Biomedical subjects
Publications and source records attributed to A S Gordon.
In a 78-year-old woman receiving perhexiline maleate for intractable angina pectoris, a syndrome of parkinsonism and peripheral neuropathy developed. The neuropathy was confirmed by electromyographic and nerve conduction studies. The parkinsonism and peripheral neuropathy disappeared when perhexiline maleate was discontinued.
Electrochemical polarization of copper and platinum was shown to affect the attachment of two marine bacteria to the surfaces of these metals in seawater. Attachment of both bacteria to copper surfaces was enhanced by polarizing the metal cathodically, whereas attachment was reduced when the copper was anodically polarized. Anodic polarization of platinum also retarded bacterial attachment but overpotentials higher then those for copper were required to produce the same effect. The pH was measured at a distance of 50 micron m from the polarized surfaces. Changes in pH at the metal-seawater interface correlated with the attachment of bacteria, and may have influenced bacterial attachment to polarized surfaces.
Explore the source record for details and available documents.
Evidence is presented for the existence of a factor in renal venous blood, evoked by subtotal hepatectomy (hepx), which inhibits the production of Ep in nephrectomized (nephrx) rats exposed to hypoxia. Significant inhibitory activity is not observed in blood obtained from sites other than the renal vein. This inhibitory effect is believed to be due to the action of a specific renal inhibitory factor (RIF) which reduces the extrarenal (hepatic) Ep response to hypoxia indirectly, by decreasing the production or effectiveness of an antagonistic liver principle, the hepatic erythropoietic factor (HEF). The HEF has previously been shown to augment hepatic Ep production following hypoxia in renally-deficient animals. The RIF has no anti-Ep action and its activity is not influenced by the accumulation of metabolic wastes. A mechanism for a renal-hepatic antagonism in the Ep response to hypoxia is hypothesized.
Experience with 29 000 cases in which the oesophageal obturator airway has been used in cardiopulmonary resuscitation indicates its safety, efficacy, and ease of use. Blood gases, fractional inspired oxygen, and pH were measured in 18 patients given both the oesophageal obturator airway and the endotracheal tube; there was no significant difference between the two. The former was found to be inserted more rapidly and reliably; moreover, paramedical staff are quickly trained to use it. It is concluded that the oesophageal obturator airway provides the technique of choice whenever ideal conditions and facilities--and trained staff--for endotracheal intubation are not immediately available.
Membrane protein phosphorylation may be a general regulatory mechanism mediating the response of cells to exogenous metabolic and physical signals. We have determined that the membrane-bound acetylcholine receptor is the major substrate phosphorylated in situ by a nearby membrane protein kinase. Moreover, these same membranes also contain phosphoprotein phosphatase activity which dephosphorylates the membrane-bound receptor. These findings suggest that reversible phosphorylation of the actylcholine receptor may be critical for receptor function at the synapse. Therefore, it is necessary to define the properties of the enzymes which mediate this phosphorylation-dephosphorylation mechanism. In this report we describe the properties of the first component of this system, the membrane-bound protein kinase in receptor-enriched membranes from the electric organ of Torpedo californica. Only ATP is effective as a phosphate donor for this cyclic AMP-independent membrane kinase; GTP does not support phosphorylation of the receptor. Both casein and histone can also be phosphorylated by the membrane protein kinase, but casein is a better substrate. Although phosphorylation of the receptor appears to be regulated by cholinergic ligands and K+, casein phosphorylation is not specifically affected by these agents. Moreover, while phosphorylation of the acetylcholine receptor is maximal in receptor=enriched membranes, casein phosphorylation is similar in all membrane fractions prepared from the electric organ. Taken together, these findings suggest that the membrane protein kinase activity in receptor-enriched membranes is similar to most other membrane kinases. Therefore, the unique characteristics of membrane-bound acetylcholine receptor phosphorylation appear to be determined by the receptor and its availability as a substrate for the membrane kinase.
RLV-A serum activity was measured by the agar colony assay to determine the effect of this erythroid dyscrasia on the granulopoietic humoral regulator, colony stimulating factor (CSF). In general, the sera of early, midstage and terminal animals not given endotoxin had high cluster forming properties compared to normal sera. The sera of early, midstage, and terminal mice treated with endotoxin had only a fraction of the colony forming ability of serum obtained from normal endotoxin-treated mice (EMS) with the earliest stages of the disease showing least activity followed by a rise in activity paralleling normal EMS, as the disease progressed. Sera from RLV-A endotoxin treated mice retained ability to stimulate cluster growth especially when compared to the slight activity displayed by normal endotoxin treated mouse sera.
