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Maturation has been shown to enhance the ability of the myocardium to contract. Whenever developmental changes in the systems that control or modulate myocardial contractility have been sought, they have indeed been found. These include an increase in the amount and organization of the myofilaments, an increase in SR amount, organization, differentiation, Ca-ATPase, phospholamban, and sensitivity to calcium and ryanodine, changes in the sarcolemmal pumps and channels, and changes in the expression of the contractile proteins. The characterization of the control systems that integrate these changes remains to be achieved. The overall gradual increase in myocardial contractility has superimposed on it an acute, sudden increase in ventricular contractility in the hours surrounding birth. In the subsequent neonatal days, the level of inotropy falls, and the reserves in contractility are replenished and expanded. Consequently, disease states that demand an increased use of or negatively affect mechanisms that bring about the neonatal enhancement in ventricular function will have their most malignant effect during the first days of neonatal life.

Neurons of the motor nerve net of Cyanea capillata were examined using video-enhanced DIC optics. A variety of organelles were visible within the axons and many were mobile. To quantify the movement organelles were divided into three classes (large, medium, and small) and the rates, direction, and types of movement displayed by the different particle types examined. The overall behavior and rates of movement of transported particles were comparable with those in axons from other species. The largest particles, mainly mitochondria were the slowest moving but were the only particles to reverse their direction of movement or to undergo interactions with other particles. The fastest movement was by the small particles, but both they and medium sized particles were transported continuously. In addition, the linear elements in these axons underwent considerable lateral movement.

This study tested the ability of first-pass radionuclide angiocardiography to detect accurately the left ventricular endocardial surface of the intact, conscious, chronically instrumented dog. A spherical phantom was used to define the influence of collimation: with a 1.0-in. collimator, the optimal count threshold was a border at 31% of the image's maximum counts; and with a 1.5-in. collimator, the optimal count threshold was at 21%. These were used to analyze cardioscintigrams obtained in 19 studies of six dogs. The dogs were provided with pulse transit sonomicrometer dimension transducers on the endocardium, right-atrial pacing electrodes, electrocardiographic leads, and catheters in the superior vena cava and right or left atria. The minor-axis dimension of the left ventricle was measured ultrasonically while the cardioscintigram was being stored. The minor-axis dimension and end-diastolic volume obtained by the two techniques had linear correlation coefficients of 0.95 and 0.98. This correlation indicates the inherent accuracy of radionuclide techniques by defining left-ventricular endocardial edges for a large range of volumes in the dog.

Mycobacterium tuberculosis antigen 5 was purified from unheated culture filtrates by absorption onto an immunoabsorbent prepared with globulin from a monospecific goat antiserum and elution with 4.0 M urea at pH 9.0. The product was a homogeneous protein giving a single stainable band in acrylamide gel electrophoresis and a single precipitin arc in immunoelectrophoresis. It was found to have a molecular weight of 28,500 to 35,000 daltons and a sedimentation constant of 2.0. Amino acid analysis demonstrated it to be rich in aspartic acid, suggesting a cytoplasmic origin.

The immunobiology and mycobacterial species distribution of immunoabsorbent affinity chromatography-purified Mycobacterium tuberculosis antigen 5 have been studied. In delayed hypersensitivity skin tests, antigen 5 was nearly equipotent with tuberculin-purified protein derivative in sensitized guinea pigs. In vitro, antigen 5 was capable of stimulating the production of migration inhibitory factor by cultured lymphocytes from sensitized guinea pigs and humans. Antigen 5 stimulated thymidine incorporation by cultured guinea pig lymphocytes but did not stimulate thymidine incorporation by cultured human lymphocytes. Although erythrocytes were readily sensitized with antigen 5 for passive hemagglutination, their use did not offer any advantage over previous hemagglutination techniques for the serodiagnosis or evaluation of patients with tuberculosis. By immunoelectrophoresis and immunodiffusion, antigen 5 was readily identified in culture filtrates of 10 strains of M. tuberculosis and M. bovis but not in those of 30 strains of 12 other myobacterial species.

