Biomedical subjects

A Chu

Publications and source records attributed to A Chu.

At least 109 records · Page 6Linked to original sources

PubMed1988

Inhibitors of sterol synthesis. Reverse phase high performance liquid chromatography for the separation of cholesterol, 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, and their fatty acid esters.

A relatively simple and rapid method was required for the separation of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of sterol synthesis, from its major metabolites. Conditions have been determined which permit the resolution of the 15-ketosterol and cholesterol and fatty acid esters of the two sterols by reverse phase high performance chromatography. This methodology also permits the resolution of the major esters of the 15-ketosterol and of cholesterol.

Cholestenes↗

PubMed1987

Prognostic effect of bundle branch block related to coronary artery bypass grafting.

The incidence and prognostic effect of the development of new perioperative ventricular conduction abnormalities were examined in all patients undergoing coronary artery bypass surgery at Duke University Medical Center between 1976 and 1981. Of the 913 patients included, transient (resolved before discharge) ventricular conduction abnormalities developed in 156 (17%) and persistent (until discharge) changes developed in 126 (14%). Complete right bundle branch block (BBB) was the most frequent type of new ventricular conduction abnormality, followed by left anterior hemiblock and incomplete right BBB (found in 60%, 26%, and 9%, respectively, of all patients with transient changes and 29%, 33% and 26% of all patients with persistent changes). Development of new ventricular conduction abnormalities was most strongly related to date of operation (p less than 0.0001, univariate chi 2 = 122), increasing from 2% transient and 7% persistent in 1976 to 36% transient and 22% persistent in 1981. The incidence was also higher in older patients. Preoperative ejection fraction and number of diseased vessels were related to development of perioperative ventricular conduction abnormalities but were not independently related after adjustment for other baseline characteristics. Contrary to findings in other studies, development of new perioperative ventricular conduction abnormalities, including isolated new left BBB, did not worsen the survival rate in patients followed up to 3 years after surgery.

Adult↗

PubMed1987

Simple method to measure power density entering a plane biological sample at millimeter wavelengths.

A simple method for measuring microwave power density is described. It is applicable to situations where exposure of samples in the near field of a horn is necessary. A transmitted power method is used to calibrate the power density entering the surface of the sample. Once the calibration is available, the power density is known in terms of the incident and reflected powers within the waveguide. The calibration has been carried out for liquid samples in a quartz cell. Formulas for calculating specific absorption rate (SAR) are derived in terms of the power density and the complex dielectric constant of the sample. An error analysis is also given.

Calibration↗

PubMed1987

Preparation and characterization of longitudinal tubules of sarcoplasmic reticulum from fast skeletal muscle.

Sarcoplasmic reticulum (SR) serves a central role in calcium uptake and release, thereby regulating muscle relaxation and contraction, respectively. Recently, we have isolated fractions referable to longitudinal tubules (R2) and terminal cisternae (R4), the two major types of sarcoplasmic reticulum (A. Saito et al. (1984) J. Cell Biol. 99, 875-885). The terminal cisternae contain two types of membranes, the calcium pump membrane and the junctional face membrane. The terminal cisternae are filled with electron-opaque contents which serve as a Ca2+ reservoir. The longitudinal tubules consist mainly of the calcium pump membrane. In this study, we describe a new longitudinal tubule fraction (F2) and characterize it together with the R2 and R4 SR fractions. The calcium pump membrane of the longitudinal tubules is a highly specialized membrane consisting of about 90% calcium pump protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive changes in morphology can be observed in the SR fractions referable to osmotic differences during the fixation conditions using either glutaraldehyde-tannic acid or osmium tetroxide fixatives. The changes include swelling or shrinkage and aggregation of the compartmental contents when the fixative contains calcium ions. The two types of SR have different osmotic permeability to the same medium, as indicated by differential swelling or shrinkage. Both longitudinal tubule and terminal cisternae vesicles of SR appear larger and are spherical vesicles when the glutaraldehyde-tannic acid fixative is isotonic as compared with the "standard" fixation method. We have previously reported that the ruthenium red-sensitive calcium release channels are localized to the terminal cisternae. The terminal cisternae as isolated are leaky to Ca2+ since these channels are in the "open state" (S. Fleischer et al. (1985) Proc. Natl. Acad. Sci USA 82, 7256-7259). Thus, the Ca2+, Mg2+-dependent ATPase (Ca2+ ATPase) rate is only slightly enhanced in the presence of a Ca2+ ionophore, which dissipates the Ca2+ gradient across the SR membrane. We now find that preincubation with ruthenium red restores the tight coupling of the Ca2+ ATPase activity to Ca2+ transport. That is to say, ATPase activity is reduced and the addition of ionophore stimulates the Ca2+ ATPase activity 4- to 7-fold. The Ca2+ ATPase activity in longitudinal tubules is already tightly coupled. It is minimal after a Ca2+ gradient has been generated, but can be stimulated 9- to 20-fold when the Ca2+ gradient is dissipated with ionophore. This finding suggests that the Ca2+ ATPase activity in SR is tightly coupled to Ca2+ transport in situ.

