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Biomedical subjects

A Mor

Publications and source records attributed to A Mor.

68 records · Page 4Linked to original sources

Susceptibility of plasminogen activators to suicide inactivation.

Halomethylated derivatives of dihydrocoumarins are efficient enzyme-activated inhibitors ("suicide" substrates) of plasminogen activators. Kinetic analysis indicate that the one-chain and two-chain forms of the human plasminogen activator are inhibited by 3,4-dihydro-3-benzyl-6-chloromethylcoumarin through a mechanism-based inactivation characterized by the following kinetic parameters (4 degrees C, pH 6.8) : k2 equal to 0.02 s-1 and 0.03 s-1 (for one- and two-chain tissue plasminogen activators, respectively) and Ki equal to 0.16 mM for both forms. Human urokinase and human tissue-type plasminogen activator can be discriminated on the basis of their inhibition by this suicide substrate. The design of a new series of suicide substrates of serine proteases (functionalized cyclopeptides possessing a potential alkylating function closely related to that found in halomethylated derivatives of dihydrocoumarins) is described.

Chemical Phenomena↗

Characterization of the receptor binding profile of (3H)-dermorphin in the rat brain.

Amphibian skin synthesizes a variety of biologically active peptides. Of these, dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) is an extraordinarily potent opioid peptide up to 1000 times more active than morphine in inducing analgesia after intracerebroventricular administration. Dermorphin has little in common with the sequence of all hitherto known mammalian opioid peptides and is unique in having a D-amino acid residue in position 2. Specific binding properties of tritium labeled dermorphin were characterized in the rat brain. Scatchard or Hill analysis of equilibrium measurements performed over a large range of concentrations revealed a single population of dermorphin binding sites with a Kd value of 0.46 nM. Dermorphin and the selective mu-receptor ligand (D-Ala2, MePhe4, Gly5-ol)-enkephalin (DAGO) had similar high potencies in competing with (3H)-dermorphin binding, whereas the inverse holds for the prototypical delta receptor ligand (D-Pen2, D-Pen5)-enkephalin (DPDPE), which exhibited a potency three orders of magnitude lower. Dermorphin was tested for its relative affinity to mu and delta binding sites by determining its potency in displacing (3H)-DAGO and (3H)-DPDPE from rat brain membrane preparations. Based on these comparisons, dermorphin exhibited a selectivity ratio Ki(DPDPE)/Ki(DAGO) = 100, a value almost identical to that of DAGO, this ligand being considered as the protypical mu-receptor probe. The high affinity and selectivity of (3H)-dermorphin together with its very low nonspecific binding make this peptide a useful tool for dissecting the role(s) of the mu-receptor(s).

Analgesics, Opioid↗

Tachycardia and heart failure after ritual circumcision.

Four newborn babies developed acute heart failure a few hours after circumcision at 8 days. During this procedure, a sponge soaked in epinephrine was applied to the circumcision site and left there for several hours. Treatment was with digoxin and diuretics and signs of heart failure disappeared within 24-72 hours.

Circumcision, Male↗

Auditory brainstem evoked potentials in asymptomatic lead-exposed subjects.

Auditory Brainstem Evoked Potentials (ABEP) were recorded from 29 adults and children, accidentally exposed to lead through food until approximately a year prior to this study. ABEP were recorded in response to 75 dBHL clicks presented at rates of 10/sec. and 55/sec. Average values were calculated for peak latency and for interpeak latency differences. Average values of the effect of increasing stimulus rate were calculated as well. Similar values were calculated for normative child and adult control groups. IPLD(I-III) showed the most significant and recurring results, with longer intervals in lead-exposed children compared with their control group. Increasing stimulus rate, on the other hand, affected the adult lead-exposed subjects more than the children. These results may imply an impairment of the peripheral portion of the auditory system with axonal and myelin involvement. ABEP is suggested as a sensitive detector of subclinical lead exposure effects on the nervous system.

Adolescent↗

Influence of digoxin and diuretic therapy on sweat fluid composition.

The effect of digitalis and diuretic therapy on sweat fluid composition was investigated. Patients treated for congestive heart failure with a combination of digoxin and diuretics demonstrated a higher concentration of sodium and chloride in their sweat fluid when compared to age-matched controls. The administration of diuretics alone did not affect sweat fluid composition. The digoxin-induced increase in sodium concentration was significantly higher than that observed for chloride. These data suggest that digoxin markedly inhibits sodium reabsorption along the sweat gland tubule, whereas chloride transport is affected to a lesser degree. A significant correlation between sweat fluid sodium and serum digoxin concentrations was observed. We conclude that the increased digoxin-induced sweat sodium and chloride losses may affect sodium homeostasis in patients with congestive heart failure.

Aged↗

Hormonal effects on the phosphorylation of glycogen synthase in rat hepatocytes.

The effects of epinephrine and vasopressin on the phosphorylation state of glycogen synthase were studied using rat hepatocytes incubated with 32P. After the incubation with hormones, 32P-labeled glycogen synthase was isolated using antibodies against rat liver enzyme. The immunoprecipitate showed a single radioactive band ( Mapp 88 kDa) when subjected to SDS-gel electrophoresis. Both epinephrine and vasopressin inactivated the enzyme and increased the 32P content of glycogen synthase. Cleavage of the immunoprecipitate with CNBr yielded two major 32P-labeled fragments of Mapp approximately 27 and 12 kDa. Both hormones increased the 32P content of both fragments. These results prove that epinephrine and vasopressin increase the phosphate content of the enzyme promoting its phosphorylation at multiple sites.

Adenosine Triphosphate↗

Contracted gallbladder in hepatitis. Value of postprandial examination.

A completely contracted gallbladder is occasionally seen in patients with acute hepatitis. We have observed that postprandial examination in these patients shows the gallbladder filling with bile to a degree that permits an adequate diagnostic examination. This simple procedure may prevent having to recall the patient for follow-up examination.

Acute Disease↗

Increased propensity for amyloidogenesis in male mice.

BACKGROUND: The male sex is a risk factor for reactive amyloidogenesis in several disease entities. Environmental, socioeconomic or genetic factors may underlie this male preponderance. This study was aimed at discovering whether male sex predisposes to reactive amyloidosis also in mice and to elucidate some of the hormonal associations of this risk. METHODS: Male and female Swiss mice were subjected to an established amyloid induction protocol and the amount of their splenic amyloid was determined and compared. The effect of estrogen, progesterone, testosterone and adrenalin on amyloidogenesis was studied in both sexes by administering these hormnones during amyloid induction and comparing the amount of splenic amyloid of the study mice with the control mice which received the amyloid induction protocol alone. RESULTS: Amyloid deposition appeared to be more abundant in male mice. This gender difference was not associated with any of the 3 sex hormones tested. Despite an expected increment, adrenalin caused an attenuation of amyloid deposition. CONCLUSIONS: The preferential expression of reactive amyloidosis in male mice seems to be unrelated to the common sex hormones. Increased production of other hormones such as adrenalin, or perhaps an augmented susceptibility to their effect, may cause gender differences by suppressing female amyloidogenesis. Our study favors the hypothesis of genetic predisposition as the mechanism leading to sex differences in amyloidogenesis. Further validation of our findings in gonadal ablated models and other amyloid induction protocols is warranted.

Amyloid↗