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Biomedical subjects

S A Kane

Publications and source records attributed to S A Kane.

At least 19 recordsLinked to original sources
PubMed1994

On the role of the bithiazole moiety in sequence-selective DNA cleavage by Fe.bleomycin.

A recent study of Fe(II).bleomycin-mediated DNA strand scission suggested that the metal binding domain of the drug is also the primary determinant of the observed sequence selectivity of strand scission (Carter, B. J., Murty, V. S., Reddy, K. S., Wang, S.-N., and Hecht, S. M. (1990) J. Biol. Chem. 265, 4193-4196). Although it is well established that the bithiazole moiety+C-terminal substituent of bleomycin are required for DNA binding, the role of the bithiazole in sequence-selective DNA recognition remains unclear. To determine whether the bithiazole moiety exhibits an intrinsic DNA binding selectivity, three synthetic EDTA-conjugated bithiazole derivatives were used to mediate DNA cleavage in the presence of Fe2+ and dithiothreitol. Incubation of these Fe(II).EDTA-bithiazoles in the presence of a 5'-32P end-labeled DNA duplex resulted in strand scission at every position to essentially the same extent. The relative cleavage efficiencies among the bithiazoles were a strong function of their ionic state. These findings imply that the bithiazoles can bind to many sites on the DNA; they support a model of bleomycin-DNA interaction in which the bithiazole moiety+C-terminal substituent are required only for DNA binding, whereas the metal binding domain is responsible for metal ion coordination and oxygen activation as well as being the primary determinant of sequence-selective DNA cleavage.

Binding Sites↗
PubMed1993

Cerebellar nuclei: rapid alternating movement, motor somatotopy, and a mechanism for the control of muscle synergy.

Monkeys were trained to make rapid alternating flexion and extension movements seriatim at each of five body parts--foot (toe grasp and release), shoulder, elbow, wrist, and thumb. "Facial movements"--mouth, tongue, jaw and pharynx--were also made to drink the fruit juice reward. Movement at a given joint could be performed simply by alternate activation of the prime mover muscle groups, and EMG analysis indicated that these primary muscles were active during movement of that joint. No muscle within any one large body part (leg or arm) was strongly active in relation to movement of another body part. Yet, within a body part (arm), synergist muscles were often more active than the primaries during movement of a given joint, only to become less active during movement of the joint at which their action was primary. Neurons in dentate and interpositus discharged in relation to these movements. In the antero-posterior dimension of both dentate and interposed nuclei, there was a significant tendency for neural modulation to be somatotopically arranged according to the preferred movement: hindlimb anteriormost, forelimb in the middle, and head posteriorly. In the medio-lateral dimension, no such localization was seen for the different movements of the upper limb. Like muscle activity, neural discharge modulation usually occurred in strong relation to a number of movements in a single body part (arm), but not to the movements of different body parts (leg, face). Lesion of the middle third of dentate and of a portion of lateral interpositus had little effect upon the movements at the single joints, and thus upon the prime movers. However, the pattern of activity of agonist, antagonist, and synergist muscles was changed. These results are consistent with the view that the dentate controls muscle synergy and movement coordination more than the prime movers per se.

Animals↗
PubMed1990

Synthesis of C-glycosylarenes by way of internal reactions of benzylated and benzoylated carbohydrate derivatives.