Continuous wave Doppler ultrasonography was utilized to detect and characterize descending aortic blood flow velocity patterns in 27 preterm and term infants with or without an aortic run-off lesion proximal to the descending aorta. The effects of coexistent intracardiac defects on the velocity time profiles were evaluated by comparing records from patients with no intracardiac defects or systemic run-off lesions to those with a variety of intracardiac defects but no systemic run-off lesion. No significant alterations were noted. In all patients, the velocity tracing in systole was triangular in shape. During diastole, however, there were qualitative and quantitative differences between patients with and without a proximal run-off lesion. In those without a run-off lesion, retrograde descending aortic flow was present only in early diastole, and aortic flow velocity oscillated around the zero baseline during mid and late diastole. In those with a run-off lesion, retrograde flow present in early diastole continued throughout diastole. Quantitatively, the ratio of the area under the retrograde flow portion of the tracing to the forward flow portion was significantly greater in those with a run-off lesion. The velocity time profiles obtained with CW Doppler were similar to those previously obtained invasively with electromagnetic flow probes of catheter-mounted velocitometers. CW Doppler ultrasonograpy provides a reliable, noninvasive method for describing descending aortic blood flow velocity in infants.

Repeat cadaver kidney transplantation using azathioprine immunosuppression carried a higher risk of graft loss than primary transplants. We analyzed the results of repeat cadaver kidney grafting with cyclosporine A immunosuppression. A total of 33 cyclosporine A-treated patients received the second kidney transplant at varying intervals after failure of the first transplant. Graft survival at 1 year was 66 per cent. A concurrent group of 189 cyclosporine A-treated first cadaver kidney recipients had a 1-year graft survival rate of 75 per cent, although this better result was not statistically significant (p greater than or equal to 0.25). A historical group of 31 azathioprine-treated second graft recipients had a significantly worse 1-year graft survival rate of 45 per cent compared to the cyclosporine A second graft group (p less than 0.1). Patient age, sex, early first graft loss, interval between transplants and the presence of panel reactive antibodies were not factors in predicting second graft outcome. A complete DR mismatch appeared to worsen the second transplant survival. These findings indicate that early graft survival of cyclosporine A-treated repeat cadaveric transplants is acceptable and is better than azathioprine-treated first or second grafts.

Myocardium is generally thought to express no more than two isoforms of troponin T (TnT). We have recently reported that TnT purified from rabbit myocardium is resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into five proteins (TnT1, TnT2, TnT3, TnT4, and TnT5). In this study, these proteins are characterized immunologically and a novel elaborate maturational profile is described. Myocardium was obtained from 23 days of gestation fetal rabbits and 2-day, 6-week, 3-month, and 6-month postnatal rabbits. The major species in the adult myocardium, TnT4, was identified on sodium dodecyl sulfate-polyacrylamide gels and excised. The protein was electroeluted and purified. An amino acid microsequence of a cleaved fragment of this protein was found to be virtually identical to residues 86-99 from adult rabbit cardiac TnT. The protein, TnT4, was used to raise a polyclonal antibody. This antibody recognized all five isoforms from purified cardiac TnT, but none of the TnT isoforms from fast skeletal muscle. A monoclonal antibody, Mab JLT-12, raised against a highly conserved epitope of rabbit fast skeletal muscle, recognized all five cardiac as well as five skeletal muscle isoforms. Western blots performed on intact myocardial preparations demonstrated that TnT1, the cardiac isoform with the slowest electrophoretic mobility, was expressed prominently in the immature hearts, in addition to TnT2, TnT3, and TnT4, but TnT1 was not evident in the 3-month and 6-month postnatal hearts. The expression of TnT2 also decreased with maturation. Thus, the number of TnT isoforms expressed in the rabbit decreases with maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurons in the ectoderm of the perirhopalial tissue of the jellyfish Cyanea capillata were exposed and fixed for electron microscopy under conditions designed to minimize exocytosis of synaptic vesicles. The structure of the bidirectional chemical synapses that connect neurons was examined and the three-dimensional organization of these synapses was determined from reconstructions of serial sections. Synapses were characterized by the accumulation of a relatively few, large synaptic vesicles. These lie in a single layer against the terminal membrane of each terminal. The cytoplasmic side of the vesicles in any one terminal was covered by a single, large, perforated cisternal sheet. In addition, there were numerous smaller, bulbous cisternae that intermingled with the vesicles in the terminal. The structure of any one terminal was mirrored by that of the opposite terminal of the pair. The organization of these synapses is discussed from the viewpoint of cnidarian synapses in general.

