts a continuous layer of epithelial cells has been observed even after reanastomosis.

Animals↗
PubMed1984

Studies of hemorrhagic and traumatic shock influence on liver oxygen tension: effects of a single large dose of dexamethasone.

Liver surface oxygen tension in response to hemorrhagic shock (hs) and to combined hemorrhagic-traumatic shock (hts) as well as to hemorrhagic-traumatic shock with glucocorticoid application ( htsc ) has been studied using male rats (Wistar strain, 250-300 g b.w.). The animals were anaesthetized by i.p. injection of ketamine/xylazine. All animals were bled through a catheter inserted into the vena jugularis until a hypotension of 40 mm Hg mean arterial blood pressure (MAP) was attained. The hts rats were traumatized by fracturing the left tibia and crushing the adjacent muscle tissue with 45 N/2.25 cm2 for 5 minutes. The htsc animals were traumatized and treated with a single injection of a large pharmacological dose of dexamethasone (6-8 mg/kg b.w.). Initial surface Po2 of the liver was higher than published by others (29 +/- 7 mm Hg) probably due to the narcotic agents. Maximal blood withdrawal was 24.4 +/- 2.2 ml/kg b.w. for hs, 17.9 +/- 3.8 ml/kg b.w. for hts and 20.6 +/- 4.5 ml/kg b.w. for htsc rats. Liver surface Po2 decreased to zero mm Hg in response to hypovolemic hypotension in all rats. Retransfusion of the shed blood caused a MAP and surface Po2 increase to only about half of the initial levels in hts and htsc rats while in hs animals the initial values were approximated. The hts and htsc rats showed signs of progressive hypotension to about 45 mm Hg MAP within 90 minutes post retransfusion. Dexamethasone improved the arterial pH to 7.15 compared with 7.05 of the control. Pao2 was elevated to 60 mm Hg vs. 49 mm Hg of the control animals. The beneficial influence of glucocorticoids on liver surface Po2 has not been substantiated as would have been desirable for the patient. Nevertheless, from a physiological standpoint a positive trend in the liver O2 supply has been evaluated as a small right shift of the surface Po2 histogram as well as the blood gas and pH data.

Animals↗
PubMed1984

The hypoxic response to hypovolemia.

The response of tissue-PO2 to hypovolemic hypotension was determined in the rat brain cortex and liver surface using needle and surface PO2 electrodes. At hypotensive MAP values of 35-40 mm Hg the cerebral cortex is preferentially supplied with blood through sympathico-adrenergic vasoconstriction of the peripheral circulation. This centralization of the blood volume is not sufficient to prevent a significant fall in cerebral PO2 from 34 +/- 18 mm Hg to 24 +/- 16 mm Hg however (n = 27 animals). The decrease in tissue PO2 during hypovolemia is dependent on body temperature and is more pronounced at lower temperatures (32-34 degrees C) than slightly raised temperatures (37.5-39 degrees C). The same degree of hypovolemia gave rise to large anoxic regions on the liver surface which showed signs of irreversible damage after 90 minutes. This was particularly obvious from the values measured after retransfusion of the missing blood with only a mean PO2 of 18 +/- 12 mm Hg compared with 28 +/- 7 mm Hg (n = 29) at the start of the experiment.

Animals↗
PubMed1984

Response of spinal cord oxygen tension to aortic occlusion.

In order to study the factors influencing spinal cord injury resulting from occlusion of the descending aorta, the local surface PO2 (sPO2) was measured in the lumbar region (L4-5) of the exposed spinal cord after laminectomy in the pig. This is the area supplied by the arteria radicularis magna anterior (ARMA). The following aspects were considered: duration of occlusion, blood supply by the ARMA, distribution and width of spinal cord collaterals. The animals were divided into two groups. In group I (n = 7) the descending aorta was occluded immediately below the left subclavian artery; in group II (n = 7) the abdominal aorta was occluded immediately superior to the ARMA. Occlusion induced a rapid sPO2 decrease in all animals, from 29 to 3 mm Hg in group I (-14 mm Hg/min) and from 28 to 8 mm Hg in group II (-12 mm Hg/min). After 45 minutes of occlusion the blood flow through the aorta was released giving a pronounced sPO2 overshoot (36 mm Hg) about 10 minutes later. After 20 minutes there had been a return to initial sPO2 values. The results of this study confirm the hypothesis that spinal cord injury during occlusion of the descending aorta is primarily due to ischemic hypoxia/anoxia.

Animals↗
PubMed1984

Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects.

The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 mg HOE 498. Peak serum concentration of M 1 between 5-50 ng/ml was observed 1.5-3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.

Adult↗
PubMed1984

2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S) -2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498)--a new and highly effective angiotensin I converting enzyme inhibitor.