Animals↗

PubMed1987

Brain metabolism and intracellular pH during ischaemia and hypoxia: an in vivo 31P and 1H nuclear magnetic resonance study in the lamb.

Brain metabolism and intracellular pH were studied during and after episodes of ischaemia and hypoxia-ischaemia in lambs anaesthetised with sodium pentobarbitone. 31P and 1H magnetic resonance spectroscopy methods were used to monitor brain pHi and brain concentrations of Pi, phosphocreatine (PCr), beta--nucleoside triphosphate (beta NTP), and lactate. Simultaneous measurements were made of cerebral blood flow and cerebral oxygen and glucose consumption. Cerebral ischaemia sufficient to reduce oxygen delivery to 75% of control values was associated with a fall in brain pHi and increase in brain Pi. Progressively severe hypoxia-ischaemia was associated with a progressive fall in brain pHi, PCr, and beta NTP and increase in brain Pi. In two animals the increase in brain lactate during hypoxia-ischaemia measured by 1H nuclear magnetic resonance (NMR) could be quantitatively accounted for by the increased net uptake of glucose by the brain in relation to oxygen, but was insufficient to account for the concomitant acidosis according to previous estimates of brain buffering capacity. In four animals brain pHi, PCr, Pi, and beta NTP had returned to normal 1 h after the hypoxic-ischaemic episode. In one animal brain pHi had reverted to normal at a time when 1H NMR indicated persistent elevation of brain lactate.

Animals↗

PubMed1987

Brain intracellular pH and metabolism during hypercapnia and hypocapnia in the new-born lamb.

1. The effects of hypercapnia and hypocapnia on brain intracellular pH (pHi) and metabolism were investigated in new-born lambs under barbiturate anaesthesia. 2. 31P nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine brain pHi and the relative concentrations of compounds containing mobile phosphorus nuclei including phosphocreatine (PCr), nucleoside triphosphates (NTP) and inorganic phosphate (Pi). Simultaneous measurements were made of the molar ratio of glucose to oxygen uptake by the brain. 3. During normocapnia (arterial partial pressure of CO2 Pa, CO2, 39 +/- 1 mmHg mean +/- S.E. of mean, n = 9) brain pHi was 7.13 +/- 0.02. Hypercapnia (Pa, CO2, 98 +/- 3 mmHg) was associated with a fall in brain pHi to 6.94 +/- 0.03 (n = 19, P less than 0.001), whereas no significant change in brain pHi occurred during hypocapnia (Pa, CO2, 16 +/- 1 mmHg; brain pHi 7.15 +/- 0.01). 4. During hypercapnia there was an increase in the ratio of Pi to NTP from 1.09 +/- 0.08 to 1.47 +/- 0.06 (P less than 0.001) and a decrease in the ratio PCr/Pi from 1.60 +/- 0.08 to 0.93 +/- 0.04 (P less than 0.001). There was a linear correlation between Pi/NTP and brain pHi. 5. Alterations in arterial PCO2 had no significant effect on the molar ratio of glucose to oxygen uptake by the brain, which remained close to unity. 6. The change in brain pHi observed during hypercapnia can be accounted for by the known physico-chemical buffering capacity of brain tissue. Homoeostasis of brain pHi during hypocapnia provides further evidence that additional regulatory mechanisms operate in these circumstances. 7. The observed changes in PCr and Pi can be accounted for in part by the [H+] dependence of the creatine kinase reaction.

