Showing papers by "University of California, San Francisco published in 1968"
TL;DR: Patients with xeroderma pigmentosum develop fatal skin cancers when exposed to sunlight, and so the failure of DNA repair in the skin must be related to carcinogenesis.
Abstract: Normal skin fibroblasts can repair ultraviolet radiation damage to DNA by inserting new bases into DNA in the form of small patches. Cells from patients with the hereditary disease xeroderma pigmentosum carry a mutation such that repair replication of DNA is either absent or much reduced in comparison to normal fibroblasts. Patients with xeroderma pigmentosum develop fatal skin cancers when exposed to sunlight, and so the failure of DNA repair in the skin must be related to carcinogenesis.
1,649 citations
TL;DR: The dynamics of insulin release in response to relatively long infusions of glucose were studied in the isolated perfused rat pancreas and Histological examination of the perfused pancreases and measurement of oxygen consumption by these tissues indicated that optimal physiological conditions were used.
Abstract: The dynamics of insulin release in response to relatively long infusions of glucose were studied in the isolated perfused rat pancreas. Insulin secretion was determined by immunochemical assay of the total portal vein effluent. Histological examination of the perfused pancreases and measurement of oxygen consumption by these tissues indicated that optimal physiological conditions were used. It was observed that, when glucose was infused for a period of approximately 1 hr into a perfused pancreas, there appeared 2 distinctly different phases of insulin release. There was an early, or rapid, release of insulin which subsided within approximately 2 min, followed by a late, or slow release phase which continually increased in rate until termination of the glucose infusion. The contribution of newly synthesized insulin to either phase was determined by comparing the insulin release by normal control preparations to that by preparations which were treated with puromycin. Incorporation of L-valine-14C was used a...
613 citations
TL;DR: In this paper, three major neural components of the mammalian ERG have been demonstrated, including the late RP (receptor potential), b-wave, and d.c. component, plus the c-wave from the pigment epithelium.
551 citations
TL;DR: It is shown that methods based on the single-compartment concept do not result in acceptable estimates of the absorption rates, and a new equation is presented, presuming the drug distributes between a central and one peripheral compartment, which results in an accurate estimate of the known rates of infusion (absorption) for the drugs studied to date.
442 citations
TL;DR: The two monocyte receptors exert a cooperative effect on ingestion by monocytes of erythrocytes coated with γG antibody in the presence of inhibitory amounts of free γE, which is independent of complement.
Abstract: Human monocytes contain two distinct receptor sites, one specific for the third component of complement (C'3), the other for immunoglobulin G(gammaG). The two receptors may function either independently or cooperatively in the induction of phagocytosis. Ingestion of erythrocytes coated with immunoglobulin M antibody requires a relatively large number of bound C'3 molecules per cell. Ingestion of erythrocytes sensitized with gammaG antibody is independent of complement; however, the reaction is inhibited by concentrations of gammaG far below those in normal serum. Inhibition by gammaG-globulin is overcome by a relatively small number of bound C'3 molecules per cell. The two monocyte receptors exert a cooperative effect on ingestion by monocytes of erythrocytes coated with gammaG antibody in the presence of inhibitory amounts of free gammaG.
438 citations
TL;DR: The two-compartmental open-system model is discussed in respect to the error introduced into the usual absorption rate and elimination rate calculations and on the estimation of the volume of distribution of various drugs.
401 citations
TL;DR: The findings indicate that azurophil granules are primary lysosomes, since they contain numerous lysOSomal, hydrolytic enzymes, but the nature of specific granules is uncertain since, except for alkaline phosphatase, their contents remain unknown.
Abstract: In the previous paper we presented findings which indicated that enzyme heterogeneity exists among PMN leukocyte granules. From histochemical staining of bone marrow smears, we obtained evidence that azurophil and specific granules differ in their enzyme content. Moreover, a given enzyme appeared to be restricted to one of the two types. Clear results were obtained with alkaline phosphatase, but those with a number of other enzymes were suggestive rather than conclusive. Since the approach used previously was indirect, it was of interest to localize the enzymes directly in the granules. Toward this end, we carried out cytochemical procedures for five enzymes on normal rabbit bone marrow cells which had been fixed and incubated in suspension. The localization of reaction product in the granules was determined by electron microscopy. In accordance with the results obtained on smears, azurophil granules were found to contain peroxidase and three lysosomal enzymes: acid phosphatase, arylsulfatase, and 59-nucleotidase; specific granules were found to contain alkaline phosphate. Specific granules also contained small amounts of phosphatasic activity at acid pH. Another finding was that enzyme activity could not be demonstrated in mature granules with metal salt methods (all except peroxidase); reaction product was seen only in immature granules. The findings confirm and extend those obtained previously, indicating that azurophil granules correspond to lysosomes whereas specific granules represent a different secretory product.
