Biomedical subjects

T W Jones

Publications and source records attributed to T W Jones.

At least 109 records · Page 6Linked to original sources

PubMed1987

Toxicity of S-pentachlorobutadienyl-L-cysteine studied with isolated rat renal cortical mitochondria.

The subcellular mechanism of alkenyl halide S-conjugate-induced nephrotoxicity was studied in mitochondria isolated from rat kidney cortex in vitro using the cysteine conjugate of hexachloro-1,3-butadiene, i.e., S-pentachlorobutadienyl-L-cysteine (PCBC) as a model substrate. Respiring mitochondria exposed to various concentrations of PCBC exhibited a dose-dependent loss of ability to retain calcium. This phenomenon was associated with a sudden collapse of the mitochondrial membrane potential. PCBC caused a slow nonenzymatic depletion of mitochondrial glutathione. This was not due to oxidation or formation of mixed disulfides, and was efficiently counteracted by preincubation with aminooxyacetic acid, an inhibitor of cysteine-conjugate beta-lyase activity. PCBC inhibited state 3 respiration in the presence of succinate as substrate, which indicates that the activity of succinate dehydrogenase was affected. Thus, the present data confirm that impairment of mitochondrial function is a feature of nephrotoxicity mediated by alkenyl halide S-conjugates. We suggest a pathway involving interaction of beta-lyase-dependent reactive metabolite with the mitochondrial inner membrane, loss of membrane potential, disturbance of Ca2+ homeostasis, and subsequent respiratory insufficiency as a mechanism for renal tubular cytotoxicity.

Aminooxyacetic Acid↗

PubMed1986

Cellular defense mechanisms against toxic substances.

Recent studies of cellular defense mechanisms against toxic substances are reviewed with particular emphasis on the critical functions of reduced glutathione. Studies of the metabolism of paracetamol and of the redox active quinone menadione in isolated rat hepatocytes, are summarized in order to illustrate how multiple defense mechanisms are involved in the protection of the cell against the toxicity of these agents. Cytotoxicity with both agents occurs only after the cellular defense mechanisms have become exhausted.

Animals↗

PubMed1986

Cryopreservation of Theileria-infected lymphoblastoid cells with functional assessment of viability.

Bovine lymphoblastoid cell cultures infected with Theileria annulata were frozen to -60 degrees C in a programmable cooling apparatus using continuous cooling rates of 1 degree C/min, 10 degrees C/min and 120 degrees C/min and a two-step cooling rate with an equilibration period of 20 min at -30 degrees C. The cryopreservative was DMSO at concentrations of 5, 10 and 15%. Aliquots of cryopreserved material were stored in the vapour phase of a liquid nitrogen refrigerator and resuscitated by rapid thawing in a 40 degrees C water bath. The efficiency of the freezing methods was compared by assessing the viability and plating efficiency of cells after resuscitation, dilution and equilibration in cell culture medium. A significant correlation was recorded between the results obtained by these two methods which showed that the two-step method yielded cells with viability of 95 to 97% and a plating efficiency equal to that of unfrozen cells. It was concluded that such a freezing method would be ideal for the cryopreservation and storage of banks of Theileria annulata-infected cells for vaccine purposes.

Animals↗

PubMed1986

Carotid endarterectomy after Doppler ultrasonographic examination without angiography.

We prospectively reviewed our experience with 32 carotid endarterectomies in 30 patients performed without angiography in a 7 year period. Although this represents 6.7 percent of our total experience with carotid endarterectomy in this period, carotid endarterectomy without angiography is increasing and comprises 17 percent of the last 2 years' total. We have adhered to strict criteria for patient selection that identifies circumstances for a safe operative experience in seven broad categories. Evidence is also presented to reduce an overriding concern for intracranial aneurysms and siphon stenosis if either one exists unrecognized. We are hopeful that in the future, the latter will be identified by intracranial Doppler studies currently being performed. Our experience in this small series has been favorable, with intraoperatively measured lesions equal to the preoperative noninvasive predictions. We suggest that Doppler ultrasonography in its current form can be effectively used in place of conventional angiography or digital subtraction angiography in selected patients.

Aged↗

PubMed1986

The mechanism of pentachlorobutadienyl-glutathione nephrotoxicity studied with isolated rat renal epithelial cells.

