Showing papers by "Tufts University published in 1968"

Immunology and biochemistry of Regan isoenzyme of alkaline phosphatase in human cancer.

Abstract: Derepression of the genome of the cancer cell may explain why certain cancer patients exhibit an isoenzyme of alkaline phosphatase biochemically and immunologically indistinguishable from human placental alkaline phosphatase.

Immunologic alterations in bronchogenic cancer. Sequential study.

Abstract: A sequential study of patients with cancer of the lung reveals that there is a marked alteration in delayed hypersensitivity as manifested by Dinitrochlorobenzene (DNCB) sensitization and purified protein derivative (PPD) reactions, when compared to age-matched controls. Short survival times (diagnosis to death) are associated with negative DNCB tests. Skin reactivity does not necessarily change as patients approach death, however. Circulating lymphocytes decrease significantly in number during the months approaching death and these counts can be plotted into a smooth regression curve with time to death as the abscissa. Humoral antibody synthesis is not altered in these patients; the circulating levels of the various serum proteins and iramunoglobulins do not alter with time nor are they biologically different from control values.

Purification and properties of molecular-weight variants of human placental alkaline phosphatase.

Abstract: 1. Alkaline phosphatase of human placenta was purified by a procedure involving homogenization with tris buffer, pH8·6, extraction with butanol, ammonium sulphate fractionation, exposure to heat, ethanol fractionation, gel filtration, triethylaminoethylcellulose anion-exchange chromatography, continuous curtain electrophoresis on paper and equilibrium dialysis. Methods for both laboratory-scale and large-scale preparation were devised. 2. Two major molecular-weight variants designated A and B were separated by molecular sieving with Sephadex G-200 and variant A was purified 4000-fold. 3. Variant B, which comes off the Sephadex G-200 column before variant A, is the electrophoretically slower-moving species on starch gel and is quite heterogeneous. 4. Purified variant A was fairly homogeneous on the basis of electrophoretic studies on starch gel and Sephadex gel, ultracentrifugation and immunodiffusion. 5. The respective molecular weights for variants A and B were 70000 and over 200000 on the basis of sucrose-density-gradient ultracentrifugation. Variant A exhibited a sedimentation coefficient of 4·2s. 6. Crystalline variant B could be converted into fast-moving variant A and vice versa. 7. Kinetic studies indicated no difference between the two variants. These include linear rates of hydrolysis, pH optimum, Michaelis constants and uncompetitive stereospecific l-phenylalanine inhibition. 8. The amino acid compositions of variants A and B and of placental albumin were determined.

Effect of Phenylbutazone on Phagocytosis and Intracellular Killing by Guinea Pig Polymorphonuclear Leukocytes

Abstract: The anti-inflammatory drug phenylbutazone has been found to inhibit both engulfment and intracellular killing of E. coli by guinea pig peritoneal polymorphonuclear (PMN) leukocytes. The bactericidal activity of leukocytic homogenates was also inhibited by the drug. Addition of the drug at various time intervals to a phagocytic reacting system caused an almost immediate cessation of bactericidal activity. Metabolic studies showed that the drug sharply curtailed glucose-l-14C and 14C-formate oxidation of both resting and phagocytizing PMN leukocytes. These data indicated an effect upon the hexose monophosphate shunt and H2O2 formation. Further investigation showed that the sites of inhibition were on glucose-6-phosphate and 6-phosphogluconate dehydrogenase. These inhibitions resulted in decreased H2O2 production. It is suggested that H2O2 activates lysosomes and subsequently complexes with the lysosomal enzyme, myeloperoxidase. This complex is a potent bactericidal agent in the phagocyte.

Ribonucleic acid synthesis in experimental cardiac hypertrophy in rats. I. Characterization and kinetics of labeling.

Abstract: Cardiac hypertrophy was induced in rats by constriction of the aortic arch. Hearts from rats with aortic constriction increased in weight about 50% above those of control rats by 7 days after operation. RNA concentration increased between 24 and 48 hours after constriction and, thereafter, returned toward the control level. DNA concentration of hearts from rats with aortic constriction remained unchanged from that of sham-operated rats. Labeling of heart RNA with 32 P was increased relative to that of sham-operated rats within the first 4 hours after aortic constriction. However, RNA labeling, relative to the labeling of AMP derived from ATP, increased above that of sham-operated rats only after 4 hours of aortic constriction and rose to maximum or near maximum values by 8 hours after operation. Various methods of extraction of RNA showed that the increase in labeling involved all the major species of RNA (28S, 18S, and 4S), and no evidence was found for the selective stimulation of a minority species. The nucleotide base composition of the various species of heart RNA of rats with aortic constriction was not significantly different from that of normal rats during the 4- to 8-hour period after operation. There was no terminal labeling of sRNA in hearts of either normal animals or those with aortic constriction.

