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Biomedical subjects

T W Jones

Publications and source records attributed to T W Jones.

At least 55 records · Page 3Linked to original sources
PubMed1994

Factors affecting the mortality of lambs in transit to or in lairage at a slaughterhouse, and reasons for carcase condemnations.

The computerised records of all the lambs slaughtered at one plant from August 1991 to July 1992 were used to determine the mortality rate throughout the year and to examine the variables that could have been associated with changes in the mortality rate. The plant processed 3.3 per cent of all the lambs that were slaughtered in the United Kingdom during the period. Lambs arriving for slaughter from a livestock auction were over four times more likely to die in lairage, or to have died during transport, than lambs which were sent directly from the farm. However, the overall mortality rate was only 0.0182 per cent and lower than that for other species for which figures were available. Changes in the mortality rate of the lambs from livestock auctions appeared to be associated with the price of slaughter lambs, and periods of increased mortality coincided with increased rates of carcase condemnations due to 'arthritis', 'abscess' and 'pleurisy'.

Abattoirs↗
PubMed1994

Early cellular events couple covalent binding of reactive metabolites to cell killing by nephrotoxic cysteine conjugates.

Addition of the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), to the LLC-PK1 line of renal epithelial cells leads to covalent binding of reactive intermediates followed by thiol depletion, lipid peroxidation, and cell death (Chen et al., 1990, J. Biol. Chem., 265:21603-21611). The present study was designed to determine if increased intracellular free calcium might play a role in this pathway of DCVC-induced toxicity by comparing the temporal relationships among increased intracellular free calcium, lipid peroxidation, and cytotoxicity. Intracellular free calcium increased 1 hr after DCVC treatment, long before LDH release occurred. The elevation of intracellular free calcium and cytotoxicity was prevented by inhibiting DCVC metabolism with AOA. The cell-permeable chelators, Quin-2AM and EGTA-AM, prevented the toxicity. Pretreatment of cells with a nontoxic concentration of ionomycin increased intracellular free calcium and potentiated DCVC-induced LDH release. However, the antioxidant, DPPD, which blocks lipid peroxidation and toxicity, did not affect the increase in intracellular free calcium, whereas buffering intracellular calcium with Quin-2AM or EGTA-AM blocked both lipid peroxidation and toxicity without preventing the depletion of nonprotein sulfhydryls by DCVC. Ruthenium red, an inhibitor of mitochondrial calcium uptake, also blocked cell death. We hypothesize that covalent binding of the reactive fragment from DCVC metabolism leads to deregulation of intracellular calcium homeostasis and elevation of intracellular free calcium. Increased intracellular free calcium may in turn be coupled to mitochondrial damage and the accumulation of endogenous oxidants which cause lipid peroxidation and cell death.

Aminooxyacetic Acid↗
PubMed1994

Early morphological and biochemical changes during 2-Br-(diglutathion-S-yl)hydroquinone-induced nephrotoxicity.

Early subcellular targets of 2-Br-(diglutathion-S-yl)hydroquinone (2-Br-(diGSyl)HQ)-mediated nephrotoxicity were investigated by morphological and biochemical criteria. After treatment of male Fischer 344 rats with 2-Br-(diGSyl)HQ (30 mumol/kg), proximal tubular morphology was examined by electron microscopy. Changes in the plasma membrane, nuclei, and endoplasmic reticulum were observed within 30 min of 2-Br-(diGSyl)HQ administration. These changes consisted of loss of the brush border membrane, margination of heterochromatin, and reorganization of the endoplasmic reticulum into discrete aggregates. The desquamation of the brush border membrane into the tubular lumen corresponded with the rapid excretion of gamma-glutamyl transpeptidase and alkaline phosphatase in urine. As the injury developed, cell swelling with loss of cytosolic density and loss of chromatin staining was observed, and between 2 and 4 hr the nuclei underwent extensive karyorrhexis and karyolysis. Agarose gel electrophoresis of DNA isolated from the corticomedullary junction at 4 hr exhibited extensive fragmentation, which was random in nature. Mitochondria assumed a condensed configuration 2 hr after 2-Br-(diGSyl)HQ administration, but this was not followed by high-amplitude swelling prior to cell death and necrosis. Biochemical assessment of mitochondria, isolated from 2-Br-(diGSyl)HQ-treated rats at 2 hr, exhibited a significant (20%) decrease in respiratory control ratios (RCR), a consequence of an increase in State 4 respiration. At later time points (8 hr) State 4 respiration returned to control values, but the respiratory control ratio (RCR) remained significantly depressed due to decreases in State 3 respiration. At this time blood urea nitrogen concentrations were significantly elevated (41 +/- 3, mean +/- SD, n = 10). The data suggest that the plasma membrane and the nucleus are early targets of 2-Br-(diGSyl)HQ-induced cytotoxicity, and that alterations in mitochondrial structure and respiratory function occur following the initial injury.

