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K Post

Publications and source records attributed to K Post.

At least 55 records · Page 3Linked to original sources

The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase.

Rat liver dihydrodiol dehydrogenase (DDH, EC 1.3.1.20) has been shown to reduce the mutagenicity of benz[a]anthracene (BA) in the bacterial Ames test. BA-3,4-dihydrodiol is a highly mutagenic and tumorigenic metabolite of BA. In order to test the hypothesis that this dihydrodiol may be a substrate of DDH, we established two novel assay systems for the NADP(+)-dependent oxidation of BA-3,4-dihydrodiol by rat liver DDH, an HPLC-based assay procedure and a radiometric assay with specifically labelled [3,4-3H]-BA-3,4-dihydrodiol as substrate. With the HPLC-based assay, the kinetic constants of the enzymatic catalysis were as follows: Km(app) = 21 microM for BA-3,4-dihydrodiol and Vmax = 20.0 nmol/min.mg enzyme. The reaction product was identified by cochromatography, fluorimetry and mass spectroscopy as BA-3,4-catechol, but interconversions between the catechol and the corresponding o-quinone during the analytical procedures were detected. With the radiolabelled substrate, a linear relationship between substrate concentration and reaction velocity was found. The V/K value for labelled substrate was 0.155 ml/min.mg enzyme and a (V/K)H/(V/K)T kinetic isotope effect of 6.7 was observed. The non-labelled substrate acted as a competitive inhibitor of the enzymatic oxidation of tritiated BA-3,4-dihydrodiol with a Ki value of 56.4 microM. The reaction rates determined in this study suggest an important role of DDH activity in the metabolism of BA.

Alcohol Oxidoreductases↗

Hearing after retrolabyrinthine vestibular neurectomy.

Thirty-four patients underwent vestibular neurectomies between September 1984 and January 1989. The first 15 patients operated on through January 1987 (and followed for a minimum of 2 years) were evaluated separately for long-term hearing preservation and freedom from vertigo spells. Audiograms taken at 1 postoperative month revealed no change in the pure tone averages of 25 patients and showed improved hearing of 20 to 30 dB in 5 patients. Two patients sustained losses of 18.5 dB and 21 dB, respectively. The speech discrimination scores remained the same in 17 patients, improved in 9, and were reduced in 6. Audiograms performed 12 to 40 months postoperatively showed preservation of the pure tone averages and speech discrimination scores when compared with the earlier 1-month postoperative audiograms in 73% of the patients. The speech discrimination scores, however, tended to fluctuate with the symptomatic course of each disease. Two patients developed major vertigo spells 1 1/2 years following surgery. Postoperative ice-caloric testing revealed no responses in 25 patients and markedly reduced responses in 6. There were no major complications or facial paralysis. The retrolabyrinthine vestibular neurectomy is an effective way to control vertigo with preservation of hearing and an acceptably low incidence of complications and side effects.

Adult↗

Mass spectrometric peptide mapping analysis and structural characterization of dihydrodiol dehydrogenase isoenzymes.

The direct molecular weight determination and structural analysis of polypeptides and peptide mixtures have become amenable by the recent development of fast atom bombardment (FABMS) and 252Cf-plasma desorption (PDMS) mass spectrometry. FABMS and PDMS peptide mapping, i.e., the direct analysis of peptide mixtures resulting from proteolytic digestion, have been developed as powerful methods for the structural characterization of epoxide-metabolizing isoenzymes. The major advantage of this approach is provided by the selectivity of the endoproteolytic cleavage, combined with the specific and accurate molecular weight determination of complex digest mixtures containing peptides up to several thousands daltons in size. Furthermore, the mass spectrometric peptide mapping analysis can be combined with a range of protein-chemical modification reactions and with sequential degradation such as by carboxypeptidases. Both FABMS and PDMS peptide mapping have already been successfully applied to the structural differentiation of glutathione transferase and epoxide hydrolase isoenzymes in cases where references sequence data for at least one isoenzyme form was available. In the application described here, for a series of dihydrodiol dehydrogenase (DDH) isoenzymes with hitherto undetermined primary structures, a direct correlation between the structural differentiation from peptide mapping data and differences in their substrate specificities could be demonstrated. The mass spectrometric peptide mapping analysis of isoenzymes proved to be an efficient basis for the elucidation of the structure of one major DDH isoenzyme form; partial sequence data for this protein are reported.