Fetal and neonatal erythropoiesis.

Abstract: The regulation of red cell production in the adult animal has been shown to be governed, at least in part, by oxygen-dependent erythropoietin production by the ‘kidney. In rodents the degree of dependency on renally produced erythropoietin approaches the absolute.’ Thus the nephrectomized rat or mouse has almost complete suppression of red cell production. Changes in the oxygen supplydemand relationship have been shown to have a profound effect upon the rate of erythropoiesis. It is to be noted, however, that such perturbations in high order mammal^^,^ do not produce as marked a change in red cell production as that in the rodent. The question has been raised as to whether regulation of erythropoiesis in fetal and neonatal life is the same as that for the “ a d ~ l t ” ~ TO answer this question, the evolution of the erythron and its regulation have been studied in the fetal and neonatal rat, which is a relatively immature animal in comparison with human beings at birth, and in the guinea pig, an animrl.1 in which the degree of maturity at birth approaches that of the human being. These data will be briefly summarized and are reviewed extensively e l~ewhere .~

Warning sounds of moths.

Abstract: Zusammenfassung Viele Neuwelt-Schmetterlinge der Familien Arctiidae und Ctenuchidae ausern Folgen sehr hoher Klick-Gerausche, wenn man sie beruhrt oder Ultraschall-Signalen aussetzt, etwa solchen von Fledermausen. Einige Arten scheinen fur Fledermause widerlich zu riechen oder zu schmecken, denn sie werden selten verletzt, selbst wenn man sie mit Fledermausen zusammen in engen Kafigen halt. Die Fledermause meiden die Klickgerausche ausernden Arctiiden und Ctenuchiden mehr oder weisen sie starker ab als die stummen. Schmetterlinge anderer Familien, die keine Gerausche erzeugen, werden unter gleichen Bedingungen von Fledermausen gern gefangen und gefressen. Die ungeniesbaren Schmetterlinge konnten Muller'sche Mimikry-Ringe bilden, denn die Fledermause scheinen die Artunterschiede in den Lautauserungen nicht zu beachten. Eine nearktische Art konnte ein Bates'scher Nachahmer sein, denn sie scheint geniesbar zu sein, ausert aber Klick-Gerausche, die sie vor Fledermausen schutzt. Die Lautauserungen dieser Schmetterlinge wirken also wohl als Warngerausche.

Direct regulatory effect of ketones on lipolysis and on glucose concentrations in man.

Abstract: IT has been repeatedly shown that the administration of ketones to animals or man produces a decrease in the concentration of glucose and free fatty acids in the blood, and this effect has been generally accepted as compatible with an increased secretion of insulin1–7. That ketones stimulate the secretion of insulin seems to have been confirmed in dogs because the concentration of insulin in pancreatic venous blood rose in response to infusions of acetoacetate and β-hydroxybutyrate4. In man a rise in the concentration of insulin in the peripheral blood has been observed following the administration of medium chain triglyceride and attributed to the induction of ketonaemia8.

An Experimental Model of Some Varieties of Petit Mai Epilepsy Electrical‐Behavioral Correlations of Acute Bilateral Epileptogenic Foci in Cerebral Cortex