The pathogenesis of anemia of the Shay chloroleukemia (SCL) was studied in rats following SC, IP and IV inoculation of chloroma cells. Little difference in survival was noted regardless of the route of inoculation. A decrease in hamatocrit occurred in all SCL rats during approximately the final 48 hours of the disease; however, the anemia was more severe in SC- and IP-inoculated terminal rats than in SCL rats inoculated IV. A reduction in the numbers of normal cellular elements was noted in the femoral bone marrow of most terminal rats studied which was found to correlate inversely with the leukemic blast cell content of the marrow. No correlation was observed between the erythroblast content of the marrow and the degree of anemia. The number of erythroblasts varied from greatly reduced to normal in terminal SCL rats despite severe anemia. Moreover, the greatest reduction of both normal marrow cellularity and erythroblast numbers was observed in IV inoculated rats which consistently displayed the highest hematocrits in the terminal stage of the disease. Thus, the terminal anemia appears to be due primarily to excessive red cell loss. The decrease in erythroblasts, when observed, was most striking in the orthochromatophilic and polychromatophilic stages of erythroid maturation.
Bacterial endotoxin was used as a granulopoietic stressor in the RLV-A infected mouse as a means of studying the marrow and spleen CFU-C response to this agent. A control group of phenylhydrazine (PHZ)-treated mice was also employed to induce a reduction in hematocrit levels equivalent to that observed in the early and mid-stage of the disease course and was used to determine whether the cloning observed was a manifestation of RLV-A disease or could be attributed solely to the resulting anemia. Both RLV-A infected and PHZ marrow from mice maintained at a hematocrit of 40% exhibited similar but higher than normal clonogenic capacities, whereas RLV-A (hematocrit 40%) spleen had an expanded number of CFU-C's when compared to PHZ treated (hematocrit 40%) mice. Examination of spleens of endotoxin-treated RLV-A (hematocrit 30%) infected mice indicated a 6 to 7-fold increase in splenic CFU-C numbers compared to endotoxin-treated normal mice. PHZ plus endotoxin-treated normal animals (hematocrit 30%) had splenic CFU-C values which were approximately half those of RLV-A infected (hematocrit 30%) endotoxin-treated animals. Results of this experiment suggest a fully operable but greater than normal CFU-C storage pool in the RLV-A infected mouse spleen which does not seem to be due entirely to the anemia.
Double partial hepatectomy (hepx) evokes an elevation in serum erythropoietin (Ep) levels in anephric hypoxic animals when compared to non-hypoxic or sham hepx controls. But this Ep response is significantly lower than that found in singly hepx, anephric hypoxic rats. Double hepx also induces numerous cytological changes in the liver. Extravascular accumulation of fat, fibrous scarring, localized necroses, and multiple abscesses, as well as decreased vascularity, occur following the second hepx. A humoral factor was detected in the serum of these animals that is capable of inducing hepatic Ep production when injected into normal rats 18 hours before nephrectomy and hypoxia. This factor, termed hepatopoietin (Hp), was previously demonstrated in the venous serum of singly hepx rats. The serum from animals subjected to double partial hepx is not as potent in inducing Ep production as the serum from singly hepx animals. The discrepancies noted between the single and double hepx groups is attributed to the necrotic cytological changes described above.
To evaluate the erythropoietic potential of rats during pathogenesis of Shay chloroleukemia (SCL), SCL animals were exposed to hypoxia initiated within two hours postinduction of SCL. Increases in hematocrit (HCT) occurred in both SCL and nonleukemic controls during the first seven days of exposure. This was followed by declines in HCT in hypoxic SCL rats similar to that observed in nonhypoxic SCL animals. HCT of nonleukemic controls remained elevated throughout hypoxic exposure. Results suggested that in SCL, erythropoietic homeostatic response mechanisms are functional prior to terminal phases of this disease, whereas anemia-producing mechanisms exceed maximum erythropoietic capacity of these animals during later stages of SCL. The HCT of most SCL rats exposed to hypoxia did not fall below 40% before death. This was in contrast to nonhypoxic SCL animals, which became severely anemic in terminal stages. No survival value was observed despite maintenance of red cell mass at or above normal. The pathogenesis of this leukemia was independent of the leukemic animal's erythropoietic potential.
