PubMed Health⌕ Search

Biomedical subjects

K Post

Publications and source records attributed to K Post.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of antisense DNA on POMC mRNA and ACTH levels in cultured human corticotroph adenoma cells.

Antisense oligonucleotides have been investigated in recent years as potential new therapeutic agents because of their ability to shut off gene expression. Antisense DNA and RNA oligomers can bind specifically to mRNA preventing protein translation. We have studied the ability of an antisense POMC oligomer to reduce the expression of POMC in human ACTH-secreting pituitary adenoma cells cultured from 2 uncommon ACTH-secreting macroadenomas. In separate experiments, tumor tissue was enzymatically dispersed, cultured for 4 days, and treated with and without an antisense POMC oligonucleotide for 18 hours. In addition, cells from one tumor were treated with dexamethasone and cells from the other tumor were treated with an unrelated oligomer as controls. RNA was prepared from cultured cells and POMC mRNA was quantitated in a RNase protection assay using a human POMC RNA probe. ACTH in the media was quantitated by RIA. Tumor cells responded to 250 nmol/L dexamethasone with diminished POMC mRNA and ACTH levels 18 hours after treatment (decreased by 28% and 67% of control respectively). In both tumors, a POMC antisense oligomer at a concentration of 50 mumol/L lowered POMC mRNA levels and detectable ACTH levels in the media 18 hours after treatment, with mRNA levels decreased by 76% and 62% of control and ACTH levels decreased by 58% and 48% of control. Conversely, tumor cells treated with an unrelated oligomer at a 50 mumol/L concentration showed minimal effect on POMC mRNA and ACTH levels 18 hours after treatment (decreased by 2.3% and 1.5% of control respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Regiospecific reduction of polycyclic aromatic quinones by rabbit liver dihydrodiol dehydrogenases.

Dihydrodiol dehydrogenase (DDH) isoenzymes were purified from rabbit liver (Klein et al., Eur. J. Biochem., 205 (1992) 1155), and the major forms CF-1, CF-5 and CM-2 were tested for their substrate specificity with dihydrodiol and quinone metabolites of polycyclic aromatic hydrocarbons. CF-5, which was shown to correspond to aldehyde reductase in rabbit liver, was found to efficiently oxidize aromatic dihydrodiol metabolites (phenanthrene-1,2-dihydrodiol, benz[a]anthracene-3,4-dihydrodiol) while CF-1, corresponding to carbonyl reductase, and CM-2 were much less active. All three enzyme forms were found to reduce polycyclic K-region o-quinones of benz[a]anthracene, chrysene and benzo[a]pyrene. CF-1 was the least active, and CM-2 was the most active form with reaction velocities of > 10 mumol/min.mg protein. Among a range of synthetic quinones tested, benz[a]anthracene-8,9-quinone and benzo[a]pyrene 9,10-quinone were also good substrates for the three enzymes, as well as p-benzoquinone and naphthalene-1,4-quinone. The reduction of polycyclic o-quinones, but not of p-benzoquinone, by enzyme CM-2 was accompanied by the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the formation of catechol metabolites from dihydrodiols and o-quinones may be catalyzed by the same enzymes in rabbit liver, and the reaction rate of the enzymatic reduction is strongly dependent on the structural type of the polycyclic quinone.

Alcohol Oxidoreductases↗
PubMed1994

c-myc, c-fos, and c-myb gene expression in human pituitary adenomas.

The possible roles of certain oncogenes in the development of pituitary tumors has not been investigated. We have examined the expression of c-myc, c-fos, and c-myb in a number of human pituitary tumors by ribonuclease protection assays, as these oncogenes have been implicated to have roles in the pathogenesis of other human tumors (12, 13, 15, 16). In several tumors examined (9 of 30) c-myc was expressed at levels 4-9 times greater than the level detected in normal postmortem pituitary. Although a larger percentage of negative immunohistochemical-staining tumors overexpressed c-myc, c-myc over-expression was not limited to this group of tumors. c-Fos was overexpressed in 1 of 30 tumors examined at a level 5.8-fold higher than that detected in normal postmortem pituitary. This tumor stained positive for ACTH by immunohistochemistry and was considered highly aggressive, demonstrating invasion beyond the sella turcica; however, when other ACTH-staining and invasive pituitary tumors were examined, no abnormality in the expression of c-fos was detected. In 30 tumors, c-myb was expressed at approximately the same level as that detected in normal postmortem pituitary. We conclude that c-myc is overexpressed in a subgroup of pituitary tumors and that this overexpression occurs broadly among the different groups of immunohistochemical-staining tumors. c-Fos overexpression appears to be much less common in pituitary tumors and does not necessarily correlate with the ability of the tumor to become invasive. c-Myb does not appear to have a role in the pathogenesis of pituitary tumors.

