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C T Fitts

Publications and source records attributed to C T Fitts.

At least 19 recordsLinked to original sources
PubMed1992

Ischemia-reperfusion injury: biochemical alterations in peroxisomes of rat kidney.

Exogenously supplied catalase, a peroxisomal enzyme, has been found to be of therapeutic value in ischemic injury. Therefore, we examined the effect of ischemic-reperfusion injury on the structure and function of kidney peroxisomes. Ischemic injury changed the density of peroxisomes from 1.21 g/cm3 (peak I) to a lighter density of 1.14 g/cm3 (peak II). The number of peroxisomes moving from the normal density population (peak I) to a lower density population (peak II) increased with an increase in ischemic injury. Latency experiments indicated both populations of peroxisomes to be of intact peroxisomes. Immunoblot analysis with antibodies against peroxisomal matrix and membrane proteins demonstrated that after 90 min of ischemia a significant number of matrix proteins were lost in the peak II population, suggesting that functions of these peroxisomes may be severally affected. Reperfusion following ischemic injury resulted in loss of peroxisomal matrix proteins in both peaks I and II, suggesting that peroxisomal functions may be drastically compromised. This change in peroxisomal functions is reflected by a significant decrease in peroxisomal catalase activity (35%) and beta-oxidation of lignoceric acid (43%) observed following 90 min of ischemia. The decrease in catalase activity was more pronounced in reperfused kidneys even after a shorter term of ischemic injury. Reperfusion restored the normal peroxisomal beta-oxidation in kidneys exposed up to 60 min of ischemia. However, 90 min of ischemia was irreversible as there was a further decrease in beta-oxidation upon reperfusion. The decrease in catalase activity during ischemia alone was due to the formation of an inactive complex, whereas during reperfusion, following 90 min of ischemia, inactivation and proteolysis or decreased synthesis of catalase contributed equally toward the injury. The observed changes in the structure and function of peroxisomes as a result of ischemic-reperfusion injury and the ubiquitous distribution of peroxisomes underlines the importance of this organelle in the pathophysiology of vascular injury in general.

Animals↗
PubMed1990

Mitochondrial membrane fluidity changes in renal ischemia.

The fluorescence polarization technique with 1,6-Diphenyl-1,3,5-hexatriene as a probe, was used to determine the lipid rotational mobility (LRM) measured by fluorescence anisotropy of isolated whole mitochondria of the rat kidney following normothermic ischemia of 30, 45, 60 and 90 minutes and upon reperfusion for 24 hours. The LRM of mitochondrial membrane lipids of the ischemic kidney decreased steadily with increasing ischemic times (0.1590 vs. 0.1705, 0.01 less than P less than 0.001 at 60 minutes). Following 24 hours reflow, there were no significant differences in the LRM of mitochondria between ischemic and control groups up to 45 minutes of ischemia, (0.1688 vs. 0.1705, 0.5 less than P less than 0.6). However, when kidney was subjected to ischemic periods longer than 60 minutes, the decreased LRM remained fixed even after reperfusion (0.1783 vs. 0.1738, 0.5 less than P less than 0.6). This suggests that 60 minutes of ischemia probably produces irreversible damage to the mitochondrial membrane whereas lesser degrees of ischemic injury is reversible upon reperfusion.

Animals↗
PubMed1989

Effect of ischemia and 24 hour reperfusion on ATP synthesis in the rat kidney.

The ability of renal tissue to synthesize ATP was examined in adult Sprague Dawley Rats immediately following normothermic ischemia of 30, 45, 60 and 90 minutes and upon reperfusion for 24 hours. Following ischemia the rate of ATP synthesis decreased progressively. It was 64.5% of the control at 45 minutes and 10.4% after 90 minutes of ischemia. Reperfusion of the ischemic kidneys for 24 hours restored ATP biosynthesis to control, nonischemic levels in kidneys subjected to ischemia up to 45 minutes (101.8 +/- 13.9% vs 64.5 +/- 2.5% p less than 0.02). However, after 60 minutes of ischemia, reperfusion had no effect (59.3 +/- 4.4% vs 51.7 +/- 7.5%) and reperfusion following 90 minutes of ischemia was associated with decrease ATP synthesis (10.4 +/- 2.2% vs 3.3 +/- 0.9% p less than .001). We conclude that mitochondrial function is restored by reperfusion when normothermic ischemic interval is 45 minutes or less. However, ischemic intervals longer than 45 minutes produce non-reversible impairment of ATP synthesis and the marked reduction following 90 minutes of ischemia signifies possible transition to a non-viable state.