Domestic kittens were used in four experiments to establish quantitative requirements for lysine and arginine. A purified L-amino acid diet (by calculation, 4,700 kcal metabolizable energy/kg diet) was employed throughout. Weight gain, gain:feed and nitrogen retention data of cats fed dietary lysine levels ranging from 0.48 to 1.92% suggested a requirement not exceeding 0.80%. The dietary arginine requirement for maximal gain was assayed at this level of lysine and found to be not greater than 0.83%. A dietary arginine level of 0.33% resulted in vomiting and extreme lethargy within 4 hours of ingestion.

We have carried out a quantitative analysis of the force-interval relationship of the human left ventricle and compared it to previous studies done in both intact subjects as well as isolated muscle. The characteristics of the force-interval relationship of the normal patient resembed those of normal isolated mammalian muscle (except when exposed to high levels of catecholamines). The relationship in group 2 (patients with increased left ventricular dimensions and normal pressure indices) resembled those obtained from isolated muscles from hypertrophied hearts. The relationship from group 3 (patients with increased left ventricular EDDs and depressed pressure indices, two of whom were in clinical heart failure) resumbled those induced in normal muscles exposed to high levels of catecholamines, and those obtained from experimentally induced heart failure. The force-interval relationships of the four patients who fell into the third group were strikingly different from the other groups. This suggests that the force-interval relationship may be useful to describe changes in the inotropic state of the patient's heart.

Reports of bleeding complications of medical therapy should be based on valid methods of classification, but the reproducibility of existing methods has not been tested. Therefore, we prospectively studied three methods to classify the severity of bleeding: a purely subjective implicit method, a previously published explicit method using brief criteria, and the bleeding severity index, which is a new explicit method using detailed criteria about the amount, rate, and consequences of bleeding. Three physicians independently reviewed abstracts of 168 patients treated with anticoagulants. The proportion of cases classified as major bleeding varied widely when the implicit method was used (2, 14 and 39%), less when the old explicit method was used (28, 40 and 47%), and not at all when the new bleeding severity index was used (20, 20 and 20%). Intraobserver agreement was excellent for both explicit methods (kappa greater than or equal to 0.95). However, interobserver agreement was better for the bleeding severity index (kappa = 0.87) than for the old explicit method (kappa = 0.69) or the implicit method (kappa = 0.39). We conclude that the classification of bleeding complications of medical therapy depends on the method used. In comparison to older methods, the bleeding severity index is highly reproducible and should be tested more widely to determine whether it can be applied to the burgeoning clinical research in anticoagulation and thrombolysis.

