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Biomedical subjects

M S Klein

Publications and source records attributed to M S Klein.

At least 19 recordsLinked to original sources

Behavioral thermoregulation in mice inoculated with influenza virus.

Mice housed at 30 degrees C and inoculated with a mouse-adapted influenza virus show a fall in body temperature (Tb) and a decrease in food intake to almost 0 grams per day. This study tested whether the fall in Tb could be accounted for by the decreased food intake and whether the fall in Tb was due to a decrease of thermoregulatory set point or to an inability to maintain Tb at set point level. The fall in Tb of influenza-infected mice was greater than that of food-deprived mice. When food deprived, mice given access to a thermal gradient increased their preference for warmer areas in the gradient and, as a result, Tb did not fall as much as Tb of starved mice not given access to a thermal gradient. When infected with influenza virus, mice given a thermal gradient decreased Tb less and at a slower rate than mice not given a gradient. However, this fall in Tb of influenza-infected mice was greater than that of food-deprived mice given a thermal gradient. Mice given a thermal gradient increased their preference for the warmer temperatures after inoculation; this returned to preinoculation preference for cooler temperatures during the later days of infection despite a continuous fall in Tb. Influenza-infected mice given a thermal gradient survived significantly fewer days than infected mice not given a thermal gradient. We conclude that the influenza-induced fall of Tb in mice cannot be explained solely by the decrease in food intake, and is partially due to a decrease in thermoregulatory set point.

Animals

Inguinal hernia.

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Hernia, Inguinal

Adapting IAIMS to a hospital library level.

The Children's Hospital of Michigan Medical Library has adapted several of the Integrated Academic Information Management Systems (IAIMS) concepts and implemented them at a hospital library level. These have included features of network development, electronic interfacing and interlinking, and implementing an integrated information system in the library. The library has incorporated several information systems into library operations, including a variety of in-house, local, and national automated systems and telecommunication networks. Hospital libraries can incorporate IAIMS features and promote an institutional framework of interconnecting communication systems and electronic linkages.

Computer Communication Networks

Assessment of myocardial perfusion in humans by contrast echocardiography. I. Evaluation of regional coronary reserve by peak contrast intensity.

Myocardial contrast echocardiography was performed during coronary angiography with 2 ml of sonicated meglumine diatrizoate sodium 76% (meglumine) in 40 patients (ranging in age from 25 to 79 years) before and 10 to 15 s after intracoronary injection of papaverine, 8 mg into the right coronary artery (n = 43) and 10 mg into the left (n = 46). The same protocol was repeated in 17 patients 5 to 10 min after completion of coronary angioplasty. In 13 patients with normal coronary angiograms, peak contrast intensity corrected for background myocardial intensity was measured in 36 regions and was found to increase after papaverine from 36 +/- 16 to 55 +/- 22 U (p less than 0.001). In contrast, in the 27 patients with angiographic evidence of coronary artery disease, peak intensity in 64 regions remained unchanged after papaverine (35 +/- 22 versus 36 +/- 23 U). An increase in peak intensity greater than or equal to 10 U was 80% sensitive and 92% specific for coronary artery disease. After successful coronary angioplasty, peak intensity in the involved regions improved significantly (p less than 0.001) during baseline contrast injections (from 32 +/- 16 to 50 +/- 25 U) as well as in the postpapaverine contrast injections (from 30 +/- 12 to 60 +/- 26 U). In conclusion, measurement of peak contrast intensity after intracoronary injections of sonicated meglumine provides a relative index of myocardial perfusion that allows assessment of regional coronary reserve in patients with coronary artery disease. This may be of particular value in evaluating the immediate effects of coronary angioplasty on myocardial perfusion.

Adult

Abnormal technetium-99m pyrophosphate images in unstable angina: ischemia versus infarction?

There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis.

Adult

External assessment of myocardial metabolism with [11C]palmitate in rabbit hearts.

To determine whether the rate of fatty acid utilization, reflecting myocardial oxygen consumption under steady-state conditions, can be assessed noninvasively, we assayed positron emission from [11C]palmitate (100 muCi) in isolated rabbit hearts and after intra-atrial injection in vivo. In 11 isolated hearts, clearance of 11C-radioactivity during a monoexponential portion of residue detection curves correlated with tension-time index (TTI)(r = 0.86) and peak dP/dt (r = 0.89). Among 9 hearts prelabeled with [14C]palmitate, 14CO2 production from neutral lipid stores correlated with TTI (r = 0.83). In vivo the decline of 11C-radioactivity was 1st order and constant when physiological conditions were maintained constant (slope of the semilog plot = 0.099 +/- 0.002 (SE) in counts/min) (n = 2 animals, 7 injections). Decline of activity changed predictably when oxygen requirements were increased by administration of methoxamine. Thus, residue detection of [11C]palmitate 1) permits external assessment of global myocardial metabolism in vitro, and 2) reflects effects of interventions that alter the rate of substrate utilization in vivo, and should, therefore, permit comparison of rates of regional myocardial metabolism in patients with detection of radioactivity by positron-emission transaxial tomography.

Animals

Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium.

Lysophosphoglycerides, products of membrane phospholipid catabolism known to influence membrane function in several systems, appeared in the effluents of anoxic isolated rabbit hearts perfused at low flow and accumulated in perfused hearts and myocardium rendered ischemic in situ. Comparable concentrations of lysophosphoglycerides bound to albumin markedly and reversibly altered action potentials of isolated canine Purkinje fibers in vitro. Changes induced included diminution of the maximum diastolic potential, peak dV/dt of phase zero, amplitude, and action potential duration--alterations resembling those seen in ischemic myocardium in vivo. These electrophysiological alterations are compatible with changes implicated in predisposing to dysrhythmia dependent on reentry, a phenomenon potentiated by the presence of zones of decreased conduction. Thus, accumulation of lysophosphoglycerides induced by ischemia may contribute to the genesis of malignant dysrhythmia early after its onset.