Adenoma↗
PubMed1994

Management of the eye after iatrogenic facial paralysis.

The aesthetic and functional morbidity associated with facial palsy is significant. Fortunately, corneal exposure and ulceration with the potential for the loss of visual acuity can be minimized by eyelid procedures such as gold weight implantation and horizontal eyelid shortening. Although primarily designed for restoration of eyelid function, these procedures also improve ocular cosmesis. However, uncertainty remains regarding the indications for eyelid surgery: When should surgery be performed, in whom, and which procedure(s)? On the basis of our series of 60 patients evaluated for facial paralysis, guidelines for the management of the paralyzed eyelids after iatrogenic injury to the facial nerve are proposed.

Corneal Ulcer↗
PubMed1994

[Stent angioplasty of the intrarenal aorta and aortic bifurcation. Clinical and angiographical results of a prospective study].

PURPOSE: The study was carried out to evaluate clinical and technical success, early and late complications and patency rates after stent angioplasty of atherosclerotic stenoses and occlusions of the infrarenal abdominal aorta and aortic bifurcation. PATIENTS AND METHODS: This was a prospective study in 20 consecutive patients treated by implantation of balloon-expandable stents. All patients were followed-up after 6 and 12 months and at yearly intervals thereafter by physical examination, Doppler sonography and angiography. RESULTS: Nineteen of 20 patients had clinical and technical success. In two patients clinically relevant complications occurred. During a mean observation time of 19 months (range 3-51 months) restenosis occurred in one stent after 15 months and was successfully treated by balloon angioplasty. Two patients became symptomatic again due to new atherosclerotic disease. CONCLUSIONS: Percutaneous stent angioplasty of the infrarenal aorta and aortic bifurcation yields high immediate and mid-term success rates with primary patency of 90% and secondary patency of 95%. These results are slightly better than those with balloon angioplasty, but the limited number of patients in our and others' studies does not yet justify general recommendations.

Adult↗
PubMed1993

A large deletion in the connection subdomain of murine leukemia virus reverse transcriptase or replacement of the RNase H domain with Escherichia coli RNase H results in altered polymerase and RNase H activities.

The functional relationship between the polymerase and RNase H domains of reverse transcriptase (RT) was investigated by studying the activities of AKR murine leukemia virus (MuLV) enzymes. In addition to the wild type, an RNase H-minus RT missing the entire RNase H domain and two other mutants having abnormal polymerase:RNase H ratios were expressed. These mutants include (i) a chimeric protein in which the MuLV RNase H domain was replaced by the entire Escherichia coli RNase H sequence and (ii) an RT with a 126 amino acid deletion in a region analogous to the "connection" subdomain in the p66 subunit of human immunodeficiency virus type 1 RT (Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1992) Science 256, 1783-1790). With the wild-type RT, the major RNase H cleavage reaction was coordinated with DNA synthesis and occurred at a position corresponding to 15 nucleotides from the 3'-terminus of the DNA primer. Additional cleavages closer to the 5'-end of the RNA were explained in terms of a model relating binding of the RNA.DNA hybrid substrate and enzyme structure. The chimeric RT behaved like E. coli RNase H, exhibited 300-fold higher RNase H activity than wild-type RT, and was limited in its ability to synthesize DNA. Qualitative and quantitative changes in the polymerase and RNase H activities of the deletion mutant were also observed. The RNase H domain appeared to function independently of the polymerase domain, supporting the idea that the proper spatial relationship between the two active centers was disrupted by the mutation. Taken together, our results indicate that alteration of the normal polymerase:RNase H ratio can have profound effects on both polymerase and RNase H cleavage activities, as expected for an enzyme with two interdependent domains.