Animals↗

PubMed1987

Relation between myocardial perfusion and left ventricular function following acute coronary occlusion: disproportionate effects of anterior vs. inferior ischemia.

This study examined the relation between left ventricular (LV) function and the severity of acute myocardial ischemia in a conscious dog model. The LV ejection fraction (EF) was measured by multigated equilibrium radionuclide angiography, and regional myocardial blood flow was measured with radioactive microspheres before and 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD, 13 dogs) or left circumflex (LC, 13 dogs) coronary artery. Two methods were used to evaluate the extent of ischemia. The first method determined the mass of myocardium that was ischemic based on different degrees of reduced blood flow. The second method estimated the severity of ischemia expressed as blood flow deficit resulting from each coronary occlusion. Global LV function was very sensitive to ischemia, and the relation between change in function and the degree of ischemia were described best by linear functions. The best linear correlation between mass of ischemic myocardium and percent reduction in EF resulted from the ischemic region defined as all tissue with 25% or greater reduction in blood flow, r = 0.84 for LAD (Y = 0.96X + 1.8) and r = 0.75 for LC (Y = 0.53X + 2.0) occlusions. Defining ischemic mass by more severe reduction in blood flow resulted in exclusion of ischemic myocardium that affected function. The myocardial blood flow deficit also correlated linearly with percent reduction in EF, r = 0.89 for LAD (Y = 1.31X + 2.7) and r = 0.81 for LC (Y = 0.83X - 0.1) occlusions. The slope of the regression lines using both analyses of ischemia were significantly greater (p less than 0.01) for LAD than LC occlusions, indicating that for comparable degrees of ischemia LAD as compared to LC occlusion decreased EF to a greater extent. Calculation of EF from attenuated corrected volumes resulted in small changes in LAD, but not LC, EF and did not account for the disproportionate effects of LAD and LC ischemia. In a separate group of studies (n = 18) EF measured by radionuclide angiography after LAD or LC occlusions correlated well with biplane contrast angiography r = 0.93, SEE 5.1. These data suggest that disproportionately greater effects of LAD compared to LC ischemia on global EF in the dog are due primarily to different pathophysiologic responses to ischemia.

Animals↗

PubMed1987

Effects of atrial natriuretic peptide on proximal epicardial coronary arteries and coronary blood flow in conscious dogs.

The effects of atrial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 micrograms) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1-5 minutes) dose-related increases in coronary blood flow; maximum increases were 28.1 +/- 6.9%, 40.2 +/- 6.2%, and 73.9 +/- 12.5% with the 10-, 50-, and 150-micrograms doses, respectively. ANP also induced prolonged (average 70.2 +/- 28.6 minutes with 150-micrograms dose) dose-related increases in coronary diameter; maximum increases were 3.1 +/- 1.0%, 3.9 +/- 1.5%, and 5.7 +/- 1.3% with the 10-, 50-, and 150-micrograms doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Vasoactive effects of serotonin on proximal coronary arteries in awake dogs.