"Internal" C-glycosylarenes [e.g., (2R,3S,3aS,9bR)-3,3a,5,9b-tetrahydro-3-methoxy- and -3,7-dimethoxy-2-methoxymethyl-2H-furo[3,2-c][2]benzopyran] were prepared by intramolecular reactions of 2-O-benzyl derivatives of methyl 3,5-di-O-methyl-D-xylofuranoside (2) and their conversion into authentic C-glycosylated aromatic systems was investigated. The auxiliary benzylic linkage could not be cleaved by hydrogenolysis; isochroman derivatives (e.g., (3S)-3,4-dihydro-3-[(1R,2R)-2-hydroxy-1,3-dimethoxypropyl]-5-metho xy-1H- 2-benzopyran) were obtained under these conditions. However, oxidation of the primary benzylic position with ruthenium tetraoxide gave the corresponding lactone (a dihydroisocoumarin derivative, e.g., (2R,3S,3aS,9bR)-2,3,3a,9b-tetrahydro-3,7-dimethoxy-2-methoxy - methyl-5H-furo[3,2-c][2]benzopyran-5-one) which could be opened by saponification, thereby leading to a stereochemically unique C-glycosylbenzoic acid derivative. The same type of lactone was obtained directly from a derivative of 2 bearing a sufficiently reactive benzoyl group at O-2 (3,5-dimethoxybenzoyl); this process provides a useful approach to a heterocyclic system present in a variety of natural products. In related studies, the 2-O-phenyl substituent was found to be much less reactive than the 2-O-benzyl group in intramolecular Friedel-Crafts reactions of 2-O-substituted glycofuranosides. The first examples of successful internal C-arylation in the pyranoid series were achieved from 2-O-(3-methoxybenzyl)-D- mannopyranosides; the resulting "internal C-glycosides" [( 2R,3S,4S,4aS,10bS)-2,3,4,4a,6,10b- hexahydro-3,4,8-trimethoxy-2-methoxymethylpyrano[3,2-c][2]benzopyr an and 3,4-bis(benzyloxy)-2-benzyloxymethyl-8-methoxy analog] contain a heterocyclic skeleton closely related to that of the natural product bergenin.

Alkylation↗
PubMed1984

Effects of angiographic contrast medium on left ventricular function: evaluation by contrast angiography and radionuclide angiography.

The purpose of this study was to evaluate the effect of angiographic contrast medium on left ventricular (LV) function in 26 patients undergoing diagnostic cardiac catheterization. Beat-by-beat analysis during contrast ventriculography showed that the ejection fraction (EF) was lower in the last beats than in the first beats (P less than .02). Radionuclide angiograms were obtained the day before, as well as 15 to 65 minutes after catheterization, which included contrast ventriculography and coronary anteriography. The EF by radionuclide angiography was lower after catheterization than before (43 +/- 14% vs 47 +/- 17%, P less than .01). The EF decreased by greater than or equal to 5% in 11 of the 26 patients (42%) after catheterization. The decrease in EF in some patients was observed up to 65 minutes after catheterization and was not associated with symptoms or ST-T changes. The EF decreased in only one of nine patients who received nitroglycerin during catheterization, whereas it decreased in 10 of 17 patients who did not receive nitroglycerin (P less than .05). The EF decreased in 9 of 14 patients (64%) who had normal resting LV function, whereas it decreased in only 2 of 12 patients (17%) who had abnormal resting function (P less than .05). Thus, contrast material may depress LV function up to 1 hr and is more frequent in patients with normal resting EF. The use of nitroglycerin during catheterization may mask this effect.

Adult↗
PubMed1984

Effect of intra-aortic balloon pumping on left ventricular function: evaluation by radionuclide ventriculography.

The purpose of this study was to evaluate the effect of intra-aortic balloon pumping (IABP) on left ventricular (LV) performance in ten patients (group I) with pump failure and in ten patients (group II) with angina pectoris. Left ventricular ejection fraction, regional ejection fraction, systolic chordal shortening and volumes were measured by first-pass radionuclide ventriculography using a computerized multicrystal gamma camera. Patients in group I had significantly lower ejection fractions, regional ejection fractions and systolic chordal shortening and larger end-diastolic and end-systolic volumes than patients in group II, both on (p greater than 0.0001) and off (p less than 0.004) IABP. With IABP, the ejection fraction increased by 0 +/- 0.5% in group I and 5.8 +/- 1.7% in group II (p = 0.004); the regional ejection fraction increased by 0.1 +/- 0.9% in group I and 10.3 +/- 2.1% in group II (p = 0.0004); the systolic chordal shortening increased by 1.1 +/- 0.6% in group I and 6.5 +/- 1.1% in group II (p = 0.0006); the end-diastolic volume decreased by -0.4 +/- 6% in group I and -14 +/- 4% in group II (p = 0.07); and the end-systolic volume decreased by -1 +/- 6% in group I and -21 +/- 5% in group II (p = 0.02). Thus, IABP results in improvement in left ventricular performance in patients with angina pectoris but not in patients with pump failure.

Aged↗
PubMed1984

Correlation between changes in R wave amplitude and left ventricular volume induced by rapid atrial pacing.

