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Showing papers by "University of Pittsburgh published in 1972"


Journal ArticleDOI
TL;DR: Observations are not consistent with permeation through a fixed-charge pore but can be explained by a model featuring constant ionic partition into a neutral-polar pore that traverses the tight junction.
Abstract: The unidirectional influxes of Na, K, and Cl into isolated strips of rabbit ileum are comprised of movements across the mucosal membrane of the epithelial cells and ionic diffusion into an extracellular shunt pathway. A large fraction of the Na influx across the mucosal membrane alone is inhibited by Li, suggesting the participation of a carrier mechanism in the influx process. The partial ionic shunt conductances of Na, K, and Cl account for at least 82% of the total tissue conductance. The calculated shunt permeabilities (P) are (in centimeters per hour) P(K) = 0.040, P(Na) = 0.035, and P(Cl) = 0.019, so that P(K):P(Na):P(Cl) = 1.14:1.00:0.55. Diffusion potentials across the tissue resulting from isotonic replacement of NaCl in the mucosal solution with mannitol or KCl are described by the Goldman constant-field equation together with the above permeabilities of the shunt pathway. These observations are not consistent with permeation through a fixed-charge pore but can be explained by a model featuring constant ionic partition into a neutral-polar pore that traverses the tight junction. Such a pore may be lined with either fixed dipoles or fixed dipolar ions oriented such that electronegative groups influence the permselective properties of the diffusion pathway. The essential feature of both models is that electroneutrality is maintained by means of fixed membrane components and does not depend upon the presence of mobile counterions.

408 citations


Journal ArticleDOI
13 Oct 1972-Science
TL;DR: Human blood monocytes in a feeder layer or by use for conditioning medium produced a colony-stimulating factor capable of stimulating the in vitro growth of colonies of granulocytes and mononuclear cells from human and murine marrow, suggesting that the monocyte may control granulocyte proliferation and maturation.
Abstract: Human blood monocytes in a feeder layer or by use for conditioning medium produced a colony-stimulating factor capable of stimulating the in vitro growth of colonies of granulocytes and mononuclear cells from human and murine marrow. Lymphocytes and neutrophils did not stimulate colony formation, and medium conditioned by neutrophils was inhibitory. This suggests that the monocyte may control granulocyte proliferation and maturation.

359 citations


Journal ArticleDOI
TL;DR: The relationship between age at beginning therapy and subsequent intelligence quotient was studied in patients with congenital hypothyroidism, and patients treated before three months of age had a significantly higher average I.Q. than those treated after three months.

310 citations


Journal ArticleDOI
29 Sep 1972-Science
TL;DR: After treatment with the monoamine oxidase inhibitor pargyline, 6-hydroxydopamine produced no further norepinephrine depletion but increased the dopamnine depletion to 95 percent and produced complete aphagia.
Abstract: Intraventricular injections of 6-hydroxydopamine produced 95 percent depletion of telencephalic norepinephrine and 62 percent depletion of striatal dopamine in rats. Treated rats maintained body weight at subnormal levels and failed to increase food intake in response to a short-term decrease in glucose utilization. After treatment with the monoamine oxidase inhibitor pargyline, 6-hydroxydopamine produced no further norepinephrine depletion but increased the dopamnine depletion to 95 percent and produced complete aphagia. These effects are comparable to events that follow bilateral electrolytic lesions of the lateral hypothalanmus.

302 citations


Journal ArticleDOI
TL;DR: It is concluded that 5'-nucleotidase is present in the endoplasmic reticulum and that the microsome fraction contains, in addition, vesicles derived from the plasma membrane.
Abstract: A procedure has been developed for the cytochemical localization of 5'-nucleotidase in isolated, unfixed, rat liver microsomes. Membranes were incubated with adenosine 5'-phosphate (5'-AMP) and Pb(NO3)2 and then isolated on sucrose density gradients: all the phosphate released was recovered with the membranes by this procedure. Adenosine 2'-phosphate (2'-AMP) and adenosine 3', 5'-cyclic phosphate (3',5'-AMP) were shown to be competitive inhibitors, but not substrates, for purified 5'-nucleotidase and were employed to determine the specificity of the cytochemical reaction. It was found that the incubation conditions for the cytochemical assay did not affect the specificity of 5'-nucleotidase. Microsomes incubated as controls with Pb2+, or Pb2+ and 2'-AMP or 3',5'-AMP were of the same density, although slightly denser than microsomes incubated without Pb2+, and were unassociated with lead precipitate when examined by electron microscopy; microsomes incubated with Pb2+ and 5'-AMP were much denser and were stained heterogeneously with lead phosphate when examined by electron microscopy. Precipitates formed artificially from Pb2+ and inorganic phosphate did not resemble the reaction product. Microsomes were, therefore, separated on sucrose gradients and the subfractions were examined cytochemically. Lead precipitates were associated with the majority of rough-surfaced vesicles, and the reaction product was distributed heterogeneously in all fractions. Vesicles which stained like the membranes of the bile canaliculi in isolated plasma membranes were observed in the lightest subfraction. The reaction product was localized on the outside surface of the microsomal membranes, and was solubilized by low concentrations of ethylenediaminetetraacetic acid. It is concluded that 5'-nucleotidase is present in the endoplasmic reticulum and that the microsome fraction contains, in addition, vesicles derived from the plasma membrane.

