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Biomedical subjects

J R Murphy

Publications and source records attributed to J R Murphy.

At least 235 records · Page 13Linked to original sources
PubMed1981

Host defenses in murine malaria: analysis of plasmodial infection-caused defects in macrophage microbicidal capacities.

Macrophage-dependent killing of facultative intracellular bacteria was markedly impaired by overt erythrocytic Plasmodium yoelii or Plasmodium berghei infection of mice. P. yoelii infection was capable of ablating not only the macrophage microbicidal capacity of "normal" animals but also the bactericidal capacities of "activated" macrophages. The uptake by spleen and liver of an intravenous challenge of Listeria monocytogenes was not altered by plasmodial infection, but within hours of injection markedly enhanced bacterial growth was found in tissues of malarious mice. The evidence gives credence to the view that the uptake of bacteria by macrophages of malarious mice was normal but that malarious mice, unlike normal mice, were unable to kill the bacteria. The plasmodial infection-caused defect in macrophage microbicidal capacity could be partially mimicked by the intravenous injection of large numbers of nonreplicating heterologous particles (i.e., killed bacteria, sheep erythrocytes). This result suggests that the uptake of particles generated during overt erythrocytic malaria may be responsible for the malaria-associated defects in macrophage bactericidal capacity.

Animals↗
PubMed1981

Host defenses in murine malaria: nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation.

Infection with Mycobacterium bovis (BCG) or injection of killed Corynebacterium parvum protected some strain B6D2 F1 (C57BL/6xDBA/2) mice but did not protect strain ICR or A mice from lethal challenge with Plasmodium berghei strain NYU-2. B6D2 mice were not protected against challenges delivered immediately after intravenous injection of these materials, but rather protection developed by day 7 and persisted through at least day 84. Infections in protected mice progressed to about 10% parasitemia in parallel with infections initiated with the same inoculum in untreated controls. However, infections in most of the protected mice were cleared subsequently, whereas infections in untreated controls were uniformly fatal. A small number of treated mice developed protracted high-level erythrocytic infections, which led to markedly delayed death. BCG-infected mice which survived P. berghei infections had a factor in their sera which protected passively immunized recipients from P. berghei. BCG-infected mice passively immunized with protective serum controlled P. berghei infections better than normal mice given the same amount of the same serum and challenged with the same P. berghei inoculum. The capacity of BCG-infected B6D2 mice to resist P. berghei infection was not directly related to the pattern of growth of BCG, to the degree of splenomegaly, or to the level of activation of macrophages (measured as microbicidal capacity) caused by BCG infection. Therefore, I concluded that (i) BCG infection or injection of killed C. parvum altered the immunological potential of B6D2 mice in such a way as to allow the production of measurable levels of a protective humoral factor in response to infection with P. berghei; (ii) BCG infection caused the generation of a capacity which, when expressed in the presence of immune serum, provided an anti-P. berghei capacity which was superior to that provided by BCG infection alone or immune serum in the absence of BCG infection; and (iii) not all strains of mice could be protected from P. berghei by BCG or C. parvum injection.

Animals↗
PubMed1981

Restriction map of corynebacteriophages beta c and beta vir and physical localization of the diphtheria tox operon.

The BamHI, EcoRI, HindIII, and KpnI restriction endonuclease maps of corynebacteriophage beta c and beta vir were constructed. beta vir appeared to be identical to beta c, except for an approximate 1-kilobase deletion that removed a BamHI site, two KpnI sites, and three EcoRI restriction sites. The diphtheria tox operon was located by hybridizing in vitro 32P-labeled tox messenger ribonucleic acid to blots of endonuclease-digested beta deoxyribonucleic acids. The messenger ribonucleic acid probe was found to hybridize to a 2.1-kilobase region of the beta genome. Since approximately 1.9 kilobases is required to encode prodiphtheria toxin, the data presented strongly suggest that the tox operon of beta is monocistronic.

Bacteriophages↗
PubMed1980

Toxicity of diphtheria toxin-related proteins produced by suppression of nonsense mutations.