The effect of heart rate on left ventricular output was examined in seven fetal lambs at ages of 128 to 140 gestational days. The fetuses had been surgically instrumented at least 4 days previously with an ascending aortic flow probe, left ventricular dimension transducers, and left and right atrial pacing electrodes. Natural variations in heart rate of the lambs taken as a group correlated positively with left ventricular output, and negatively with ventricular end-diastolic dimension and stroke volume (P less than 0.0001). Rate did not affect output with right atrial pacing. With left atrial pacing, it correlated negatively with output (P less than 0.0001). At both pacing sites, rate correlated negatively with end-diastolic dimension and stroke volume (P less than 0.0001). The introduction of a longer interval during each pacing rate circumvented the rate-related changes in dimension and allowed the ventricle to fill to the same end-diastolic dimension. The systole at the end of the longer interval had a greater stroke volume than the preceding systoles. The faster the preceding paced rate, the greater was the stroke volume (P less than 0.0001). This study demonstrates that experimentally induced variations in heart rate produce changes in end-diastolic volume and contractility which prominently affect stroke volume. Over a broad range of rates, however, the effect of rate on left ventricular output is either negative or absent. With naturally occurring rate changes, there are additional changes in contractility and venous return which affect stroke volume. These combine to produce a positive relation between heart rate and left ventricular output. These effects of heart rate on output are qualitatively similar to those described for the adult animal.

We examined cardiac troponin T (TnT) isoform expression in rabbit left ventricular myocardium at three different stages of postnatal development. Using sodium dodecyl sulfate gel electrophoresis (PAGE), we resolved five isoforms: TnT1, TnT2, TnT3, TnT4, and TnT5. TnT1 had the slowest electrophoretic mobility and TnT5 the fastest. The predominant isoforms were TnT2, TnT3, and TnT4. The relative amounts of TnT2, TnT3, TnT4, and TnT5 were examined in myocardium from three age-groups: 3 days (Group 1), 21-22 days (Group 2), and 99-109 days (Group 3). The amount of TnT2 relative to the total amount of TnT (determined by the ratio of the areas under the densitometric curves) decreased significantly (p less than 0.01) with age from 42 +/- 4% in Group 1 to 25 +/- 3% in Group 3. In contrast, the relative amount of TnT4 increased with age from 23 +/- 2% in Group 1 to 33 +/- 4% in Group 3 (p less than 0.01). The relative amounts of the other two isoforms change biphasically with development: TnT3 decreased from Group 1 to Group 2 and increased from Group 2 to Group 3. TnT5, a minor isoform, increased from Group 1 to Group 2 and decreased from Group 2 to Group 3. These developmental changes in troponin T expression may account for some of the maturational changes observed in the physiological and biochemical properties of the myocardium.

Cardiac involvement by systemic sarcoidosis is well known, but occurs rarely. It usually manifests as either heart block, heart failure due to direct myocardial involvement, or cor pulmonale. We present the case of a patient with cardiac sarcoidosis who had ventricular tachycardia and congestive heart failure. Although there was other organ system involvement, the cardiac manifestation was the first to become clinically apparent. Therapy consisted of quinidine sulfate to control the arrhythmias and chronic diuretic therapy to control congestive heart failure. Steroid therapy was initially associated with recurrence of the ventricular tachycardia and was discontinued. It was reinstituted 18 months later when other organ system involvement developed with no recurrence of the ventricular tachyarrhythmia. The patient responded well to therapy and is currently doing well. This case is presented to illustrate a somewhat unusual, but nevertheless important, etiology of ventricular tachyarrhythmias. The recognition of underlying sarcoidosis is critical because of the propensity for other organ system involvement by this disease process.

A young boy who presents with an acutely painful scrotum can be a diagnostic challenge to his physician. It is important to differentiate the various causes of this symptom and to institute prompt management. Failure to do so could jeopardize the patient's future fertility. In a review of 113 consecutive cases of a painful scrotum at a children's hospital, torsion of the testicle was found in 51 patients (45%). Torsion of the appendix testis was found in 40 patients (35%) and acute epididymitis, once considered rare in children, was diagnosed in 17 (15%). The importance of prompt diagnosis of torsion is emphasized. The clinical diagnosis of the acutely painful scrotum is notoriously difficult, and in this series of cases surgical exploration was required in 92%. Only 2 of the 17 cases of epididymitis were associated with a bacterial urinary tract infection.

