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Biomedical subjects

K Mueller

Publications and source records attributed to K Mueller.

At least 91 records · Page 5Linked to original sources

Progressive cardiac involvement by Fabry's disease despite successful renal allotransplantation.

Enzyme replacement by renal allotransplantation has been suggested as a specific mode of therapy for Fabry's disease. We report a case of Fabry's disease who developed symptoms and signs of heart failure despite successful renal transplantation 14 years ago. Echo- and angiocardiographic features resembled findings in patients with hypertrophic non-obstructive cardiomyopathy. Endomyocardial biopsy specimens demonstrated cardiac manifestation of Fabry's disease.

Biopsy↗

Isolation and characterization of DNA-dependent RNA polymerase I of Tetrahymena pyriformis.

A procedure for the separation and purification of DNA-dependent RNA polymerases [EC 2.7.7.6] from macronuclei of Tetrahymena pyriformis is described. We have used it to isolate and characterize the class I enzyme. RNA polymerase I was identified by its resistance against alpha-amanitin and its location in nucleoli. The purified enzyme consists of at least 12 major subunits with approximate molecular weights of 180,000, 118,000, 37,500, 36,000, 29,000, 27,500, 20,000, 18,500, 15,600, 14,500, 13,500, and 12,600. Chromatography on DEAE-Sephadex separated two forms of RNA polymerase I which differed in the presence of an additional polypeptide of 25 kDa. Independently of this polypeptide, the enzyme was found to segregate on DNA cellulose into a binding and a non-binding fraction. This type of heterogeneity was found to be unrelated to differences in molar ratios or molecular weights of the enzyme subunits. The catalytic properties of all enzyme subfractions were very similar and complied with the general characteristics of RNA polymerase I [cf. Roeder, R.G. (1976) in RNA Polymerase (Losick, R. & Chamberlin, M., eds.) pp. 285-329, Cold Spring Harbor Publ. Co., New York].

Animals↗

Effect of DNA gyrase inactivation on RNA synthesis in Escherichia coli.

The average chain growth rates of rRNA and of total RNA were not affected by a thermal inactivation of DNA gyrase in a temperature-sensitive gyrB mutant of Escherichia coli. The fact that total RNA synthesis decreased under these conditions suggests that transcription is primarily affected at the step of chain initiation. The fraction of rRNA in total pulse-labeled RNA was not altered by inactivation of the enzyme, indicating that the latter is not required to actively maintain a high rate of synthesis of this RNA species.

Escherichia coli↗

Gene expression in a temperature-sensitive gyrB mutant of Escherichia coli.

The effect of gyrase inactivation on gene expression was studied by examining the activities of different promoters in a temperature-sensitive gyrB mutant of Escherichia coli. The relative activities of promoters affected by cAMP-binding protein (CAP), e.g., the lac promoter, are not reduced by gyrase inactivation but can, on the contrary, be enhanced. This stimulation depends on the promoter location or its structure. The tnaA promoter is activated when located near the origin of replication, suggesting a differential effect of gyrase inactivation on various chromosomal domains. Only silent or mutant promoters such as the non-functional wild-type bgl or the lacIq can be activated. No differential effect of gyrase inactivation on the lambda pL and the trp promoters carried by the phage can be detected.

Bacterial Proteins↗

Clonidine potentiates drug induced self-injurious behavior in rats.

Caffeine and amphetamine have been regarded as dramatically dissimilar drugs, both structurally and behaviorally. However, both are stimulants and (under certain conditions) both produce self-injurious behavior in rats which is potentiated by clonidine. Rats were pretreated with various doses of clonidine prior to daily administration of caffeine. In another experiment, rats which had been implanted with continuous release amphetamine pellets were injected twice daily with various doses of clonidine. Clonidine produced a high rate of self-biting when combined with subthreshold doses of caffeine. Clonidine was less effective in potentiating amphetamine induced self-biting; the highest dose tested raised the incidence from 28 to 64%. Clonidine tended to decrease the incidence of behaviors other than self-biting. Thus although caffeine and amphetamine clearly do not have identical behavioral effects, there is increasing evidence that certain of their effects are mediated by similar mechanisms.

Amphetamine↗

Ultrashort hemodiafiltration: efficiency and hemodynamic tolerance.

During hemodiafiltration, solutes are removed simultaneously by diffusion and convection. Increase of the fraction removed by diffusion, by using large surface area hemodiafilters, allows a further reduction of treatment time by hemodiafiltration. To assess the efficiency and biochemical safety of ultrashort treatment (mean duration 3 X 105 +/- 14 min/week) six patients (age 22-64) have been observed for six months. There were no differences in the clinical state or in the biochemical parameters compared to those found during the preceding hemodialysis period (3 X 240 min/week). In a second study, hemodynamic measurements in six individual patients aged 34-72 have been compared during a 90 min ultrashort hemodiafiltration (90 min) and during a 240 min hemodialysis. Circulatory stability was maintained during hemodiafiltration despite a rate of fluid removal that was 2.5 times that which occurred during hemodialysis. During both techniques there was a reduction of stroke volume and an adequate norepinephrine-induced rise of peripheral resistance. Plasma levels of vasopressin did not change during treatment. There were no differences in the frequency and quality of premature ventricular beats between the two treatments. The data from the two studies suggests that ultrashort hemodiafiltration (3 X 1.5-2 hr/week) provides biochemical safety as well as hemodynamic stability.