This study evaluates the vasoactive effects and mechanisms of action of serotonin on epicardial arteries in awake dogs chronically instrumented with miniature piezoelectric dimension crystals on the proximal circumflex coronary artery. Serotonin (2-16 micrograms) infused as a bolus in the left atrium effected a dose-related biphasic response, which was characterized by an initial increase in vessel dimension with a peak response at 45-75 seconds, followed by a delayed and more sustained vasoconstriction, with a maximum response at 2-8 minutes. The magnitude of the initial vasodilation was generally greater than the delayed vasoconstriction. The initial vasodilation remained unchanged after selective S2 blockade with ketanserin (0.3 mg/kg) and was only minimally but insignificantly attenuated when flow was held constant but was reduced after S1 and S2 blockade with methysergide (0.25 mg/kg). Selective S2 blockade with ketanserin (0.3 mg/kg) attenuated the delayed vasoconstriction in most but not all dogs; the effect of ketanserin was, however, not significant when the entire group was considered. Selective endothelial denudation effectively eliminated the initial vasodilation response to serotonin and significantly augmented the delayed vasoconstriction when the dogs were studied 1-2 days after denudation. The data indicate that in the awake dog, serotonin effects a biphasic vasomotor response characterized by an initial vasodilation that is mediated primarily through a direct endothelium-dependent S1 mechanism followed by a delayed vasoconstriction that is probably mediated via a direct S2 effect on the vascular smooth muscle and is attenuated by the normal endothelium.

Animals↗

PubMed1986

Functional characterization of junctional terminal cisternae from mammalian fast skeletal muscle sarcoplasmic reticulum.

Junctional terminal cisternae are a recently isolated sarcoplasmic reticulum fraction containing two types of membranes, the junctional face membrane with morphologically intact "feet" structures and the calcium pump membrane [Saito, A., Seiler, S., Chu, A., & Fleischer, S. (1984) J. Cell Biol. 99, 875-885]. In this study, the Ca2+ fluxes of junctional terminal cisternae are characterized and compared with three other well-defined fractions derived from the sarcotubular system of fast-twitch skeletal muscle, including light and heavy sarcoplasmic reticulum, corresponding to longitudinal and terminal cisternae regions of the sarcoplasmic reticulum, and isolated triads. Functionally, junctional terminal cisternae have low net energized Ca2+ transport measured in the presence or absence of a Ca2+-trapping anion, as compared to light and heavy sarcoplasmic reticulum and triads. Ca2+ transport and Ca2+ pumping efficiency can be restored to values similar to those of light sarcoplasmic reticulum with ruthenium red or high [Mg2+]. In contrast to junctional terminal cisternae, heavy sarcoplasmic reticulum and triads have higher Ca2+ transport and are stimulated less by ruthenium red. Heavy sarcoplasmic reticulum appears to be derived from the nonjunctional portion of the terminal cisternae. Our studies indicate that the decreased Ca2+ transport is referable to the enhanced permeability to Ca2+, reflecting the predominant localization of Ca2+ release channels in junctional terminal cisternae. This conclusion is based on the following observations: The Ca2+, -Mg2+ -dependent ATPase activity of junctional terminal cisternae in the presence of a Ca2+ ionophore is comparable to that of light sarcoplasmic reticulum when normalized for the calcium pump protein content; i.e., the enhanced Ca2+ transport cannot be explained by a faster turnover of the pump. Ruthenium red or elevated [Mg2+] enhances energized Ca2+ transport and Ca2+ pumping efficiency in junctional terminal cisternae so that values approaching those of light sarcoplasmic reticulum are obtained. Rapid Ca2+ efflux in junctional terminal cisternae can be directly measured and is blocked by ruthenium red or high [Mg2+]. Ryanodine at pharmacologically significant concentrations blocks the ruthenium red stimulation of Ca2+ loading. Ryanodine binding in junctional terminal cisternae, which appears to titrate Ca2+ release channels, is 2 orders of magnitude lower than the concentration of the calcium pump protein. By contrast, light sarcoplasmic reticulum has a high Ca2+ loading rate and slow Ca2+ efflux that are not modulated by ruthenium red, ryanodine, or Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1986

Psoriatic skin lesions contain biologically active amounts of an interleukin 1-like compound.

