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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 163 records · Page 9Linked to original sources
PubMed1988

Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class.

The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A)+ RNA from human dermal fibroblasts detects a major (approximately 5.7 kb) and a minor (approximately 4.8 kb) transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an approximately equal to 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF (i.e., PDGF dimers composed of two B chains or an A and a B chain). Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class.

Amino Acid Sequence↗
PubMed1987

The equine colonic mucosal granular cell: identification and X-ray microanalysis of apical granules and nuclear bodies.

The granular columnar epithelial cell of the equine dorsal large colon has been studied by transmission electron microscopy and X-ray microanalysis. Particular attention was focused on nuclear bodies commonly observed as central clusters of spherical, electron-dense inclusions within the nucleus. Ultrastructural morphology as well as X-ray microanalysis spectra reveal great similarity between colonic nuclear bodies and the numerous small granules of the apical cytoplasm in these epithelial cells. X-ray spectra of these cells were distinct from those of goblet cell mucous granules and mast cell granules. No evidence was found indicating transit of nuclear body granules through the nuclear envelope, or for morphologic association with the nucleoli. Of the diverse types of nuclear bodies previously reported in other species, equine colon nuclear bodies morphologically most closely resemble those seen in rabbit adenohypophysis. Colon epithelial cell nuclear bodies are likely identical to equine small intestine nuclear bodies, but their origin and role remain unknown.

Animals↗
PubMed1987

Suppression of T-helper cell function in mice following exposure to the carcinogen 7,12-dimethylbenz[a]anthracene and its restoration by interleukin-2.

Previous studies in this laboratory have demonstrated that exposure of mice to the carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthrance (DMBA) results in suppression of cell-mediated immunity (CMI), specifically the ability to generate cytotoxic T cells. This is accompanied by an increased susceptibility to challenge with transplantable tumors. Our previous studies have demonstrated no appreciable change in the composition of splenic lymphocyte populations following exposure to DMBA, suggesting a modulation of lymphocyte function, probably at the level of the T lymphocyte. The purpose of this study was to examine the mechanism of DMBA-induced T lymphocyte dysfunction following DMBA exposure, and to determine whether CTL function could be reconstituted by the addition of untreated lymphocytes or lymphokines. Exposure to DMBA in vivo at doses of 50 and 100 micrograms/g and in vitro at doses of 20 and 40 microM suppressed the ability of splenic lymphocytes to generate cytotoxic T-lymphocytes (CTL). CTL-mediated lysis of allogeneic tumor target cells could be restored by the addition of 20% T cell-enriched naive lymphocytes and by 10% T-helper cell-enriched lymphocytes. DMBA suppressed splenocyte production of the lymphokine interleukin-2 (IL-2) in response to mitogenic or allogeneic stimulation by greater than 70% following in vitro exposure and greater than 45% following in vivo exposure. Although DMBA-exposed lymphocytes were impaired in their ability to produce IL-2, CTL responsiveness could be reconstituted by the addition of exogenous IL-2 (purified or recombinant DNA-produced). Complete restoration of CTL responsiveness by the addition of exogenous IL-2 suggests that the T-helper cell, rather than the T-cytotoxic cell, is the target for the DMBA-induced CMI lesion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation.

Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats.

Base Sequence↗
PubMed1986

Functions of mononuclear phagocytes in mice exposed to diethylstilbestrol: a model of aberrant macrophage development.

Administration of the synthetic estrogen diethylstilbestrol (DES) lowers the systemic resistance of mice to challenge with either tumor cells or the facultative intracellular parasite Listeria monocytogenes. To assess the potential role of impaired mononuclear phagocyte system (MPS) function in this depression of host resistance, we addressed the question of systemic perturbations of the MPS induced by administration of DES. A panel of objective quantitative markers which have been previously shown to identify and characterize macrophages in the several stages of development of activation was employed. DES perturbed the resident population of peritoneal macrophages by increasing their number approximately twofold and by enhancing their competence for phagocytosis, cytostasis of tumor cells, and secretion of plasminogen activator. When we examined the competence of the MPS in DES-treated mice to respond to challenge with activating stimuli, we found that DES systemically suppressed the development of macrophages, in response to either pyran copolymer or BCG, to develop tumoricidal function and to gain competence for secretion of reactive oxygen intermediates such as H2O2. Since these data suggested that DES inhibited the development of macrophages from a precursor stage (i.e., responsive macrophages) to activated macrophages in vivo, we tested this possibility directly by applying known activating signals in vitro to responsive macrophages. Responsive macrophages from DES-treated mice did not become activated in response to the application of two known potent activating signals (i.e., MAF + LPS). Taken together, the data indicate that DES systemically perturbs the MPS and does so by enhancing development of the early stages of maturation and suppressing subsequent development.

