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Biomedical subjects

G Lazar

Publications and source records attributed to G Lazar.

At least 37 records · Page 2Linked to original sources
PubMed1986

Physiological action and receptor binding of a newly synthesized and novel antiglucocorticoid.

RU 38486, a newly synthesized molecule, reversed glucocorticoid mediated enzyme induction and gluconeogenesis in the liver, and RNA synthesis in rat thymocytes. The transfer of radiolabelled dexamethasone from the cytoplasm to the nucleus was also opposed by RU 38486 in intact thymocytes. Although RU 38486 saturated the same molecular species of the receptor as the hormone in the liver, differences seemed to appear when thymus was taken into account. Along with the ongoing clinical trials, an important new tool thus appears at hand to understand and harness the molecular action of glucocorticoid hormones in mammalian systems.

Animals↗
PubMed1986

Evidence for an antagonist specific receptor that does not bind mineralocorticoid agonists.

Kinetics of association--dissociation, competition and chromatography on two different resins, all revealed the presence of a new binding site which: specifically accepts 7-alpha-propyl spirolactone (3H-RU-26752), has little affinity for aldosterone, is present only in the target tissue (rat kidney), and is wanting in a non-target organ (liver). The presence of such sites could explain syndromes of mineralocorticoid excess where even trace amounts of an unusual aldosterone analogue, with little affinity for the classical mineralocorticoid receptor, can nevertheless produce hypertension through the intervention of an entirely new and abundant receptor system. This new molecule thus forms a novel tool to understand the nature and function of the soluble mineralocorticoid receptor in target organs.

Aldosterone↗
PubMed1986

The influence of a novel glucocorticoid antagonist on endotoxin lethality in mice strains.

Ru 38486 is a recently synthesized molecule which has little intrinsic agonist or antagonist activity but which is specifically capable of antagonizing selected glucocorticoid-induced processes such as liver enzyme induction and gluconeogenesis. This material sensitized both the Swiss albino OF1 and the refractory C3H/HeJ strain of mice to endotoxin lethality and impaired the protective effect of dexamethasone under these conditions. The effect of Ru 38486 and endotoxin was not additive on liver tryptophan pyrrolase and tyrosine transaminase but hepatic glycogen depletion was significantly greater than both agents were given as compared to either of them alone. Ru 38486 was without effect on the activity of the reticuloendothelial system as evidenced by both the clearance of carbon and the distribution of foreign red blood cells. In doses that protected OF1 mice against Ru 38486-mediated sensitization to endotoxin lethality, liver enzyme and glycogen levels were still below normal, albeit significantly greater than in animals succumbing to the toxin. These results constitute the first evidence that a drug acting specifically at the level of the glucocorticoid receptor can modulate the course of endotoxicosis.

Animals↗
PubMed1985

The influence of diabetic state on endotoxicosis.

Bacterial endotoxins deplete glycogen reserves in the host, oppose the gluconeogenic action of steroid hormones, and lower energy reserves in mammals. For the past 50 years the intermediary metabolism has been regarded as causal to the eventual outcome of endotoxicosis. Whereas some diabetogenic agents such as streptozotocin actually enhance the toxic effects of endotoxins, others (alloxan) do not appear to influence this parameter. Force feeding of glucose does not alter the outcome of endotoxicosis. Yet, endotoxins are believed to elicit insulin-like mediators from macrophages. In addition, the C3H/HeJ strain of mice which exhibits refractoriness to the lethal effects of the toxin undergoes just as severe a loss in total glycogen reserves as Swiss albino mice which are highly sensitive to endotoxin mediated death. These and similar observations suggest that the prime target(s) in endotoxicosis still remain elusive. However, endotoxins appear to form an important and interesting tool to elucidate various aspects of host physiology.

Animals↗
PubMed1984

Kaposi's sarcoma associated with hairy cell leukemia, immune thrombocytopenia, and opportunistic infection.

A 73-year-old man developed Kaposi's sarcoma 6 years after the diagnosis of hairy-cell leukemia, at which time a splenectomy was performed. He received no additional treatment. The Kaposi's sarcoma was complicated by the development of immune thrombocytopenia and Listeria monocytogenes meningitis. Evaluation during the course of his disease revealed lymphopenia, decreased OKT4 + subset, and increased OKT8 + subset. The clinical and immunologic findings in this patient have similarities to the acquired immunodeficiency syndrome.

Aged↗
PubMed1984

Splenectomy for hematologic disease. The UCLA experience with 306 patients.

Between 1956 and 1981, 306 splenectomies for hematologic diseases were performed at the UCLA Medical Center. Of these operations, more than 75% were performed for therapeutic reasons to control anemia, thrombocytopenia, neutropenia, or painful symptoms of splenomegaly. Of the 65 patients who had idiopathic thrombocytopenic purpura, 77% showed an excellent response, and of the 39 patients who had hereditary spherocytosis, 90% responded. Other diseases with predictably good response rates were autoimmune hemolytic anemias, Felty's syndrome, and hairy cell leukemia. Forty patients with Hodgkin's disease had splenectomies for diagnostic purposes the last 10 years. The overall morbidity and mortality were 24% and 6%, respectively, the most common complications being pneumonia, wound infections, and local postoperative bleeding, and the most common cause of death being sepsis. The review supports the thesis that in carefully selected patients, therapeutic splenectomy can have desirable palliative effects and that diagnostic splenectomy has a sufficiently low risk to warrant its consideration in patients with Hodgkin's disease.

Adolescent↗
PubMed1983

Isolation and structural elucidation of naphthomycins B and C.