We studied the detectability of dichoptically presented vertical grating patterns that varied in the ratio of the contrasts presented to the two eyes. The resulting threshold data fall on a binocular summation contour well described by a power summation equation with an exponent near 2. We studied the effect of adding one-dimensional visual noise, either correlated or uncorrelated between the eyes, to the grating patterns. The addition of uncorrelated noise elevated thresholds uniformly for all interocular ratios, while correlated noise elevated thresholds for stimuli whose ratios were near 1 more than thresholds for other stimuli. We also examined the effects of monocular adaptation to a high-contrast grating on the form of the summation contour. Such adaptation elevates threshold in a manner that varies continuously with the interocular contrast ratio of the test targets, and increases the amount of binocular summation. Each of several current models can explain some of our results, but no one of them seems capable of accounting for all three sets of data. We therefore develop a new multiple-channel model, the distribution model, which postulates a family of linear binocular channels that vary in their sensitivities to the two monocular inputs. This model can account for our data and those of others concerning binocular summation, masking, adaptation and interocular transfer. We conclude that there exists a system of ocular dominance channels in the human visual system.

1. The effect of heart rate on right ventricular output was examined in six lambs during a period extending from 126 to 139 days of gestation. The fetuses had been surgically instrumented at least four days previously with a main pulmonary artery flow probe, right ventricular dimension transducers and left and right atrial pacing electrodes. 2. During spontaneous variations in heart rate, rate was correlated positively with right ventricular output (P less than 0.0001) and end-diastolic dimension (P less than 0.0001) among the lambs considered as a group, but no significant effect of rate on stroke volume was found. When individual responses were examined, output increased significantly with rate in sixteen out of seventeen observations. 3. With left atrial pacing, heart rate did not affect output. With right atrial pacing, rate correlated negatively with output (P less than 0.0001). With pacing from either site, rate correlated negatively with end-diastolic dimension (P less than 0.0001) and stroke volume (P less than 0.0001). 4. The introduction of a longer period interval during each pacing rate inhibited the rate-related decrease in dimension and allowed the ventricle to fill to the same end-diastolic dimension. The systole following these longer intervals had a greater stroke volume than did the preceding systoles with smaller end-diastolic dimension. The faster the preceding paced rate, the greater was the increase in stroke volume (P less than 0.001). 5. Right ventricular dimensions and volumes were measured in vitro, and the relationship was found to be linear using regression analysis. 6. This study demonstrates that experimentally induced variations in heart rate produce changes in end-diastolic volume and contractility which prominently affect right ventricular stroke volume. As a consequence, rate has, over a broad range, either no significant effect on output or a negative one. With spontaneous variations in rate, additional changes in contractility and venous return occur which affect stroke volume and end-diastolic volume and enhance right ventricular output. These relationships are similar to those in the adult heart, and demonstrate the absence of a maturational change in the effects of rate on ventricular function from the fetus to the adult.

The effects of two carcinogens benzo[a]pyrene (BP) and symmetrical 1,2-dimethylhydrazine dihydrochloride (DMH), on plasma amino acid concentrations and on excretion of lipids and nitrogenous metabolites were studied in 7- to 8-wk-old male and female B6C3F1 mice. BP and DMH were fed at concentrations of 0.3125 and 0.0225 g/kg, respectively, in purified diets containing 10 or 40% soybean protein. Nutritional balances were measured over a 7-d period after 7 d of acclimatization. Females excreted less urea and more NH3 than males. Urinary urea-nitrogen, NH3, allantoin, uric acid and total urinary nitrogen were consistently higher in mice fed 40% protein than in those fed 10% protein. The increases in total and NH3 nitrogen paralleled the increase in nitrogen intake. Nitrogen of urea rose more, while that of allantoin and uric acid rose less, than nitrogen intake. Fecal lipid excretion, as a percentage of intake, was consistently higher in mice fed the 40% protein diets than in mice fed 10% protein. Plasma glycine and branched-chain amino acids were higher, but citrulline was lower, when the 40% protein diet was fed. Body weight gain was higher when the 10% protein diet was fed with BP than without it, but BP made no apparent difference in weight gain when the 40% protein diet was fed. BP interacted with dietary protein to influence the excretion of nitrogenous metabolites. In addition, BP feeding produced numerous BP X sex and BP X protein interactions for plasma amino acid concentrations. Compared to controls, feed intake and weight gain were, respectively, 8 and 61% lower in DMH-fed animals during wk 1, but no differences in intake or weight gain were found during wk 2. In contrast to BP, DMH had no significant effects on urinary or fecal nitrogen metabolites, except that urinary uric acid (relative to nitrogen intake) was 9% higher in DMH-fed mice than in controls. DMH-fed mice had 43% higher serum glutamate and 6% lower glutamine than controls.