Alkaline Phosphatase↗
PubMed1994

Efficacy of Cymelarsan in Friesian Holstein calves infected with Trypanosoma evansi.

Two studies on the efficacy of mel Cy (Cymelarsan, Rhone Merieux, France) for the treatment of cattle infected with Trypanosoma evansi were carried out with groups of 5 Friesian Holstein calves infected with an Indonesian stock of T. evansi and treated 14 days after infection. In the first study 3 groups were injected subcutaneously with Cymelarsan at dose rates of 0.125, 0.25 and 0.50 mg/kg and in the second study 2 i/m at 0.50 and 0.75 mg/kg. The response to treatment was monitored parasitologically by daily microhaematocrit centrifugation technique and weekly mouse inoculation. Enzyme linked immunosorbent assays were used to monitor trypanosomal antibodies and trypanosomal antigens in serum samples collected weekly. Relapse infections occurred in all the groups given the drug s/c whilst all the animals treated i/m remained parasitologically negative up to 80 days after treatment. Results from serological assays, however, suggested the possible persistence of trypanosome infection in the animals treated at a dose rate of 0.50 mg/kg i/m although trypanosomes could not be demonstrated parasitologically. A dose rate of 0.75 mg/kg administered i/m is recommended, therefore, for the treatment of T. evansi infection in Friesian Holstein cattle.

Animals↗
PubMed1994

Protection conferred by Trypanosoma evansi infection against homologous and heterologous trypanosome challenge in rabbits.

The response of rabbits, infected with Trypanosoma evansi, to challenge with homologous and heterologous trypanosome species was investigated. Protection against homologous challenge was complete with partial protection observed against heterologous T. evansi and Trypanosoma brucei challenge. No protection was seen against challenges with Trypanosoma vivax or Trypanosoma congolense. The recognition of the surface components of the parasite by the host antibodies was closely linked with complete protection. However, the degree of antigenic relatedness between infection and challenge parasite populations and the magnitude of antibody response to several non-surface components of the parasites appeared to influence the outcome of the challenge infections. Non-antibody dependent factors also appeared to influence the host response to challenge.

Animals↗
PubMed1994

Fludrocortisone induced heart failure in Addison's disease.

The first reported case of congestive cardiac failure in a child with Addison's disease secondary to fludrocortisone therapy is presented. A renal adaptation to compensate for chronic salt and water deprivation is suggested as a possible mechanism for the development of congestive cardiac failure in this patient.

Addison Disease↗
PubMed1993

Effect of complement (C3) depletion on the generation of memory in rabbits primed with antigens of Trypanosoma evansi.

Using the antibody response during secondary exposure of rabbits primed with antigens of Trypanosoma evansi as an indirect measure of immunological memory, it was shown that C3 decomplementaemia resulted in a reduced antibody response, with IgM being predominant in the sera samples followed by IgG and then IgA [corrected]. While significant differences were observed in the levels of IgG produced by the C3-depleted and C3-intact rabbits no differences were recorded in the levels of IgM and IgA produced by the two groups after C3 decomplementaemia. These results demonstrate that C3 depletion did not abolish memory of the T. evansi antigen in these rabbits but only modified the magnitude and pattern of their response. The host response to reinfection may be affected by such changes as those observed in this study.

Animals↗
PubMed1993

The effect of Trypanosoma evansi infection on the oestrous cycle of Friesian Holstein heifers.

