Showing papers by "University of California, San Francisco published in 1972"
TL;DR: This study studied subendocardial ischemia without anatomic coronary artery obstruction in open-chest anesthetized dogs and measured pressures in aorta and left ventricle, phasic left coronary arterial blood flow by electromagnetic flowmeter and altered flow ratios were best predicted by relating them to the ratio of DPTI to TTI.
Abstract: Subendocardial ischemia without anatomic coronary artery obstruction may result from a discrepancy between metabolic needs and available blood supply. We studied this in open-chest anesthetized dogs and measured pressures in aorta and left ventricle (LV), phasic left coronary arterial blood flow (CBF) by electromagnetic flowmeter, total CBF and LV subendocardial (endo) and subepicardial (epi) flow with radioactive microspheres 8-10µ, in diameter. Since LV Subendocardial flow is mainly or entirely diastolic, it should depend on coronary driving pressure and duration of diastole (i.e., the area between aortic and left ventricular diastolic pressures). This diastolic pressure time index (DPTI) was varied by opening arteriovenous fistulas to lower aortic diastolic pressure, constricting the ascending aorta to raise LV diastolic pressure and pacing to shorten diastole. Myocardial oxygen needs were estimated from the tension time index (TTI). Normal endo-epi flow ratios per gram (1:1) fell to 0.1:1 with these procedures and paralleled a fall in diastolic flow fraction (often nearly zero) and postischemic coronary reactive hyperemic responses. These changes occurred despite normal or raised mean CBF and 300-500% increase in systolic CBF. The altered flow ratios were best predicted by relating them to the ratio of DPTI (supply) to TTI (demand).
828 citations
TL;DR: One of the major proteins present gave a maximal rate of esterification similar to that found with the native lipoprotein, while the other major lipop protein was inactive as a cofactor but significantly reduced activity produced by the cofactor protein.
700 citations
TL;DR: A protein of molecular weight ∼ 12,000 which binds long-chain fatty acids and certain other lipids has been identified in cytosol of intestinal mucosa, liver, myocardium, adipose tissue, and kidney and appears to be identical with the smaller of two previously described cytoplasmic anion-binding proteins.
Abstract: A protein of molecular weight approximately 12,000 which binds long-chain fatty acids and certain other lipids has been identified in cytosol of intestinal mucosa, liver, myocardium, adipose tissue, and kidney. Binding is noncovalent and is greater for unsaturated than for saturated and medium-chain fatty acids. This protein appears to be identical with the smaller of two previously described cytoplasmic anion-binding proteins. Binding of long-chain fatty acids by this protein is greater than that of other anions tested, including sulfobromophthalein, and does not depend on negative charge alone. The presence of this binding protein may explain previously observed differences in intestinal absorption among fatty acids, and the protein may participate in the utilization of long-chain fatty acids by many mammalian tissues.
660 citations
TL;DR: The fine structure and distribution of tight and gap junctions in epithelia of the rat pancreas, liver, adrenal cortex, epididymis, and duodenum, and in smooth muscle were examined in paraformaldehyde-glutaraldehyde-fixed, tracer-permeated, and freeze-fractured tissue preparations.
Abstract: The fine structure and distribution of tight (zonula occludens) and gap junctions in epithelia of the rat pancreas, liver, adrenal cortex, epididymis, and duodenum, and in smooth muscle were examined in paraformaldehyde-glutaraldehyde-fixed, tracer-permeated (K-pyroantimonate and lanthanum), and freeze-fractured tissue preparations. While many pentalaminar and septilaminar foci seen in thin-section and tracer preparations can be recognized as corresponding to well-characterized freeze-fracture images of tight and gap junction membrane modifications, many others cannot be unequivocally categorized—nor can all freeze-etched aggregates of membrane particles. Generally, epithelia of exocrine glands (pancreas and liver) have moderate-sized tight junctions and large gap junctions, with many of their gap junctions basal to the junctional complex. In contrast, the adrenal cortex, a ductless gland, may not have a tight junction but does possess large gap junctions. Mucosal epithelia (epididymis and intestine) have extensive tight junctions, but their gap junctions are not as well developed as those of glandular tissue. Smooth muscle contains numerous small gap junctions The incidence, size, and configuration of the junctions we observed correlate well with the known functions of the junctions and of the tissues where they are found.
640 citations
TL;DR: A clear discrepancy is reported between the product of certain cell-free reactions and authentic light chain and it is proposed that light chains are initially synthesized as a precursor of slightly higher molecular weight and subsequently converted into the authentic product.