Animals↗
PubMed1993

Effects of four different extenders and three different freezing rates on post-thaw viability of dog semen.

Ejaculates were collected from 17 dogs. After initial evaluation the ejaculates were split into four equal aliquots and diluted with either Triladyl, Pipes, IMV Universal or Tris-fructose-citric acid extender, all containing egg yolk and glycerol. The extended semen was frozen in 0.5 ml straws at a slow, intermediate or fast freezing rate. After thawing, the percentage of progressively motile spermatozoa and the velocity of forward motion was evaluated. There was no difference between the extenders with regard to progressive motility. The slow, intermediate and fast freezing rates resulted in the highest, intermediate and lowest motility values, respectively, regardless of extender. All four extenders were equally suitable for freezing canine semen at a slow freezing rate.

Animals↗
PubMed1993

Lack of effect of trimethoprim and sulfadiazine in combination in mid- to late gestation on thyroid function in neonatal dogs.

Four pregnant bitches were randomly selected and were given 25 mg sulfadiazine kg-1 and 5 mg trimethoprim kg-1 orally once daily, starting on day 29 of dioestrus until parturition. Five untreated pregnant bitches were used as controls. At the end of the treatment period (parturition = week 0), one to three pups of each litter, treatment and control group, were randomly selected and blood was obtained by cardiac puncture for serum thyroxine (T4) and triiodothyronine (T3) concentrations. These pups were then killed and the thyroids were harvested and examined histologically. This protocol was repeated three times at weekly intervals. There were no significant differences in mean T4 and T3 concentrations between treated and control groups at any time during the study. Mean concentration of serum T4 and T3 did increase significantly over the 3 weeks of study. Histologically, no significant differences in thyroid structure were observed between treated and control groups. The numbers of stillborn or weak pups did not increase in the treatment group. No differences were observed in the length of gestation between the treated and control groups. Administration of sulfadiazine and trimethoprim does not affect the thyroid gland in the neonate.

Animals↗
PubMed1993

[Dialysis-associated amyloidosis. Part 1: Biochemistry, clinical aspects, roentgen morphology].

Dialysis-related amyloidosis is characterized clinically by the carpal tunnel syndrome, pain and swelling of joints. These alterations are due to amyloid deposits in the carpal tunnel, in the synovia, ligaments and bones. It has been shown that beta 2m is the major component of this amyloidosis. Serum and urine concentration of beta 2m are markedly elevated in chronic renal failure due to failure of filtration and lack of metabolism by the renal tubular epithelium. beta 2m-derived amyloid is identified by immunohistochemistry using antibodies derived against beta 2m. Radiology shows cyst-like periarticular bone defects, destructive arthropathy and spondylarthropathy.

Amyloidosis↗
PubMed1993

[Dialysis-associated amyloidosis. Part 2: Incidence and site of osseous amyloidosis. Dialysis characteristics and clinical findings].

In a conventional radiographic skeletal survey of 90 hemodialyzed patients, 28% (25 patients) showed renal osteopathy; 27 patients (30%) had periarticular bone cysts and 3 patients (3%) presented radiological evidence of destructive spondylarthropathy. The bone cysts were most commonly identified in the carpal bones and around the hips and shoulders; destructive spondylarthropathy was seen in the cervical and lumbar spine. Whereas characteristic radiographic changes of renal osteodystrophy could already be identified in the 1st year of dialysis, periarticular bone cysts occurred at the earliest after 2 years, most frequently after 5 years of dialysis. Destructive spondylarthropathy was seen after more than 10 years of dialysis. A positive correlation between these bone lesions and secondary hyperparathyreoidism, dialysis membranes or renal diseases was not found.

Adult↗
PubMed1992

Quinone reduction and redox cycling catalysed by purified rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase.