The effect of Trypanosoma evansi infection on oestrous cycling was studied in 12 Friesian Holstein heifers. In the Phase 1 of the investigation, six heifers were infected with T. evansi, the remaining six acted as uninfected controls. Daily body temperature, packed red cell volume (PCV) and parasitaemia measurements were obtained from each animal for 90 days. The animals were examined for external signs of oestrous activity twice daily, blood samples were taken three times a week and subjected to an enzyme-linked immunosorbent assay to detect plasma progesterone. Body weights were measured weekly. Parasites were eliminated by trypanocidal drug treatment 90 days after infection. In Phase 2 of the trial, the uninfected heifers were injected with a different stock of parasites and monitoring was continued as before. Infection with T. evansi resulted in a marked reduction in the rate of weight gain, an increase in body temperatures and a fall in PCV values. Eleven of the heifers continued to cycle normally for the duration of the study, irrespective of their infective status. One animal which stopped cycling lost 16.2% of its pre-infection body weight as a result of the infection and cessation of oestrous activity was considered to have been due to weight loss.

Animals↗
PubMed1993

Early events following challenge of rabbits with Trypanosoma evansi and T. evansi components.

The intradermal injection of Trypanosoma evansi or T. evansi components into rabbits evoked trypanosome-specific responses in the skin. The strongest responses, which were those against the parasite surface-associated components, had the characteristics of an immediate type hypersensitivity reaction, followed by a delayed type. The responses were greater in rabbits from which infections had been cleared by chemotherapy than in animals with patient infections. These findings suggest that variant surface glycoprotein (VSG)-specific antibody activity and immunosuppression are effective in the skin and influence the outcome of infection with T. evansi in previously infected animals.

Animals↗
PubMed1993

Pathways of complement (C3) activation in rabbits infected with Trypanosoma evansi.

Immunoelectrophoresis was used to evaluate the pathways of complement (C3) activation with sera from rabbits infected with Trypanosoma evansi. C3 activation via the classical pathway was of a higher magnitude than via the alternative pathway using both the intact parasite and soluble parasite antigens. This observation indicates that although the two pathways may be activated during infection, the activation of the classical pathway may be dominant in a host's response to a T. evansi infection during both the early and late stages of the disease.

Animals↗
PubMed1993

Correction of hyperinsulinemia by glyburide treatment in nondiabetic patients with thalassemia major.

Hyperinsulinemia and insulin resistance precede the development of diabetes in patients with thalassemia major on hypertransfusion/desferoxamine therapy. To examine whether these early metabolic defects could be reversed, seven nondiabetic patients with thalassemia (17 +/- 4 y) were studied for 12 mo before and during 12 mo of low-dose treatment with glyburide (1.25 to 3.75 mg/d), a second-generation oral hypoglycemic agent. Plasma glucose responses to oral glucose (1.75 g/kg body weight) were normal before and after glyburide. Plasma insulin responses were markedly increased before glyburide therapy (area under insulin response curve 86 +/- 15 and 96 +/- 15 versus 40 +/- 5 nmol/min/L in normal controls, p < 0.001). However, insulin responses to glucose fell significantly after 3 mo of glyburide (to 52 +/- 7 nmol/min/L, p < 0.05 versus pretreatment) and were normalized after 12 mo (42 +/- 7 nmol/min/L, p = NS versus controls). The rate of insulin-stimulated glucose metabolism during euglycemic insulin clamps (40 mU/m2/min) was low in the patients before treatment (163 +/- 10 versus 215 +/- 17 mg/m2/min in controls, p < 0.05) and increased to 205 +/- 30 mg/m2/min after 3 mo of glyburide. The treatment was well tolerated. In conclusion, in nondiabetic, hyperinsulinemic, thalassemic patients, chronic glyburide therapy normalizes insulin responses to oral glucose. To the extent that insulin hypersecretion contributes to the development of diabetes in thalassemia, glyburide therapy may provide a means of postponing this complication of the disease.

Adolescent↗
PubMed1993

Antibodies to glutamic acid decarboxylase in Australian children with insulin-dependent diabetes mellitus and their first-degree relatives.

Antibodies to glutamic acid decarboxylase (GAD), previously known as the 64-kD pancreatic islet cell autoantigen, are an important serologic marker of insulin-dependent diabetes mellitus (IDDM). Antibodies to GAD (anti-GAD) were examined in sera from Australian children with newly diagnosed IDDM (within 1 mo of diagnosis), IDDM of longer duration (mean +/- SD, 4.8 +/- 3.3 y), and in first-degree relatives, using a radioimmuno-precipitation assay with purified porcine brain GAD as antigen. Antibodies to islet cell cytoplasmic antigens (ICAb) were tested concurrently. The frequency of anti-GAD was not significantly different in children with newly diagnosed IDDM (31 of 42, 74%) and with IDDM of longer duration (14 of 21, 67%), whereas ICAb were present more frequently in children with newly diagnosed IDDM (64%) than in those with longer duration IDDM (14%). In all, 90% of children with newly diagnosed IDDM had either anti-GAD or ICAb, whereas only 48% had both. For the 77 first-degree relatives, the frequency of anti-GAD was 2% (one of 44) in parents and 6% (two of 33) in siblings; ICAb were not detected in any of these relatives. The presence of anti-GAD in the majority of children with IDDM, irrespective of the duration of their disease, represents a useful diagnostic marker for IDDM, and should be of value in ascertaining individuals at risk for developing IDDM.