176 citations


Journal ArticleDOI
TL;DR: The stimulatory effect of prostaglandin together with gonadotropins was more than additive and was not inhibited in the presence of 7-oxa-13-prostynoic acid or inhibitors of protein synthesis.
Abstract: Incubation of porcine granulosa cells with 2 μg/ml FSH or LH resulted in a three- to five-fold augmentation of cyclic 3′,5′-AMP content. When gonadotropins were added in the presence of 3 HIM aminophylline a ten-fold stimulation of cyclic 3′,5′-AMP was found. The stimulatory effect of LH was greater than that of FSH. The effect of maximal doses of LH and FSH were not additive, whereas, the effects of submaximal doses were additive. LH stimulated cyclic 3′,5′-AMP within 5 min and the levels remained elevated for 3 hr. No increase in progestin secretion was found until after 3 hr. After this time the content of cyclic 3′,5′-AMP in cells dropped and secretion of progestin increased further. The addition of prostaglandin E1 and E2 stimulated the formation of cyclic 3′,5′-AMP in granulosa cells. The stimulatory effect of prostaglandin together with gonadotropins was more than additive and was not inhibited in the presence of 7-oxa-13-prostynoic acid or inhibitors of protein synthesis. These results strongly su...

172 citations


Journal ArticleDOI
TL;DR: In this paper, molecular orbital calculations on methanediol have been used to predict the favored orientations and interatomic distances of the C-O-C-O R portion in pyranoses.

169 citations


Journal ArticleDOI
TL;DR: The double isotope technique with radioactive leucine as a precursor has been modified to yield accurate values for rate constants of protein degradation as discussed by the authors, which is both rapid and reproducible in that the protein whose half-life is being measured is isolated only once from one experimental organism.

160 citations


Journal ArticleDOI
TL;DR: Several pieces of evidence are given to show that the TAGH solution does not induce DNA replication by damaging some of the cells of the intact liver.

157 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that the operator forms of Euler-Lagrange equations of motion and Noether's theorem for a wide class of perturbation Lagrangian theories for scalar fields are valid under the assumption that the time-ordered products are given by Feynman rules with Bogoliubov's renormalization scheme.
Abstract: Under the assumption that the time-ordered products are given by Feynman rules with Bogoliubov's renormalization scheme, it is shown that the operator forms of Euler-Lagrange equations of motion and Noether's theorem for a wide class of perturbation Lagrangian theories for scalar fields are valid. Ward-Takahashi identities for currents in Noether's theorem are also proved without recourse to equal-time commutators, and current-algebra results follow naturally in a subclass of Lagrangian field theories. Covariant Schwinger terms are present in these identities and their nature is determined.

156 citations


Journal ArticleDOI
TL;DR: Eustachian tube function studies were carried out in patients with concurrent or recent middle ear effusions and depended on the presence of either a perforation or a tympanostomy tube.
Abstract: Eustachian tube function studies were carried out in patients with concurrent or recent middle ear effusions. Radiographic techniques were employed in assessing tubal response to liquid flow. Studies of air flow and air pressure were carried out using a Madsen bridge, and depended on the presence of either a perforation or a tympanostomy tube. Most of the Eustachian tubes studied showed varying degrees of obstruction or abnormal distensibility or both, often depending on the direction of flow, or on whether pressures were increased or reduced. Quite apart from other factors which may contribute to intrinsic oxextrinsic obstruction of the Eustachian tube, its compliance appears to play an important role in determining its function. In particular, compli. ance appears to be an important factor in the response of the Eustachian tube to increased positive or to negative pressures. Elimination of the causes of both nasal obstruction and abnormal nasopharyngeal secretions may alleviate problems in the function of the Eustachian tube which seem attributable to increased tubal compliance.