Animals↗
PubMed1986

Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice--II. Altered cell-mediated immunity and tumor resistance.

We have previously demonstrated that the polycyclic aromatic hydrocarbons benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) produce a marked decrease in spleen weight, spleen and bone marrow cellularity and the number of IgM plaque forming cells generated in response to a T-dependent antigen. Exposure to DMBA, but not B[a]P, increased susceptibility to challenge with PYB6 tumor cells and Listeria monocytogenes suggesting that DMBA produces immune impairment involving cell-mediated immunity (CMI) and tumor resistance mechanisms. In this study, female B6C3F1 mice received total doses of 5, 50 and 100 micrograms DMBA/g of body weight in ten subcutaneous injections of 0.5, 5, or 10 micrograms/g over a 2 week period and CMI and tumoricidal functions were examined 3-5 days following the final injection of DMBA. DMBA exposed mice exhibited suppressed splenic cellularity (decreased 62%) and decreased numbers of resident peritoneal cells (down to 47% of control), although the proportion of T cell and T cell subsets, B cells and macrophages in spleens from exposed mice was not altered. Lymphocyte blastogenesis in response to mitogens was suppressed up to 49% with PHA, 48% with Con A and 76% with LPS. The response to alloantigens in unidirectional mixed lymphocyte culture was depressed as much as 73% following exposure to DMBA. Tumor cytolysis mediated by cytotoxic T cells (CTL) was impaired at doses of 50 and 100 micrograms DMBA/g body weight (88-95% suppressed respectively) as was natural killer cell (NK)-mediated tumor cytolysis (24% and 55% suppressed). Antibody-dependent cytotoxicity was significantly depressed in the highest exposure group. Peritoneal macrophage accumulation was decreased in DMBA-treated mice, but the macrophages present were pushed towards activation. The ability of DMBA-exposed mice to eliminate intravenously injected B16F10 tumor cells from the lungs was not impaired. Since NK- and M phi-mediated tumor cytotoxicity are thought to be primarily responsible for pulmonary elimination of B16F10 melanoma cells, the extent of NK suppression observed following DMBA exposure appeared to be insufficient to alter in vivo B16F10 pulmonary elimination. In contrast, the loss of the CTL tumoricidal response correlated with an increased frequency of tumors following challenge with PYB6 tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Persistent suppression of humoral and cell-mediated immunity in mice following exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene.

Carcinogen-induced immunosuppression has been implicated as an epigenetic mechanism in promoting the outgrowth and metastasis of neoplastic cells. It has previously been reported that the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) suppresses both humoral immunity (HI) and cell-mediated immunity (CMI) 3-5 days following exposure. Since persistent systemic immunosuppression may be more relevant in tumor outgrowth, assays quantitating HI and CMI, including those functions involved in tumor resistance, were performed 4 and 8 weeks following exposure to tumorigenic doses of DMBA. Adult B6C3F1 female mice were administered DMBA dissolved in corn oil subcutaneously at 5, 50 and 100 micrograms/g body weight in ten equal doses over 2 weeks (corn oil = vehicle control). The number of splenocytes producing IgM antibody to the T-dependent antigen, sheep erythrocytes, was suppressed up to 95% and 98% at 4 and 8 weeks, respectively. The IgG response was similarly depressed 75% and 98% at 4 and 8 weeks, respectively. Lymphoproliferation of splenocytes in response to the mitogens LPS, PHA and Con A were depressed up to 88%, 78% and 83% at 4 weeks and 63%, 63% and 67% respectively, at 8 weeks. In addition, alloantigen-induced proliferation of splenocytes in a one-way mixed lymphocyte culture was suppressed up to 90% at 8 weeks. The ability to generate cytotoxic T-lymphocytes (CTL) in vitro against P815 tumor cells was depressed at both time periods (88% and 60%, respectively) as was natural killer (NK) cell cytolysis of YAC-1 tumor targets (84% and 55%, respectively). The immunosuppression noted in these parameters was similar to that observed within 3-5 days following DMBA dosing. The persistent immunosuppression induced by the PAH carcinogen DMBA, including CTL and NK cell tumoricidal functions, may represent an important epigenetic mechanism contributing to tumor outgrowth or metastasis by this class of agents.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Enterotoxin activity of a Salmonella typhimurium of equine origin in vivo in rabbits and the effect of Salmonella culture lysates and cholera toxin on equine colonic mucosa in vitro.