To examine the Brody effect in humans, we studied 15 patients by means of coronary sinus pacing. We measured left ventricular (LV) volumes from the cardiac output (measured by the thermodilution technique) and LV ejection fraction (measured by radionuclide ventriculography). Pulmonary blood volume was determined by means of cardiac output and mean pulmonary transit time. In six patients, pacing was performed at two different rates, resulting in 21 pacing measurements. The heart rate increased with pacing from 73 +/- 11 to 119 +/- 19 bpm (mean +/- standard deviation, p less than 0.001). The end-diastolic volume (EDV) and the end-systolic volume (ESV) decreased with pacing (p less than 0.001 each). The R wave amplitude decreased with pacing (1.44 +/- 0.63 mV control vs 1.32 +/- 0.58 mV with pacing; p less than 0.01). R wave amplitude decreased in 19 of the 21 pacing studies (90%); EDV and ESV decreased in all 21 pacing studies, and pulmonary blood volume decreased in 14 of the 15 pacing studies (93%) performed in 11 patients. There was a significant correlation between the percentage of change in R wave amplitude with the percentage of change in EDV (r = 0.54, p less than 0.01) and with the percentage of change in ESV (r = 0.54, p less than 0.01). These results, therefore, validate Brody's hypothesis and indicate that changes in LV volumes affect the R wave amplitude.

Adult↗
PubMed1984

Thallium-201 myocardial scintigraphy and left ventricular function at rest in patients with rest angina pectoris.

The purpose of this study was to examine the rest thallium-201 perfusion pattern during angina-free periods in 40 patients with rest angina pectoris secondary to coronary artery disease (greater than or equal to 70% diameter narrowing). Seventeen patients had previous Q wave myocardial infarction. The perfusion defects were considered fixed or reversible, depending on the absence or presence of redistribution in the 4-hour delayed images. There were 40 perfusion defects (26 fixed and 14 reversible) in 27 patients whereas 13 patients had normal scans. Reversible perfusion defects were present in 10 patients (25%). Of the 26 fixed perfusion defects, 17 did not have corresponding Q waves. Occluded vessels (63%) had more perfusion defects than vessels with subtotal occlusion (30%) (p less than 0.01). The perfusion defect size was larger in patients with lower ejection fraction than in patients with higher ejection fraction. We conclude: (1) perfusion defects are common in patients with rest angina and are reversible in 25% of patients indicating reduced regional coronary blood flow; (2) the degree of stenosis affects the presence of perfusion defect; (3) fixed defects may be present without corresponding Q waves; and (4) global left ventricular function is related to the size of perfusion defects.

Adult↗
PubMed1984

Correlation among right ventricular preload, afterload and ejection fraction in mitral valve disease: radionuclide, echocardiographic and hemodynamic evaluation.

The relation among right ventricular preload, afterload and ejection fraction in patients with mitral valve disease has not been well elucidated. In this study, measurements were made of intracardiac pressures and forward cardiac output during cardiac catheterization (n = 43), the ejection fraction by radionuclide angiography (n = 43) and end-systolic radius and wall thickness by M-mode echocardiography (n = 22). There was a linear correlation between pulmonary artery pressure and right atrial pressure (r = 0.57, p less than 0.01). The right ventricular peak circumferential systolic wall stress was increased in 68% of the patients (in comparison with wall stress measurements obtained in 10 normal subjects). The right ventricular ejection fraction was abnormal in 38 patients (88%) and abnormal in 14 of the 15 patients with high wall stress. There was an inverse correlation between ejection fraction and end-diastolic volume (r = -0.61, p less than 0.001). The right ventricular ejection fraction measurement was repeated within 3 months after mitral valve replacement in 16 patients; the ejection fraction increased from 21 +/- 9 to 29 +/- 10% (mean +/- standard deviation) after surgery (p less than 0.01), but normalization of the ejection fraction was observed in only 3 patients (19%). Thus, abnormal right ventricular ejection fraction, which is observed in most patients with rheumatic mitral valve disease, results from inappropriate wall stress or depressed inotropic response of the right ventricle due to damage. Right ventricular dilation appears to be a compensatory mechanism to maintain the cardiac output.

Aged↗
PubMed1984

Resting kinetics of thallium-201 in patients with coronary artery disease.

The thallium washout was analyzed in 40 patients with angiographically documented CAD, using circumferential time-activity profiles of the initial and four-hour delayed images. A net washout pattern (fewer counts in delayed images than initial images) was observed in the distribution of normal and diseased vessels. A negative washout (wash-in) (a net increase in counts in the four-hour delayed images) was observed only in the presence of diseased vessels, even if the initial scans were normal. Quantitative analysis of thallium kinetics was shown to be important in rest images, and should be performed even if the initial images appear normal.