325 citations
TL;DR: Findings confirm and extend those obtained previously, indicating that azurophil granules correspond to lysosomes whereas specific granules represent a different secretory product.
Abstract: Histochemical procedures for PMN granule enzymes were carried out on smears prepared from normal rabbit bone marrow, and the smears were examined by light microscopy. For each of the enzymes tested, azo dye and heavy metal techniques were utilized when possible. The distribution and intensity of each reaction were compared to the distribution of azurophil and specific granules in developing PMN. The distribution of peroxidase and six lysosomal enzymes (acid phosphatase, arylsulfatase, β-galactosidase, β-glucuronidase, esterase, and 5'-nucleotidase) corresponded to that of azurophil granules. Progranulocytes contained numerous reactive granules, and later stages contained only a few. The distribution of one enzyme, alkaline phosphatase, corresponded to that of specific granules. Reaction product first appeared in myelocytes, and later stages contained numerous reactive granules. The results of tests for lipase and thiolacetic acid esterase were negative at all developmental stages. Both types of granules stained for basic protein and arginine. It is concluded that azurophil and specific granules differ in their enzyme content. Moreover, a given enzyme appears to be restricted to one of the granules. The findings further indicate that azurophil granules are primary lysosomes, since they contain numerous lysosomal, hydrolytic enzymes, but the nature of specific granules is uncertain since, except for alkaline phosphatase, their contents remain unknown.
307 citations
TL;DR: Inhibition of this synthesis of brain 5-hydroxytryptamine with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.
Abstract: Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.
249 citations
TL;DR: It was postulated that the placental polypeptide, rather than pituitary hormone, functioned as an important “metabolic hormone” of late pregnancy; the adaptive and homeostatic advantages to the mother and fetus of such a placental function were pointed out.
Abstract: It is now firmly established that the human placenta synthesizes and secretes a polypeptide hormone that is chemically and immunologically similar to human pituitary growth hormone and that has prolactin-like and growth hormone-like activity (see Josimovich & Brande, 1964; Grumbach & Kaplan, 1964a & b; and Kaplan & Grumbach, 1964, for historical review and a summary of early observations). A comparable simian placental hormone was identified (Kaplan & Grumbach, 1964) that bears an even closer immunochemical relationship to the human placental hormone than either has to its respective pituitary growth hormone. Josimovich isolated this hormone and emphasized its prolactin and luteotropic activity in animals (Josimovich & MacLaren, 1962; Josimovich et at., 1963; Josimovich & Atwood, 1964) and named it “human placental lactogen.” In our early studies, we obtained data suggesting that this placental polypeptide also exhibited growth hormone-like activity on bioassay. The hypothesis was advanced that changes in carbohydrate, fat, and protein metabolism in the last half of pregnancy, previously ascribed to pituitary growth hormone, were effected, a t least in part, by the placental hormone (Grumbach & Kaplan, 1964a & b; Kaplan & Grumbach, 1964). I t was postulated that the placental polypeptide, rather than pituitary hormone, functioned as an important “metabolic hormone” of late pregnancy; the adaptive and homeostatic advantages to the mother and fetus of such a placental function were pointed out. To indicate the duality of biologic properties of the placental protein which simulated those of human pituitary growth hormone and its origin in the syncytiotrophoblast, we proposed the tentative designation human “chorionic growth hormone-prolactin” (CGP) . Subsequently, additional evidence was obtained in this laboratory to support the growth hormone-like properties of CGP in man and its metabolic role in pregnancy (Grumbach, 1965; Kaplan & Grumbach, 1965b; Grumbach et al . , 1966). *Supported by grants from the National Institute of Child Health and Human Development and the National Institute of Arthritis and Metabolic Diseases, NIH, USPHS
219 citations
TL;DR: Human monocytes isolated from peripheral blood phagocytized polystyrene particles, Escherichia coli, Staphylococcus aureus, Candida albicans, Cryptococcus neoformans, and red cells coated with IgG antibody in vitro were studied for ingestion of fungi and bacteria.