Journal ArticleDOI
TL;DR: In this paper, the authors focus on the education of the young child in the pre-school and elementary school years, although what they have to say seems applicable to all levels of our educational system.
Abstract: or, in other terms, adapting educational environments to individual differences. I shall focus on the education of the young child in the pre-school and elementary school years, although what I have to say seems applicable to all levels of our educational system. The problem obviously has been a persistent one; it has been recognized and proclaimed at least since the beginning of this century, three generations ago. Very early in the century, Edward L. Thorndike (1911) published a monograph entitled "Individuality." His editor's introduction summarizes the then

Journal ArticleDOI
TL;DR: In this paper, the presence of a dense scattering layer near 80 km over the geographic pole during the local summer was detected on all satellite passes above 80° latitude beginning 15 days before the solstice.
Abstract: Observations with a horizon scanning airglow photometer on OGO-6 have revealed the presence of a dense scattering layer near 80 km over the geographic pole during the local summer. The layer is detected on all satellite passes above 80° latitude beginning 15 days before the solstice. The optical depth of the layer increases by more than a factor of 50 between 70° and 85°. It is suggested that noctilucent clouds are weak sporadic manifestations of these persistent polar layers.

Journal ArticleDOI
TL;DR: This paper examined the influence of deliberate vs accidental help and, to a lesser extent, high vs low help on the magnitude of reciprocity, and clarified the role of obligation and attribution of motivation as mediators of reciprocality.

Journal ArticleDOI
15 Dec 1972-Science
TL;DR: Learning by rats was facilitated when response-relevant cues were provided by other rats; learning increased as a function of number of cues provided, suggesting that rats can learn by imitation.
Abstract: Learning by rats was facilitated when response-relevant cues were provided by other rats; learning increased as a function of number of cues provided. These results suggest that rats can learn by imitation. Learning by rats that observed conspecifics not emitting response-relevant cues was retarded compared to learning by rats that did not observe conspecifics. This indicates that a conspecific's presence can also inhibit learning, a result consistent with social facilitation theory.

Journal ArticleDOI
TL;DR: It is suggested that at least one of the functions of the alkaline phosphatase of the liver membrane is to hydrolyze phosphorylcholine so that choline can be transported across the bile canalicular membrane.

Journal ArticleDOI
TL;DR: It has become apparent, based on data collected using these and the more recently developed techniques for radioimmunoassay, that T3, despite the small quantities present in human serum, plays an important role in the maintenance of the euthyroid state.
Abstract: RIIODOTHYRONINE (T3) was originally identified in human plasma by Gross and Pitt-Rivers in 1952.’ Shortly thereafter, it was shown by those authors and by Lerman that T3 was approximately 3-4 times as effective in the treatment of human myxedema as was thyroxine (T4)ja Considerable speculation was raised at that time as to the role of this hormone in normal man and in patients with thyroid pathology, but little new data accumulated on this subject in the ensuing 15 yr. This was primarily due to the low concentration of the hormone in human serum and the tedious methods required for quantitation. In the last 5 yr, novel approaches to the measurement of T3 were suggested by Nauman, Nauman, and Werner and by Sterling, Bellabarba, Newman, and Brenner which led to a new interest in the role of this hormone.5,s It has become apparent, based on data collected using these and the more recently developed techniques for radioimmunoassay, that T3, despite the small quantities present in human serum, plays an important role in the maintenance of the euthyroid state. Initial estimates were that perhaps onehalf of the body’s thyroid hormone needs were suppIied by T3. Even more recently, extrathyroidal conversion of T4 to T3 has been demonstrated in vivo and the original speculation of Gross and Pitt-Rivers that T4 is converted to T3 before it can exert its metabolic action has again been raised.3 It is the purpose of this review to examine the recent literature with respect to the role of T3 in normal and pathologic thyroid states. In addition some unpublished studies from our own laboratory will also be presented which bear on this subject. The reader is referred to previous reviews for a more thorough discussion of material published prior to 1969.“* The physiologic role of T3 in normals will be examined first followed by a discussion of T3 in patients with various thyroid diseases.