Abstract: UMMARY This discussion has examined 2 central questions regarding the pathophysiology of petit mal epilepsy. First, what is the locus of the lesion responsible for the bilateral synchronous and symmetrical spike-slow wave discharges and the associated behavioral absence of petit mal epilepsy? We have demonstrated that it is possible to produce an experimental model of petit mal epilepsy in the otherwise intact cat or monkey without the necessity of lesions in the brain stem or diencephalic structures. The essential lesion in this model is solely cortical and bilateral in location. In particular our experiments have involved the production of acute relatively large bilateral and symmetrical cortical epileptogenic foci. The interaction of these foci resulted in the development of synchronous and symmetrical patterns of bilateral discharge resembling the various forms of human primary bilateral synchrony including the 2½-4 c/s spike-slow wave complex. In the monkey, regional variations in capacity for bilateral discharge were noted, related to regional differences in callosal projection. Particularly well regulated bilaterally synchronous and symmetrical bursts of 2½-4 c/s spike-slow wave complexes occurred with bilateral foci in the premotor area of monkey frontal lobe. Studies of behavior and simultaneously recorded electroencephalogram indicated that bilateral synchronous discharges of 3 c/s spike-slow wave complex resulting from bilateral foci in anterior premotor area were closely correlated with short staring spells resembling petit mal (absence) seizures. Second, irrespective of where the responsible lesion(s) may be located, are the brain stem and diencephalic structures essential for the development of these bilateral symmetrical and synchronous discharges of 2½-3 c/s spike-slow wave complexes which are the hallmark of petit mal epilepsy? From the standpoint of the present model, it is demonstrated that section of the corpus callosum in the cat or of all major commissures in the monkey markedly disrupted the synchrony of discharge of bilateral foci. Alternate pathways for coarse synchrony at low rates of discharge were demonstrated. These results should be compared to the high degree of synchrony of bilateral discharge obtained in the cat or monkey preparation in which large blocks of cerebral cortex in each hemisphere were isolated from subcortical structures but remained connected via the corpus callosum. The spike discharges of bilateral foci in this preparation were synchronized within 10–20 msec, well within the limits noted in the intact animal and in the patient with petit mal epilepsy. The patterns of bilateral discharge in this cortical-callosal preparation included bilateral synchronous bursts of 2½-3 c/s spike-slow wave complexes. RESUME Ce travail envisage deux questions essentielles concernant la physiopathologie de l'epilepsie petit mal. Premiere question: Quel est le siege de la lesion responsable des decharges bilaterales, synchrones et symetriques de pointes-ondes qui accompagnent les absences petit mal? Nous avons demontrea ce propos qu'il est possible de reproduire une epilepsie du type petit mal chez un chat ou un singe d'autre part normal independamment de toutes lesions du tronc cerebral ou du diencephale. II suffit de realiser chez ces animaux des lesions corticales bilaterales, notamment des foyeis epileptogenes corticaux aigus, bilateraux et symetriques, assez etendus. L'interaction de ces foyers aboutit a la production de decharges bilaterales synchrones et symetriques ressemblant aux differents types de synchronic bilaterale primaire observee chez FHomme, y compris la pointe-onde a 2½-4 c/s. Chez le singe on observe des variations regionales dans la capacitye de produire des decharges bilaterales qui dependent des differences regionales dans les projections commissurales calleuses; c'est ainsi que les bouffees de pointes-ondes bilaterales synchrones et symetriques a 2½-4 c/s particulierement regulieres, accompagnees de troubles du comportement evoquant une absence, surviennent sous l'effet de foyers bilateraux dans l'aire premotrice des lobes frontaux. Deuxieme question: Quel que soit le siege des lesions responsables, le tronc cerebral et le diencephale sont-ils indispensables pour le developpement des decharges bilaterales synchrones et symetriques de pointes-ondes a 2½-4 c/s qui sont caracte-ristiques des epilepsies petit mal? En ce qui concerne nos propres experiences, il apparait que la section du corps calleux du chat ou celle de toutes les grandes commissures chez le singe altere considerablement la synchronic des decharges de foyers bilateraux. Ces resultats contrasted avec le haut degre de synchronic des decharges bilaterales obtenues dans les larges etendues de cortex cerebral qui, dans chaque hemisphere, sont isolees des structures sous-corticales mais demeurent interconnectees a travers le corps calleux. Dans de telles preparations cortico-callosales, les decharges de pointes des complexes pointes-ondes recueillies dans les foyers bilateraux sont synchronises dans des limites de 10–20 msec qui correspondent a celles observees chez l'animal intact ou chez le sujet humain presentant une epilepsie petit mal.

Regulation of erythropoiesis. XX. Kinetics of red cell production.