TL;DR: Primary gonadal failure may be part of a polyendocrinopathy of which idiopathic Addison's disease is an integral part and which is characterised by the formation of autoantibodies to the respective tissues.
TL;DR: Aspirin, like cortisone, reduces the tensile strength of the healing skin wound in rats, and the possible mechanism of action of these anti-inflammatory agents has been discussed.
TL;DR: In this article, the pharmacokinetics of ASA and salicylic acid were studied following intravenous administration in males, and the resultant plasma concentration-time curves were described by bi-exponential equations.
TL;DR: A mathematical relationship between the volume of distribution at steady state and those estimated by often used but incorrect methods is presented and experimental data on acetylsalicylate, salicylates, griseofulvin, and several barbiturates are presented.
TL;DR: Studies involving preincubation of the electron transport particle with various unlabeled inhibitors, prior to addition of rotenone-14C for determination of its subsequent binding, provide strong evidence that it is possible to distinguish between the portion of rotonone- 14C that is specifically bound and the portion that is unspecifically bound.
TL;DR: Vitamin A and vitamin E reverse the skin-wound healing retardation action of aspirin in rats and the possible mechanisms of action of vitamin A and aspirin on wound healing are discussed.
TL;DR: It is concluded that Amytal, rotenone, and piericidin block NADH oxidation on the O2 side of the non-heme iron of NADH dehydrogenase.
TL;DR: The suggestion that there is a high incidence (perhaps 50%) of spontaneous closure of VSD during childhood and that this may occur frequently after childhood is supported.
Abstract: It is difficult to make prognoses and decisions on therapy of individuals with congenital heart disease (CHD) and plan efficiently for medical services and training programs because studies on the incidence and relative frequency of different types of CHD at birth, mortality rates, times of death, and prevalence rates in children and adults are incomplete or unrepresentative. The present study assesses the merits of previous surveys and attempts to indicate the best information about these rates. Specific attention has been directed to data on ventricular septal defect (VSD), with an estimated incidence of at least 20/10,000 live births; about 10% of these children died before 15 years of age. There should thus be about 18/10,000 surviving school children with VSD, yet the most intensive school surveys show only about half this number. This supports the suggestion that there is a high incidence (perhaps 50%) of spontaneous closure of VSD during childhood. Spontaneous closure may also occur frequently afte...
TL;DR: In five conscious dogs and two anesthetized dogs, the pressure gradient between the left ventricle and the ascending aorta was measured with high fidelity micromanometers and confirmed that at this time blood is flowing out of the Ventricle under its own momentum and that the aorte is a pressure source for the ventricles.
Abstract: In five conscious dogs and two anesthetized dogs, the pressure gradient between the left ventricle and the ascending aorta was measured with high fidelity micromanometers. Left ventricular pressure exceeded aortic pressure in the first 30 to 50% of the ejection period. Aortic pressure exceeded left ventricular pressure during the remainder of the ejection period. The magnitude of these differences varied from 5 to 20 mm Hg. This finding in late systole implies that at this time blood is flowing out of the ventricle under its own momentum and that the aorta is a pressure source for the ventricle. The ascending aorta was suddenly occluded in five dogs to verify this hypothesis. When occlusion occurred in the last third of the ejection period, there was an abrupt fall of left ventricular pressure, apparently confirming the momentum hypothesis.
TL;DR: Studying the optimal conditions of exposure to monocytes to PPD and to autologous lymphocytes showed that viable, metabolically intact monocytes are required and direct contact between monocytes and lymphocytes was required for consistent transformation.
Abstract: Monocytes isolated from the peripheral blood of tuberculin-positive and tuberculin-negative donors were exposed to PPD, extensively washed, and incubated with autologous or homologous lymphocytes. Lymphocyte transformation was measured morphologically and by incorporation of 14 C-labeled thymidine. Monocytes from tuberculin-positive subjects induced transformation of autologous lymphocytes in 19 of 29 experiments. Studies to define the optimal conditions of exposure to monocytes to PPD and to autologous lymphocytes showed that viable, metabolically intact monocytes are required. A ratio of only 1 monocyte to 100 lymphocytes sufficed to induce transformation; neutrophils were inactive. In general, PPD-sensitized monocytes failed to induce transformation of homologous lymphocytes from either tuberculin-positive or tuberculin-negative subjects. Direct contact between monocytes and lymphocytes was required for consistent transformation, and islands of transforming lymphocytes were observed around a central core of monocytes.