2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl] - (1S,3S,5S) -2-azabicyclo [3.3.0] octane-3-carboxylic acid (Hoe 498) is a new, very effective and long lasting, nonsulfhydryl angiotensin I converting enzyme inhibitor. Using hip-his-leu as substrate, the IC50-values for Hoe 498 and its diacid derivative were 26 or 4.2 nmol/l, respectively. Hoe 498 acts as a prodrug. It is hydrolyzed by an esterase into its active diacid derivative. Sera contain high esterase activities. In comparison to sera from man, dog and rabbit, rat sera have the highest esterase activity. Hoe 498 or its diacid derivative do not modulate the membrane bound adenylatecyclase system of tissues under investigation. The results are discussed in respect of the regulation of the angiotensin II-synthesis and to the regulation of Ca2+-channels in membranes.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Tolerance and pharmacodynamics of the angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) in healthy volunteers.

In healthy volunteers a single oral dose of 5 mg 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) was well tolerated. Following 5 mg Hoe 498 plasma angiotensin converting enzyme (ACE) activity was inhibited by almost 100% up to 8 h. A marked effect on plasma ACE was observed for more than 8 days. Plasma renin activity increased whereas aldosterone plasma levels decreased only slightly. Sodium and potassium excretion was not influenced by the compound. Systolic and diastolic blood pressure was slightly lowered by Hoe 498, whereas no relevant changes in pulse rate were observed.

Adult↗
PubMed1984

[Adverse effects of curative radiotherapy of prostate cancer].

The side effects of primary percutaneous radiotherapy in 100 patients with prostatic cancer were evaluated and classified into different degrees of gravity. It was shown that especially chronic side effects are benign in most of all cases. Severe - but not vitally dangerous - complications in bladder and intestine are rare (3%); their percentage corresponds roughly to the average mortality rate of surgical intervention (radical prostatectomy). Contrary to operation, troubles of the sexual function appear only in one third of the patients. Taking into consideration the similar therapeutic results of surgical intervention and radiotherapy, radiotherapy is more favorable with respect to side effects. This essential aspect should be considered when making a decision whether to apply a surgical or a radiotherapeutic treatment treatment.

Female↗
PubMed1983

A previously unrecognized subunit of the receptor for immunoglobulin E.

Our laboratory previously found that under conditions that stabilized the interaction between the alpha and beta subunits of the receptor for immunoglobulin E, two new components were recovered having apparent molecular weights of 45 000 and 20 000, respectively. In this paper, we characterize the 20-kDa material. We demonstrate that it consists of a disulfide-linked dimer of 10-kDa polypeptides and that these have all the characteristics expected for subunits of the receptor. We propose that they be termed gamma chains and that the receptor consists of four chains: one alpha, one beta, and two gamma chains. The gamma chains share many of the labeling properties of the beta chain and, like the latter, are likely to be embedded in the plasma membrane and exposed on the internal but not the external surface of the bilayer.

Animals↗
PubMed1983

Covalent cross-linking of subunits of the receptor for immunoglobulin E induced by immunoprecipitation.

The receptor on rat basophilic leukemia and related normal cells that binds monomeric immunoglobulin E (IgE) with high affinity contains four polypeptide chains: alpha (to which the IgE binds), beta, and a disulfide-linked dimer of gamma chains. In this study, we have analyzed a further component variably seen when the purified receptors are analyzed on polyacrylamide gels. This component has an apparent Mr of approximately 43 000 and, after treatment with reducing agents, yields one beta and two gamma chains. This complex is generated by immunoprecipitation of preparations totally lacking in it. This novel in vitro phenomenon has provided additional information about the structure of the receptor. Its possible relationship to in vivo aggregation that triggers degranulation of the cells is of interest.

Animals↗
PubMed1983

Changes in the receptor for immunoglobulin E coincident with receptor-mediated stimulation of basophilic leukemia cells.

Aggregation of the receptor for immunoglobulin E on mast cells and related tumor cells initiates exocytosis. We examined tumor cells that had incorporated [3H]leucine and 32P to see if stimulating them produced modifications in the receptors themselves. No changes were observed in the yield of receptors or in the relative proportion and the molecular weights of their alpha, beta, and gamma subunits. In addition, no new "receptor-associated" components were observed. However, after the cells were stimulated, the gamma chains of the receptors showed an average 35% decrease in their associated 32P. Changes in the beta subunits were more variable but on the average showed a similar-sized increase in 32P. Using a novel protocol that permitted examination of aggregated and unaggregated receptors from the same cell, we found that changes in the unaggregated receptors were quantitatively indistinguishable from those exhibited by the aggregated receptors. These findings raise the possibility that the changes are related to one of the inactivation reactions thought to accompany the activation sequence.

Animals↗
PubMed1983

Isolation of homologous and heterologous complexes between catalytic and regulatory components of adenylate cyclase by forskolin-Sepharose.

Homologous and heterologous complexes between catalytic and GTP-binding components can be isolated by means of immobilized succinyldeacetylforskolin (forskolin-Sepharose). A heterologous complex is formed by reconstitution of forskolin-Sepharose bound catalytic function from rabbit myocardial membranes with the homogenous [3H]methyl-GTP-binding protein from duck erythrocyte membranes. Analysis of the reconstituted complex by sodium dodecyl sulfate polyacrylamide gelelectrophoresis reveals that only the Mr 42 000 component of the GTP-binding protein's Mr 42 000/Mr 35 000 heterodimer contributes to the formation of active adenylate cyclase.

Adenylyl Cyclases↗