Action Potentials

Mechanisms contributing to myocardial accumulation of technetium-99m stannous pyrophosphate after coronary arterial occlusion.

The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the "myocardial" CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart.

Animals

Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise-induced ischemia and patients with a calcified valve.

Although technetium-99m stannous (99mTc[Sn]) pyrophosphate has been shown to be a specific and sensitive index of myocardial infarction, abnormal images have been reported in patients with unstable angina or ventricular aneurysm. Sixty-one subjects--33 patients subjected to maximal treadmill stress testing, 23 normal subjects and 5 patients with a calcified aortic or mitral valve--underwent imaging with 99mTc(Sn) pyrophosphate to determine whether abnormal images are associated with (1) exercise-induced ischemia, (2) delayed clearance of tracer from the blood pool, or (3) calcified intracardiac structures. Myocardial injury was excluded on the basis of normal MB creatine kinase (CK) values in all patients with stress testing. All eight patients with an abnormal exercise stress test had normal images. Four of 25 patients with a normal exercise stress test had diffusely abnormal images. In some normal subjects diffusely abnormal images were present 60 minutes after injection of the tracer, but became normal 90 to 120 minutes after injection. Variations in clearance of tracer from the blood pool were noted in this group. Patients with a calcified aortic or mitral valve had normal images. We conclude that (1) exercise-induced ischemia is not associated with abnormal 99mTC(SN) pyrophosphate images; (2) images are not necessarily abnormal in patients with a calcified valve; and (3) delayed removal of tracer from the cardiac blood pool may result in diffusely abnormal images even in normal subjects; in these cases, repeat images should be obtained at least 2 hours after injection of the tracer to avoid false abnormal images.

Adult

Perioperative mortality rate in patients with unstable angina selected by exclusion of myocardial infarction.

Coronary bypass surgery may be associated with an increased perioperative mortality rate in patients with unstable compared to stable angina. The mortality rate is excessively high when surgery is performed during evolving myocardial infarction. Elevated plasma MB CPK isoenzyme activity is a remarkably sensitive and specific marker of myocardial damage. Accordingly, we studied 111 patients with unstable angina to determine whether exclusion of patients with initially elevated MB CPK improves the perioperative mortality rate. Plasma MB CPK activity was assayed prior to catheterization and every 2 hours therafter. Of the 111 patients, 16, with initially elevated MB CPK activity, were excluded and managed medically. Catheterization was performed in 59 patients, and severe vessel obstruction was documented in 55. Coronary bypass surgery performed in 47 patients was associated with a mortality rate of 4 per cent. Thus, after exclusion of patients with evolving infarction by MB CPK isoenzyme analysis, catheterization and coronary bypass surgery in patients with unstable angina resulted in a mortality rate comparable to that in patients with stable angina.

Adult

Structure of beef heart mitochondrial F1-ATPase. Arrangement of subunits as disclosed by cross-linking reagents and selective labeling by radioactive ligands.

1. The following bifunctional reagents, dimethylsuberimidiate, dimethyladipimidate, methylmercaptobutyrimidate have been used to produce dimers between the neighboring subunits of beef heart F1-ATPase. 2. Treatment of beef heart F1-ATPase with dimethylsuberimidate or dimethyladipimidate resulted in the formation of four cross-linked products. Their molecular weights determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 11 500, 105 000, 95 000 and 80 000, respectively. The products of molecular weight 115 000 and 105 000 were predominant and could be detected at the early stage of the cross-linking reaction. Treatment of beef heart F1-ATPase with methylmercaptobutyrimidate resulted in the accumulation of the product of molecular weight 115 000 and in traces of products of lower molecular weight. When the cross-linked products obtained with methylmercaptobutyrimidate were cleaved by beta-mercaptoethanol, the original gel electrophoresis pattern was restored. 3. Cross-linking of beef heart F1-ATPase by dimethylsuberimidate, dimethyladipimidate and methylmercaptobutyrimidate was accompanied by a loss of the ATPase activity. Cleavage of the cross-linked products obtained with methylmercaptobutyrimidate did not restore the original ATPase activity. 4. Identification of subunits A and B in the products of molecular weight 115 000 and 105 000 was achieved by specific labeling of subunit A with N-[14C]ethylmaleimide and of subunit B by chloronitro [14C]benzooxodiazole. Both products were able to bind N-[14C]ethylmaleimide; only the 105 000 dalton product was able to bind chloronitro [14C]benzooxodiazole. 5. The product of molecular weight 115 000 obtained by treatment of beef heart ATPase with methylmercaptobutyrimidate could bind N-[14C]ethylmaleimide. Its cleavage, following N-[14C]ethylmaleimide binding, yielded one labeled peptide identified with subunit A by polyacrylamide gel electrophoresis. 6. The above results indicate that the product of molecular weight 115 000 is a dimer containing two subunits A and that the product of molecular weight 105 000 is a dimer containing one subunit A and one subunit B. It can therefore be concluded that, in beef heart F1-ATPase, the A subunits are close to each other and that subunit A is close to subunit B. In contrast the B sublnits are probably too far from each other to be cross-linked by dimethylsuberimidate, dimethyladipimidate or methylmercaptobutyrimidate.

Adenosine Triphosphatases