Abstract: IMMUNOGLOBULIN light chains are synthesized in heterologous cell-free systems from reticulocytes1 and Krebs II ascites cells2 and in reconstituted homologous systems from lymph nodes3,4 and myeloma tumours5,6. Although the synthesis appeared to be essentially faithful, absolute identity with authentic light chains was not demonstrated and some small differences were observed. We report here a clear discrepancy between the product of certain cell-free reactions and authentic light chain. With the product of other cell-free reactions no such discrepancy is seen. We propose that light chains are initially synthesized as a precursor of slightly higher molecular weight and subsequently converted into the authentic product.
551 citations
TL;DR: In this article, an allosteric model was proposed to explain the differential effects of inducer, suboptimal inducer and anti-inducer steroids on the conformational changes in the receptor molecules.
533 citations
TL;DR: The morphological observations of this study are consistent with the previously proposed biphasic model of differentiation for the exocrine and endocrine B cells, and the development of specific organelles correlates with the pattern of accumulation of the specific exocrine proteins and insulin.
516 citations
TL;DR: Overall, skin of miniature swine has the closest permeability characteristics to that of human skin with this series of compounds, which indicates that skin permeability decreases in the following order: rabbit, rat, pig and man.
486 citations
TL;DR: It was postulated that constriction of the ductus arteriosus after birth would produce obstruction, and this was confirmed experimentally in fetal lambs with surgically simulated juxtaductal coarctation.
Abstract: In the normal fetus the level of blood flow across the aortic isthmus is lower than after birth. This is reflected by a smaller diameter of the isthmus in relation to the ascending and descending aorta. We postulated the effects of various congenital heart lesions on aortic isthmus development in the fetus on the basis of assumed changes in flow patterns. These alterations have been confirmed by studies of cineangiograms in newborn infants. In congenital heart lesions with reduced pulmonary arterial outflow, the diameter of the aortic isthmus is wider than normal, presumably because it carries a greater than normal flow in the fetus. In lesions interfering with left ventricular outflow the aortic isthmus may be underdeveloped. However, in aortic atresia the isthmus is normally developed since it carries a normal flow but in a retrograde manner. We reviewed the clinical data and angiograms of 41 infants less than 3 months old who had aortic obstruction. They could be divided into 2 distinct groups. Twenty-three with aortic isthmus narrowing or interruption had a large ventricular septal defect and a high incidence of complex anomalies such as double outlet right ventricle. The remaining 18 infants with localized juxtaductal narrowing had a low incidence of associated intracardiac lesions. The appearance of the localized juxtaductal coarctation suggested that aortic obstruction may not be present during fetal life because the widely patent ductus arteriosus obviates aortic obstruction. We postulated that constriction of the ductus arteriosus after birth would produce obstruction. This was confirmed experimentally in fetal lambs with surgically simulated juxtaductal coarctation.
430 citations
TL;DR: A methodology is described for the analysis of tissue SH components of a single tissue sample in terms of soluble and insoluble, reactive and unreactive, SH, using the SH reagent DTNB.
417 citations
TL;DR: A conceptual scheme and associated statistical methodology is presented which is designed to provide the basis for a clinically useful computer program to suggest optimal dosage regimens for a number of drugs for individual patients.
TL;DR: The administration of haematoporphyrin followed by light therapy proved lethal to glioma cells in culture and produced massive destruction of porphyrIn-containing gliomas transplanted subcutaneously in rats.
TL;DR: The results are consistent with the concept that the erythrocyte ghost membrane is a planar fluid domain formed by a bilayer membrane continuum which is interrupted by localized, yet mobile, proteic intercalations.
Abstract: This paper demonstrates the translational movement along the plane of the human erythrocyte ghost of the membrane particles exposed by freeze-fracture. The membrane particles can be aggregated by incubation of the ghosts in media with a pH in the vicinity of 5 5 or 3 5. The particles are disaggregated in neutral and alkaline media (pH 9 5) and also at pH 4.5 Aggregation of the particles at pH 5.5 is reversible, prevented by prefixation in glutaraldehyde and by media of high ionic strength. Particle aggregation occurs within 2–4 min. These results are consistent with the concept that the erythrocyte ghost membrane is a planar fluid domain formed by a bilayer membrane continuum which is interrupted by localized, yet mobile, proteic intercalations.
TL;DR: The basis of determining clearance from the area under the blood or plasma concentration-time curve following an intravenous dose is examined and an equation is derived which allows an estimate of the availability of a completely absorbed, orally administered drug.
TL;DR: Auditory evoked potentials to ‘clicks’ were averaged from the scalps of litters of anesthetized rat pups and kittens throughout neonatal development, consistent with the hypothesis that significant limitations in both the immature and mature auditory system, as measured by peak latencies, occur before the VIIIth nerve.
