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M MacFarlane

Publications and source records attributed to M MacFarlane.

47 records · Page 3Linked to original sources
PubMed1993

Dose-dependent induction or depression of cysteine conjugate beta-lyase in rat kidney by N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine.

The influence of N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine (NAc-PCBD) on cysteine conjugate beta-lyase in female rat kidney has been examined. After a single, non-nephrotoxic dose of NAc-PCBD (3 mg/kg), cytosolic beta-lyase enzyme activity was increased 1.5 to 3-fold commensurate with a corresponding increase in enzyme protein levels as assessed by both Western blot and ELISA analyses. Using a cDNA probe for beta-lyase, this induction was found to be accompanied by an increase in the cognate mRNA. In contrast, a higher, nephrotoxic dose of NAc-PCBD (10 mg/kg) decreased all the above parameters. These effects appeared to be specific to the cytosolic form of the enzyme as no changes in kidney mitochondrial beta-lyase or enzyme protein levels were observed. Repeated dosing with the lower dose level (3 mg/kg) resulted in either no change, or in some instances, a reduction in the above parameters, suggesting an accumulation of the xenobiotic and a masking of the induction phenomenon. The molecular mechanisms underlying these observations are discussed in terms of the nephrotoxicity of halogenated xenobiotics.

Acetylcysteine↗
PubMed1993

Isolation and expression of a cDNA coding for rat kidney cytosolic cysteine conjugate beta-lyase.

The role of rat kidney cysteine conjugate beta-lyase in the production of nephrotoxic thiols from S-cysteine conjugates of xenobiotics has been well established. However, the factors controlling the cellular distribution and substrate specificity of the enzyme have yet to be elucidated. As an approach to this we have isolated a cDNA for cysteine conjugate beta-lyase from a rat kidney cDNA library, using a combination of immunological and hybridization screening. A full length cDNA was sequenced and its identity was confirmed by deduced molecular weight, deduced amino acid composition, the presence of a consensus pyridoxal phosphate (PLP) binding site in the deduced amino acid sequence, kidney-specific expression of the corresponding mRNA, and the expression of beta-lyase and glutamine transaminase K activities in tissue culture cells transfected with the cDNA. The cDNA coded for a protein of 48 kDa containing the sequence Ser-Ala-Gly-Lys-Ser-Phe, which corresponds closely to the PLP binding site in other PLP-containing enzymes. Use of the cDNA to detect beta-lyase mRNA sequences in rat liver and kidney RNA demonstrated that expression was kidney specific and that the mRNA size (2.1 kilobases) was in good agreement with the size of the cDNA. When the cDNA was inserted into the expression vector pUS1000 and transfected into COS-1 tissue culture cells, a 7-10-fold increase in cytosolic beta-lyase and glutamine transaminase K activities could be detected. The use of beta-lyase cDNA for the elucidation of the mechanism of action of this enzyme and for the development of in vitro systems to examine xenobiotic cysteine conjugate toxicity is discussed.

Amino Acid Sequence↗
PubMed1989

Cysteine conjugate beta-lyase of rat kidney cytosol: characterization, immunocytochemical localization, and correlation with hexachlorobutadiene nephrotoxicity.

Cysteine conjugate beta-lyase (beta-lyase) was purified to electrophoretic homogeneity from the kidney cytosol of male Wistar rats. The highly purified enzyme exhibited a monomeric molecular weight of 50,000 Da and was active in the alpha-beta elimination of cysteine conjugates including S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), and S-(2-benzothiazolyl)-L-cysteine, particularly toward DCVC and TFEC. The purified enzyme also exhibited glutamine transaminase K activity with phenylalanine and alpha-keto-gamma-methiolbutyrate as substrates. An antibody was raised to the purified rat protein in sheep and the crude immune serum affinity purified, yielding a specific antibody that recognized only the beta-lyase protein in whole kidney homogenates. Immunocytochemical studies on rat kidney sections stained with the purified antibody revealed that the cytosolic beta-lyase enzyme was mainly localized in the pars recta of the proximal tubule in untreated rats. This localization is coincident with the site-specific kidney necrosis produced by hexachloro-1,3-butadiene (HCBD). These results indicate that the tissue localization of beta-lyase in the proximal tubule plays an important role in determining the specific nephrotoxicity produced by halogenated alkenes such as HCBD.