Two new ansamycin antibiotics, the naphthomycins B and C, were isolated from two different strains of Streptomyces. The structures were determined by comparison of the spectra (UV, 1H NMR, 13C NMR) with those of the known naphthomycin A, by spin decoupling experiments (300 MHz) and in one case by a two dimensional NMR analysis. Naphthomycin B (II) is 30-chloronaphthomycin C. Strikingly, naphthomycin A (I) differs from B and C not only by the presence of an additional methyl group at C (2), but also in the configuration of some of the double bonds. A fourth ansamycin antibiotic of the naphthomycin subgroup, actamycin, is 30-hydroxynaphthomycin C.

Anti-Bacterial Agents↗
PubMed1982

Additive effect of glucan and streptozotocin on endotoxicosis in mice.

Mice were sensitized to endotoxin lethality after pretreatment with either glucan, or a single intraperitoneal injection of streptozotocin (SZN); the effect of glucan plus SZN was clearly additive. Triamcinolone acetonide (TA) protected animals under all these conditions. SZN alone did not influence the activity of the reticuloendothelial system (RES) in either normal or glucan-injected mice. TA actually diminished the RES activation as a result of glucan pretreatment and this was also true in normal mice. Within 4 h, SZN and/or TA did not influence glycaemia in either normal or glucan-injected animals. Endotoxin very quickly depressed glycaemia and this was unaltered when various combinations of TA and SZN were given with the toxin in glucan-pretreated mice. Glucan and/or SZN did not influence basal liver carbohydrate levels but TA induced liver glycogen within 4 h in glucan-injected mice, even in presence of SZN. Endotoxin depleted liver carbohydrates within 4 h and these could not be increased even by a dose of TA that fully protected against death. These observations stress the need to redefine the hypotheses regarding the mechanism of action of bacterial endotoxins.

Animals↗
PubMed1980

Intramedullary structure of human metacarpals.

External and internal measurements were taken of the metacarpal bones of 25 fresh adult, Caucasian cadaver hands. The shape of the intramedullary canal of each of the five metacarpals was different. There was also great variation between metacarpals in both cortical thickness and the diameter of the canals. The volar cortical wall of all metacarpals was approximately 20% thicker than the dorsal cortex. With the exception of the thumb, there was no difference between the radial and ulnar cortical thickness. The data obtained from these studies suggested strongly that the shape and dimensions of the intramedullary canal should be taken into consideration when designing intramedullary fixation devices or prostheses.

Adult↗
PubMed1979

Search for antiglucocorticoid activity in rat liver in vivo.

Estradiol and testosterone both lowered endogenous liver glycogen and at 20-fold higher doses impaired triamcinolone acetonide mediated glyconeogenesis in adult adrenalectomized male rats. Neither steroid influenced liver tyrosine transaminase although tryptophan pyrrolase activity was depressed by testosterone. Progesterone increased liver tryptophan pyrrolase but did not influence other parameters. Cortexolone did not alter either of these processes whereas cortisol induced both enzymes and, at much higher dose levels, gluconeogenesis. Binding of 3H-triamcinolone acetonide to its cytoplasmic receptor in vitro was left unaffected in presence of 20-fold greater concentration of either sex steroid but almost totally abolished by cold, homologous molecules. Similar results were obtained by 3H-cortisol except that estradiol partially competed for 3H-cortisol binding sites even at 20-fold greater concentrations of cold estradiol. Separation on DEAE-cellulose-52 and Ultrogel 44 columns revealed binding of all steroids to macromolecules of comparable physicochemical properties although the ratios of binding to the various subpopulations of the receptor were a function of the steroid in question. These results are discussed in terms of sex steroid binding to different moieties of a complex, heterogeneous, polymorphic protein rather than inhibition of binding to the active configuration acquired in presence of an inducer.

Animals↗
PubMed1979

Two cases of choreatic syndrome caused by polycythemia vera.

Two patients with choreatic syndromes caused by polycythemia vera recovered after treatment of the polycythemia by only two venesections: this proves that the syndrome is due to reversible alterations. Investigations of the cerebral circulation in one of the patients showed that blood flow was lowest in the grey matter at the basal region of the brain: this suggests that the alterations might mainly occur there. However, investigation of erythrocyte rheology, glucose-6-phosphate dehydrogenase, serum concentrations of caeruloplasmin and serotonin, and urinary excretion of epinephrine, norepinephrine and vanillylmandelic acid gave normal results in both patients. There are therefore no indications as to the possible pathophysiology of these alterations. There are now 24 cases reported, including our 2 patients, which suggests that the association of these two diseases may not be so rare as supposed.

Adult↗
PubMed1977

Influence of steroid structure in relation to liver metabolism during endotoxin lethality in mice.

The influence of a number of steroid molecules on hepatic metabolism was determined in relationship to their ability to alter endotoxin lethality in intact mice. Progesterone, testosterone, estradiol, pregnenolone-16-alpha-carbonitrile and spironolactone did not alter endotoxin lethality, liver glycogen or tryptophan pyrrolase (TP) levels; all these materials increased liver tyrosine transaminase (TT) levels most probably due to mediation by endogenously liberated glucocorticoid hormones. Aldosterone and deoxycorticosterone induced liver TP, TT and glycogen but did not protect against lethality. Cortisone, hydrocortisone, triamcinolone, dexamethasone and 9-alpha-fluorohydrocortisone protected against lethality, increased liver glycogen and TT, but only triamcinolone induced liver TP. Collectively, there was no clear relationship between the protective effect and the increase or decrease of a given liver process. These further emphasize the need to reconsider molecular mechanisms of endotoxic reactions.

Animals↗