TL;DR: In conclusion, isolated and partially purified renal nuclear proteins which have many of the properties to be expected of the specific mineralocorticoid receptors are presented.
TL;DR: The hypothesis that kinins play a pathogenetic role in the early phase of endotoxin-induced shock and that the severity of the earlyphase may influence the animal's survival is supported.
Abstract: The effects of endotoxin ( Escherichia coli and Pseudomonas pseudomallei ) were studied in 18 unanesthetized rhesus monkeys restrained in primate chairs. Indwelling arterial and venous catheters were used for hemodynamic measurements and blood sampling. Whole blood kinin, plasma kininogen, lysosomal enzymes, complete blood counts, and blood gas tensions were measured. Within an hour of beginning the infusion of the endotoxin, the mean arterial pressure and systemic peripheral resistance decreased significantly in the 18 experimental monkeys compared to 13 control monkeys. These early changes were associated with significant elevation in whole blood kinin concentration and a decrease in plasma kininogen. All of these early changes were most marked in the animals that died. Granulocytopenia occurred within 15 minutes, and the concentration of free lysosomal enzyme in the plasma rose 2 hours after endotoxin infusion. The preterminal phase of shock was characterized by a low peripheral vascular resistance and decreasing cardiac output without elevation of kinin levels. These findings support the hypothesis that kinins play a pathogenetic role in the early phase of endotoxin-induced shock and that the severity of the early phase may influence the animal's survival. The relation of kinins to other vasoactive substances released after endotoxin-induced shock is unknown.
01 Jan 1968
TL;DR: It is suggested that endogenous histamine in the lung is involved in the vasoconstrictor response to acute alveolar hypoxia, and the hypoxic pressor response could not be abolished by α-receptor-, serotonin-, or ATP-blocking agents.
Abstract: Pharmacological agents that block or potentiate the effects of naturally occurring vasoactive substances were used to try to determine which substance, if any, mediates the vasoconstrictor response to acute alveolar hypoxia in isolated rat lungs. Isolated and ventilated lungs of rats were perfused at 37°C with homologous blood at constant-volume, pulsatile inflow, and pressor responses to brief periods of ventilation hypoxia (2% O2) were recorded (control, 21% O2). Antihistamines of four different chemical classes in concentrations of 70 to 140 µg/ml abolished all pressor responses to alveolar hypoxia without interfering with the effects of injected bradykinin, ATP, or serotonin. A histaminase-inhibiting compound, semicarbazide, potentiated the hypoxic pressor response. The hypoxic pressor response could not be abolished by α-receptor-, serotonin-, or ATP-blocking agents. The results suggest that endogenous histamine in the lung is involved in the vasoconstrictor response to acute alveolar hypoxia.
TL;DR: Stimulation at a number of brain sites did not produce retrograde impairment of passive avoidance, and control electrode placements negated current spread, antidromic effects due to excitation of fibers of passage, and downstream peripheral effects mediated by internal capsular fibers as significant influences in the mediation of the retention deficits obtained.
TL;DR: In the past 40 years monumental efforts have been devot,ed to the measurement of profiles, teeth, and dental arches in an attempt to focus on how the human head and face grow and how teeth become malaligned.
TL;DR: Four of five infants with maternal deprivation included in this study showed evidence of increased insulin sensitivity, but the mean maximum SGH response was not significantly different from that of the control group, and there was no significant correlation of the level of FSGH with age in children over four years, or according to sex.
Abstract: Growth and Growth Hormone: I. changes in Serum Level of Growth Hormone Following Hypoglycemia in 134 children with Growth Rctardation
TL;DR: One hundred and seventeen white adults with oral leukoplakia were examined and followed up from 1 to 11 years to correlate the clinical and histologic characteristics with the natural history of this disease.
Abstract: One hundred and seventeen white adults with oral leukoplakia were examined and followed up from 1 to 11 years to correlate the clinical and histologic characteristics with the natural history of this disease.