To determine whether a strain of Salmonella typhimurium (UCD 1755) of equine origin had enterotoxin activity, 2 ml of a cell-free culture lysate of strain UCD 1755 and approximately 10(9) viable strain UCD 1755 organisms were inoculated into ligated small intestinal segments of rabbits. Intestinal segments inoculated with viable strain UCD 1755 organisms and those inoculated with a cell-free culture lysate of strain UCD 1755 had significant (P less than 0.05) accumulations of fluid 10 hours after inoculation when compared with ligated intestinal segments either inoculated with sterile brain-heart infusion broth or left empty. There was not a statistically significant difference between fluid accumulation of intestinal segments inoculated with viable strain UCD 1755 and that of segments inoculated with a cell-free culture lysate of strain UCD 1755. The responses of equine colonic mucosa to culture filtrates of 2 strains of salmonella typhimurium (UCD 1755 and SL 1027) and purified cholera toxin were studied in vitro. Isolated smaples of colonic mucosa were incubated for 4 hours at 37 C in Krebs-Henseleit bicarbonate buffer (KHB) alone, KHB plus culture lysate of strain UCD 1755, KHB plus culture lysate of strain SL 1027, and KHB plus 1 microgram of cholera toxin/ml. Cyclic adenosine monophosphate (cAMP) content of each sample was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The B chain of PDGF alone is sufficient for mitogenesis.

The platelet-derived growth factor (PDGF) is a mitogen derived from human platelets consisting of two related polypeptides termed A and B chains. The entire B chain of PDGF is highly (96%) homologous to a portion of p28sis, the transforming protein of simian sarcoma virus. It has been suggested that p28sis exerts its transforming potential by mimicking the growth promoting activity of PDGF and stimulating the cell in an autocrine manner. We have directly examined the mitogenic potential of p28sis and the B chain homologous region by expressing these heterologous sequences in the yeast Saccharomyces cerevisiae. In our constructions, these proteins are encoded by portions of the v-sis gene. Expression and secretion from the yeast cell is achieved by using a yeast promoter and the alpha-factor pheromone secretory leader. The sis proteins thus expressed and secreted are immunoreactive with anti-PDGF antisera and are mitogenic for cultured fibroblasts. Furthermore, they mediate this mitogenic activity by specific binding to the PDGF cell surface receptor. Gel electrophoresis and cell binding analysis indicates that the mitogenic species is primarily a disulphide-bonded dimer. We are able to conclude that p28sis is a mitogen and that a polypeptide corresponding to the B chain alone is sufficient to account for the mitogenic activity attributed to PDGF.

Animals↗
PubMed1985

Psychogenic colic in a horse.

A 4-year-old mixed-breed gelding was presented with colic-type behavior of 5 days' duration that included pawing, looking at the flank area, and kicking and biting at the abdomen and flank when it was eating hay or grain. Medical evaluation did not reveal the cause of the "colic." During its stay in the hospital, the horse improved as regarded the colic-type behavior while eating, but resumed this behavior when it was able to see hay that it was not allowed to eat. It was determined that the persistent colic-type behavior developed as a result of the horse having been repeatedly displaced from its food by other horses. When the horse performed the colic-type behavior, the owner would remain with it and effectively protect it from competitors. The initial bout of colic may have been a result of true colic, psychosomatic colic secondary to stress, redirected aggression, or displacement activity.

Animals↗
PubMed1985

Immunological studies in B6C3F1 mice following exposure to ethylene glycol monomethyl ether and its principal metabolite methoxyacetic acid.

Exposure to glycol ethers has been associated with adverse effects in laboratory animals including thymus atrophy and mild leukopenia. These effects may involve depletion of immunoresponsive cells. This study examined possible alterations in immune function and host resistance of B6C3F1 mice following exposure to ethylene glycol monomethyl ether (EGME) or its principal metabolite, methoxyacetic acid (MOAA). EGME and MOAA were administered by gavage to mice in 10 doses over a 2-week period at total dosages of 250, 500, and 1000 micrograms/g of body weight. Following exposure, immunopathology, humoral immunity, cell-mediated immunity, macrophage function, and host resistance to Listeria monocytogenes bacterial challenge were examined. A 48% reduction in thymus weight was observed at the intermediate and high doses of both chemicals. No significant alterations in immune function or host resistance to L. monocytogenes were observed in animals exposed to either EGME or MOAA.