Alcohol Oxidoreductases↗

[Diagnosis and differential diagnosis of hepatic artery aneurysms].

Four cases of intra- and extrahepatic aneurysms of the hepatic artery are discussed concerning the etiology, symptoms, therapy and complication rate. The diagnostic approach and problems in differential diagnosis are specified. Localization of the aneurysm and especially the relationship of the collateral circulation of the hepatic bed are essential to plan the therapy and are based on angiography. Interventional therapeutic techniques are favored for intrahepatic localization. Reconstructive or ablative surgery is indicated to treat the extrahepatic aneurysm.

Aneurysm↗

Effect of hypolipidemic compounds on lauric acid hydroxylation and phase II enzymes.

Treatment of male Fischer 344 rats with various hypolipidemic drugs of different peroxisome proliferating potency (1-benzylimidazole, acetylsalicylic acid, clofibrate, tiadenol) led to an induction of liver lauric acid hydroxylase, whereas probucol, which is not a peroxisome proliferator, did not induce this enzyme. Activity of bilirubin UDP-glucuronosyltransferase was increased by all the compounds tested. The highest increase was observed after treatment with acetylsalicylic acid (2.3-fold). High correlation (r = 0.953) was observed between the activities of lauric acid hydroxylase and the corresponding activities of cytosolic epoxide hydrolase reported previously. The amount of microsomal epoxide hydrolase was not changed by any of the compounds. Whereas clofibrate and tiadenol decreased glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as substrate, 1-benzylimidazole and probucol increased this activity. With 4-hydroxynonenal as a substrate qualitatively the same results were obtained with the exception that probucol did not affect the enzyme activity. When glutathione S-transferase activity was measured with cis-stilbene oxide as substrate only the more than five-fold increase after treatment with 1-benzylimidazole was significantly different from control values. Activity of dihydrodiol dehydrogenase was increased after treatment of rats with 1-benzylimidazole (1.5-fold), whereas application of tiadenol led to a decrease of enzyme activity. Feeding of male guinea pigs with clofibrate did not change the activity of peroxisomal beta-oxidation, cytosolic epoxide hydrolase or lauric acid hydroxylase. However, treatment with tiadenol caused an increase of these activities.

Animals↗

Congenital central diabetes insipidus in two sibling Afghan hound pups.

Congenital central diabetes insipidus was determined to be the cause of polydipsia and polyuria in sibling pups. Both pups were lacking adequate plasma arginine vasopressin concentration, compared with that in control dogs. Microscopic abnormalities were confined to the brain and pituitary gland in one pup. Without breeding trials of these dogs or their relatives, it cannot be determined whether the cause was familial.

Animals↗

Effects on pseudopregnancy, pregnancy and interoestrous intervals of pharmacological suppression of prolactin secretion in female dogs and cats.

Cabergoline, a new ergoline derivative, is a potent prolactin inhibitor. In this review, results are combined from previously published and unpublished blind laboratory and open clinical studies with cabergoline in pseudopregnant, pregnant and lactating bitches, in bitches with normal and prolonged cycles, and in pregnant queens. Dose-response studies in nursing bitches, using puppy weight as an endpoint, revealed that a dose of 5 micrograms/kg/day orally (for 5 days) was the optimal dose with a minimum of side effects. This dose effectively lowered blood prolactin concentrations in pregnant bitches and was partly luteolytic during the 1st half of gestation, and fully luteolytic during the 2nd half of gestation. Consequently, pregnancies were terminated in the 2nd half of pregnancy in the bitch, and in the queen. Treatment successes with pseudopregnancy and true and false lactation, including cases of eclampsia, were greater than 90%. The same level of success was seen in bitches with prolonged cycles (anoestrus). A 7-10-day treatment period resulted almost uniformly in oestrus, and restored fertility in greater than 80% of all bitches mated. Cycles were occasionally shortened in bitches treated for false lactation. Attempts to shorten cycles routinely in beagle bitches, in a commercial breeding operation, with a dose of 5 micrograms/kg/day for 14 days during months 4, 5 or 6 of the cycle were unsuccessful.