Animals↗
PubMed1986

Time course of the effect of streptozotocin on serum concentration of glucose and triglycerides and on hepatic drug metabolism in the male rat.

Streptozotocin (STZ) causes a rise in serum glucose, triglycerides and ketones and a fall in insulin and also leads to changes in drug metabolism. Results from rats left for 20 days indicate that there is no correlation between the effects of STZ on hepatic and serum parameters. The present study investigated the time course of the effect of STZ on hepatic drug metabolism, protein and cytochrome P-450 content and serum glucose and triglyceride concentration. STZ caused the induction of diabetes by 2 h which disappeared at 8 h and reappeared at 24 h. Drug metabolism was reduced after 1 h, returned to control levels at 2 h and remained there until 24 h. Liver protein was increased at 1 and 72 h but cytochrome P-450 was unaffected. The initial increase in serum parameters was not accompanied by changes in hepatic parameters and, thus, the two effects of streptozotocin may not be related.

Animals↗
PubMed1973

The first word.

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Community Mental Health Services↗
PubMedDate not supplied

Force-feedback grasper helps restore sense of touch in minimally invasive surgery.

The age of minimally invasive surgery has brought forth astounding changes in the health care field. Less pain and quicker patient recovery have been demonstrated with several types of operations that were once performed by an open technique. With these changes have come reports of complications. The decreased sense of touch is just one of several limitations inherent to current techniques of minimally invasive surgery that limit detection of subtle or unapparent lesions on palpation, such as common duct stones and liver lesions. The purpose of this study is to demonstrate the ability of a force-feedback-equipped grasper to restore some of the sense of touch that is lost in minimally invasive surgery. To demonstrate this ability, we created six silicone phantoms of identical dimensions but graded compliance, and asked 10 subjects to place them in increasing/decreasing order of compliance. They used three tools (their dominant gloved hand, a standard laparoscopic Babcock grasper, and our force-feedback device fitted with the identical Babcock grasper) to rate the compliance of the samples in a blinded fashion. These conditions thus approximated the conditions of open surgery, minimally invasive surgery, and minimally invasive surgery fitted with a force-sensing device, in terms of palpating tissues. Five surgeons skilled in minimally invasive surgery and five nonsurgeons participated in the study. The results indicate that the force-feedback device is significantly (P <0.05) better than a standard Babcock grasper at rating tissue compliance, but was not as successful as a gloved hand (mean of squared errors = 1.06, 3. 15, and 0.25, respectively). There was no significant difference between surgeons and nonsurgeons in rating compliance. We conclude that this force-feedback instrument is able to partially restore the sense of touch in minimally invasive surgery. This restored ability may thus potentially result in more efficient operations with improved diagnostic capabilities and fewer complications during minimally invasive surgery.

Biocompatible Materials↗
PubMedDate not supplied

"Have you seen this?" Diffuse hepatic apoptosis.

One important cell death pathway involves binding of the cell surface receptor Fas, which recruits and activates specific initiator and effector caspases. In this study Balb/c mice were injected with monoclonal antibody to Fas either alone or followed by the tripeptide caspase inhibitor Z-VAD.fmk. At four hours mice were killed along with concurrent controls and tissues processed for histological examination and immunocytochemical staining for cleaved caspase-3. The livers in all animals treated with Fas alone showed massive apoptosis and positive staining for cleaved caspase-3 whereas those treated with Fas and Z-VAD.fmk or controls showed little or no apoptosis or staining for cleaved caspase-3. These features suggest that massive apoptosis may be important in fulminant liver disease.

Amino Acid Chloromethyl Ketones↗