The presence of neutrophil chemoattractant material in aqueous extracts of lesional psoriatic scale has been investigated by use of an agarose microdroplet chemokinesis method in combination with ultrafiltration and high-performance liquid chromatography (HPLC). Fractions were also assayed for murine thymocyte co-stimulating activity. Aqueous extracts of psoriatic scale contained significantly greater neutrophil chemokinetic activity than extracts of scale from normal skin. Successive ultrafiltration of extracts showed that the chemokinetic material was 10 to 30 kd. Heat lability and gel filtration HPLC characteristics suggested that the major chemokinetically active material in aqueous extracts of psoriatic scale is different from C5a des arg. Reversed-phase HPLC of 0.1% trifluoroacetic acid/acetonitrile extracts of psoriatic scale revealed two clearly resolved peaks of chemokinetic activity, the major peak consistently containing thymocyte co-stimulating activity. No significant neutrophil chemokinetic activity was seen in fractions after reversed-phase HPLC of scale from normal skin. These findings suggest that a major portion of the neutrophil chemoattractant activity in aqueous extracts of psoriatic scale is due to interleukin 1-like material, which may play a role in the pathogenesis of this disease.

Adult↗

PubMed1986

Roussel award for cardiology. The mechanism of nucleotide induced calcium translocation across sarcoplasmic reticulum membranes: evidence for a non-translocated intermediate pool of calcium.

Our previous data suggested that, in cardiac muscle sarcoplasmic reticulum fragments, GTP hydrolysis occurs by an alternative enzyme cycle of the Ca2+ ATPase which is insensitive to (Ca2+) and does not involve an acyl phosphate intermediate. Despite this, GTP induces the incorporation of calcium into a membrane pool that is not translocated to the vesicular lumen. The present study suggests that this GTP-induced intermediate calcium pool is identical to a modulable component of the calcium translocation process in that: it has an identical pH sensitivity; the initial incorporation of calcium in response to GTP eliminates the initial rapid burst and lag component of the typical ATP-induced calcium uptake curve when ATP is added during GTP-induced calcium accumulation. Instead, the addition of ATP during GTP-induced calcium accumulation results in the prompt onset of the linear phase of calcium translocation; GTP-induced calcium accumulation directly affects the pH sensitivity of subsequent ATP-induced calcium accumulation. We suggest that the intermediate calcium pool is in series with calcium translocation and is the site of the pH sensitivity observed in calcium flux.

4-Nitrophenylphosphatase↗

PubMed1986

Characterization of the junctional face membrane from terminal cisternae of sarcoplasmic reticulum.

We have recently described a preparation of junctional terminal cisternae (JTC) from fast skeletal muscle of rabbit hind leg. The fraction differs from other heavy sarcoplasmic reticulum (SR) fractions in that it contains a substantial amount of junctional face membrane (JFM) (15-20% of the membrane) with morphologically well-defined junctional feet structures. In common with other heavy SR preparations, it contains predominantly the calcium pump membrane (80-85% of the membrane) and compartmental contents (CC), consisting mainly of calcium-binding protein (calsequestrin). In this study, a modified procedure for the preparation of JTC from frozen rabbit back muscle is described. The yield is substantially greater (threefold per weight of muscle), yet retaining characteristics similar to JTC from fresh hind leg muscles. Methodology has been developed for the disassembly of the JTC. This is achieved by selectively extracting the calcium pump membrane with 0.5% Triton X-100 in the presence of 1 mM CaCl2 to yield a complex of JFM with CC. The CC are then solubilized in the presence of EDTA to yield JFM. This fraction contains unidirectionally aligned junctional feet structures protruding from the cytoplasmic face of the membrane with repeat spacings comparable to that observed in JTC. The JFM contains 0.16 mumol phosphorus (lipid) per milligram protein. Characteristic proteins include 340 and 79-kD bands, a doublet at 28 kD, and a component that migrates somewhat slower than or equivalent to the calcium pump protein. Approximately 10% of the calcium-binding protein remains bound to the JFM after EDTA extraction, indicating the presence of a specific binding component in the JFM. The JFM, which is involved in junctional association with transverse tubule and likely in the Ca2+ release process in excitation-contraction coupling, is now available in the test tube.