Journal ArticleDOI
05 May 1972-Science
TL;DR: Poliovirus virion RNA contains a single covalently bound sequence of polyadenylic acid which is approximately 49 nucleotides long, which may play a common role in viral replication, possibly in translation of the viral RNA.
Abstract: Poliovirus virion RNA contains a single covalently bound sequence of polyadenylic acid which is approximately 49 nucleotides long. A single, slightly longer polyadenylic acid sequence is contained in Eastern Equine Encephalitis virus RNA. Since these viruses are otherwise dissimilar these sequences may play a common role in viral replication, possibly in translation of the viral RNA.


Journal ArticleDOI
TL;DR: An infant with Byler's disease from the originally described Amish kindred was studied by the use of isotopic bile acids and electron microscopy to further delineate the hepatic defects in this recessively inherited fatal intrahepatic cholestatic disease.


Journal ArticleDOI
TL;DR: Evidence is adduced in support of the view that these discharges of LH, as observed in ovariectomized monkeys, are the consequence of intermittant dopaminergic and/or nor-adrenergic signals to the LRF secreting cells of the hypothalamu...
Abstract: In ovariectomized rhesus monkeys, single injections into the right atrium of the neuroleptic drugs chlorpromazine and haloperidol or of the α-adrenergic blockers phentolamine and phenoxybenzamine were followed, within min, by an interruption in the circhoral pulsatile discharge of LH and a resultant fall in the plasma concentration of the hormone. This inhibition of LH secretion was usually sustained for some hr and was terminated by an abrupt resumption of the pulsatile secretory pattern. These responses were qualitatively indistinguishable from those previously reported to follow single injections of estradiol. In contrast, the p-adrenergic blocking agent propanolol or pentobarbital in anesthetic doses had no, or equivocal effects on the pulsatile pattern of LH discharge. Evidence is adduced in support of the view that these discharges of LH, as observed in ovariectomized monkeys, are the consequence of intermittant dopaminergic and/or nor-adrenergic signals to the LRF secreting cells of the hypothalamu...

Journal ArticleDOI
TL;DR: Pyocine types of P. aeruginosa isolated from clinical specimens were frequently identical to those recovered from vegetables, thus implicating tomatoes and other vegetables as an important source and vehicle for colonizing the intestinal tract of patients.
Abstract: Pseudomonas aeruginosa was isolated from tomatoes, radishes, celery, carrots, endive, cabbage, cucumbers, onions, and lettuce obtained from the kitchen of a general hospital, with tomatoes yielding both highest frequencies of isolation and highest counts. Presence of P. aeruginosa on the hands of kitchen personnel and cutting boards and knives which they used suggests acquisition of the organism through contact with these vegetables. It is estimated that a patient consuming an average portion of tomato salad might ingest as many as 5 × 103 colony-forming units of P. aeruginosa. Pyocine types of P. aeruginosa isolated from clinical specimens were frequently identical to those recovered from vegetables, thus implicating tomatoes and other vegetables as an important source and vehicle by which P. aeruginosa colonizes the intestinal tract of patients.

Journal ArticleDOI
TL;DR: The results indicate that the levels of cyclic GMP and cyclic AMP in dog thyroid slices are regulated by separate hormonal and metabolic mechanisms.

Journal ArticleDOI
TL;DR: The distribution of intracellular calcium was determined in isolated kidney cells by kinetic analyses of45Ca fluxes as discussed by the authors, which indicated that mitochondria play an important role in the control and regulation of cytoplasmic calcium activity.
Abstract: The distribution of intracellular calcium was determined in isolated kidney cells by kinetic analyses of45Ca fluxes. Isotopic desaturation curves reveal an intracellular calcium compartment with a very slow time constant. The size of this calcium compartment is markedly increased by raising the extracellular calcium, by increasing the extracellular phosphate and may contain up to 99% of the intracellular exchangeable calcium. Accumulation of calcium in this pool is completely abolished by two specific inhibitors of mitochondrial calcium uptake, Antimycin A and Warfarin®. These results suggest that this compartment represents a pool of calcium in the cell mitochondria. The sudden removal of phosphate from the medium immediately stimulates calcium efflux from the cell. Conversely, an increase in medium phosphate immediately inhibits calcium efflux. Both effects are rapidly reversible. Finally, calcium efflux from the cells is stimulated after the cells are exposed to low temperature suggesting that calcium transport out of the cell may be regulated by the cytoplasmic calcium activity. These experiments are consistent with the view that mitochondria play an important role in the control and regulation of cytoplasmic calcium activity and of calcium transport.