Abstract: Since the last conference on erythropoiesis, much information has accumulated which has necessitated a revision of some of our notions as to the mechanism of red cell formation. It is still clear that the erythroid compartment is not a self-maintaining compartment, but is fed from a primitive stem cell pool. The work of Becker et a1.I and Whang et aL2 appeared to settle the long standing issue whether this is a unipotential or totipotential compartment. More recent evidence, however, raises the question as to whether there may not be two levels of stem cells, a more primitive totipotential stem cell compartment equivalent to the colony-forming unit of Till and McCulloch3 and a more differentiated precursor cell for each of the identifiable hematopoietic elements. This issue is by no means settled, but data will be presented favoring the latter explanation, i.e., two levels of precursor cells. The studies on the effect of erythropoietin in the hypertransfused rodent clearly demonstrated that erythropoietin is capable of differentiating the stem cell into an identifiable erythroid precursor. The mechanism by which this is accomplished is moot and the question of whether the action of erythropoietin is confined to the stem cell or whether it may also affect differentiated cells is at present undecided. In this paper it is our purpose to present data bearing on these points. The effect of erythropoietin has been studied in normal animals and in rats in which red cell production has been perturbed by hypertransfusion and/or vincristine. Critical to these considerations are studies on megakaryocytopoiesis using tritiated thymidine. These also will be reported briefly.

Teaching Effectiveness and Government Awards Study shows that publication and government awards are good indicators of ability in teaching undergraduates

Abstract: Three bodies of available data at Tufts University were used in determining whether there are meaningful relationships between teaching effectiveness, publication, and the receipt of government support. A search of the literature showed that virtually all comments in the popular literature and most references in professional journals suggest that publication and receipt of support for research somehow detract from teaching performance in the classroom. The empirical data of the Tufts study do not support these previous conclusions. The students rated as their best instructors those faculty members who had published articles and who had received or were receiving government support for research.

Chronic allogeneic disease : i. development of glomerulonephritis

Abstract: Glomerulonephritis, often accompanied by the nephrotic syndrome, developed in CAF1 mice following the administration of spleen cells from normal BALB/c mice. The renal lesion was membranous glomerulonephritis. When studied with fluorescein-conjugated antisera to either mouse gamma globulin or β1C-globulin, the glomeruli contained beaded and irregular deposits of these immunoproteins. The ultrastructure of the lesion was characterized by thickening of the glomerular basement membranes and the presence of electron-dense subepithelial deposits. Acid eluates of the diseased kidneys contained gamma globulin that failed to bind to sections of normal kidneys. These findings conform to the type of nephritis provoked by immune complexes. They indicate that this type of immune injury can be based on the reaction of intolerant immunocytes to normal antigens.

The Action of Microwave Radiation on the Eye

Abstract: Microwave power can cause formation of opacities in the lens of the rabbit eye exposed to continuous wave or pulsed wave radiation at frequencies from 2.45 GHz to 10 GHz. When the eye is irradiated in a free field, the opacity (cataract) develops in the posterior part of the lens; in location, form and growth, it resembles cataracts caused by ionizing radiation. When the eye is irradiated at the same frequencies as part of a ‗closed‘ waveguide system, the cataract develops in the anterior part of the lens, like those caused by infrared radiation. Although for every power level there is a minimal exposure period which will cause an opacity, repeated shorter exposures can have a cumulative effect, the main determining factor being the time interval between successive exposures. Experimental evidence suggests that micro-wave cataracts are not simply a result of microwave heating but are caused by some other property of the radiation.

Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats

Abstract: The sequence of events which lead to increased RNA synthesis in the heart following aortic constriction was studied with the use of inhibitors of protein and RNA synthesis. Puromycin given during the first 4 hours after operation inhibited the increase in RNA labeling with [32P] H3PO4 that occurred after 4 hours of aortic constriction without inhibiting RNA labeling in sham-operated rats. Puromycin had no effect on the 32P labeling of the alpha-phosphate of AMP which suggests that the effect on labeling of RNA is not mediated by the lowering of precursor specific activity. The dose of puromycin used inhibited the labeling of heart muscle protein with 3H leucine. Parafluorophenylalanine had no selective inhibitory effect on the increase of RNA labeling in the hypertrophying heart. The most likely interpretation of these data is that, following aortic constriction, synthesis of protein is required for subsequent stimulation of RNA synthesis, and this protein may be dependent upon the synthesis of new RNA templates. Any early increased synthesis would be of a minority species of protein since there was no increase in amino acid labeling of total heart protein until 4 to 6 hours after aortic constriction. The stimulation of RNA labeling by aortic constriction was unaffected by digitalis treatment. The pressure-time index did not correlate with the increased labeling of RNA.