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C Whiteside

Publications and source records attributed to C Whiteside.

At least 37 records · Page 2Linked to original sources

Accurate measurement of impaired glomerular filtration using single-dose oral cimetidine.

To improve the validity of a timed creatinine clearance as a measure of glomerular filtration rate (GFR), we investigated whether a single 800-mg dose of oral cimetidine was sufficient to inhibit tubular secretion of creatinine (TScr). Forty-five 3-hour timed creatinine clearances (Clcr) with single 800-mg dose oral cimetidine (TCC) in 17 renal transplant recipients with marked renal function impairment (creatinine 2.0 to 7.1 mg/dL) were compared with simultaneous [125I]-iothalamate GFR (Cliothal). For comparison, 13 timed Clcr without cimetidine (TC), and 36 24-hour Clcr were performed. The TCC was the most accurate: the ratio (mean +/- SD) of TCC:Cliothal was 1.12 +/- 0.02, compared with 1.33 +/- 0.08 for Clcr:Cliothal and 1.53 +/- 1.02 for TC:Cliothal. The difference between Cliothal and TCC was small over the range of GFRs tested (mean +/- 2 SD), 0.9 +/- 2.5 mL/min/1.73 m2. The intraclass correlation (R) for within-subject reproducibility of the TCC in five subjects was 0.8 (95 percent CI; 0.5, 0.9), and in 11 subjects who had at least three GFR determinations over 24 weeks, the TCC was as responsive to change in GFR as Cliothal. There was an inverse relationship between fractional excretion of cimetidine and GFR (r2 = -0.70), suggesting increased tubular secretion of cimetidine with decreasing GFR. In conclusion, a single 800-mg oral dose of cimetidine was effective in inhibiting TScr such that the TCC was an accurate, reproducible, and responsive test of GFR.

Administration, Oral↗

Training for rural practice. Are graduates of a UBC program well prepared?

OBJECTIVE: To evaluate preparedness for rural practice and to ascertain where graduates of a community-based rural training program practise. DESIGN: Mailed cross-sectional survey. SETTING: Rural communities in British Columbia. PARTICIPANTS: Graduates of the University of British Columbia's (UBC) rural training program from 1982 to 1991 and a random sample of non-program-trained rural BC physicians. MAIN OUTCOME MEASURES: Self-reported preparedness for rural practice in various areas of family medicine and in aspects of professional and personal life in rural settings. Locations of practice. RESULTS: Rural program graduates reported themselves better prepared in family medicine, community medicine, practice management, and behavioural science. Non-program-trained rural physicians thought themselves better prepared in medical subspecialties. Responses in pediatrics, obstetrics and gynecology, and surgical preparation showed no important differences. Rural program residents were located in rural areas (51%), regional settings (20.5%), and metropolitan areas (17.9%). CONCLUSION: Graduates of the UBC rural training program consider themselves better prepared for rural family practice than non-program-trained rural physicians in several areas of family practice. Most graduates of the program were practising in rural and regional settings.

Adult↗

Chloride is required for receptor-mediated divalent cation entry in mesangial cells.