Adult↗
PubMed1983

Rest and redistribution thallium-201 myocardial scintigraphy to predict improvement in left ventricular function after coronary arterial bypass grafting.

To examine the value of rest and redistribution thallium-201 imaging in predicting improvement in left ventricular (LV) ejection fraction (EF) after coronary artery bypass grafting (CABG), 26 patients with coronary artery disease (CAD) and abnormal LV function were studied. Nineteen patients had pathologic Q waves preoperatively. Rest and redistribution thallium-201 images and radionuclide ventriculograms were obtained before and after CABG, and the thallium scintigrams were evaluated both quantitatively and qualitatively. The patients were divided according to the preoperative thallium scintigrams into 2 groups: Group I (16 patients) had either normal resting thallium-201 images or reversible resting perfusion defects, and Group II (10 patients) had fixed resting perfusion defects. The resting EF was less than 50% preoperatively in all patients. Fourteen patients (54%) showed improvement in EF postoperatively. Three patients (2 in Group I and 1 in Group II) showed new postoperative perfusion defects, and none of the 3 showed improvement in LV function. Of the remaining 14 patients in Group I, 12 (86%) showed improvement in LV function, compared with 2 of 9 patients in Group II (p less than 0.01). Improvement in LV function was observed in 8 of the 19 patients (42%) with abnormal Q waves. Nitroglycerin intervention radionuclide ventriculograms were obtained in 20 patients before CABG. Of the 6 patients who showed improvement in LV function with nitroglycerin, 4 also showed improvement postoperatively. Postoperative improvement in LV function was also observed in 6 of the 14 patients who did not improve with nitroglycerin. Thus, rest and redistribution thallium imaging is useful in identifying patients whose LV function will improve after CABG. Normal rest thallium-201 images or reversible resting defects correctly identified 12 of 14 patients (86%) who showed improvement in LV function postoperatively. Nitroglycerin-intervention ventriculography and abnormal Q waves were less useful in this differentiation.

Adult↗
PubMed1983

Cardiac performance in thyrotoxicosis: analysis of 10 untreated patients.

This study attempts to define cardiac performance at rest and during exercise in patients with untreated thyrotoxicosis. We studied 7 women and 3 men, aged 23 to 59 years (40 +/- 10, mean +/- standard deviation [SD]) and compared the results with those obtained in 12 normal subjects. In patients with thyrotoxicosis, the rhythm was sinus and the only untoward symptom was palpitations; the resting electrocardiographic results were normal in 8 patients and showed left ventricular hypertrophy in 2 patients; the left ventricular ejection fraction and volumes (measured by radionuclide ventriculography) were normal at rest. During exercise, 1 patient had dyspnea and 7 had leg fatigue; 2 were asymptomatic. Also, 7 patients had greater than or equal to 5% increase in left ventricular ejection fraction, 2 had no change, and 1 had a decrease. In all 10 patients, the exercise ejection fraction was greater than or equal to 60%. All normal subjects had a greater than or equal to 5% increase in ejection fraction during exercise. There were no significant differences at rest between patients with thyrotoxicosis and normal subjects in blood pressure, ejection fraction, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output, but the heart rate was significantly higher in patients with thyrotoxicosis (91 +/- 10 versus 80 +/- 12 beats/min, p less than 0.05). During exercise, there were no significant differences between patients with thyrotoxicosis and normal subjects in blood pressure, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output. The exercise ejection fraction was significantly lower in patients with thyrotoxicosis than in normal subjects (68 +/- 10% versus 75 +/- 4%, p less than 0.05). Cardiac performance is normal at rest in patients with thyrotoxicosis, but during exercise abnormal left ventricular reserve occurs in some patients.

Adult↗
PubMed1983

Usefulness of left ventricular wall thickness-to-diameter ratio in thallium-201 scintigraphy.