Adenosine Triphosphate↗
PubMed1988

Fatty acid metabolism in renal ischemia.

The increase in free fatty acids in the ischemic tissue is a consistent observation and these free fatty acids are considered to play a role in the cellular toxicity. To elucidate the cause of higher levels of free fatty acids in ischemic tissue, we examined the catabolism of fatty acids. The beta-oxidation of lignoceric (24:0), palmitic (16:0) and octanoic (8:0) acids and the peroxidation of fatty acids were measured at different times of renal ischemia in whole kidney homogenate. The enzymatic activities for the oxidation of fatty acids decreased with the increase in ischemia time. However, the lipid peroxide levels increased 2.5-fold of control with ischemic injury. Sixty min of ischemia reduced the rate of oxidation of octanoic, palmitic and lignoceric acids by 57, 59 and 69%, respectively. Almost similar loss of fatty acid oxidation activity was observed in the peroxisomes and mitochondria. These data suggest that loss of mitochondrial and peroxisomal fatty acid beta-oxidation enzyme activities from ischemic injury may be one of the factors responsible for the higher levels of free fatty acids.

Animals↗
PubMed1988

Necrotizing fasciitis in a renal transplant patient.

We have described a 28-year-old diabetic woman who had necrotizing fasciitis of the perineum three years after receiving a living related renal transplant. The diagnosis of necrotizing fasciitis was made early and she was referred to a tertiary care center where she received radical perineal debridement and aggressive medical and surgical follow-up. Necrotizing fasciitis in a transplant patient is rare; review of the literature shows few cases and no survivors. Our patient has returned to a normal life despite continuation of all immunosuppressive therapy throughout the entire hospital course. In addition, she had a good cosmetic result despite the large necrotic perineal infection. Her survival can be attributed to early diagnosis and referral, immediate and extensive debridement, and aggressive protein replacement.

Adult↗
PubMed1986

Prevention of acute tubular necrosis after transplantation: effect of pretransplantation volume expansion.

We reviewed our experience with 100 consecutive cadaveric transplants of kidneys from satisfactory donors with respect to immediate function after transplantation. The management was the same in all patients except that 66 of them received 1,000 ml of 0.9 N saline IV preoperatively. The overall incidence of acute tubular necrosis (ATN) was 23.2%, but the incidence of ATN in the group of patients who received saline was 7.6%, as compared to 53% in those that did not (P less than .001). There was no other significant difference between the two groups. We conclude that when cadaver kidneys are harvested and preserved under satisfactory conditions, preoperative volume expansion markedly lowers the incidence of posttransplantation ATN, suggesting that the recipient volume status is an important consideration.

Acute Kidney Injury↗
PubMed1985

Renal transplantation in Alport's syndrome.

Nineteen patients (3 women and 16 men) with Alport's Syndrome and endstage renal failure received 23 allograft kidneys at two medical centers between 1972 and 1983. Ten patients had pretransplant splenectomies, and four patients had pretransplant thoracic duct drainage. After a mean follow-up time of 49 months, analysis revealed total allograft survival was 65 per cent at 1 year, 50 per cent at 2 years, and 57 per cent at 5 years. Pretransplant splenectomy resulted in 60 per cent allograft survival at 24 months mean follow-up. Pretransplant thoracic duct drainage resulted in 100 per cent allograft survival at 15.6 months mean follow-up. The overall allograft survival was greatest for three and four antigen-matched kidneys and for living related donor kidneys. Data indicated that 50 per cent of all allografts in men were functional at 50.8 months mean follow-up. All allografts in women were functional at 48.3 months mean follow-up. Three of four patients who expired had pretransplant splenectomies. From this study, the authors conclude that renal transplantation is the preferred method of treatment for patients with Alport's Syndrome.

Adolescent↗
PubMed1983

Characterization of the preformed antibodies involved in the xenograft reaction.

The dog-to-sheep renal xenograft model was utilized to isolate the antibodies that participate in xenograft hyperacute rejection. These sheep antibodies, which were isolated from the rejected dog kidney, agglutinated and killed only dog blood and kidney cells whereas the whole sheep serum reacted with both dog and rabbit cells. The purified antibody was also utilized to obtain in pure form the antigens involved in the hyperacute rejection. When this antigen was tested for its ability to bind the serum of various species, this particular antigen was highly specific for sheep serum and would not react with rabbit, horse, calf, or mouse sera.

