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Biomedical subjects

L M Greenbaum

Publications and source records attributed to L M Greenbaum.

At least 19 recordsLinked to original sources
PubMed1992

T-kininogen, processing and functions.

Studies are presented which indicate that T-kininogen, the acute phase kininogen of the rat, could be a healing protein because of its properties as a cysteine protease inhibitor. Evidence is also presented that mRNA of T-kininogen synthesis may be a function of interleukin 6 production. A regulatory mechanism is postulated by which SH cofactors could determine if T-kinin is released or whether the T-kininogen molecule would remain intact. Evidence is also presented that T-kinin acts through kinin B2 receptors. No specific binding of bradykinin or T-kinin could be detected in rat heart preparations.

Acute-Phase Proteins↗
PubMed1992

Characterization of the kinin system in the ovary during ovulation in the rat.

Ovulation has been noted for some time to bear a remarkable similarity to an inflammatory response. One of the principal components that is activated and helps mediate the events during an inflammatory response is the kinin system. Therefore, the purpose of the present study was to examine whether this system could be similarly activated and involved in the cascade of events that leads to ovulation. To answer this question, immature 23-day-old female rats were primed with eCG (10 IU) and ovulation was induced by administration of hCG (10 IU) 48 h later. Groups of rats were killed at 0 h, 10 h, 20 h, and 30 h after hCG for determination of ovulation, ovarian steroid levels, and changes in the levels of kinin system components. Plasma total kininogen levels did not change during the entire period studied. In contrast, ovarian total kininogen levels rose from 0 h to reach a peak at 10 h--a time immediately preceding the beginning of ovulation--after which the levels fell at 20 h, only to rise again at 30 h. Three species of kininogens, high molecular weight (HMW), low molecular weight (LMW), and T-kininogen, were shown to be present in the ovary. T-kininogen was the major kininogen present in the ovary, accounting for 60-92% of the total kininogen at any given time point during the ovulatory process. HMW kininogen levels accounted for only 1.2% of the total ovarian kininogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Lack of specific binding of bradykinin and D-Arg [Hyp3, Thi5, D-Tic, Oic8] bradykinin in membranes from rat heart.

Recent data demonstrated effects of bradykinin (BK) in the isolated perfused rat heart which could be blocked by BK antagonists. However, so far BK receptors in heart tissue have not been characterized. To search for BK receptors in rat hearts iodinated D-Arg[Hyp3,Thi5,D-Tic,Oic8]BK (Hoe 140) was used as a ligand for binding due to its high affinity and to its resistance to degradation. The labeled antagonist bound well to membranes prepared from rat ileum and could be displaced by the unlabeled antagonist as well as by BK and T-kinin in a concentration dependent manner. However, there was no specific binding detectable when membranes from rat left cardiac ventricle were used. To assure integrity of at least one other receptor in these membranes, binding of 3H-methylscopolamine and its displacement by the respective cold ligand was demonstrated. To rule out an occupation of the BK receptors by endogenous formed BK, the tissue was treated with an acidic buffer with high ionic strength to remove surface bound BK. However, this treatment did not unmask any specific binding for the BK antagonist. In view of the possibility that the structure of the labeled antagonist prevented its binding, experiments were carried out using tritiated BK itself. These experiments also failed to demonstrate specific binding sites which indicate that the structural aspects of Hoe 140 are probably not interfering in binding of the antagonist, especially since it binds to ileum. It is concluded, that there are too few binding sites for BK in the rat heart homogenate for ordinary binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Reduction of T-kininogen messenger RNA levels by dexamethasone in the adjuvant-treated rat.

When inflammation is induced in rats following injection of Freund's complete adjuvant, steady state levels of T-I and T-II kininogen mRNAs increase markedly as do plasma levels of T-I and T-II kininogens. When rats are additionally treated with dexamethasone, T-I and T-II steady state mRNA levels and plasma levels of T-kininogens are reduced. The results suggest that dexamethasone may affect the magnitude of T-kininogen gene induction caused by inflammation.

Animals↗
PubMed1979

Further studies of the effect of pepstatin on ascites accumulation in tumor-bearing mice.

Studies were done of the effect of pepstatin on ascites accumulation in mice bearing MM46, Ehrlich, CCM, SN36, L1210, and NTF ascites tumors. When pepstatin was injected subcutaneously at 80 mg/kg body wt before ascites accumulation, it inhibited the accumulation in all strains of the tumors tested. In MM46, CCM and NTF tumor strains there was also a decrease in the tumor cell numbers following pepstatin treatment. Kinetic studies on ascites accumulation with tumor strain MM46 demonstrated that even when pepstatin was injected after ascites accumulation it reduced the ascites volume. A dose-dependent effect was observed in this tumor strain when pepstatin was injected both before and after ascites accumulation. The results confirm previous studies of pepstatin's ability to retard ascites in L1210 and P-815Y ascites tumors and also broaden the concept of the mechanisms by which petstatin may be acting.

Animals↗
PubMed1979

Pepstatin, an inhibitor of acid kininogenases and ascites retardant in neoplastic disease.

Evidence is reviewed that pepstatin, an inhibitor of acid kininogenases such as cathepsin D, may be an effective therapeutic agent in retarding ascites accumulation in certain cancers. The evidence for this conclusion is based on the actions of pepstatin in retarding ascites in six different tumor strains inoculated into various species of mice, as well as the demonstration that cathepsin D activity is reduced in vivo in several organs following pepstatin administration. The latter is significant since we have postulated that ascites formation, in good part, is due to leukokinin formation, which is catalyzed by cellular-released cathepsin D.

Animals↗
PubMed1979

The isolation of leukokinin-H and leukokininogen from human ascites fluid; their properties and role.

The leukokinin-leukokininogen system is a pathological kinin generating system which is catalyzed by acid proteases present in neoplastic cells, white cells and even normal tissues. The components of the human system including leukokinin-H and leukokininogen have now been isolated and characterized. Very specific protease inhibitors of the system such as pepstatin have been found and are now known to prevent "in vivo" the formation of pathological fluids such as neoplastic ascites. Strong evidence has been previously published and additional evidence has been presented here which indicates that pepstatin's actions are related to the inhibition of cathepsin-D in vivo and the inhibition of leukokinin formation. Both leukokinins and leukokininogens have been clearly defined and shown to differ from bradykinin and human bradykininogens. This clearly demonstrates the presence in pathological systems of a kinin-generating system which is separate and distinct from the bradykinin generating system. The importance of the leukokinin-leukokininogen system in disease would seem to be very great. The finding that pepstatin can inhibit the system in vivo opens the way for studies of pepstatin and related protease inhibitors as therapeutic agents in neoplastic disease and protease mediated inflammatory disorders.

Amino Acids↗
PubMed1977

Pepstatin, an ascites retardant of L1210 tumor-bearing mice.

The effect of pepstatin on the kinetics of ascitic fluid accumulation in L1210 tumor-bearing mice (DBA/2) was observed. Following inoculation of 1.5x10(6) tumor cells, untreated mice reached a peak of fluid accumulation on day 6 and remained at this level until death on day 9. A "lag" phase of 4 days occurred before fluid accumulation was seen. Pepstatin administered SC in a single dose of 80 mg/kg during the lag phase, significantly retarded fluid accumulation as compared to untreated animals. Pepstatin administered following fluid accumulation was much less effective. We concluded that pepstatin prevents fluid accumulation rather than acts as a diuretic agent. The term "ascites retardant" is suggested for the pharmacologic actions of pepstatin, since it prevents fluid accumulation without diminishing the cell count.

Animals↗