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Biomedical subjects

M Zimmerman

Publications and source records attributed to M Zimmerman.

At least 199 records · Page 11Linked to original sources
PubMed1982

Failure of one method of simultaneous chest compression, ventilation, and abdominal binding during CPR.

Some modified methods of CPR improve carotid blood flow, but there are no studies to show that these modified techniques improve survival, Accordingly, an experimental CPR technique using simultaneous chest compression, ventilation (SCV-CPR), and abdominal binding was compared to standard CPR in beagle dogs. The modified technique utilized a broad-based bellows device that was mechanically compressed, producing chest compression, delivering a volume of air to the endotracheal tube, and pressurizing an abdominal binder. The duration of ventricular fibrillation and CPR was 5 min. Five of the 6 dogs could be resuscitated with standard CPR. None of 6 dogs could be resuscitated using this modified method of SCV-CPR and abdominal binding. The aortic diastolic pressure and the diastolic gradient between the aorta and right atrium was significantly different between the 2 groups. Because these pressures relate to the coronary perfusion pressure, they may explain the discrepancy in the survival rate. This study suggests increasing carotid blood flow during CPR will not necessarily improve survival.

Animals↗
PubMed1982

Comparison of the incidence of oncogenic transformation produced by X rays, misonidazole, and chemotherapy agents.

An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro was used to compare the incidence of oncogenic transformation produced by x rays, the hypoxic cell radiosensitizer misonidazole, and a range of commonly used chemotherapy agents. A 3-day exposure to misonidazole at a concentration obtainable during treatment produced an incidence of transformation similar to that of about 50 rad. When chemotherapy agents were tested at concentrations comparable to those used clinically and matched to produce similar cell killing, the incidence of transformation varied widely: some agents, such as vincristine, did not produce transformation at a level detectable above background, while others, such as cis-platinum, appear to be potent carcinogens and produce transformation at a rate orders of magnitude higher than that achieved with x rays.

Animals↗
PubMed1981

Selective inhibition of human leukocyte elastase and bovine alpha-chymotrypsin by novel heterocycles.

A number of N-arylbenzisothiazolinone 1,1-dioxides have been synthesized and examined for inhibitory activity against human leukocyte and porcine pancreatic elastase (EC 3.4.21.11), bovine alpha-chymotrypsin (EC 2.4.21.1), human leukocyte cathepsin G (EC 3.4.21.20), and bovine trypsin (EC 3.4.21.4). They are potent, selective, competitive inhibitors of human leukocyte elastase and chymotrypsin. The inhibitory capacity of these compounds is directly related to the electron-withdrawing capability of the aryl substituents. When sufficiently activated, the amide bond in the heterocyclic ring can be cleaved by the enzyme, resulting in inhibition which is highly specific. The most potent inhibitor of hummotrypsin. The inhibitory capacity of these compounds is directly related to the electron-withdrawing capability of the aryl substituents. When sufficiently activated, the amide bond in the heterocyclic ring can be cleaved by the enzyme, resulting in inhibition which is highly specific. The most potent inhibitor of human leukocyte elastase, the 2,4-dinitrophenyl derivative, has a Ki of 2.16 microM with elastase and 0.77 microM with chymotrypsin. This study demonstrates that it is possible to design specificity into non-peptide, low molecular weight serine protease inhibitors, which may have considerable pharmacologic potential.

Animals↗
PubMed1981

Purification of a membrane-bound metalloendopeptidase from porcine kidney that degrades peptide hormones.

A porcine kidney microsomal metalloendopeptidase has been enriched 3900-fold. Gel filtration on a calibrated Toyo-Soda G-3000 SW column indicated an appropriate molecular weight for the endopeptidase of 88,000 +/- 2000. The purified enzyme is inhibited by a number of synthetic inhibitors of thermolysin. The endopeptidase hydrolyzes the succinyl (Suc)-containing fluorogenic peptide substrate Suc-Ala-Ala-Phe-(7-amino-4-methylcoumarin) at the Ala-Phe position with a Km of 2.9 X 10(-4) M. The endopeptidase also hydrolyzes a variety of peptides including corticotropin, substance P, angiotensin I and II, neurotensin, somatostatin, bradykinin, and the renin tetradecapeptide substrate. The endopeptidase hydrolyzes both [Leu]- and [Met]enkephalin at the Gly-Phe bond.