The Mr = 62,000 diphtheria toxin-related proteins produced from the suppression of nonsense mutations within the tox gene of corynephage beta were purified by affinity chromatography. Except for the toxin 111-sup2-62, the Mr = 62,000 polypeptides were found to have the same specific toxicity as does wild type toxin. 111-sup2-62 was found to have a prolonged lag period prior to the onset of inhibition of protein synthesis and ADP-ribosylation of elongation factor 2. 111-sup2-62 differs from wild type toxin by an amino acid substitution at a site approximatley 47,000 daltons from the NH2 terminus. The data presented provide genetic support for the Boquet-Pappenheimer model (Boquet, P., and Pappenheimer, A. M. Jr (1978) J. Biol. Chem. 251, 5770-5778) of fragment A translocation into the eukaryotic cell cytosol.

Animals↗
PubMed1980

Specific disruption of vimentin filament organization in monkey kidney CV-1 cells by diphtheria toxin, exotoxin A, and cycloheximide.

We have examined the effect of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and cycloheximide on the CV-1 cell cytoskeleton. Within a few hours after producing an inhibition of cellular protein synthesis, all these agents specifically disrupted the organization of the vimentin filament system with no discernable effect on microtubules or microfilaments during the period of observation. Furthermore, just as the inhibition of protein synthesis by cycloheximide is reversible, so was the disruption of vimentin filaments by cycloheximide.

Animals↗
PubMed1980

Enterotoxigenic Escherichia coli carrying plasmids coding for antibiotic resistance and enterotoxin production.

Nine strains of enterotoxigenic Escherichia coli that were resistant to antibiotics were tested for their ability to transfer both antibiotic resistance and enterotoxigenicity to E. coli K12. All nine isolates transferred antibiotic resistance in bacterial conjugation experiments, and in seven of these matings enterotoxigenicity was also transferred. To determine whether the genetic information coding for the production of enterotoxin and antibiotic resistance was located on the same plasmid in these strains, phage P1 transduction experiments were performed. P1 lysates prepared from enterotoxigenic antibiotic-resistant transconjugants were tested for their ability to transduce both phenotypes. Only P1 lysates prepared from transconjugants of E. coli 719B5 (O18ab:H27) were found to transduce resistance to streptomycin, sulfisoxazole, and tetracycline, as well as the ability to produce heat-labile and heat-stable enterotoxin. The results of these experiments strongly suggest that the genetic data coding for antibiotic resistance and enterotoxin production in E. coli 719B5 are carried on the same plasmid replicon.

Drug Resistance, Microbial↗
PubMed1980

Biometrics in the medical school curriculum: making the necessary relevant.

Biometrics has been perceived by freshman medical students as a necessary but not immediately relevant part of their medical training. Because a student is more likely to learn and retain course content if he feels it is relevant, an attempt was made to change the students' perception of the biometrics course by introducing statistical methods as a means of solving some problems in the interpretation of clinical laboratory data. Retrospective analysis of student course evaluations over the last five years indicates that a significant change in student perception of the relevance of the course did occur.

Biometry↗
PubMed1980

Chronic obstructive pulmonary disease (COPD): effects of bronchodilator drugs on normal and affected horses.

The effects of the bronchodilator drugs, atropine, isoprenaline and terbutaline, on normal horses and on horses affected with chronic obstructive pulmonary disease (COPD), were assessed by pulmonary function tests and clinical examination. Normal horses were not affected but COPD horses responded by a marked decrease in intrathoracic pressure, a decrease in respiratory rate, an initial decrease followed by an increase in arterial oxygen partial pressure and clinical improvement after treatment with all 3 drugs. These changes were temporary.

Animals↗
PubMed1980

Host defenses in murine malaria: immunological characteristics of a protracted state of immunity to Plasmodium yoelii.

Random-bred ICR mice recovered from infection with avirulent Plasmodium yoelii were challenged at various later times with virulent P. yoelii or with another species of Plasmodium, P. berghei, to characterize the immunological nature of the long-term state of immunity generated in response to the avirulent infection. It was found that recovered mice resisted lethal challenge with virulent P. yoelii through at least 416 days after primary infection. However, the quality of this immunity changed as the time after avirulent infection increased. Mice challenged early after recovery were able to prevent the development of patent parasitemia. Later, these immune animals lost this capacity and after challenge infections progressed to patency at the same rate as did nonimmune controls. However, after the establishment of parasitemia, those animals which had encountered the homologous parasite a long time before controlled, and then eliminated, blood infection and survived. The "early" state of immunity was expressed by animals which may have harbored small numbers of viable avirulent parasites and possessed a protective humoral factor which could passively transfer anti-P. yoelii activity to naive recipients. In contrast, animals with "late" immunity showed evidence of neither persisting avirulent parasites nor serum anti-P. yoelii activity. The results support the proposition that immunity to this parasite exists as two distinct but interrelated states of immunological reactivity: an early "active" immunity and a later state which has characteristics suggestive of a state of immunological memory wherewith the animals were capable of anamnestically responding to P. yoelii challenge. Little evidence of heterologous immunity to P. berghei was observed for animals recovered from P. yoelii.