Isolated renal epithelial cells were used to study the mechanism of toxicity of pentachlorobutadienyl-glutathione (PCBG), a nephrotoxic glutathione conjugate of hexachlorobutadiene. The cytotoxicity of PCBG displayed a very steep dose-response relationship; at 10 microM PCBG no toxicity was observed whereas 25, 50, and 100 microM PCBG all resulted in a similar degree of toxicity. In all cases, loss of cell viability was observed only after a 30-min lag period and reached a plateau of 50 to 60% nonviable cells between 90 and 100 min. Toxic doses of PCBG also resulted in the depletion of cellular thiols. Blocking PCBG metabolism by inhibition of gamma-glutamyl transpeptidase [1-gamma-L-glutamyl-2-(2-carboxyphenyl)hydrazine (anthglutin), 2 mM] or renal cysteine conjugate beta-lyase (aminooxyacetic acid, 0.5 mM) resulted in complete protection against PCBG-induced cell damage. Exposure of isolated renal epithelial cells to 100 microM PCBG resulted in the rapid formation of plasma membrane blebs which appeared to be associated with a loss of Ca2+ from the mitochondrial compartment and an elevation of cytosolic Ca2+ concentration as measured by Quin-2. PCBG treatment also resulted in the inhibition of cell respiration and a marked depletion of cellular ATP content, indicating additional mitochondrial effects of the toxin. Our results support a role for renal cysteine conjugate beta-lyase in the metabolic activation of PCBG and suggest that PCBG-induced renal cell injury may be the result of selective effects on mitochondrial function.

Adenosine Triphosphate↗

PubMed1986

Phospholipid degradation in, and protein content of, rat fistula bile. Contamination of bile with pancreatic juice.

The extent to which pancreatic juice can contaminate bile collected from a rat with a biliary fistula has been investigated by cannulating the bile duct proximal to either the duodenum or the liver, and by stimulating pancreatic flow with secretin. Bile collected via a fistula proximal to the duodenum showed marked pancreatic contamination. Thus, bile collected via a fistula proximal to the duodenum has a higher flow rate, a greater total protein and amylase content and a different polypeptide profile than bile collected via a fistula proximal to the liver. The phospholipid content also differed in that phosphatidylcholine was converted enzymically to lysophosphatidylcholine. Secretin increased bile flow and the biliary output of total protein and amylase when the fistula was proximal to the duodenum, but had no effect upon these parameters when the fistula was proximal to the liver, or in the isolated perfused rat liver.

Amylases↗

PubMed1986

Reduced enzyme activity and starch level in an induced mutant of chloroplast phosphoglucose isomerase.

Ethyl methane sulfonate treatment was used to induce a mutation in the nuclear gene encoding the chloroplast isozyme of phosphoglucose isomerase in Clarkia xantiana. The mutation, which proved allelic to wild type activity, was backcrossed to wild type for five generations so that the two could be compared in a near isogenic background. An immunological analysis showed that the mutant, when homozygous, reduced the activity of the isozyme by about 50%. In contrast to wild type, the mutant showed little change in leaf starch level over a diurnal period or following a 72-hour continuous light treatment. By the end of the diurnal light period, the mutant accumulated only about 60% as much starch as wild type. However, mutant leaves had an increased sucrose level presumably because photosynthate was directly exported from the chloroplasts. The mutant also exhibited reduced leaf weight. These changes in metabolism and growth suggest that the wild type level of plastid phosphoglucose isomerase activity is necessary to achieve wild type carbohydrate status.

Journal Article↗

PubMed1985

The formation of both a mono- and a bis-substituted glutathione conjugate of hexachlorobutadiene by isolated hepatocytes and following in vivo administration to the rat.

The nephrotoxicity of hexachloro-1,3-butadiene (HCBD) appears to depend on the initial formation of a glutathione (GSH) conjugate in the liver. In the present study we have examined the hepatic metabolism of HCBD using isolated hepatocytes and following in vivo administration. Exposure of isolated hepatocytes to HCBD resulted in a dose-dependent depletion of GSH. HPLC analysis of the incubation medium demonstrated the formation of two products. When isolated hepatocytes containing [3H]GSH were exposed to [14C]HCBD, coincident elution of 3H and 14C corresponding to the previously recognized HPLC peaks was observed. Both products were sensitive to treatment with gamma-glutamyl transpeptidase (gamma-GT), providing additional support for their identification as GSH conjugates. The ratio of 3H to 14C in the two peaks indicated the formation of both a mono- and a bis-substituted GSH conjugate of HCBD. The identification of the mono- and bis-GSH conjugates was further confirmed by the preparation of synthetic standards which displayed retention times by HPLC identical to the biological products. The production of the total and individual GSH conjugates displayed both dose and time dependence. The production of the total as well as the ratio of mono- to bis-conjugate was found to depend on the availability of GSH. At low HCBD exposure levels the bis-substituted conjugate accounted for more than 20% of the total conjugate produced by isolated hepatocytes. This value decreased at higher HCBD concentrations. Analysis of bile collected from rats following intraportal administration of [14C]HCBD revealed the presence of both the mono- and bis-substituted GSH conjugates of HCBD as well as additional 14C-containing metabolites. The results of the present study clearly demonstrate the production of both a mono- and a bis-substituted GSH conjugate of HCBD. The potential importance of this finding in terms of the nephrotoxicity of HCBD is discussed.