Animals↗

PubMed1986

Calcium-gated calcium channels in sarcoplasmic reticulum of rabbit skinned skeletal muscle fibers.

The action of ruthenium red (RR) on Ca2+ loading by and Ca2+ release from the sarcoplasmic reticulum (SR) of chemically skinned skeletal muscle fibers of the rabbit was investigated. Ca2+ loading, in the presence of the precipitating anion pyrophosphate, was monitored by a light-scattering method. Ca2+ release was indirectly measured by following tension development evoked by caffeine. Stimulation of the Ca2+ loading rate by 5 microM RR was dependent on free Ca2+, being maximal at pCa 5.56. Isometric force development induced by 5 mM caffeine was reversibly antagonized by RR. IC50 for the rate of tension rise was 0.5 microM; that for the extent of tension was 4 microM. RR slightly shifted the steady state isometric force/pCa curve toward lower pCa values. At 5 microM RR, the pCa required for half-maximal force was 0.2 log units lower than that of the control, and maximal force was depressed by approximately 16%. These results suggest that RR inhibited Ca2+ release from the SR and stimulated Ca2+ loading into the SR by closing Ca2+-gated Ca2+ channels. Previous studies on isolated SR have indicated the selective presence of such channels in junctional terminal cisternae.

Animals↗

PubMed1985

Nucleotide specificity of cardiac sarcoplasmic reticulum. GTP-induced calcium accumulation and GTPase activity.

We previously demonstrated that the hydrolysis of GTP by canine cardiac sarcoplasmic reticulum is not sensitive to calcium and does not support the translocation of calcium and oxalate into the vesicular space. In response to GTP, however, calcium is accumulated into a compartment which is sensitive to pH and ionophore. In the present paper, we further explored the relationship between GTP hydrolysis and GTP-induced calcium accumulation. Both ATP- and GTP-induced calcium accumulation were prevented by the sulfhydryl reagent, N-ethylmaleimide (NEM; I50 = 0.2 mM). In contrast, the sensitivity of NTP hydrolysis to NEM differed markedly; GTPase activity was not affected by NEM, whereas ATPase activity was markedly inhibited. Conversely, although the GTPase was noncompetitively inhibited by the ATP analogue, adenylyl imidodiphosphate (Ki = 8 microM), and was competitively inhibited by the GTP analogue, guanylyl imidodiphosphate (Ki = 60 microM), GTP-induced calcium accumulation was not affected by the NTP analogues at any concentration. Therefore, the GTP-dependent accumulation of calcium into the pH- and ionophore-sensitive compartment of cardiac SR may not require GTP hydrolysis but may be dependent on GTP binding. The previously reported noncompetitive inhibition of the GTPase by ATP was also observed when the calcium-dependent hydrolysis of ATP was prevented by NEM (Ki = 1.2 microM). Along with the noncompetitive inhibition of the GTPase by adenylyl imidodiphosphate, the inhibition of the GTP by ATP in the presence of NEM suggests that ATP binding may be involved in the observed inhibition. The Ki for the noncompetitive inhibition of GTPase activity is compatible with ATP binding to the high affinity catalytic site of the ATPase. Thus, although GTP-induced calcium accumulation differs somewhat from ATP-dependent calcium translocation, the similarities between the two processes (i.e. similar time courses and sensitivity to pH, ionophore, and sulfhydryl modification) suggest that they may be related in some manner.

Adenosine Triphosphate↗

PubMed1985

Effects of reestablishing blood flow on extent of myocardial infarction in conscious dogs.