Adult↗

Modulation of the behavioral effects of amphetamine in rats by clonidine.

Clonidine (0.01, 0.05, 0.5 mg/kg) dramatically reduced the locomotor response to amphetamine (2 mg/kg) in a dose related fashion. In contrast, the same doses of clonidine had no effect on locomotions produced by a higher dose of amphetamine (6 mg/kg). Clonidine also had no effect on stereotyped head movements or the duration of the behavioral response to amphetamine. The lower dose of clonidine reduced amphetamine induced licking/biting while the two higher doses potentiated amphetamine induced licking/biting. Thus the behavioral effects of clonidine vary depending upon the dose of amphetamine and the particular behavior selected for study. The known neurochemical effects of clonidine do not account for this phenomenon.

Animals↗

Pharmacologic control of pemoline induced self-injurious behavior in rats.

Administration of oral Pemoline produces long lasting amphetamine-type stereotyped behavior and persistent self-biting behavior in rats. The effects of haloperidol, pimozide, diazepam, and serotonin depletion by pretreatment with p-chlorophenylalanine (PCPA) or chronic pretreatment with p-chloroamphetamine (PCA) on abnormal behavior produced by pemoline were studied. Diazepam consistently increased the duration of stereotyped behavior. It also reduced licking/biting and self-biting but the latter effects were not consistent. Pretreatment with PCA had negligible effects on stereotyped behavior. Pretreatment with PCPA dramatically increased locomotion and rearing without affecting the other components of stereotypy--stereotyped head movements, licking/biting, and self-biting. Haloperidol (0.2 and 0.3 mg/kg) produced a dose related normalization of pemoline induced behaviors, including elimination of self-biting. Pimozide (0.5, 0.8 and 1.3 mg/kg) had little or no effect on behaviors such as locomotions, rears, licking/biting, or stereotyped head movements but eliminated self-biting at 1.3 mg/kg. These data suggest that pemoline, like amphetamine, produces stereotyped behavior through central dopaminergic mechanisms. Dopaminergic mechanisms also appear to be involved in pemoline induced self-biting. pemoline is apparently pharmacologically and behaviorally very similar to amphetamine. Pemoline may provide a useful animal model for syndromes characterized by self-injurious behavior and other repetitive behaviors.

Amphetamines↗

Self-injurious behavior produced in rats by daily caffeine and continuous amphetamine.

Self-biting (SB) is an unusual behavioral effect of high doses of certain amphetamine-like drugs in rats. This bizarre behavior has received little attention, perhaps because the high doses of drug required and the dramatic disturbance of the animals' behavioral repertoire have raised the possibility that SB is a high dose phenomenon. However, we have found that continuous administration of very low amounts of amphetamine reliably produces SB in rats, and that this behavioral change can be very selective. We compared SB produced by continuous amphetamine to SB produced by daily caffeine; the latter has been proposed as an animal model for self-injurious behavior (SIB) in the Lesch-Nyhan syndrome. Subcutaneous silicone pellets containing amphetamine base were implanted for 4.5 days; caffeine was administered daily for 10 days. The amphetamine pellets produced the highest rate of SB (75% vs 40%) with the least toxic effects (no deaths vs three deaths). Neither drug produced stereotypy. The dopamine antagonist haloperidol was only marginally effective in controlling SB produced by daily caffeine but the dopamine antagonist pimozide (which has a longer duration of action) prevented SB by amphetamine pellet rats. Continuous release amphetamine pellets may provide an alternative to the caffeine model of SIB in humans, particularly for the Lesch-Nyhan syndrome.

Amphetamine↗

Involvement of DNA gyrase in rRNA synthesis in vivo.

The effects of oxolinic acid and novobiocin, two known inhibitors of DNA gyrase, on in vivo transcription in E. coli were investigated. The drugs inhibit the incorporation of 3H-uridine into RNA. It is shown that the effect is due to a direct influence of DNA gyrase on transcription, independent of interference with replication. By the use of rifampicin and hybridization experiments it was found that treatment with intermediate concentrations of DNA gyrase inhibitors reduces the rate of rRNA synthesis to a smaller extent than the rate of total RNA synthesis. By following the completion of growing rRNA chains we have also obtained evidence indicating that the average rate of rRNA chain growth is decreased in cells treated with inhibitors of DNA gyrase.

DNA Topoisomerases, Type II↗

Pemoline-induced self-biting in rats and self-mutilation in the deLange syndrome.