Animals↗
PubMed1980

Mechanisms of immunity in typhus infection: analysis of immunity to Rickettsia mooseri infection of guinea pigs.

To study the mechanisms of immunity to Rickettsia mooseri (R. typhi) infection, sera and splenic cells collected from nonimmune and immune guinea pigs were inoculated separately into syngeneic nonimmune recipients which were subsequently challenged intradermally. Protection was measured by comparing the course of the challenge infections of recipients with infections initiated with the same rickettsial inocula in nonimmune animals. Recipients of splenic cells collected 21 days after donor infection were protected from lesion development at sites of intradermal challenge and showed fewer rickettsiae in their kidneys. Cells obtained from nonimmune donors did not protect against either skin lesion development at sites of challenge or kidney infection. Antibody-containing sera collected 21 days after donor infection, but not normal sera, reduced levels of kidney infection, but immune sera did not protect against the development of lesions at sites of intradermal challenge. It was concluded that both immune sera and immune splenic cells possess capacities to effect a partial control of the systemic phase of R. mooseri infection in guinea pigs, but that immune splenic cells possess a capacity not shared by immune sera, i.e., the capacity to protect from infection at local sites of intradermal inoculation.

Animals↗
PubMed1980

Precursor in cotranslational secretion of diphtheria toxin.

By extracellular labeling of peptides of intact Corynebacterium diphtheriae, followed by fractionation of the cells and chain completion by isolated polysomes, it is shown that diphtheria toxin is formed and secreted cotranslationally by membrane-bound polysomes; free polysomes from none. Moreover, when the chains on these polysomes were completed in vitro, in the absence of membrane they were found to include not only diphtheria toxin of a molecular weight of 62,000, but also a larger precursor of a molecular weight of 68,000. The precursor was identified by several properties: immune precipitation; conversion into toxin fragments A and B; adenosine diphosphate ribosyl-transferase activity after activation with trypsin; and cleavage to 62,000 daltons by membrane enzymes. The precursor yields an N-terminal A fragment with a broadened molecular weight distribution, compared with that from authentic toxin, thus supporting the expectation that the extra segment of the precursor is N-terminal.

Adenosine Diphosphate Ribose↗
PubMed1980

Regulation of cholera toxin production in Vibrio cholerae: genetic analysis of phenotypic instability in hypertoxinogenic mutants.

Hypertoxinogenic mutants of Vibrio cholerae frequently possess mutations in a chromosomal locus called htx. Spontaneously occurring phenotypic revertants were shown to fall into three classes. One class retained the htx mutation and therefore represented a second-site mutation(s) capable of suppressing the Htx phenotype, whereas the other two classes represented strains that had lost the htx mutation. One of the latter two classes appeared to be composed of true genetic revertants, whereas the third class consisted of clones that had replaced htx with a new mutation conferring a hypotoxinogenic phenotype. Several rare N-methyl-N'-nitro-N-nitrosoguanidine-induced hypotoxinogenic mutants selected by rif comutation also map in the same region as htx. This new locus, which mediates the hypotoxinogenic phenotype in these trains and potentially in some hypertoxinogenic phenotypic revertants, has been designated ltx. htx and ltx appear to be regulatory loci, since mutations in both sites alter the level of cholera toxin A and B subunit production coordinately. The genetic data also support a model in which htx- and ltx- are allelic states of the same Tox regulatory locus.

Cholera Toxin↗
PubMed1980

Cholera toxin is synthesized in precursor form on free polysomes in Vibrio cholerae 569B.