Animals↗
PubMed1983

Antigen-coated immunoadsorbents utilized for in vivo depletion of antibodies and lymphocytes with specificity for the antigen.

Hyperacute rejection of xenografts is thought to be triggered by humoral antibodies. It is known that natural antibodies against dog blood cells have been identified in sheep serum. Dog kidney antigen immunoadsorbent columns were placed in the extracorporeal lymph circuit of two sheep. In vivo studies have shown that these immunoadsorbent columns were effective in depleting the thoracic duct lymph of all antibodies with specificity for the dog kidney antigen. However, these columns were not effective in depleting the thoracic duct lymphocytes bearing surface receptors for the dog kidney antigen. When in vitro studies were carried out, the immunoadsorbent columns were effective in the depletion of both lymphocytes and antibody for the dog kidney antigen. Thus, since a humoral antibody response is thought to be responsible for the hyperacute rejection seen in xenografts, it is possible that these columns might be effective in prolonging xenograft survival.

Adsorption↗
PubMed1983

Reversal of acute renal failure using hemodilution with hydroxyethyl starch.

Acute renal failure (ARF) was induced in two groups of unilaterally nephrectomized dogs by occluding the renal artery, vein, and ureter of the remaining kidney for 2 hours. The control group (Group I), had no therapy; in the experimental group (Group II), isovolemic hemodilution was carried out using 6% hydroxy ethyl starch (HES) as diluent. The hematocrit in the experimental animals was lowered from 41.62 +/- 3.6% to 23.75 +/- 5.2% after renal occlusion. The mean arterial pressure and the mean pulmonary arterial pressure were unchanged in either group. Cardiac output increased following hemodilution from 1.66 +/- 0.35 to 2.70 +/- 0.50 L/min while it remained unchanged in Group I. Control animals developed ARF characterized by progressive rise in serum creatinine concentration and death. Only 1/7 Group I animals was alive on day 7 compared to 7/7 of Group II (p less than 0.01). ARF that developed initially in Group II began to resolve after day 4. There was a progressive and significant fall in serum creatinine concentration from 6.48 +/- 0.67 mg/dl on day 4 to 4.08 +/- 0.83 mg/dl on day 7 (p less than 0.001). Immediate isovolemic hemodilution with HES can reverse ARF induced by ischemia.

Acute Kidney Injury↗
PubMed1980

Dialysis enhances renal epithelial proliferations.

Study of 115 kidneys from 60 patients with chronic renal failure maintained by dialysis for two months to five years revealed an unexpected number and variety of epithelial proliferative processes, several types of which are hitherto unreported. Proliferative activity was defined either by the presence of epithelial structures in ectopic situations, continuity with existing structures being demonstrable by serial sections, or by mitotic figures, or by both. The tendency for renal carcinoma development may relate to these dialysis-related epithelial proliferations originating in both glomerular and tubular epithelia. Enhanced renal epithelial proliferative capacity in dialysis may be employable in the experimental study of renal regeneration and in the therapy of patients with preterminal renal disease.

Epithelium↗
PubMed1979

Studies of end-stage kidneys. III. Glycogen deposition in interstitial cells of the renal medulla.

Examination of kidneys of ten patients with uremia and severe hypertension treated by chronic intermittent hemodialysis revealed a deposition of glycogen within interstitial cells of the renal medulla. This is unlike any described renal distribution of glycogen. Electron microscopic studies performed in one case demonstrated monoparticulate glycogen both diffuse in the interstitial cell cytoplasm and locally aggregated beside lipid droplets. The findings provide evidence for a metabolic abnormality of renal medullary interstitial cells in patients who have protracted uremia.

Adult↗
PubMed1979

Brief note. Induction of experimental allergic encephalomyelitis in sheep with purified bovine basic protein and adjuvant.

A large animal model for the induction of experimental allergic encephalomyelitis to study the immunological disease parameters through closed-circuit extracorporeal thoracic duct filtration was successfully produced in two different strains of sheep. This study demonstrates the advantages of using a well-defined antigen to obtain both rapid onset of disease and a higher percentage of animals succumbing to the illness.

Animals↗