A highly active preparation of rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase was obtained using a newly developed, rapid purification scheme involving affinity chromatography on Red Sepharose. Depending on the coenzyme present, the purified enzyme was found to catalyse the oxidation of dihydrodiols and steroids or the reduction of substrates with carbonyl or quinone moieties. Using a wide range of synthetic quinones derived from polycyclic aromatic hydrocarbons (PAHs), we observed a pronounced regioselectivity of the quinone reductase activity. Good substrates were the o-quinones of phenanthrene, benz(a)anthracene, chrysene and benzo(a)pyrene with the quinonoid moiety in the K-region which were reduced at rates of 1-10 mumol/min.mg enzyme. 1,4-Benzoquinone, naphthalene-1,2-quinone and benz(a)anthracene-8,9-quinone were also reduced at high rates. In contrast, alkyl-substituted quinones such as duroquinone and menadione were poor substrates for the enzyme. During the enzymatic reduction of several o-quinones, but not 1,4-benzoquinone, we observed the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the reduction of quinones of PAHs may lead to a facilitated conjugation and excretion of these highly lipophilic compounds, but may also initiate toxic processes due to the formation of reactive oxygen species.

Animals↗
PubMed1992

Dihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.

1. Dihydrodiol dehydrogenase activities were investigated in rabbit liver. Using a five-step purification scheme, eight isoenzymes of dihydrodiol dehydrogenase with isoelectric points of 5.55-9.3 and promoter molecular masses of 34-35 kDa were purified to apparent homogeneity and designated CF-1 to CF-6, CM-1 and CM-2. 2. CF-1 and CF-2 had near-neutral isoelectric points of 7.4 and 6.8 and molecular masses of about 125 kDa in the native state. Both enzymes readily accepted NAD+ as well as NADP+ as coenzymes, had relatively low Km values of 0.33 mM and 0.47 mM for benzene dihydrodiol and resembled previously described carbonyl reductases in their substrate specificity towards ketones and quinones. 3. CF-5 and CF-6 had acidic isoelectric points of 5.9 and 5.55 and native molecular masses of approximately 60 kDa. They displayed a strong preference for NADP(H) as coenzyme and had high Km and Vmax with benzene dihydrodiol. Since these enzymes reduced p-nitrobenzaldehyde and glucuronic acid efficiently, they appeared to be closely related to aldehyde reductase. 4. CF-4 had a high 3 alpha-hydroxysteroid dehydrogenase activity for the diagnostic substrate androsterone, a moderate activity for other 3 alpha-hydroxysteroids as well as 17 alpha-hydroxysteroids, and relatively low activities for 3 beta-hydroxysteroids and 17 beta-hydroxysteroids. CF-5 and CM-1 had high 17 beta-hydroxysteroid dehydrogenase activity for the diagnostic substrate 5 alpha-dihydrotestosterone, and low to moderate activities for other 17 beta-hydroxysteroids as well as 3 alpha-hydroxysteroids. 5. The isoenzyme CM-2 had an isoelectric point of 9.3 and was a very active quinone reductase with phenanthrene-9,10-quinone as substrate. It was potently inhibited by phenobarbital. 6. We conclude that the dihydrodiol dehydrogenase activities of rabbit liver are associated with aldehyde and carbonyl reductase and with 3 alpha-hydroxysteroid and 17 beta-hydroxysteroid dehydrogenases.

Alcohol Oxidoreductases↗
PubMed1992

Renal artery aneurysm: surgical indications and results.

The clinical course of 23 patients with 28 renal artery aneurysms (RAAs) is reported. The RAAs were recorded over a period of 10 years. Thirty-five per cent of the RAAs (eight of 23 patients) were detected during the investigation of hypertension, whereas 26% (six of 23 patients) were discovered incidentally while imaging atherosclerotic arterial disease in the aorto-iliac region by angiography. Twenty-two aneurysms were treated surgically and primary nephrectomy was necessary in one case. The surgical technique used was excision of the aneurysm with bypass grafting in 13 cases (seven Dacron, five vein, one arterial bypass), a running suture following aneurysm excision in four cases and an end-to-end anastomosis in two cases. The results (for a period of 1-10 years) were excellent in all but three cases: two early graft occlusions (vein interposition) and one late occlusion (Dacron bypass) in the course of a re-operation which had become necessary because of a ruptured aneurysm of the gastro-epiploic artery after 3 months. Three of 23 patients were treated by embolisation of four intraparenchymal aneurysms. The follow-up of a non-treated saccular aneurysm showed a total thrombosis of the aneurysm within 4 years and fixed renal hypertension developed later in this patient. We suggest surgical repair of an RAA regardless of its size and the clinical symptoms, in order to prevent microembolism into the renal parenchyma and to avoid the development of fixed renal hypertension. Intrarenal aneurysms can be treated by embolisation to stop severe haematuria thus preserving the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Immediate reversible rehabilitation of the paralyzed eyelid.