Agonists which stimulate the inositol 1,4,5 trisphosphate ([1,4,5]-IP3)-dependent mobilization of Ca2+ from intracellular stores also stimulate entry of divalent cations across the cell membrane. Under appropriate experimental conditions, divalent cation entry across the cell membrane can be monitored as the rate at which the intracellular fluorescence of divalent cation indicators is quenched by the addition of Mn2+ to the extracellular medium. We report that addition of vasopressin to fura-2-loaded glomerular mesangial cells in culture markedly accelerated the rate at which Mn2+ quenched fura-2 fluorescence at its Ca(2+)-insensitive wavelength in the presence of extracellular NaCl, but that this quench response was attenuated when Cl- was removed from the extracellular medium by equimolar substitution with impermeant anions (gluconate, methanesulfonate, acetate, lactate). Similarly, loss of agonist-induced quench also occurred when Cl- was substituted with gluconate in K(+)-containing media. Addition of the Cl- channel inhibitor, 5-nitro-2-(3-phenylpropylaminobenzoic acid) (NPPB), also inhibited Mn(2+)-induced quench of fura-2 fluorescence following vasopressin addition. In contrast, in the presence of gramicidin to provide an alternate conductance pathway to accompany divalent cation entry, agonist-dependent Mn2+ quench occurred even in the absence of extracellular Cl-, indicating that the requirement for Cl- was not the result of cotransport on a common transporter nor the result of Cl- serving as a necessary cofactor for divalent cation entry. A similar dependence on extracellular Cl- was observed for other Ca(2+)-mobilizing agonists such as endothelin, as well as the intracellular Ca2+ ATPase inhibitor, thapsigargin. Extracellular Cl- dependence for agonist-induced divalent cation entry was also reflected in a corresponding extracellular Cl- dependence for agonist-induced mesangial cell contraction. It has been previously shown by ourselves (Kremer et al., 1992a, Am. J. Physiol., 262:F668-F678) and others that agonist-stimulated calcium mobilization in mesangial cells is accompanied by inhibition of K+ conductance and increased Cl- conductance. Accordingly, we conclude that the current findings suggest that activation of Cl- conductance provides regulated charge compensation for receptor-mediated divalent cation entry in response to Ca(2+)-mobilizing vasoconstrictor agonists in mesangial cells.

Animals↗

Cytokeratin intermediate filament expression in benign and malignant breast disease.

AIM: To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade. METHODS: Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies. RESULTS: The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies. CONCLUSION: The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.

Antibodies, Monoclonal↗

Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the prostate.

AIM: To assess the value of vimentin and cytokeratin (CK) intermediate filament proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of the prostate and in predicting prognosis in prostatic cancer. METHODS: Fifteen carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections and monoclonal antibodies to CK and vimentin IFPs. RESULTS: There was no statistically significant difference in vimentin expression between nodular hyperplasia and carcinoma. The luminal epithelium in both also reacted with antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases of nodular hyperplasia and was not identified in any carcinoma. There was a reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of cases. There was no statistically significant difference in vimentin and CK reactivity in high and low grade carcinomas. CONCLUSION: Neither vimentin nor CK expression assists in establishing whether a prostatic lesion is benign or malignant or in predicting the biological behaviour of a prostatic carcinoma.

Diagnosis, Differential↗

Immunohistochemical staining of plastic embedded bone marrow trephine biopsy specimens after microwave heating.

AIMS: To investigate (1) whether adequate immunohistochemical staining can be achieved on sections cut from plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer; and (2) whether this immunohistochemical staining is comparable with that achieved on routine sections cut from paraffin wax embedded trephine biopsy specimens after decalcification procedures. METHODS: Sixty five consecutive bone marrow trephine biopsy specimens of more than 1 cm in length were divided transversely into two equal parts. One part was processed in paraffin wax followed by decalcification. The other part was embedded in the epoxyresin Polarbed 812 followed by the cutting of 1 micron sections. Both parts underwent immunohistochemical staining by an identical panel of antibodies. With Polarbed 812 plastic embedded sections, microwave heating in citrate buffer was undertaken before the application of antisera. RESULTS: On sections cut from plastic embedded material, immunohistochemical staining was generally satisfactory, easy to interpret and comparable with that achieved with paraffin wax embedded material. Exceptions were antibodies to neutrophil elastase and CD61 where immunostaining was consistently negative on plastic embedded sections. Immunohistochemical staining for CD20 was consistently more reliable on plastic embedded sections. CONCLUSIONS: The results provide evidence that, with few exceptions, satisfactory immunohistochemical staining is possible on plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer. This, combined with the advantage of superior cellular morphology with semi-thin (1 micron) sections of plastic embedded material, make such embedding procedures the preferred method for the processing of bone marrow trephine biopsy specimens.