Acetates↗
PubMed1985

Correlation of murine susceptibility to tumor, parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the tumor promoter phorbol myristate acetate.

Phorbol myristate acetate (PMA), the most potent of the tumor promoting phorbol diesters, modulates function in several immunoresponsive cells following in vitro exposure. Since suppression of cellular mechanisms capable of limiting tumors and infections can adversely affect health, these experiments were designed to evaluate relevant components of cell-mediated immunity (CMI) following in vivo PMA exposure, and to determine the biological significance of any alterations utilizing assays of host resistance. Adult, female B6C3F1 mice were administered 0.2, 2.0, 20.0 or 40.0 micrograms PMA/g body weight subcutaneously over a two-week period. Mechanisms of cell-mediated host resistance were assessed by quantitating natural killer (NK), cytotoxic T-lymphocyte (CTL) and macrophage-mediated lysis of radiolabelled tumor target cells, and macrophage-induced cytostasis in tumor cell populations. Macrophages from PMA-treated mice were cytostatic to tumor cells, inhibiting up to 90% of growth in cultured tumor cells, but were not tumoricidal. Furthermore, pyran-elicited (primed) macrophages, which are activated to fully cytotoxic states by in vitro exposure to lipopolysaccharide, were inhibited in tumoricidal activation by in vivo PMA exposure. The induction of responsive but not cytotoxic macrophages by in vivo PMA exposure is consistent with the enhanced resistance to Listeria bacterial challenge, and increased susceptibility to B16F10 tumor and Trichinella parasitic challenges observed in these mice. Furthermore, previous reports of decreased in vitro NK activity following in vivo PMA exposure and present observations of correlative decreases of in vivo NK activity (55% decrease in mice exposed to 20 micrograms PMA/g) suggest an important role for NK activity in limiting in vivo B16F10 melanoma growth. CTL effector function was less susceptible to PMA-induced suppression than NK function at similar dosages, further supporting a predominant role of macrophages and NK cells or possibly other effector functions in the resistance to Listeria, Trichinella, or B16F10 challenge. Nevertheless, significant suppressive effects of PMA on CTL function at higher dosages cannot be excluded as contributing to altered host resistance to these agents. These studies demonstrate that in vivo exposure to PMA can modify cell-mediated mechanisms of host resistance with coincident alterations in the incidence of infections and tumors.

Animals↗
PubMed1985

Mechanisms of dimethylbenzanthracene-induced immunotoxicity.

Traditional methods for toxicological assessment have implicated the immune system as a frequent target organ of toxic insult following chronic exposure to certain environmental chemicals, radiation or therapeutic drugs (xenobiotics). Immunotoxicity is expressed as autoimmunity, chemical hypersensitivity or immunosuppression. A tiered approach for characterizing chemical and drug-induced immunomodulation has been developed and validated in laboratory animals. Polycyclic aromatic hydrocarbons (PAH) have been studied because of their ubiquitous presence in the environment and carcinogenic potential. Since immunosuppression induced by PAH carcinogens has been implicated as an epigenetic mechanism in the outgrowth of initiated cells, this tiered approach was used to characterize the mechanism of PAH immunosuppressive capacity. Previously, studies in this laboratory have demonstrated that subchronic exposure of B6C3F1 mice to PAH carcinogens suppresses both humoral immunity (HI) and cell-mediated immunity (CMI), concurrently with decreased resistance to tumor challenge. The potent carcinogenic PAH, 7,12-dimethylbenz[a]anthracene (DMBA) was subchronically administered subcutaneously at 5, 50, or 100 micrograms/g of body weight. Natural killer (NK) cell tumor cytolysis, generation of cytotoxic T-cells (CTL), and lymphoproliferation to mitogens and allogeneic splenocytes in mixed leukocyte cultures (MLC) were quantitated 3-5 days after exposure to assess CMI. Mitogen and alloantigen-induced proliferation (MLC) of splenocytes was suppressed up to 90%. CTL and NK tumor cytolysis of radiolabelled target cells were similarly depressed up to 88 and 82%, respectively. Impairment of MLC or CTL responses correlated with increased susceptibility to challenge with PYB6 sarcoma cells. HI was measured by quantitating the number of antibody (IgM) plaque-forming cells (PFC) produced in response to T-cell dependent antigen challenge (sheep erythrocytes) and was similarly suppressed up to 95%. To understand the mechanism of PAH-induced immunotoxicity, splenocytes from DMBA-exposed mice were sensitized to alloantigens in the presence of interleukin-2 (IL-2) because there were indications that T-helper cell function was suppressed. In these preliminary studies, CTL suppression could be completely restored by the addition of the T-cell growth supporting lymphokine (IL-2) during the inductive phase of CTL generation, suggesting that DMBA exposure directly or indirectly induced deficits in T-helper cell function.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice. I. Effects on humoral immunity and host resistance.