Animals↗

PubMed1985

Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials.

The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants.

Adult↗

PubMed1985

Allyl alcohol toxicity in isolated renal epithelial cells: protective effects of low molecular weight thiols.

The toxicity of allyl alcohol was studied in freshly isolated renal epithelial cells prepared from male and female rats. Cells from female rats demonstrated a greater susceptibility to allyl alcohol toxicity as assessed by glutathione depletion and loss of cell viability. The sensitivity of female rat renal cells appears to relate to the higher activity of alcohol dehydrogenase found in the female rat kidney, which metabolizes allyl alcohol to the highly reactive aldehyde, acrolein. Pyrazole, an inhibitor of alcohol dehydrogenase, abolished the cytotoxic effects of allyl alcohol whereas inhibition of aldehyde dehydrogenase by disulfiram treatment was found to increase the sensitivity of renal cells to the effects of allyl alcohol. The toxicity of allyl alcohol was decreased by a number of treatments which resulted in increased levels of glutathione or other low molecular weight thiols. These results indicate that acrolein is the toxic metabolite responsible for the renal cell injury following exposure to allyl alcohol, and unless immediately inactivated acrolein interacts with critical nucleophilic sites of the cell and initiates cell injury. These studies demonstrate that freshly isolated kidney cells represent a convenient model system for studies of thiol-mediated protective mechanisms against toxic renal cell injury.

1-Propanol↗

PubMed1985

Myectomy for essential blepharospasm.

Essential blepharospasm is a progressive, bilateral, involuntary facial spasm. In this study, we conducted a prospective analysis of myectomy for the treatment of this condition in 21 patients. The procedure consisted of extirpation of the muscles that close the eyelids (protractors), which include the pretarsal, preseptal, and orbital components of the orbicularis oculi, as well as the procerus and corrugator supercilii muscles of the brow. In addition, the muscles that open the eyelids (retractors) were strengthened (by resection of the frontalis muscle and repair of disinsertion of the levator aponeuroses). The most common symptoms that necessitated myectomy were difficulty with driving (20 patients), watching television (17 patients), reading (15 patients), and eating (5 patients). Overall, the 21 patients had a 70% mean decrease in symptoms postoperatively. Five patients required an additional operation for management of residual blepharospasm.

Aged↗

PubMed1985

Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat: enzyme histochemical studies.

Enzyme histochemical techniques were utilized to examine the progression and extent of proximal tubular injury during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure. Acute renal failure was induced in male rats by the intraperitoneal administration of 10 mg CDDP/kg body weight. At 6, 24, 48, 72, and 96 hr following treatment, renal function was assessed and tissue was collected for renal morphologic and enzyme histochemical studies. The enzymes examined were gamma-glutamyl transpeptidase, alkaline phosphatase, sodium-potassium ATPase (nitrophenyl phosphatase), acid phosphatase, glucose-6-phosphatase, succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase. By 24 hr, the activity of acid phosphatase was reduced throughout the proximal tubule, with the greatest decrease occurring in the P3 segment of the proximal tubule located in the outer stripe of the outer medulla. Changes in the histochemical staining of the remaining enzymes were not consistently observed until 48 or, in some cases, 72 hr. These alterations involved all portions of the proximal tubule with the most severe changes involving P3. The results of the enzyme histochemical studies along with the morphologic findings indicating that the initiation of CDDP-induced acute renal failure, first apparent at 48 hr in this model, is associated with cell injury throughout the proximal tubule. The majority of the histochemical changes did not become apparent until late in the course of tubular injury. This suggests that most of the changes in enzyme activity represent nonspecific effects of CDDP-induced tubular injury, as opposed to direct enzyme inhibition by the drug.

Acid Phosphatase↗

PubMed1985

Antigenic variation in Trypanosoma evansi: variable antigen type (VAT) composition of first relapse populations in mice.

The variable antigen type (VAT) composition of first relapse populations developing in mice infected with 11 VAT populations of a stock of T. evansi was shown to be independent of the infecting VAT. Trypanosomes representing three of the VATs were found in all relapse populations resulting from infection with each VAT. A further seven VATs were detected in at least one relapse population from each VAT. These 10 VATs had previously been classed as predominant VATs from studies on VAT development in rabbits, sheep and goats. It is probable, therefore, that the VAT composition of first relapse populations can be used as a basis for the classification of T. evansi stocks into serodemes according to their predominant VAT repertoires.

Animals↗

PubMed1985

Antigenic variation in Trypanosoma evansi: a comparison of the predominant variable antigen type repertoire of stocks from Sudan.