Antibodies, Monoclonal↗

Dietary intervention in primary care: validity of the DINE method for diet assessment.

Primary health care staff are involved increasingly in the provision of dietary advice for health promotion, often without adequate training in nutrition assessment or counselling. At present no brief diet assessment methods are available which have been validated for this purpose in the UK. We report on the accuracy of the Dietary Instrument for Nutrition Education (DINE) in classifying dietary fat and fibre intakes. This structured questionnaire can be administered and scored in under 10 minutes by primary care staff without specialized nutritional knowledge, and includes a dietary counselling component. The classification of fat and fibre intakes as low, medium or high by the DINE method was compared to that of a detailed 4-day diet record in a population of 206 factory workers. There was exact agreement of categorization for 53% of fat intakes and 52% of fibre intakes, and only 6% of fat intakes and 5% of fibre intakes were grossly misclassified (placed in a high category by one method and a low category by another). Pearson correlation coefficients between the two methods were 0.51 for fat, 0.46 for fibre and 0.43 for the polyunsaturated:saturated fat ratio. The DINE method is a brief and inexpensive tool for diet assessment in primary care health promotion programmes.

Counseling↗

C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human breast carcinoma.

Although over-expression of the C-erbB-2 oncogene product can be detected on formalin-fixed, paraffin-embedded sections from tumours of the human breast, fixation results in a considerable loss of immunostaining for this protein. In this study, C-erbB-2 expression was studied immunohistochemically on frozen sections in 63 infiltrating carcinomas, 3 phyllodes tumours, 15 fibroadenomas and 16 cases of fibrocystic disease. The value of C-erbB-2 expression as a prognostic indicator in ductal carcinomas was examined by seeking an association with known prognostic indicators. C-erbB-2 over-expression was confined to ductal carcinomas of the breast and was positively correlated with tumour size, grade, oestrogen receptor status and the presence of metastatic deposits in axillary lymph nodes. Only the association with lymph node and oestrogen receptor status were statistically significant. No evidence of a correlation between C-erbB-2 expression and growth fraction (as assessed with the Ki-67 antibody) was demonstrated in the cases studied. Formalin fixation was associated with the loss of immunoreactivity in all cases studied. 75% of cases which were positive on frozen sections were negative in paraffin sections. These results highlight the significance of the method of fixation used in studying C-erbB-2 expression. They confirm the association between C-erbB-2 expression and known prognostic indicators.

Breast Neoplasms↗

Vimentin expression in benign and malignant breast epithelium.

AIMS: To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma. METHODS: Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions. RESULTS: Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas. CONCLUSION: There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma.

Adenofibroma↗

Increased microalbuminuria in diabetic rats is independent of angiotensin II or glomerular proteoglycan synthesis.

Increased microalbuminuria is seen early in rats with both streptozotocin-induced and genetic (Bio-Breeding) diabetes. This study examines the roles of angiotensin II-dependent mechanism(s) and sulfation of glomerular proteoglycans in this phenomenon, as both processes have been implicated by several lines of circumstantial evidence. Anionic sites in the glomerular basement membrane, attributed to the presence of heparan sulfate, were quantitated by polyethyleneimine staining at 15, 21, and 70 days of diabetes in rats treated with streptozotocin, with or without insulin, and at 70 days in the Bio-Breeding rats. All diabetic rats developed increased microalbuminuria: control, 0.08 +/- 0.03 microgram/mL glomerular filtration rate, mean +/- SD; streptozotocin without insulin at 15 days, 0.92 +/- 0.06 microgram/mL (p < 0.05); streptozotocin with insulin at 21 days, 0.61 +/- 0.37 microgram/mL (p < 0.05 vs. control). At 70 days, both the Bio-Breeding and the streptozotocin rats sustained their microalbuminuria to the same degree (p < 0.05 vs. control). Enalapril (250 mg/L) in the drinking water of diabetic animals did not reduce the microalbuminuria. Although the polyethyleneimine-stained heparan sulfate sites decreased significantly in the streptozotocin rats, they remained unchanged in the Bio-Breeding rats. To determine the cause of reduced heparan sulfate staining, the in vitro synthesis and degree of sulfation of proteoglycans by glomeruli isolated from control and streptozotocin diabetic rat kidneys were compared. The amount of heparan sulfate synthesis and degree of sulfation were unchanged in diabetic glomeruli, although lower incorporation into the extracellular matrix and greater secretion into the medium were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