TL;DR: Cells producing Rous sarcoma virus contain virus-specific ribonucleic acid (RNA) which can be identified by hybridization to single-stranded deoxyribonucleics acid (DNA) synthesized with RNA-directed DNA polymerase, and the hybrids formed have a high order of thermal stability.
Abstract: Cells producing Rous sarcoma virus contain virus-specific ribonucleic acid (RNA) which can be identified by hybridization to single-stranded deoxyribonucleic acid (DNA) synthesized with RNA-directed DNA polymerase. Hybridization was detected by either fractionation on hydroxyapatite or hydrolysis with single strand-specific nucleases. Similar results were obtained with both procedures. The hybrids formed between enzymatically synthesized DNA and viral RNA have a high order of thermal stability, with only minor evidence of mismatched nucleotide sequences. Virus-specific RNA is present in both nuclei and cytoplasm of infected cells. This RNA is remarkably heterogeneous in size, including molecules which are probably restricted to the nucleus and which sediment in their native state more rapidly than the viral genome. The nature of the RNA found in cytoplasmic fractions varies from preparation to preparation, but heterogeneous RNA (ca. 4-50S), smaller than the viral genome, is always present in substantial amounts.
TL;DR: A two-compartment model for both aspirin and its metabolite, salicylic acid, involving a constant fractional hydrolysis of aspirin during absorption, satisfactorily described both the aspirin and resultant salicyric acid plasma data.
TL;DR: The subjects are three patients with distinct symptoms of xeroderma pigmentosum in which the cultured fibroblasts are different from those usually found in this disease, and a minority of those cases which are clinically diagnosed as XP constitute a biochemically distinct condition.
TL;DR: LRF release, however, is minimal in prepubertal children and increases strikingly at puberty, and the magnitude of LH and possibly FSH release induced by LRF appears to be affected by the degree of prior exposure of LRF.
Abstract: The effect of puberty and hyper- and hypogonadotropism on the pituitary responsiveness to the intravenous injection of 5 μg/m2 to 600 μg of synthetic luteinizing hormone releasing factor (LRF) was studied in 32 subjects Sixteen subjects were prepubertal (2–13 years), 5 were pubertal (12–18 years), 6 were adult males, 3 had hypergonadotropic hypogonadism and 2 had hypogonadotropic hypogonadism and anosmia We conclude from our data that: 1) LRF releases comparable amounts of FSH in prepubertal, pubertal, and adult subjects LH release, however, is minimal in prepubertal children and increases strikingly at puberty; 2) LRF releases relatively more-LH and FSH in hypergonadotropic patients than in adult males; 3) LRF deficiency due to a selective hypothalamic defect is the origin of isolated FSH and LH deficiency in at least some patients with hypogonadotropic hypogonadism; and U) the magnitude of LH and possibly FSH release induced by LRF appears to be affected by the degree of prior exposure of th
TL;DR: The prognosis is good in infants in whom onset of PDA is not associated with progressively worsening IRDS, and cardiac catheterization and operative closure of the PDA in neonates when heart failure cannot be controlled medically.
Abstract: Patent ductus arteriosus (PDA) developed in 17 of 111 premature infants (birth weight 1750 g or less) born during a four-year period (15.3 per cent incidence). During that time we treated 29 such infants, 17 born at our own institution and 12 similar infants transferred from other hospitals. Sixteen of the 29 had cardiac catheterization, 10 had operative closure of the PDA, and 24 survived. When the PDA became evident, 23 infants had no pulmonary disease, were recovering from the idiopathic respiratory-distress syndrome (IRDS) or had chronic lung disease; all survived. In six infants with severe IRDS, onset of PDA was associated with a worsening of the pulmonary status; only one survived. We recommend cardiac catheterization and operative closure of the PDA in neonates when heart failure cannot be controlled medically. The prognosis is good in infants in whom onset of PDA is not associated with progressively worsening IRDS.
TL;DR: Renal and peripheral venous plasmarenin activities were determined by radioimmunoassay of angiotensin I in 13 hypertensive patients with radiologically normal kidneys and in 110 patients with suspected renal hypertension, confirming the predictive value of a renal-vein-renin ratio greater than 1·5 and suggesting that this ratio is also useful in patients with other types of renal hypertension.
TL;DR: This paper presents some very simplified general treatments which will allow workers to derive equations for any linear mammillary compartment model with any first- or zero-order or impulse input process through the use of general input and disposition functions, the method of partial fractions for solving Laplace transforms, and a multiple-dosing function.
TL;DR: In a family with intermittent acute porphyria five affected members were found to have decreased erythrocyte uroporphyrinogen I (URO)-synthetase activity, when compared to unaffected members.
Abstract: In a family with intermittent acute porphyria (IAP) five affected members were found to have decreased erythrocyte uroporphyrinogen I (URO)-synthetase activity, when compared to unaffected...