This study describes the overall arrangement of geniculocortical input representing the system of cortical ocular dominance bands in layer IV of striate cortex in the adult cat. The pattern of ocular dominance bands was revealed by transneuronal transport of the intraocularly injected tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Our data indicate that this procedure does not damage the retina and that it results in relatively uniform uptake and transport of the tracer. Using previously published techniques (Olavarria and Van Sluyters, 1983, 1985), both cortical hemispheres of each cat were unfolded, flattened and tangentially sectioned. Analysis of the WGA-HRP labeling patterns in these sections revealed a relatively continuous network of irregularly branching bands in layer IV of area 17 in both hemispheres. Because of a systematic difference in the level of interband labeling, ocular dominance bands appear less distinct in the hemisphere contralateral to the injected eye. There is also a tendency for interband labeling to be greater in cortical regions that represent the more peripheral aspects of the binocular portion of the visual field. The width of an individual ocular dominance band in the cat fluctuates, so that it appears to be made up of a series of uniformly sized, roughly circular beads of label. The diameter of these beads averages 667 micron, and preliminary counts indicate that there are 650-675 beads in each striate cortex. Contrary to earlier suggestions, in 4 out of 6 hemispheres analyzed quantitatively there was no tendency for ocular dominance bands to be oriented along a preferred axis in cat striate cortex, including an axis orthogonal to the border between areas 17 and 18. Ocular dominance bands in area 18 appear to be broader than those in area 17, and they seem to have a greater tendency to be oriented orthogonal to the 17/18 border than those in area 17. Compared with the ocular dominance pattern in monkey striate cortex, the ocular dominance pattern in the cat is much less regular. In general, cat ocular dominance bands appear to fluctuate more in width, to change direction more often, and to be less likely to run orthogonal to the 17/18 border. The greater regularity of the primate ocular dominance pattern may be related to differences in the way in which the visual hemifield is mapped onto the striate cortex in these 2 species.

A comprehensive laboratory admission screen can be instituted in any large laboratory but only in one in command of conventional technology and with the co-operation of the laboratory, medical, nursing and admitting staff.The capital equipment required is costly and subject to early obsolescence. The operating costs are initially high, but the influence of the screen on the general work load indicates that the total overall procedures ordered by the physician will be reduced in number and that over a three-year period, in an economy subject to continuous inflationary pressure, the total cost will approach what might have been expected had the screen not been instituted.By presenting, shortly after admission, a truly comprehensive laboratory profile, the total number of procedures ordered will be reduced and this reduction bears no relationship to whether or not the data supplied are medically useful.The equipment more recently available for a large admission screen is far superior, from the point of view of speed of assay and cost of maintenance and production, to the equipment that has been available to us in this study.It is believed that the unit cost of assay will continue to decline and that the principle of unsolicited testing will be expanded in the future to include procedures not presently in the profile.It is predicted that in the relatively near future almost all of the laboratory procedures that a clinician could conceivably request will have been done prior to his examination of the patient.

A procedure which establishes steady states in cultures of microorganisms and also provides continuous automatic recording of their growth rates is described.