Skull base surgeons are frequently required to operate in close proximity to the facial nerve. At times, a skull base tumor is resected with the facial nerve grossly infact, only to have the patient awaken with a unilateral facial paresis or paralysis. In the selected cases where the surgeon is certain that the facial nerve has been left intact and return of function is expected, methods are needed to ameliorate the temporary paresis or paralysis of the eyelids. In our institution, eyelid closure has been achieved by placement of a gold weight in the upper eyelid. These weights were placed with the knowledge that they could be removed once facial nerve function returned. We report on 11 such patients who had gold weights placed within 3 weeks of their original intracranial or skull base procedure. All patients were discharged with adequate eyelid closure. Three patients later required lower lid surgery for poor tone or persistence of paralysis. Our experience is reviewed and our recommendations concerning the management of temporary facial paralysis of the eyelids is presented.

Journal Article↗
PubMed1992

Measurement of 3-D facial contours for the design of half-face respirators.

A portable anthropometric test rig capable of obtaining three-dimensional face shape data was developed and used to obtain information relating to facial shape, stiffness, and variance for a selected subgroup of respirator users in the Australian work force. A respirator seal shape most suited to the sample population was obtained by studying the central portion of the face of all the subjects. The optimum seal shape was established by following the path of minimum variance among all the faces; the method provided information on the shape, dimensions, and stiffness of the optimum seal for a respirator suited to the sample population. The seal surface flexibility required for a comfortable fit was determined by measuring the deflection of the skin caused by an applied pressure and using this information along with face shape variance data. Results indicated that the required flexibility in the seal surface increased toward the lower portion of the face.

Anthropometry↗
PubMed1992

Effect of oral administration of sulfadiazine and trimethoprim in combination on thyroid function in dogs.

The effect of oral administration of sulfadiazine and trimethoprim in combination on serum concentrations of thyroxine (T4), triiodothyronine (T3) and free thyroxine (fT4) and the thyroid hormone response to thyrotropin administration was assessed. Six dogs were administered sulfadiazine (12.5 mg/kg) and trimethoprim (2.5 mg/kg) orally for 28 days; six untreated dogs acted as controls. Serum T4, T3 and fT4 were determined weekly during and for four weeks after treatment. Thyrotropin response tests were performed prior to treatment, after four weeks of treatment and three weeks after stopping treatment. There were no significant differences in mean serum T4, T3 or fT4 concentrations between treated and control groups at any time during the study. Mean concentration of serum T4 over time did not differ significantly from baseline concentration in either group. Significant differences in the mean serum T3 and fT4 concentrations occurred at several time points in treatment and control groups, and were apparently unrelated to treatment. Significant differences in the T4 or T3 response to thyrotropin administration within or between groups were not present. Serum T3 and fT4 concentrations fluctuate in normal dogs. Administration of sulfadiazine and trimethoprim in combination does not affect tests of thyroid function in the dog.

Administration, Oral↗
PubMed1991

[Renal artery aneurysms].

Between 1980 and 1990, 21 patients with 26 renal artery aneurysms (0.4-16.5 cm in diameter) were diagnosed and treated at the Surgical Center, University of Heidelberg. Surgical reconstructive methods were applied to treat extrarenal and interventional embolization to treat intrarenal aneurysms. The most effective diagnostic method is selective intraarterial angiography. The etiology, age distribution, localization and clinical aspects are discussed. Four bleeding intrarenal aneurysms were embolized with full preservation of renal function (one solitary kidney). After surgical reconstruction of the aneurysmatic vessel, 80% of the hypertensive patients turned normotensive. Follow-up of a nontreated sacciform aneurysm showed total thrombosis within 4 years. In the same period, fixed renal hypertension developed in the patient because of recurrent microembolism in the renal parenchyma. Therefore, we suggest immediate treatment of a renal aneurysm to prevent the development of renal hypertension.

Adult↗