The ratio of left ventricular wall thickness to the cavity dimension, as seen on thallium-201 images, was used in this study to predict left ventricular ejection fraction and volume. We obtained rest thallium-201 images in 50 patients with symptomatic coronary artery disease. The thickness of a normal-appearing segment of the left ventricular wall and the transverse diameter of the cavity were measured in the left anterior oblique projection. The left ventricular ejection fraction and volume in these patients were determined by radionuclide ventriculography. There was a good correlation between thickness-to-diameter ratio and ejection fraction (r = 0.80) and end-systolic volume (r = -0.71). In 18 patients with a thickness-to-diameter ratio less than 0.70, the ejection fraction was lower than in the 16 patients with thickness-to-diameter ratio greater than or equal to 1.0 (22 +/- 2% versus 49 +/- 3%, mean +/- SEM, p less than 0.001). Similarly, in patients with a thickness-to-diameter ratio less than 0.70, the end-diastolic and end-systolic volume were higher than in the remaining patients with higher thickness-to-diameter ratios (p less than 0.02, p less than 0.001, respectively). All 18 patients with a thickness-to-diameter ratio less than 0.70 had ejection fractions less than 40%; 14 of 15 patients with a thickness-to-diameter ratio greater than or equal to 1.0 had an ejection fraction greater than 40% (p less than 0.001). The remaining 16 patients with a thickness-to-diameter ratio of 0.7-0.99 had intermediate ejection fractions and volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Assessment of the myocardial perfusion pattern in patients with multivessel coronary artery disease.

We studied 42 symptomatic patients with coronary artery disease involving two or three vessels using exercise thallium-201 myocardial scintigraphy. Qualitative analysis of the images predicted multivessel disease in 75% of the patients with two-vessel disease and in 82% of the patients with three-vessel disease. Quantitative analysis of the size of the perfusion defect indicated that approximately 40% of the left ventricular perimeter showed abnormal perfusion pattern during stress in these patients, and there was no significant difference in the size of the defect in patients with two-vessel disease or three-vessel disease (41 +/- 17% vs 42 +/- 14%, respectively, mean +/- SD). The exercise heart rate, exercise ECG response, and severity of narrowing did not correlate with the size of the perfusion defect. Patients with anterior infarction had larger defects in the distribution of the left anterior descending artery than those without infarction. Collaterals offered partial protection during exercise only when they were not jeopardized. This study confirms the value of qualitative analysis of exercise thallium-201 imaging in predicting multivessel disease, and describes a simple method of assessing the extent of perfusion abnormalities during stress in patients with multivessel disease. The results may be important in patient management and prognosis.

Adult↗
PubMed1983

Expression of GFAP immunoreactivity during development of long fiber tracts in the rat CNS.

Astrocyte maturation in the developing corpus callosum and dorsal columns of the spinal cord was studied immunocytochemically in the rat, using antiserum to glial fibrillary acidic protein (GFAP) with a view to determining the relationships of astrocytes to the advancing axons of the corpus callosum and corticospinal tract. Between the eighteenth and nineteenth days of gestation, when the corpus callosum commences forming, most of the GFAP staining in the cerebral hemispheres is contained in radial processes, but some staining of glial cell bodies is also seen in the ventricular zone. At the region of interhemispheric fusion, where the corpus callosum will form, an accumulation of astrocytic processes demonstrable electron microscopically shows light immunocytochemical staining for GFAP. These processes do not adopt a stereotyped orientation. Rather, the overall impression as one moves towards the midline, is of radially disposed processes being disrupted and disoriented by the growing callosal axons at the fusion of the hemispheres. At no time can any orderly arrangement of GFAP-containing processes be seen which might indicate that the processes are serving to guide the growing axons across the midline. There is no immunoreactive staining of cell bodies or processes ventral to the corpus callosum, except in postnatal animals. Prior to the arrival of corticospinal axons in the spinal cord on the first postnatal day (PO)21, GFAP immunoreactivity is greatest in radial processes of the lateral funiculi and in the dorsal median septum. Oblique or vertical processes increase in the cuneate fasciculus from P0 tot P4 but do not appear in the gracile fasciculus until P4. Virtually no stained processes appear in the region to be traversed by the principal corticospinal tract, nor later in the tract itself until late in postnatal development. Only by 3 weeks postnatal is the adult pattern of GFAP staining observed in the corticospinal tract. These results also indicate that the expression of GFAP immunoreactivity is a relatively late phenomenon in astrocytes associated with advancing axons and implies that this aspect of astrocytic maturation is unrelated to any guidance that the immature astrocytes might provide for the growing axons.

Animals↗