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C Wittenberg

Publications and source records attributed to C Wittenberg.

61 records · Page 4Linked to original sources

Effect of dehydration and rapid rehydration on renal function and on plasma renin and aldosterone levels in the black Bedouin goat.

Bedouin goats in the extreme deserts of the Middle East are regularly subjected to severe dehydration and possess a capacity to rapidly rehydrate by drinking large volumes of water. Urine flow, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the fully hydrated animals amounted to 0.74 +/- 0.4 ml X min-1, 76 +/- 29 ml X min-1 and 344 +/- 146 ml X min-1 respectively. In goats that were dehydrated to a loss of about 30% of their initial body weight, urine flow dropped to 24% of the value recorded in the hydrated animals and GFR and ERPF dropped to half their level recorded in the hydrated phase. Na and K+ excretion decreased in the water depleted goats and further decrease was recorded following drinking. Following drinking the urine flow, GFR and ERPF of the recently rehydrated goats dropped to below the rates recorded in the dehydrated animals. During the 3 h of the continuous recording that followed the drinking, all three rates did not exceed the predrinking level. Plasma renin activity amounted to 0.37 +/- 0.32 ng AI X ml-1 X h-1 in the hydrated animals. In dehydrated ones it amounted to 4.8 +/- 2.8 ng AI X ml-1 X h-1 and a further increase was recorded following drinking. Aldosterone in the hydrated goats was 5.5 +/- 4.3 ng% and increased to 13.9 +/- 2.3 ng% in the dehydrated animal and amounted to 20.1 +/- 5.5 ng% 2 h following drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

A detergent-activated tyrosinase from Xenopus laevis. I. Purification and partial characterization.

A tyrosinase has been purified from the skin of the frog Xenopus laevis. Dihydroxyphenylalanine oxidase and tyrosine hydroxylase activities co-purify throughout the procedure. The enzyme is isolated in an inactive form, but both enzymatic activities are activated by a variety of anionic detergents. Of these, sodium dodecyl sulfate (NaDodSO4) is the most effective. The enzyme activation occurs at NaDodSO4 concentrations well below the critical micelle concentration and it remains active at concentrations as high as 30 mM (1%). Neither activity is stimulated by cationic or nonionic detergents, or a variety of other agents, including trypsin. The purified tyrosinase is a glycoprotein having a polypeptide Mr = 175,000 by NaDodSO4-polyacrylamide gel electrophoresis. This monomeric species is enzymatically active in the presence of NaDodSO4. Detergent-activated tyrosinase has a KM for dihydroxyphenylalanine of 6 X 10(-4) M and a KM for tyrosine of 4 X 10(-4) M. Both activities are inhibited by copper chelators but not by an iron chelator. Further characterization of the detergent activation of this enzyme is presented in a companion paper (Wittenberg, C., and Triplett, E. L. (1985) J. Biol. Chem. 260, 12542-12546).

Animals↗

A detergent-activated tyrosinase from Xenopus laevis. II. Detergent activation and binding.

Tyrosinase purified from Xenopus is enzymatically inactive in aqueous buffers but is activated for both of its substrates by exposure to a variety of anionic detergents. Cationic and nonionic detergents, as well as a variety of other agents are ineffective. This stimulation by detergents is observed at all stages of the purification (Wittenberg, C., and Triplett, E. L. (1985) J. Biol. Chem. 260, 12535-12541). Sodium dodecyl sulfate (NaDodSO4) is the most effective activator, and it was chosen for further characterization. Activation of both activities by NaDodSO4 is rapid and concentration dependent, resulting in maximal activity after 4 min at 1 mM NaDodSO4. NaDodSO4 treatment also results in both long and short term stabilization of the enzyme. The activation and stabilization are separable but stoichiometrically related. Both effects occur well below the critical micelle concentration suggesting that the interaction of NaDodSO4 monomers with the enzyme is involved in these processes. In support of this suggestion, the enzyme is shown to bind NaDodSO4 with high affinity, as determined by equilibrium dialysis. The isotherm for this binding correlates well with the requirement of NaDodSO4 for both activation and stabilization. All three effects are observable at 3 X 10(-5) M NaDodSO4 in the presence of 0.1 M sodium chloride. Activation and stabilization are maximal at 6 X 10(-4) M NaDodSO4, the critical micelle concentration of NaDodSO4 under these conditions.

Animals↗

Empiric antibiotic treatment of infections in myelosuppressed cancer patients. Preliminary results.

A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B). Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients. About two-thirds of the patients treated with either regimen responded to this antibacterial therapy. The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D). With these schedules, the over-all response rate was increased to about 90%. The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.

Adult↗

Is secondary hyperparathyroidism an important etiologic factor in the anemia of chronic renal failure?

Twenty patients with chronic renal failure being treated with hemodialysis were investigated in an attempt to ascertain whether hyperparathyroidism is an important etiologic factor in these patients' anemia. The patients were divided into two groups, one with hemoglobin of greater than 8 g/dl and the other with hemoglobin of less than 8 g/dl. These groups differed in blood transfusion requirements and in serum iron saturation. There was no difference between their levels of serum calcium, serum phosphate, serum alkaline phosphatase or serum parathyroid hormone. On bone biopsy endosteal fibrosis with bone marrow involvement was found in 2 of the 11 patients with high hemoglobin and in 5 of the 9 patients with low hemoglobin. Endosteal fibrosis with bone marrow involvement may thus be an important factor in the pathogenesis of anemia, and its presence or absence in association with hyperparathyroidism may explain the controversial observations reported by other investigators.

Adult↗

The effects of proxazole on renal function in chronic renal failure.

3-alpha-Phenyl-propyl-5-beta-diethylaminoethyl-1,2,3-oxadiazole (proxazole), a spasmolytic papaverine-like agent, was i.v. administered to 13 patients with chronic renal failure (mean creatinine clearance 46.4 ml/min/1.73 m2), but did not improve renal plasma flow (p-aminohippurate clearance) or glomerular filtration rate (inulin clearance), nor did this agent prevent or modify nor-adrenaline induced renal ischemia. The oral administration of 400 mg proxazole (5.2--6.5 mg/kg/day) for a period of at least 90 days did not improve renal function in 11 patients with chronic renal failure. It is concluded that both i.v. and p.o. administration of proxazole in the dosages used is ineffective in improving renal function in patients with chronic renal failure.

Administration, Oral↗

Amphibian embryo protease inhibitor. V. Effect of calcium on the distribution of amphibian trypsin inhibitor during fertilization and subsequent development of Rana pipiens.

In previous publications we have documented the existence in oocytes and embryos of a variety of forms (notably Rana pipiens), massive amounts of a powerful inhibitor of trypsin-like enzymes (ATI). The bulk of the inhibitor in Rana pipiens is localized in yolk platelets. We present evidence here that the distribution of the inhibitor between yolk platelets and cytosol changes and that this change is mediated by variations in the distribution of calcium ions. There is an inverse relationship between ATI and free calcium in the cytosol. Several workers have demonstrated a dramatic rise in free cytosol calcium immediately following fertilization. We confirm this observation, and demonstrate that there is a parallel and equally dramatic decrease in free cytosol ATI during this period. Experiments with purified yolk platelets indicate that calcium effects a release of sequestered inhibitor from these particles. Other experiments indicate that calcium mediates ATI-lippovitellin associations. A calcium mediated flux of ATI from cytosol to yolk is proposed as a device for controlling limited proteolysis in the cytoplasm. We offer this as a model for studying the unmasking of mRNA which follows fertilization.

Animals↗