Biomedical subjects
P Timms
Publications and source records attributed to P Timms.
Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency.
Developmental retardation was a prominent clinical feature in six infants from three kindreds deficient in the enzyme purine nucleoside phosphorylase (PNP) and was present before development of T cell immunodeficiency. Guanosine triphosphate (GTP) depletion was noted in the erythrocytes of all surviving homozygotes and was of equivalent magnitude to that found in the Lesch-Nyhan syndrome (complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency). The similarity between the neurological complications in both disorders indicates that the two major clinical consequences of complete PNP deficiency have differing aetiologies: neurological effects resulting from deficiency of the PNP enzyme products, which are the substrates for HGPRT, leading to functional deficiency of this enzyme. immunodeficiency caused by accumulation of the PNP enzyme substrates, one of which, deoxyguanosine, is toxic to T cells. These studies show the need to consider PNP deficiency (suggested by the finding of hypouricaemia) in patients with neurological dysfunction, as well as in T cell immunodeficiency. They suggest an important role for GTP in normal central nervous system function.
Erythrocyte GTP depletion in PNP deficiency presenting with haemolytic anaemia and hypouricaemia.
Explore the source record for details and available documents.
Severe hypocalcemia and increased creatine kinase activity.
Explore the source record for details and available documents.
Lead poisoning and euthyroid hyperthyroxinaemia.
Explore the source record for details and available documents.
Hypokalaemia presenting with leg pain in Bartter's syndrome.
Explore the source record for details and available documents.
DNA polymorphisms and subpopulations in Babesia bovis.
Independent isolates of Babesia bovis differ by only a limited number of polypeptides, some of which may be important as host protective antigens. Avirulent derivatives of these parasites also differ from their virulent counterparts in only a few polypeptides. To identify genes encoding such polypeptides we have isolated cDNA clones corresponding to poly(A)+ RNAs that are expressed only in certain isolates. For this purpose a cDNA clone library was constructed from poly(A)+ RNA of the K-avirulent isolate (KA). These clones were screened by colony hybridization using [32P]cDNA complementary to poly(A)+ RNA from KA and from virulent isolates, in order to identify clones that selectively hybridize to one cDNA probe. Hybridization of DNA from three clones, designated pK4, pK5 and pK6 to poly(A)+ RNA from various isolates revealed different and complex patterns. The gene represented by clone pK5 appeared to be transcribed predominantly in avirulent parasites. Analysis of genomic DNA by the Southern procedure enabled each isolate to be distinguished and suggested that most isolates are comprised of a heterogeneous mixture of subpopulations. Analysis of genomic DNA from parasites obtained after passage of KA through the tick vector (Boophilus microplus) suggested that a subpopulation was being selected that more closely resembled KV than KA.
Immune responses of cattle following vaccination with living and non-living Babesia bovis antigens.
Twenty-four yearling Hereford (Bos taurus) cattle were vaccinated against Babesia bovis using either live parasites or non-living antigens obtained from the supernatant of in vitro cultures. A single dose of live parasites was given subcutaneously, while the non-living supernatant antigen (NLSA) was combined with saponin and 2 doses given, 2 weeks apart. Following vaccination with live parasites, serum antibodies remained at high levels for 6 months, but the lymphocyte transformation response was low and lasted only 10-18 days. In contrast, NLSA vaccination was followed, after 21-28 days, by a peak of serum antibodies which then slowly declined. The lymphocyte transformation response in these animals was much higher and persisted for 6 months. Following heterologous challenge all unvaccinated cattle had severe reactions and required treatment to prevent death. Cattle vaccinated with live parasites had mild reactions with only 1 of the 12 requiring treatment. Cattle vaccinated with NLSA were only partially protected and 6 of the 12 required treatment.
Reduction of fensulfothion and accumulation of the product, fensulfothion sulfide, by selected microbes.
Explore the source record for details and available documents.
Babesia bovis: proteins of virulent and avirulent parasites passaged through ticks and splenectomized or intact calves.