Abortion, Spontaneous↗

Immunological approaches to contraception in dogs.

The demand for safe, effective and cost-efficient means of pet population control has generated interest in the development of alternatives to surgical gonadectomy. The purpose of this review is to discuss the potential of immunological approaches to fertility control and to outline recent developments that may aid their design. Among the most promising candidates for immunoneutralization is gonadotrophin releasing hormone (GnRH). We have developed a reliable and reproducible GnRH-protein conjugate antigen and demonstrated that immunologically induced infertility is possible in dogs.

Adjuvants, Immunologic↗

Functional organization of the murine leukemia virus reverse transcriptase: characterization of a bacterially expressed AKR DNA polymerase deficient in RNase H activity.

The functional organization of the murine leukemia virus reverse transcriptase was investigated by expressing a molecular clone containing AKR MuLV reverse transcriptase-coding sequences in Escherichia coli. A purified preparation of the expressed enzyme (pRT250 reverse transcriptase) consisted primarily of a 69-kilodalton protein that has normal levels of murine leukemia virus polymerase activity but 10-fold-reduced levels of RNase H compared with the viral enzyme. The deficit in RNase H activity was correlated with the absence of 60 to 65 amino acids normally present at the carboxyl end of murine leukemia virus reverse transcriptase. The results provide additional experimental evidence for the localization of polymerase and RNase H domains to the N- and C-terminal regions of reverse transcriptase, respectively.

AKR murine leukemia virus↗

Medium dose cyproterone acetate (CPA): effects on hormone secretion and on spermatogenesis in men.

Medium dose cyproterone acetate (CPA; 10 mg daily p.o.) was administered to 10 fertile men for 12 weeks. Hormonal measurements and semen analyses were performed before, during (4th and 12th week) and after CPA treatment. At the hypothalamo-pituitary level CPA significantly reduced the hypophyseal storage and synthesis capacity for gonadotropins. Basal LH and FSH concentrations were suppressed by 30% and 40%, respectively; while basal prolactin was elevated by 75%. The episodic fluctuations of peripheral gonadotropins remained unaffected. At the testicular level CPA significantly decreased basal testosterone and dihydrotestosterone concentrations by 70% and 50%, respectively. The pulsatile pattern of androgen secretion was abolished. CPA also inhibited spermatogenesis and motility. No serious clinical side effects were observed. All changes appeared to be completely reversible. It is concluded that medium dose CPA induces progestational/anti-gonadotropic effects at the hypothalamo-pituitary level in addition to its antiandrogenic action at the testicular level.

Adult↗

Feline urological syndrome.

A case of feline urolithiasis is described. It was demonstrated that serial determinations of renal function were mandatory in order to provide a favorable prognosis. Because hyperkalemia was present, the fluid of choice for the initial treatment was saline. The various considerations in the prevention, treatment and monitoring of cats with feline urolithiasis syndrome are discussed.

Animals↗

Leukophages in canine semen.

Spermiophages and leukophages were found in teratozoospermic canine semen. Spermiophagy was the role of neutrophilic granulocytes. Leukophages are believed to be oversize macrophages transformed by and released from a chronic inflammatory lesion in the pelvic urethra or the prostate. The term leukophages was adopted to indicate that the cells phagocytize leukocytes, specifically neutrophilic granulocytes. Direct observations on living cells revealed a surprising interaction between these two cell types. It is inferred that neither of the phagocytic cells are related to the disturbed spermiogenesis nor the teratozoospermia.

Animals↗