A new computer-assisted three-dimensional reconstruction method provides accurate measurement of glomerular mesangial volume.

Many glomerulopathies are characterized by progressive mesangial (interstitial) expansion which can be quantitated by morphometric analysis. The purpose of this study was to analyze mesangial and glomerular volumes using a new computer-assisted reconstruction (CAR) method. CAR was compared to two standard planar methods, point-counting and linear integration, for accuracy and time efficiency. In Phase I of the study, a computer-based model of the mesangial space was created by placing spherical and ellipsoidal objects of known volume into an enclosing volume mimicking the glomerulus. The simulated mesangium occupied approximately 10 percent of the glomerular volume. The model glomerulus was sectioned serially into ten sections of equal thickness and the three morphometric methods applied to determine the mesangial/glomerular volume. The complexity of the mesangial model was varied by increasing the number of mesangial regions from one to ten to 100. The CAR method estimated the model mesangial volume more accurately (1-9 percent error) through each level of complexity compared to point-counting (3-17 percent error) and linear integration (3-18 percent error). The point-counting method consistently overestimated (P less than 0.05) the fractional mesangial volume for the ten- and 100-region mesangium models. In Phase II of the study, a normal rat glomerulus was sectioned serially (215 sections) and a transmission electron micrograph (TEM) of every fifth section (n = 43) was obtained. Each TEM image (2% of glomerular surface) was digitized for analysis by CAR. Point-counting and linear integration were also performed on the whole glomerular TEMs (n = 10, randomly chosen). The estimated relative mesangial/glomerular volume was 6.6 +/- 0.1 percent by CAR (mean +/- SD), 9.7 +/- 1.5 by linear integration, and 14.9 +/- 3.4 by point-counting. The point-counting method was most efficient, requiring 40 +/- 8 sec/section, followed by CAR at 85 +/- 24 sec/section. Linear integration was least efficient (93 +/- 23 sec/section). We conclude that CAR is the most accurate morphometric method of the three compared for estimating mesangial and glomerular methods, although it is more time consuming than the point-counting method and requires more complex instrumentation. CAR is the only method that will analyze the shape and three-dimensional complexity of glomerular structures using TEMs.

Animals↗

Diabetic glomerulopathy following unilateral nephrectomy in the dog.

To elucidate the important features of early renal disease in the diabetic dog, renal capillary permselectivity and fractional mesangial expansion with and without unilateral nephrectomy (NX) were examined. Pancreatectomized mongrel dogs (N = 9) received 10-20 U Regular and NPH insulin daily. Weekly blood glucose monitoring, 300 +/- 75 mg/dl (means +/- SD). Three dogs without NX had serial open needle biopsies 6-23 months post-pancreatectomy, revealing significant glomerular basement membrane widening and mesangial expansion. Without NX, inulin clearance increased from 2.55 +/- 0.89 (pre-diabetes) to 4.30 +/- 0.70 ml/min/kg body weight (N = 4, means +/- SD, p less than 0.05), whereas albuminuria, measured by radioimmunoassay, remained unchanged 2.57 +/- 1.03 (pre-diabetes) to 2.83 +/- 1.63 micrograms/min/kg body weight up to 23 months post-pancreatectomy. To determine whether altered renal capillary permselectivity occurred despite normal albuminuria, glomerular charge and size selectivity was analysed with serial fractional anionic dextran (20-44 A Stokes Einstein Radius) clearances. Furthermore, peritubular capillary permselectivity was probed with anionic and neutral 3H-dextran (26 A) using the multiple indicator dilution method. Fractional anionic dextran clearances remained unchanged up to 23 months, as did peritubular capillary permselectivity. Five diabetic dogs were compared to non-diabetic dogs with (N = 4) and without (N = 10) NX. To identify whether angiotensin II converting enzyme inhibition modified glomerular function or morphology, 3 diabetic + NX dogs received Captopril (5 mg/kg/day). At one year, diabetes + NX had an additive effect on renal hypertrophy, although fractional mesangial expansion was not enhanced by NX. Albuminuria was unaffected by NX or Captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