Self-mutilation in humans occasionally accompanies physiological disorders such as the deLange syndrome. If pemoline-induced self-biting is behaviorally similar to self-mutilation in the deLange syndrome, similar neurochemical mechanisms may be involved in both. Oral administration of 140 and 220 mg/kg pemoline reliably induced persistent self-biting in rats. This behavior was indistinguishable from stereotyped grooming and its most common target was the medial digits of the foreleg. Pemoline-induced self-biting was accompanied by hyperactivity, stereotyped behavior, abnormal social behavior, abnormal sensorimotor behavior, and unresponsiveness or avoidance of moderate levels of sensory stimuli. Several of these behaviors have also been reported in deLange patients.

Animals↗

Estrus- and ovariectomy-induced body weight changes: evidence for two estrogenic mechanisms.

Estrogenic modulation of body weight in female rats is usually thought to result indirectly from estrogenic modulation of food intake. The data presented here suggest, however, that estrogens influence body weight by at least two mechanisms, one of which is independent of changes in food intake. When female rats were ovariectomized (Ovx) and food intake was limited to preoperative levels, the Ovx animals nonetheless gained large amounts of body weight. Although Ovx rats gained more weight than controls on the same amount of food, during 33 hr of food deprivation Ovx and control animals lost body weight at the same rate, which indicates that the prefasting metabolic rates of the two groups were generally similar. Examination of recovery from food deprivation suggested that the rate of weight gain after Ovx was very gradual. During the first 40 days after surgery, the ano-nasal lengths of Ovx rats increased twice as fast as the ano-nasal lengths of the intact rats, which suggests a mechanism for the gradual increase in body weight induced by Ovx. The body weights of intact rats followed a regular 4-day cycle during ad lib feeding but when the estrus-associated decrease in food intake was prevented the cyclic body weight changes were dramatically altered. Thus estrogens appear to regulate body weight by at least two mechanisms: modulation of food intake (cycling females) and modulation of ano-nasal growth or other metabolic processes (Ovx females).

Animals↗

Recurrent laryngeal nerve dissection: a case report involving return of spastic dysphonia after initial surgery.

This case study describes successful management of spastic dysphonia using a procedure whereby the right recurrent laryngeal nerve was severed. Thirteen months following the surgical treatment, the subject reported a return of the preoperative vocal characteristics of spastic dysphonia. Tests and inspection revealed that the right recurrent nerve was again intact and the right vocal fold was functional. A second surgical procedure was performed, modified to prevent neural reconnection, with a return of the improved voice observed following the initial surgery. The results are discussed in terms of etiological considerations of spastic dysphonia.

Female↗

The morphology of polymethylmethacrylate (PMMA) bone cement: surface structures and causes of their origin.

This study deals with the correlation between the polymerizing bone cement and the surrounding tissue. The surface structures of bone cements, polymerized in air, in tissue medium (in vitro) and in human bone during implantation were investigated and compared with the contours of the tissue of the implant bed. Basing on the dimensional differences it was differentiated between contours of 1st order and 2nd order: contours of 1st order are within the macroscopic range, contours of 2nd order within the microscopic range. The surface of bone cement polymerized in living human tissue differed essentially from samples polymerized under laboratory conditions. The differences are to be seen macroscopically in the coarse relief as well as microscopically in the shape and the connection of the superficial methylmethacrylate beads. Bone cements, polymerized in air show an ideal, even and closed surface. Bone cements, polymerized in tissue medium exhibit macroscopically some wrinkles, in the microscopic range their contours are either closed (samples prepolymerized at 22 degrees C) or partly open and partly closed (samples prepolymerized at 24 degrees C). The surface of bone cement implants, retrieved from human bones are characterized macroscopically by a marked wrinkled and papillary relief, microscopically by flattened beads, and most often by an irregular, rough and open surface with isolated beads giving almost the impression of a porous surface structure. The character of the surface of the bone cement originates from external, mechanical influences, from changes in the volume of the bone cement and from effects of the surrounding tissues. The surface of the bone cement implanted in human bone conforms exactly with the contour of the adjacent tissue; the tissue contour is infact a negative of the cement surface. The incomplete connection between the superficial PMMA beads seems to be of some practical value: In areas, where the PMMA beads are largely isolated, the mechanical stressability of the "polymer composite" is relatively low. Under high load, beads and bead-clusters may break off the surface. Shattering of bone cement implants possibly may start from such an open, porous surface area where PMMA beads are extensive isolated.

Acrylic Resins↗

[Dysfibrinogenemia. A new case: dysfibrinogenemia Giessen III (author's transl)].

A new case of dysfibrinogenemia is reported which shows no signs of a haermorrhagic diathesis (dysfibrinogenemia Giessen III). The abnormal fibrinogen was detected by only slight but characteristic alterations of some parameter of the coagulation analysis (prolonged clotting times after addition of thrombin, Reptilase and thrombin coagulase; low fibrinogen concentration determined by methods based on clot formation in comparison to the immunological fibrinogen determination; delayed fibrin polymerization). In addition, clinical features and diagnosis of dysfibrinogenemia are described in general.

Batroxobin↗