Journal ArticleDOI
01 Jan 1972-Networks
TL;DR: Multi-stage connection networks in which each input terminal can be connected to any number of output terminals are developed and it is shown that such networks have fewer cross-points than the product of input and output terminals for a sufficiently large number of inputand output terminals.
Abstract: This paper develops multi-stage connection networks in which each input terminal can be connected to any number of output terminals. Conditions are given such that these networks are strictly nonblocking or are rearrangeable. Rearrangement algorithms and upper bounds on the required number of moves are developed and it is shown that such networks have fewer cross-points than the product of input and output terminals for a sufficiently large number of input and output terminals.

Journal ArticleDOI
TL;DR: In the authors' opinion the supinated position of the forearm should be avoided in the treatment of supracondylar fractures of the elbow in children.
Abstract: 1. A comparative study of six methods of treatment in sixty-seven supracondylar fractures in children is presented. They were handled as orthopaedic emergencies, and, perhaps because of the prompt treatment, vascular complications were avoided. 2. Normal elbow motion resulted following each method of closed treatment but open reduction caused some loss in extension. 3. The seven nerve palsies recorded were transitory. 4. Myositis ossificans complicated one case following open reduction but was not otherwise observed in this series. 5. Overhead threaded pin traction was safe and the swelling of the elbow rapidly decreased as gravity hastened venous and lymphatic drainage. 6. Overhead pin traction prevented residual varus deformity possibly because it provided a position of mild pronation of the forearm. 7. Closed reduction followed by a collar and cuff also prevented residual varus deformity, possibly because of the neutral or pronated position of the forearm. 8. In our opinion the supinated position of the forearm should be avoided in the treatment of supracondylar fractures of the elbow in children.

Journal ArticleDOI
TL;DR: The pulsatile, circhoral discharges of LH observed in ovariectomized rhesus monkeys were blocked within min following single intravenous injections of 17β-estradiol or the initiation of estradiol infusions which achieved physiologic plasma levels of the steroid.
Abstract: The pulsatile, circhoral discharges of LH observed in ovariectomized rhesus monkeys were blocked within min following single intravenous injections of 17β-estradiol or the initiation of estradiol infusions which achieved physiologic plasma levels of the steroid. The resulting depression in plasma LH concentrations was maintained for several hr after circulating estrogen levels had declined to undetectable values. Pulsatile LH discharges resumed abruptly following this period of inhibition but with a lower frequency and larger magnitude. In contrast, intravenous injections of progesterone had no effect on LH secretion unless massive doses were given, with resultant plasma concentrations of the steroid a thousand fold greater than luteal phase levels. These but caused irregularities in the circhoral rhythm. Similarly, the daily subcutaneous administration of progesterone, in oil, for 2 weeks failed to reduce the elevated plasma LH concentrations in ovariectomized animals. It is concluded that estrogen is th...

Journal ArticleDOI
TL;DR: In this article, a forced choice procedure was used to obtain confusion matrices for 22 patients on four sets of nonsense syllables, using a forced-choice procedure and two multidimensional scaling procedures, MDSCAL and IND-SCAL.
Abstract: Confusion matrices were obtained for 22 patients on four sets of nonsense syllables, using a forced‐choice procedure. Each syllable set considered of 16 consonants in combination with the vowels /i,a,u/ either in CV or VC form. Syllables were presented at a comfortable listening level approximately 40 dB above the audiologic SRT. Over‐all performance varied as a function of syllable set, vowel, and hearing loss. The confusions were analyzed by two multidimensional scaling procedures, MDSCAL and IND‐SCAL. In addition, an iterative feature analysis of transmitted information was performed, in which the feature system of Miller and Nicely and Chomsky and Halle were compared. [Research supported by grants from SRS and NINDS.]

Journal ArticleDOI
TL;DR: For the past two years, the authors have been studying a group of over forty eminent physical scientists and have repeatedly interviewed there are over 220 hours of tape-recorded interviews and questioned them about their methodology and attitudes towards science and scientists.
Abstract: For the past two years I have been studying a group of over forty eminent physical scientists. I have repeatedly interviewed there are over 220 hours of tape-recorded interviews and questioned them about their methodology and attitudes towards science and scientists. The purpose of my study has been to find out how practicing scientists actually do science and what they think about the nature of science.