Passage of the avirulent vaccine (K) strain of Babesia bovis (KA) through either Boophilus microplus ticks, intact calves, or intact calves and then ticks, resulted in two distinct protein and protein antigen profiles as analyzed by two-dimensional gel electrophoresis of biosynthetically labeled proteins and immunoprecipitates. Different degrees of expression of two major acidic antigens of KA designated Ka1 (Mr 47,500) and Ka2 (Mr 43,000) were observed. Ka1 was apparently lost following passage of KA B. bovis through intact calves but was strongly represented in the parasite population following a single tick passage. In contrast, passage through ticks of the virulent KV B. bovis (from which KA was derived by passage in splenectomized calves) did not lead to strong representation of the Ka1 protein although there was increased representation of another major acidic protein antigen, designated KV (Mr 35,000). These data suggest that the previously recognized reversion to a strain-dependent basal antigenic type in the tick vector depends also on intrastrain characteristics such as virulence and strain heterogeneity. The data suggest that KA is a more heterogeneous population than KV although cloned isolates are required to establish this point. Comparable syringe passage of another strain of B. bovis, designated C strain, through splenectomized calves resulted in less marked differences between the putative CA and CV B. bovis. This may explain the less stable avirulence of CA compared to KA B. bovis. Various selection pressures must act, in either the tick or the vertebrate host, on subpopulations in heterogeneous isolates to produce the changes described in protein antigen profiles of B. bovis. The possible relevance of changes in representation of proteins to biological characteristics of B. bovis (such as virulence and tick transmissibility) is discussed.
Babesia bovis: comparison of culture-derived parasites, non-living antigen and conventional vaccine in the protection of cattle against heterologous challenge.
Twenty Bos taurus cattle were vaccinated with either live commercial Babesia bovis vaccine, live parasites from in vitro culture or non-living supernatant antigen (NLSA) derived from in vitro culture and combined with the adjuvant saponin. Heterologous strain challenge 10 weeks later indicated that cattle vaccinated with live parasites from either source were strongly protected, those given 2 doses of NLSA 2 weeks apart were partially protected, and those given one dose of NLSA were poorly protected. Enzyme immunoassay detected comparable, increasing levels of specific babesial antibody in all vaccinated cattle during the 2 to 3 weeks following vaccination, after which levels in cattle given NLSA decreased. Antibody to bovine blood group factors was detected in 4 of the 10 animals given NLSA. Titres peaked after 3 to 4 weeks and then declined rapidly.
Comparison of tick and blood challenge for assessing immunity to Babesia bovis.
Explore the source record for details and available documents.
Development of a Babesia rodhaini mouse assay for quality control of the serum component of a bovine babesiosis vaccine.
The rodent babesia, Babesia rodhaini, survived equally well in basal medium containing either 10 per cent rat serum or 10 per cent bovine serum. As a result, a B rodhaini mouse assay is now performed routinely to determine the suitability of batches of bovine serum for use in a commercial Babesia bovis vaccine issued in Australia. Heat inactivation of bovine serum at 56 degrees C for two hours did not affect the survival of either B bovis or B rodhaini.
Conversion of fensulfothion by Klebsiella pneumoniae to fensulfothion sulfide and its accumulation.
In a detailed study it was shown that washed cell suspensions of K. pneumoniae reduced the organophosphorus pesticide fensulfothion to fensulfothion sulfide. Temperature and pH optima for this conversion plus sensitivity to sulfhydryl-reacting agents strongly suggested enzyme involvement. The reaction was also quite sensitive to molecular oxygen, only proceeding under conditions of low oxygen tension. Once formed, the fensulfothion sulfide was rapidly bound by living and heat-killed cells. A combination of lysozyme treatment and differential centrifugation showed 90% of the sulfide to be concentrated in the cell membrane fraction of exposed cells.
A microplate enzyme immunoassay for detecting and measuring antibodies to Babesia bovis in cattle serum.
A microplate enzyme immunoassay (EIA) is described for measuring IgG antibody to Babesia bovis in cattle serum. B. Bovis antibody status (whether positive or negative) and the amount of B. Bovis antibody (EIA score), were measured by comparison with reference serums. The EIA was shown to be specific for B. Bovis, and EIA score correlated well with EIA titre. Comparison of EIA with the Indirect Fluorescent Antibody Test (IFAT) showed more than 95% agreement between the methods and disagreement in only 1.6% of serum samples tested. The remaining 3.2% were positive by EIA and suspected positive by IFAT. The EIA was shown, by titrating positive serums, to be more sensitive than IFAT, which explained its tendency to detect more positive serums than IFAT. EIA detected B. bovis antibody in experimentally infected cattle by day 14 post infection (pi) and for at least 268 days pi. EIA score for B. bovis antibody in immune cattle increased significantly (p less than 0.05) following heterologous strain challenge.
Thryo-endocrine pathology, obstetric morbidity and schizophrenia: survey of a hundred families with a schizophrenic proband.
This preliminary communication reports that the mothers of 104 schizophrenic patients had: (1) a significantly higher incidence of thyroid disease than a carefully matched control group; (2) significantly more abortions, still-births and greater infant mortality. The findings and possible relevance of thyroid disease to schizophrenia are discussed. Three prospective studies currently in progress are outlined.