Animals↗
PubMed1980

Inhibition of elastase and other serine proteases by heterocyclic acylating agents.

The N-acylsaccharins and N-acylbenzoisothiazolinones form a new class of acylating inhibitors of the serine proteases with a broad spectrum of activity. However, they are unique in that they are able to differentiate between various serine proteases because of the differential stability of the presumptive acyl-enzyme formed. Furoyl saccharin was the best studied among this class of inhibitors. We report evidence that the amide bond in the heterocyclic ring of this compound is cleaved by porcine pancreatic and human leukocyte elastases and chymotrypsin, forming acyl-enzymes. Radioisotope studies indicate that the saccharin portion of furoyl saccharin is attached to these enzymes in approximately a 1:1 molar ratio with enzyme, blocking the active site serine. The acylelastases thus prepared are unusually stable to hydrolysis, with kdeacyl values at neutral pH of 2.3 x 10(-6) s-1 for porcine pancreatic elastase and 1.4 x 10(-6) s-1 for human leukocyte elastase. Trypsin appears to be inhibited by a different mechanism. These data suggest a new approach to the design of specific synthetic protease inhibitors.

Animals↗
PubMed1980

A zinc metalloendopeptidase associated with dog pancreatic membranes.

Assay of solubilized dog pancreas microsomes revealed the presence of an endopeptidase which hydrolyzed the fluorogenic peptide substrate Suc-Ala-Ala-Phe-7-amino-4-methylcoumarin (AMC) between the alanine and phenylalanine positions. This activity was inhibited by phosphoramidon, 1,10-phenanthroline, and a number of synthetic inhibitors of thermolysin indicating that the enzyme is a zinc metallopeptidase. Endopeptidase activity was not inhibited by the serine protease inhibitors elastatinal, antipain, leupeptin, N-carbobenzyloxy-L-phenylethyl chloromethyl ketone, L-tosylamido-2-lysyethyl chloromethyl ketone, L-tosylamido-2-phenylethyl chloromethyl ketone, phenyl-methanesulfonyl fluoride, or low levels of chymostatin. The endopeptidase had a pH optimum between 7.0 and 7.5. The enzyme also hydrolyzed Suc-Ala-Ala-Ala-AMC and Suc-Ala-Gly-Ala-AMC in an analogous way to yield Ala-AMC. Thermolysis hydrolyzed Suc-Ala-Ala-Phe-AMC in an analogous way to the endopeptidase. However, thermolysin did not hydrolyze Suc-Ala-Ala-Ala-AMC or Suc-Ala-Gly-Ala-AMC, demonstrating that its substrate specificity differs from the endopeptidase.

Amino Acid Sequence↗
PubMed1980

Physiological effects of controlled concussive brain trauma.

Utilizing a fluid percussion device, we measured the physiological effects of brain trauma in cats exposed to controlled levels of injury. Concussive brain injury at 3-4 atm of intensity led to profound elevations of the mean systemic arterial blood pressure from 128 +/- 26 to 229 +/- 33 mmHg, left ventricular end-diastolic pressure from 4 +/- 2 to 24 +/- 15 mmHg, and pulmonary wedge pressures (PWP) from 5 +/- 3 to 27 +/- 17 mmHg and a relatively moderate increase in intracranial pressure (ICP) from 6 +/- 3 to 38 +/- 31 mmHg (all P < 0.001). Pulmonary edema was evidenced by a significant increase in lung tissue wet-to-dry weight ratios to 3.74 +/- 0.81 as compared with a control group of 2.29 +/- 0.23 (P < 0.001). There was poor correlation between wet-to-dry weight ratios and PWP. Approximately 60% of all spontaneously breathing animals become permanently apneic within 6 min after injury, while the remaining 40% developed transient apnea. Arterial O2 or CO2 pressure alterations, in contrast to pretreatment with phentolamine did not affect the hemodynamic or edemogenic response to trauma. Phentolamine did not block the apneic response or increase in ICP. Comparative studies using intravenous levarterenol without trauma produced responses similar to trauma. Concussive brain injury of 3-4 atm results in pulmonary edema, apnea, sympathetically mediated peripheral vasoconstriction and left ventricular failure effect.

Animals↗