Cholesterol knowledge and practices among patients compared with physician management in a university primary care setting.

Lowering elevated serum cholesterol has been shown to reduce the risk of symptomatic coronary heart disease. The National Institute of Health and National Cholesterol Education Program recommend that all adults obtain a cholesterol screening and state that desirable adult levels are less than 200 mg/dl. This study examined the knowledge and practices regarding cholesterol among patients and physicians in a university-based primary care clinic that serves a large proportion of elderly and indigent patients. One hundred fifty-nine patients were interviewed and their medical records were examined. Twenty-four percent of patients were aware of their elevated cholesterol levels, 60% were aware of the health risks associated with hypercholesterolemia, and 83% were able to state methods of lowering cholesterol levels. Approximately 50% stated that they were making considerable efforts to lower fat and cholesterol consumption. Physicians listed cholesterol as a problem in 29% of patients with elevated values (greater than 200 mg/dl) and counseled 17%. Results indicate a good level of knowledge and interest in cholesterol as a health risk even in this group of patients with the multiple problems associated with low socioeconomic status. Knowledge of personal risk status, however, was poor. Physicians need to improve documentation, counseling, and monitoring of patients with elevated cholesterol levels. Long-term follow-up is needed to evaluate efficacy.

California↗

In vivo indicator dilution kinetics of PAH transport in dog kidney.

In vivo multiple indicator-dilution (MID) data were analyzed using a computer-assisted mathematical model of transepithelial cell transport to determine p-aminohippuric acid (PAH) transport kinetics across the proximal tubular antiluminal (ALM) and luminal (LM) membranes. A bolus of 125I-labeled albumin (plasma reference), [14C]creatinine (interstitial reference), and tracer [3H]PAH was injected into the left renal artery of anesthetized mongrel dogs (n = 21), and immediate serial sampling of the left renal venous and left and right urine outputs was performed (control). MID runs were then repeated in the same dog following intravenous infusion of unlabeled PAH. For all plasma PAH concentrations ([PAH]P), the steady-state unidirectional flux coefficients were calculated at the ALM and LM. The computer-derived unidirectional flux coefficients were in keeping with active ALM transport and passive, carrier-mediated LM transport. The Km calculated for ALM uptake (interstitium to cell) was 0.51 mM. PAH transport was completely inhibited by probenecid. As [PAH]P increased, the renal vein mean transit time ratio t[3H]PAH/t[14C]creatinine was greater than 1.0, indicating backflux from cells into the interstitium, then declined toward unity, as ALM and LM transport became saturated. This study, which used PAH as a model substrate demonstrated the feasibility of utilizing computer-assisted mathematical models to quantitate the kinetics of transepithelial transport from in vivo experimentation.

Animals↗

Glomerular epithelial detachment, not reduced charge density, correlates with proteinuria in adriamycin and puromycin nephrosis.