It has previously been demonstrated that the polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (B[a]P), suppresses the terminal step in B-cell differentiation, resulting in a decrease in antibody production to T-dependent and B-2 T-independent antigens. The purpose of this study was to ascertain if this effect was common to carcinogenic PAHs or specific for B[a]P. The PAH 7,12-dimethylbenz[a]anthracene (DMBA) was administered to B6C3F1 female mice by ten sc injections of 0.5, 5, or 10 micrograms/g over a 2-week period (i.e., total dose of 5, 50, and 100 micrograms/g). Immune function and host resistance assays were performed 3 to 5 days following the last injection. The 10 micrograms/g dosage resulted in a marked decrease in spleen weights and spleen and bone marrow cellularity, while thymus and body weights were not significantly altered. The ability to generate B-lymphocyte colonies in vitro from spleen precursor cells was also suppressed at the 10 micrograms/g dose. Exposure to DMBA at 5 micrograms/g or greater resulted in a reduction of up to 97% in the number of IgM plaque-forming cells in response to the T-dependent antigen sheep red blood cells (SRBC). The IgG response to SRBC was similarly depressed. The IgM response to the hapten-conjugated T-independent antigens trinitrophenyl-lipopolysaccharide (TNP-LPS) (specific for B-1 cells) and trinitrophenyl (TNP)-Ficoll (specific for B-2 cells) was also depressed (88 and 97%, respectively) at 10 micrograms/g. DMBA exposure resulted in an increased susceptibility to challenge with the PYB6 transplantable sarcoma and the bacterium Listeria monocytogenes, in contrast to B[a]P exposure, which had no effect on host resistance assays. Thus, DMBA, a more potent carcinogen than B[a]P, produces a more extensive B-cell suppression than B[a]P as well as alters host resistance to tumor and bacterial challenge.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Studies of immune function and host resistance in B6C3F1 mice exposed to formaldehyde.

A series of immune function and host resistance parameters were examined in female B6C3F1 mice following a 21-day (6 hr/day) inhalation exposure to 15 ppm of formaldehyde (HCHO). Immune parameters examined included delayed hypersensitivity to keyhole limpet hemocyanin, antibody plaque-forming cell response to sheep erythrocytes (T-lymphocyte-dependent antigen) and TNP-Ficoll (T-lymphocyte-independent antigen), lymphoid organ weights and histopathology, routine hematology, bone marrow cellularity and CFU progenitor cell enumeration, lymphocyte subpopulation quantitation by cell surface markers, mitogen-induced lymphocyte blastogenesis, macrophage function parameters, and host resistance to challenge with the bacterium Listeria monocytogenes and transplantable tumor cells. Lymphoid organ weight, bone marrow cellularity, and hematology parameters were unchanged in HCHO exposed mice. Similarly, the percentage of T and B lymphocytes and their proliferative responses to mitogens were not significantly altered. Antibody (IgM) plaque-forming cell response following antigen challenge was unchanged. Macrophage function was normal although some evidence of enhanced H2O2 production associated with elevated bactericidal activity was observed in resident macrophages. Resistance to challenge with the bacteria Listeria monocytogenes was significantly enhanced, while resistance to tumor challenge remained unchanged. No evidence of immunosuppression following short-term exposure to HCHO was observed.

Animals↗
PubMed1984

Physiologic correlates of the ERG hyperventilatory response in dogs.

Previous studies in man have shown that hyperventilation consistently enhances the amplitude of the electroretinogram (ERG) b-wave, but has little effect on the a-wave. The present study examined this phenomenon in the dog; central (centrifugal) and peripheral (sympathetic) neural effects and changes in arterial pO2 and blood pH were excluded as physiologic bases for the phenomenon. It was concluded, therefore, that the underlying mechanism must be decreased pCO2 (hypocapnia), although the specific site of action and the method by which the ERG b-wave is enhanced remain topics for future research.

Adrenergic beta-Antagonists↗