The predominant VAT repertoire of 15 stocks of T. evansi from Sudan was characterised using 30 predominant VATs isolated from six of the stocks. The 15 stocks were grouped into three distinct serodemes, each member of a serodeme being associated by the presence of 6-7 particular VATs as part of their predominant VAT repertoire. Two VATs were part of the predominant VAT repertoire of all 15 stocks and were considered to represent isoVATs of T. evansi. The limited antigenic diversity found among these stocks of T. evansi compared with that found in other salivarian trypanosome species suggests that host immunity might have an important role to play in the natural regulation of T. evansi infection of livestock. Furthermore, control regimes based on immunoprophylactic methods may be more of a practical possibility in the case of T. evansi infections than in the case of other trypanosome species infecting livestock.

Animals↗

PubMed1985

Antigenic variation in Trypanosoma evansi: variable antigen type development in mice, sheep and goats.

The early VAT development of a stock of Trypanosoma evansi was studied in mice, sheep and goats. Host species did not appear to influence the range of VATs which were detected early in infection, although differences were seen in the VAT composition of individual trypanosome populations isolated at similar periods after infection in the different hosts. Ten VATs, previously classed as predominant VATs from studies on T. evansi-infected rabbits, were also found to act as predominant VATs in sheep and goats. These 10 VATs were also found in first relapse populations from mice infected with this stock of T. evansi. Such relapse populations could serve as a source of predominant VATs for serodeme analysis of stocks of T. evansi.

Animals↗

PubMed1985

Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat. Correlation of structural and functional alterations.

Studies were undertaken to examine the relationship between renal morphologic and functional alterations during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure (ARF). Control and CDDP-treated rats (10 mg/kg, intraperitoneally) were housed in metabolic cages for the purpose of renal function determinations. Renal morphology was studied by light and electron microscopy at 6, 24, 48, 72, and 96 hours following treatment. Six hours following CDDP administration, morphologic alterations consisting of nucleolar segregation, ribosome dispersion, and the formation of aggregates of smooth endoplasmic reticulum were observed throughout the P3 portion of the proximal tubule located in the outer stripe of the outer medulla and medullary rays. These changes became more frequently observed throughout P3 during the course of the study. At 24 and 48 hours, focal changes were also observed involving the P1 and P2 segments of the proximal tubule which make up the pars convoluta. ARF, indicated by a reduced creatinine clearance, was first apparent 48 hours following CDDP administration. The development of ARF was associated with focal, primarily sublethal, cell injury throughout the proximal tubule. By 72 and 96 hours necrosis primarily affecting P3 became widespread, and renal function progressively worsened. The establishment of ARF prior to the development of tubular necrosis suggests that the processes of tubular obstruction and/or tubular fluid backleak are not involved in the initiation of ARF in this model. Instead, the alterations involving P1 and P2 appear to be most important during the early stages of CDDP-induced ARF. The severity of the convoluted tubular injury at 48 hours showed a significant correlation with the degree of renal function impairment. The tubular injury affecting P3 did not correlate with the loss of renal function at any of the time points studied. However, tubular injury in P3 did appear responsible for some degree of renal function impairment at 72 and 96 hours, probably as a result of tubular obstruction and/or tubular fluid backleak.

Acute Kidney Injury↗

PubMed1984

Infection by leptospires of the Pomona serogroup in cattle and pigs in south west England.

Leptospires belonging to the Pomona serogroup were isolated from calves involved in two outbreaks of acute haemolytic disease which were characterised by jaundice, haemoglobinuria and high death rates. Retrospective case studies in which serological evidence of Pomona serogroup infection was found are also presented. Serovar pomona is the leptospire of the Pomona serogroup most commonly incriminated in clinical disease in domestic species, but the organisms isolated in this study were antigenically different to pomona and may represent a new serovar. The limited information available on the epidemiology of sporadic infection with leptospires of the Pomona serogroup in domestic species in the south west of England supports the contention that a serovar other than pomona is involved.

Animals↗

PubMed1984

Inferior oblique surgery. Experience at the Mayo Clinic from 1960 to 1981.

Three hundred thirty-seven patients underwent inferior oblique disinsertions at the Mayo Clinic Rochester, Minn, from 1960 to 1981. Versions and hyperdeviations in the primary position were recorded preoperatively and postoperatively. The criteria of a successful result were (1) correction of diplopia, (2) correction of hyperdeviation in the field of action of the inferior oblique, and (3) correction of versions in adduction. Clinical failure was reflected in persistence of hyperdeviation in primary gaze and persistence of overaction of the inferior oblique muscle in adduction. A successful result was found in 88% of primary inferior oblique disinsertions. For secondary inferior oblique overaction, a successful result was found in 72% of patients. We have found that inferior oblique disinsertion is a safe, fast, reliable, and effective weakening procedure with good results.

Adolescent↗