To identify the structural change coincident with increased glomerular permeability in both adriamycin (ADR) and puromycin-aminonucleoside (PAN) nephrosis, we explored the temporal correlation between developing proteinuria, the reduction in glomerular polyanions, and the detachment of epithelium from glomerular basement membrane (GBM). Sprague-Dawley rats received a single tail-vein injection of PAN (150 mg/kg), ADR (7.5 mg/kg) or saline. Nephrotic-range proteinuria appeared between days 2 to 5 in the PAN-treated and days 5 to 10 in the ADR-treated rats. The GBM heparan sulfate charge density and epithelial membrane sialic acid (SA) content were determined before, during and after the rise in proteinuria. Polyethyleneimine was used to detect heparan sulfate and the number staining of renal cortical slices was used to detect heparin sulfate and the number of sites/microns GBM in the lamina rara externa were counted on electron micrographs (magnification x60,000). Controls had a regular distribution of polyethyleneimine 20.19 +/- 1.72 sites/microns (X + SD). In ADR rats, the polyethyleneimine density decreased by day 5, 18.61 +/- 1.79 sites/microns (p less than 0.05) which persisted to day 15, 17.38 +/- 1.27 sites/microns (p less than 0.02). PAN rats, by day 1, had significant reduction, 14.94 +/- 1.47 sites/microns (p less than 0.05), which persisted to day 20. The total membrane-bound SA content of isolated glomeruli was analyzed with a modified Warren's method. The SA content in control glomeruli was 46.8 +/- 8.0 nmol/mg glomerular protein (X +/- SD). In ADR rats, there was significant decrease in SA content to 84 +/- 3% of control (p less than 0.01) at day 15. In PAN rats, by day 2, the SA content was decreased to 73 +/- 18% of control (p less than 0.05). In both models, scanning and transmission electron microscopy revealed epithelial foot process fusion, loss of slit diaphragms, and vacuolization before increased proteinuria. Epithelial detachment from the GBM and rupture of vacuoles occurred coincidently with rapid development of nephrotic proteinuria in both models. In summary, reduced GBM heparan sulfate and epithelial SA content do not correlate with the onset of altered glomerular permeability, whereas epithelial detachment is coincident with the development of massive proteinuria in both ADR and PAN nephrosis.

Animals↗

Role of oxyradicals in the inactivation of catalase by ozone.

The antioxidant enzymes, catalase and superoxide dismutase, are inactivated upon exposure to ozone. In this study, the mechanism of this inactivation was examined using catalase as a model system. The data show that the inactivation of catalase is dependent on ozone concentration, time of exposure, and pH. Loss of catalase activity is accompanied with loss of the heme spectra. Tiron, desferal-Mn, trolox-c, and pyruvate protect the enzyme against ozone inactivation. SOD is less effective due to its inactivation by ozone. On the other hand, alcohols do not provide significant protection. The data suggest the possible involvement of superoxide radicals in the inactivation of catalase by ozone.

Animals↗

Induction and inactivation of catalase and superoxide dismutase of Escherichia coli by ozone.

Oxyradicals have been implicated in ozone (O3) toxicity and in other oxidant stress. In this study, we investigated the effects of O3 on the biosynthesis of the antioxidant enzymes catalase and superoxide dismutase in Escherichia coli to determine their role in the defense against ozone toxicity. Inhibition of growth and loss of viability were observed in cultures exposed to ozone. Results also showed an increase in the activities of catalase and superoxide dismutase in cultures exposed to ozone, which was shown to be due to true induction rather than activation of preexisting apoproteins. Cessation of O3 exposure resulted in 30 min of continual high rate of catalase biosynthesis followed by a gradual decrease in the level of the enzyme approaching that of control cultures. This decrease was attributed to a concomitant cessation of de novo enzyme synthesis and dilution of preexisting enzyme by cellular growth. Ozonation of cell-free extracts showed that superoxide dismutase and catalase are subject to oxidative inactivation by ozone. In vivo induction of these enzymes may represent an adaptive response evolved to protect cells against ozone toxicity.

Catalase↗