Membrane-bound and free polysomes have been isolated from Vibrio cholerae 569B. Nacent polypeptide chains were completed in a cell-free translation mixture containing Escherichia coli S-300 extracts and [3H]leucine or [35S]methionine. Cholera toxin-related polypeptides synthesized in vitro were immunologically detected after treatment with either anti-subunit A or anti-subunit B serum. Immunoreactive translation products were removed from reaction mixtures with formalinized Cowan's strain of Staphylococcus aureus, electrophoresed on sodium dodecyl sulfate-polyacrylamide gels, and visualized by fluorography. Anti-subunit A serum precipitated two major polypeptide species (molecular weights 52,000 and 45,000) from translation mixtures programed with free polysomes, whereas anti-subunit B serum precipitated only the 45,000-molecular-weight polypeptide. No cholera toxin-related polypeptides were detectable in translation mixtures programed with membrane-bound polysomes. Purified subunit A and cholera toxin competed for anti-subunit A binding sites and blocked the immunoprecipitation of the 35S-labeled 52,000- and 45,000-dalton polypeptides from in vitro translation mixtures. The data presented suggest that cholera toxin is synthesized in the cytoplasm in a precursor form on free polysomes and is secreted post-translationally.

Cholera Toxin↗
PubMed1979

The effects of sodium cromoglycate on antigen inhalation challenge in two horses affected with chronic obstructive pulmonary disease (COPD).

80 mg sodium cromoglycate (SCG) was administered by inhalation to two COPD-affected animals known to have respiratory hypersensitivity to Micropolyspora faeni. SCG treatment 20-30 minutes prior to inhalation challenge with M. faeni prevented exacerbation of respiratory disease, usually seen 4-8 hours after challenge. duration of protection against antigen challenge after a single SCG treatment was 4-5 days. The duration of protection was not prolonged by reducing the frequency of antigen challenge. Multiple antigen challenge, using M. faeni and Aspergillus fumigatus, shortened the protective period of SCG to 3 days.

Administration, Inhalation↗
PubMed1979

Chronic obstructive pulmonary disease (COPD) in horses: aetiological studies: responses to intradermal and inhalation antigenic challenge.

Micropolyspora faeni and Aspergillus fumigatus were identified as common causes of respiratory hypersensitivity in horses affected with chronic obstructive pulmonary disease (COPD). Rye grass pollen and an Actinomycete evoked respiratory allergy in a few horses. Not infrequently, individual horses were found to have respiratory hypersensitivity to two or more antigens. The methods used to examine for allergy were intradermal testing and inhalation challenge with environmental antigens. An intradermal test using an M faeni extract was demonstrated to be suitable for diagnostic use in horses previously accurately diagnosed as suffering from COPD. In contrast, the A fumigatus antigen used proved unsatisfactory for such a purpose. Skin reaction to M faeni and A fumigatus extracts by horses affected with COPD indicated that the hypersensitivity was a dual one--a weak response shortly after injection followed by an Arthus-like response 4 to 8 hours later. As a parameter for monitoring responses to inhalation challenge, maximum intrathoracic pressure change (max delta Ppl) proved satisfactory, whereas changes in partial pressure of arterial oxygen (PaO2) did not.

Animals↗
PubMed1979

Chronic obstructive pulmonary disease (COPD): factors influencing the occurrence.

Breed, age, weight, type of work performed, seasonal onset, poor ventilation and exposure to moulds in the habitat were investigated in relation to the occurrence of chronic obstructive pulmonary disease (COPD). COPD was most commonly detected in showjumping and hacking horses. The older a horse, the more likely it was to become affected although most were 6 to 10 years of age. Of the horses in this sample of the population, which was not a random one, thoroughbred horses were affected least and ponies most often. The high incidence in ponies was related to their more frequent exposure to poor quality fodder and bedding. Most horses are exposed to the hazard of moulds, but more affected horses were so exposed than those not affected with COPD. Poor ventilation of the stable increased the chance of a horse becoming affected. Sex, body weight and season of onset of coughing had no influence on the occurrence of the disease.

Age Factors↗
PubMed1979

The presence of precipitating antibodies in the sera of horses with chronic obstructive pulmonary disease (COPD).

The sera of horses affected and not affected with chronic obstructive pulmonary disease (COPD) were examined for precipitins to Micropolyspora faeni and Aspergillus fumigatus. Precipitins to both antigens were not restricted to COPD cases but occurred more frequently in animals affected with COPD. Many animals without detectable precipitins responded clinically to inhalation challenge with these antigens.

Animals↗