TL;DR: The posttranscriptional control model for inducible enzymes is supported by evidence that the action of the RNA synthesis inhibitor, actinomycin D, in inhibiting the deinduction of inducibles tyrosine aminotransferase is not due to its inhibition of enzyme degradation.
Abstract: The posttranscriptional control model for inducible enzymes is supported by evidence that the action of the RNA synthesis inhibitor, actinomycin D, in inhibiting the deinduction of inducible tyrosine aminotransferase is not due to its inhibition of enzyme degradation.
TL;DR: Although masses of neurofilaments are found in peripheral axons in other disorders, none approaches the proportions encountered in this unique case of a six-year-old girl with distal mixed polyneuropathy.
Abstract: Sural nerve biopsy was performed on a six-year-old girl with a slowly progressive distal mixed polyneuropathy. The nerve fiber population was reduced, and of those remaining, approximately half were greatly enlarged, measuring up to 35 microns in cross section. Longitudinal sections showed axonal enlargement to be segmental. Ultrastructurally, swollen axonal segments were filled with neurofilaments in closely-packed swirls which appeared to tie on occasion into granular electron-opaque condensations. Both, myelinated and unmyelinated fibers were involved, and some degree of onion-bulb formation was observed. Although masses of neurofilaments are found in peripheral axons in other disorders, none approaches the proportions encountered in this unique case.
TL;DR: It is suggested that the term burr cell for echinocyte and spur cells for the acanthocytes of liver disease be abandoned because they are redundant and do not allow for designation of the mixed forms of acantho-echinocytes which are of diagnostic importance.
TL;DR: It is suggested that the major defect is not in the lungs or at the peripheral chemoreceptors but at the respiratory center (or central receptors) of preterm infants.
Abstract: We made 84 studies on 20 "healthy" preterm infants during the first 34 days of life to discover whether infants breathing periodically hypoventilate or hyperventilate and whether the major defect is at the central or peripheral chemoreceptors. Six infants breathed periodically (n = 26) and seven regularly (n = 27) at all times; seven infants breathed periodically (n = 15) or regularly (n = 16) in different studies. In these three groups (periodic, regular, and intermediate), we compared respiratory minute volume and frequency, heart rate, alveolar oxygen tension (PAO2) and alveolar carbon dioxide tension (PACO2) and PO2, PCO2 and pH of arterialized capillary blood, alveolar-capillary differences for PO2 and PCO2, peripheral chemoreceptor sensitivity and CO2 responses. We measured ventilation with a nosepiece and a screen flowmeter. The mean values for the intermediate and periodic groups were similar. There were major differences between the periodic and regular groups. The infants breathing periodically (1) hypoventilated, (2) showed a significant shift of the CO2 response curve to the right with a 22% decrease in slope, and (3) had an increased response to O2. However, the two groups had similar alveolar-capillary PO2 and PCO2 differences. These findings suggest that the major defect is not in the lungs or at the peripheral chemoreceptors but at the respiratory center (or central receptors).
TL;DR: The study of intramolluscan single and double trematode infections has proved to be a useful approach in better understanding host–parasite relationship.
Abstract: Publisher Summary The study of intramolluscan single and double trematode infections has proved to be a useful approach in better understanding host–parasite relationship Modification and disruption of snail infection with trematodes is reviewed and the parameters and characteristics of various infection combinations are described Biologically, however, the inter-trematode reactions and the responses of the snail host offer remarkable opportunities to examine and isolate various aspects of this host–parasite relationship The single species infection patterns differ widely between the pure sporocyst type, exemplified by S mansoni, and the redial type, typified by P segregatum Characteristics of each are reviewed Their interaction is then reviewed, based on original data and comparison with other studies Redial predation (“direct antagonism”) is discussed in terms of relative activity, efficiency, and predatory response to triggering stimuli in the snail Possible mechanisms of indirect antagonism are reviewed, with a fuller consideration of snail immunity as induced by these infections and measured experimentally The parameters or characteristics of single-species infection are described and related to one another in a preliminary fashion as an “adaptation index” (AI), which includes such parameters as infection rate, period for 50% snail death, and period to cercarial shed The trematode method is locally applicable, using indigenous strains supplied and sustained at a high level by continual reseeding with eggs of the controlling trematode (or processed faeces from the appropriate final hosts) Effective biocontrol as a self-sustaining life-cycle appears highly improbable, as is the expectation that this method can be adopted on a wide scale with the same controlling agent
TL;DR: It is concluded that although intraluminal solubility of palmitate is less than that of linoleate, initial uptake of the two lipids by intestinal mucosa is similar, and significant differences in rates of entry into the cell and/or rate of microsomal metabolism result in a significantly less rapid reesterification and, therefore, overall absorption.