The effects of permanent circumflex coronary artery occlusion (PO) compared with reestablishing blood flow (OR) at 2 and 6 h after occlusion on the final extent of histological infarction (HI) was assessed in chronically instrumented awake dogs. The relationships between the extent of left ventricular ischemia measured by microsphere techniques and HI in the PO group were used as models to predict the expected infarction in the 2- and 6-h OR groups. Mean HI (+/-SD) in the PO and 6- and 2-h OR groups was 21 +/- 13, 19 +/- 10, and 13 +/- 12% of left ventricular weight, respectively; values were not significantly different. The extent of HI in samples grouped according to epicardial and endocardial layers and ischemic blood flow ranges (0-15, 16-30, 31-50, 51-75% of control region blood flow) was reduced in the 2-h but not 6-h OR group. Analysis of individual animals using total ischemic region blood flow to epicardial and endocardial layers demonstrated that OR at 2 h but not 6 h reduced infarction in most animals but not in certain animals with the largest ischemic regions.

Animals↗

PubMed1985

Left ventricular ejection fraction after acute coronary occlusion in conscious dogs: relation to the extent and site of myocardial infarction.

The change in left ventricular radionuclide ejection fraction after acute occlusion of the left anterior descending (LAD) or circumflex (LC) coronary artery was compared with the ultimate histologic extent of myocardial infarction in conscious dogs. The acute change in ejection fraction correlated with size of infarction in 14 dogs with occlusions of the LAD coronary artery (r = .89, y = 1.12x + 14.2) and in 27 dogs with occlusions of the LC coronary artery (r = .71, y = 0.73x + 7.9); the slope of the regression equation was greater (p less than .05) for those with LAD than for those with LC occlusions. Multivariate analysis revealed no independent contribution of left ventricular weight, the subendocardial extent of infarction, or change in heart rate to the acute change in ejection fraction. These data indicate that the decrease in ejection fraction after coronary occlusion is determined primarily by the size of the ischemic area, which also determines size of infarction. In dogs instrumented over a long term, infarcts in the LAD myocardial distribution result in greater decreases in ejection fraction than infarcts of comparable size in the LC distribution.

Animals↗

PubMed1984

In situ study of T-cell subpopulations in cutaneous T-cell lymphoma. Diagnostic criteria.

The T-cell subpopulations present in skin biopsy specimens from 91 patients with cutaneous T-cell lymphoma (CTCL) and from 19 patients with benign lymphocytic infiltrates of the skin were examined in situ to define criteria for the differentiation of benign from malignant lymphocytic infiltrates. The monoclonal antibodies OKT 1 (pan T-cell), BE 3 (pan T-cell), OKT 4 (helper/inducer T-cell), OKT 6 (cortical thymocyte and Langerhans' cell), OKT 8 (suppressor T-cell), and OKT 10 (pan thymocyte) were used in direct or indirect immunoperoxidase reactions. Sections were examined at high magnification, and the distribution and percentage of cells reactive with each antibody were assessed. Three main patterns of staining were observed in the CTCL patients: (1) 64% of the biopsy specimens showed that 60% of the cells present in the dermis were T-cells that were OKT 1+ and BE 3+ and there was an even distribution of the different T-cell subpopulations, with 54% being OKT 4+ and 8% OKT 8+; (2) 21% patients showed selective loss of OKT 1 antigen, and 80% of these also showed loss of BE 3 antigen; and (3) 15% patients showed large numbers of OKT 8+ cells (range, 50%-90%) but the percentages of OKT 1+ and OKT 4+ cells were within the ranges seen in Group 1, indicating the presence of a population of T-cells simultaneously expressing OKT 4 (helper/inducer) and OKT 8 (suppressor) reactivity. In 95% of the CTCL patients, 3.5% OKT 6+ cells were present in the dermal infiltrate, and in 92% of patients, 3% OKT 10+ cells were present. Comparing sections from CTCL and benign dermatoses, no single diagnostic feature was identified, but helpful differentiating features were: (1) the even, rather than nodular, distribution of the T-cell subpopulation; (2) the selective loss of OKT 1 and BE 3 antigens; (3) the presence of T-cells simultaneously expressing OKT 4 and OKT 8 antigens; and (4) the presence of OKT 10+ cells.

Antibodies, Monoclonal↗