Adolescent↗
PubMed1993

Class-specific antibody response in rabbits experimentally infected with Trypanosoma evansi.

The antibody response to Trypanosoma evansi antigens in rabbits experimentally infected with T. evansi was monitored by SDS-PAGE and "Western" blotting. As defined by the number of antigenic components recognised and the intensity with which they were labelled, responses were predominantly IgG, followed by IgM and IgA. During infection and subsequent drug treatment seven major antigenic components (94, 85, 75.5, 67, 60.5, 43, and 28.6 kDa) were identified by IgG. Antibodies to a 32.4 kDa and three other components (30, 28.6 and 12.5 kDa) appeared during infection and after chemotherapy respectively. Three components (94, 67 and 60.5 kDa) recognised by IgG were also detected by IgM and IgA. Furthermore, two bands (30 and 12.5 kDa) were identified by IgM and one (12.5 kDa) by IgA only after drug treatment, while a 28.6 kDa component was recognised by IgM and IgA during the same period. These findings constitute a basis for the exploration of class-specific antibody responses to T. evansi antigens with relevance to diagnosis, protection and pathology.

Animals↗
PubMed1992

Antibody patterns in rabbits showing different levels of susceptibility to an experimental Trypanosoma evansi infection.

Using SDS-PAGE and Western blotting, the antibody spectrum of rabbits infected with Trypanosoma evansi to homologous T. evansi antigens was monitored. Animals that developed parasitaemia later or had lower levels of parasitaemia as the infection progressed were considered to have a degree of resistance to the infection. Sera of these resistant animals recognised the T. evansi antigens earlier and subsequently identified more antigens than their susceptible counterparts. The susceptible animals developed patent parasitaemia earlier and had higher parasite counts as the infection progressed, and their sera recognised T. evansi antigens later with fewer parasite components labelled during the course of the infection. These observations demonstrate clear differences between animals in response to T. evansi infections. Selection of T. evansi-tolerant animals on an individual basis may be possible as has been suggested for other trypanosome species.

Animals↗
PubMed1992

Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus.

Intensive insulin therapy directed at elimination of hyperglycemia is advocated during pregnancy in women with insulin-dependent diabetes mellitus. Because such treatment is complicated by frequent hypoglycemic episodes, we evaluated maternal and fetal responses in nine intensively treated pregnant women with insulin-dependent diabetes mellitus during an insulin-induced, gradual, controlled fall in plasma glucose levels. In contrast to values in nonpregnant control women, reductions in glucose to 44 +/- 2 mg/dl in pregnant diabetic patients failed to elicit an increase in glucagon levels. Epinephrine release during hypoglycemia was also markedly suppressed in the pregnant diabetic subjects (106 +/- 32 vs 327 +/- 52 pg/ml in controls, p less than 0.001). Furthermore, the plasma glucose level at which epinephrine and growth hormone were released was 5 to 10 mg/dl lower in the pregnant women with insulin-dependent diabetes mellitus (p less than 0.05). The basal fetal heart rate remained unchanged and continued to manifest accelerations during the hypoglycemic state. We conclude that the high frequency of hypoglycemia in intensively treated pregnant women with insulin-dependent diabetes mellitus may be due in part to impaired counterregulatory hormonal responses.

Adult↗
PubMed1992

Pathology of experimental Trypanosoma evansi infection in rabbits.

Histopathological examination of tissue sections from the organs of rabbits experimentally infected with Trypanosoma evansi revealed evidence of a vigorous immunological response. Changes in the spleen, lymph nodes, vulva, eyelids and ears indicated a protective immune response, but changes in the kidneys, lungs and heart were destructive in nature and capable of causing sudden death of the host. Hepatic damage capable of interfering with the host's immune response was also observed. The presence of many parasites in the vulval tissue calls for further investigation into the possibility of sexual transmission of T. evansi.

Animals↗