We have found that the acetylcholine receptor (AChR) of Torpedo californica is phosphorylated and dephosphorylated in situ by a membrane-bound protein kinase and phosphatase [1]. There is increasing evidence that other neurotransmitters [2], light [3-6], polypeptide hormones [7], and growth factors [8-12] also may act by regulating the level of phosphorylation of membrane proteins. These observations suggest that membrane protein phosphorylation may be a general regulatory mechanism affecting the response of cells to exogenous metabolic and physical signals. To understand the role of membrane protein phosphorylation, we have chosen to study acetylcholine receptor-enriched membranes purified from the electric organ of T californica. This organ is an ideal model system for such studies since it is a rich source of the acetylcholine receptor. Membranes can be purified from the electric organ that are enriched in the AChR[13] and that show cholinergic agonist-dependent changes in cation flux [14]. Moreover, the AChR from T californica has been purified [15[, biochemically characterized [16], and used to generate specific antibodies [17]. Receptor, enriched membranes contain only a few other proteins that are closely associated with the receptor in the postsynaptic membrane. Such associated proteins may play a critical role in regulating the function of the AChR in the postsynaptic membrane. We have taken advantage of these conditions to study phosphorylation of the membrane-bound AChR in this well-defined, homogeneous system.
This study was designed to examine the interconnection of paternal factors and adolescent personality attributes and their impact on the adolescent girls' use of marijuana. Analysis of the data suggested that fathers who are affectionate and child-centered and whose daughters identify with them are less likely to have daughters who use marijuana. Adolescent nonusers differed from users on a number of personality attributes reflecting conventionality and a cognitive style of receptivity to change. In general, the results suggest that paternal factors and adolescent personality attributes each have an independent impact on the adolescents' marijuana use.
Erythropoietin (Ep) is a glycoprotein hormone that is responsible for mammalian red blood cell production. Adult rat liver regenerating 48-72 h after hepatectomy (hepx) produces elevated levels of Ep in response to hypoxia when compared to sham-operated, anephric hypoxic controls. A factor, termed hepatopoietin (Hp), found in the serum of hepx rats, is capable of stimulating hepatic Ep production when administered to normal rats 18 h prior to hypoxic exposure. Although the hepatic vein is the most potent source of this factor, Hp can also be demonstrated in the systemic arterial circulation. Bilateral nephrectomy (nephrx) of the donor hepx animal 24 h prior to bleeding abolishes this variation, and highest Ep levels are noted when serum from a hepx and nephrx rat is administered to animals immediatley after nephrx and 18 h before hypoxic exposure. Serum derived from hepx male rats displays a greater ability to evoke hepatic Ep production in normal recipients than serum from similarly treated female rats. Regardless of the sex of the hepx donor, Ep elaboration after hypoxia is highest in male recipients. The results indicate that there is a sexual variation in the production of Hp as well as Ep.
Explore the source record for details and available documents.
The pathogenesis of the anemia which occurs in rats bearing the Shay chloroleukemia (SCL) was investigated. Severe anemia, shown not to result from hemodilution, developed in the terminal stage of the disease. The rapid progression of the anemia suggested that reduced erythropoiesis was of no more than minor importance in the development of this anomaly. No evidence for a major hemolytic event was observed. Data are presented which suggest that hemostatic defects may be primarily responsible for the anemia of SCL. Because of many similarities with the pathogenesis of human myelogenous leukemia, SCL is proposed as a useful model for further studies on interreactions between the leukemic environment and the erythrocyte population.
Explore the source record for details and available documents.
Evidence is presented for production, by the subtotally hepatectomized (hepx) rat, of a factor which induces morphological and physiological hyperactivity of the Kupffer (K) cells and increased formation of Ep by the regenerating liver. This factor, originally termed hepatopoietin (Hp), and more recently the hepatic erythropoietic factor (HEF), is detectable in higher concentration in the hepatic venous blood than in blood draining other organs, thus supporting its hepatic origin. Production of the HEF is best related to hyperactivity of the K cells and not to the parenchymal (P) cells. The HEF can be demonstrated by administering serum from hepx donors to normal rats which respond with increased production of Ep when nephrectomized (nephrx) and rendered hypoxic. Removal of the kidneys from hepx donors further augments the Ep response to this serum in recipients. Subtotal hepx also evokes the production of a renal inhibitory factor (RIF) which reduces the ability of the liver to function as an extrarenal source of Ep. This inhibitor is found in renal venous blood and not in blood draining other organs. It is suggested that the RIF reduces the hepatic Ep response to hypoxia by diminishing the production and/or activity of the HEF. The RIF possesses no anti-Ep activity and its appearance and actions are not influenced by accumulation of metabolic wastes (as in the nephrx or ureterally-ligated rat). Erythroblastic nests have been observed in regenerating livers at 24-48 hr after subtotal hepx. It would seem that removal of a considerable part of the liver, which stimulates hepatic regeneration, confers upon this organ an increased ability to produce Ep and to function as a hematopoietic inductive microenvironment (HIM) for erythropoiesis.