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Biomedical subjects

R Ott

Publications and source records attributed to R Ott.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cell proliferation after lesions in the cerebellum of adult teleost fish: time course, origin, and type of new cells produced.

In contrast to mammals, fish exhibit an enormous capacity to replace damaged neurons following injuries to the adult central nervous system. As the mechanisms controlling this so-called neuronal regeneration are unknown, we have, in the present study, examined the role of cell proliferation in this process. Lesions were applied to one subdivision of the cerebellum, the corpus cerebelli, in the teleost fish Apteronotus leptorhynchus. Proliferative activity was monitored through incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine into replicating DNA. Cerebellar lesions induce high proliferative activity especially in areas in close vicinity to the injury, although the number of cells produced is also increased in other regions of the corpus cerebelli. Many of the cells generated in these areas become, after migration, specifically incorporated at the site of the lesion. The vast majority of them is dividing between 1 and 10 days following the lesion, with the maximum proliferative activity occurring at 5 days. Remarkably, also cells dividing 2 days prior to applying a lesion participate, at a significant number, in the regenerative process. Combination of 5-bromo-2'-deoxyuridine labeling with retrograde tract-tracing techniques demonstrated that at least some of the new cells that replace damaged neurons are cerebellar granule cells. This ability to generate new neurons, together with the previously described occurrence of apoptosis to remove damaged cells, is likely to form the basis for the enormous capacity of teleost fish to perform neuronal regeneration.

Animals↗
PubMed1999

Prospective study on post-traumatic and postoperative sensory disturbances of the inferior alveolar nerve and infraorbital nerve in mandibular and midfacial fractures.

In a prospective study (January 1999 to December 1997), 34 patients with 26 mandibular and 20 midfacial fractures were investigated. All the fractures were managed by osteosynthesis. To evaluate the incidence and duration of recovery of post-traumatic and postoperative sensory disturbances, the following tests were carried out: sharp/blunt testing, and the two-point discrimination test as conventional clinical examination methods, and electromyographic recording of the masseter reflex to calibrate the clinical findings. To establish the sensory status of the inferior alveolar and the infraorbital nerves in the region of the fracture, and on the intact and control sides, the tests were performed pre-operatively and postoperatively on the seventh day, after 4 weeks and after 3, 6 and 12 months. The incidence of post-traumatic sensory disturbance was 46% for mandibular fractures and 65% for fractures to the midface (sharp/blunt test, two-point discrimination test). The rate of postoperative sensory disturbance in surgical treatment of mandibular fracture involving the region of the intra bony course of the inferior alveolar nerve, including the post-traumatic sensory disturbance, was 76.9%, and 55% following surgical treatment of midfacial fractures. The incidence of persistent sensory disturbances following surgical treatment was 7.7% in the case of mandibular fractures, and 15% in the case of midfacial fractures (sharp/blunt test, two-point discrimination test, masseter reflex). Recovery of neurological function is delayed in the presence of a displaced fracture (> 1 mm) as compared with non-displaced fractures. For the postoperative calibration of sensory disturbances, electromyographic recording of the masseter reflex from the fourth postoperative week onwards has proved useful.

Adolescent↗
PubMed1999

Initial experience with a new Yamakawa-type prosthesis for long-term percutaneous transhepatic drainage.

BACKGROUND AND STUDY AIMS: In a previous study evaluating the problems of long-term percutaneous transhepatic biliary drainage (PTBD) using Yamakawa-type prostheses in patients with benign and malignant stenoses, breakage of the tube proved to be a serious problem, occurring in 19.7 % of PTBD exchanges. As a consequence of these results, a new PTBD tube made of Tecothane has been developed. PATIENTS AND METHODS: From September 1997 to September 1998, this new PTBD tube was applied in 64 patients (39 men, 25 women; median age: 70, range 29-89) in the treatment of benign (n = 30) or malignant stenoses (n=31; three stenoses remained indeterminate), and the course was followed. RESULTS: A total of 134 stent exchanges were performed, 52 of these being ahead of schedule (39 %). Not a single case of breakage occurred. However, other PTBD-related problems remained unchanged. Patients accepted the new prosthesis very well; among 19 patients who had experience of both the new one and the conventional one, 11 had preferences-eight for the new one and three for the old one. CONCLUSIONS: This new Tecothane prosthesis has solved the problem of PTBD breakage, which was often accompanied by serious problems. As was to be expected, other PTBD-related problems were not substantially affected. Nevertheless, this new tube represents progress in the percutaneous treatment of biliary stenoses.

Adult↗
PubMed1999

Cell cycle-dependent regulation of human DNA polymerase alpha-primase activity by phosphorylation.

DNA polymerase alpha-primase is known to be phosphorylated in human and yeast cells in a cell cycle-dependent manner on the p180 and p68 subunits. Here we show that phosphorylation of purified human DNA polymerase alpha-primase by purified cyclin A/cdk2 in vitro reduced its ability to initiate simian virus 40 (SV40) DNA replication in vitro, while phosphorylation by cyclin E/cdk2 stimulated its initiation activity. Tryptic phosphopeptide mapping revealed a family of p68 peptides that was modified well by cyclin A/cdk2 and poorly by cyclin E/cdk2. The p180 phosphopeptides were identical with both kinases. By mass spectrometry, the p68 peptide family was identified as residues 141 to 160. Cyclin A/cdk2- and cyclin A/cdc2-modified p68 also displayed a phosphorylation-dependent shift to slower electrophoretic mobility. Mutation of the four putative phosphorylation sites within p68 peptide residues 141 to 160 prevented its phosphorylation by cyclin A/cdk2 and the inhibition of replication activity. Phosphopeptide maps of the p68 subunit of DNA polymerase alpha-primase from human cells, synchronized and labeled in G1/S and in G2, revealed a cyclin E/cdk2-like pattern in G1/S and a cyclin A/cdk2-like pattern in G2. The slower-electrophoretic-mobility form of p68 was absent in human cells in G1/S and appeared as the cells entered G2/M. Consistent with this, the ability of DNA polymerase alpha-primase isolated from synchronized human cells to initiate SV40 replication was maximal in G1/S, decreased as the cells completed S phase, and reached a minimum in G2/M. These results suggest that the replication activity of DNA polymerase alpha-primase in human cells is regulated by phosphorylation in a cell cycle-dependent manner.

Animals↗
PubMed1999

Total antioxidative capacity is normal in sera from psoriasis patients despite elevated bilirubin, tocopherol and urate levels.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Reactive oxygen species are thought to play a critical role in inflammation and are scavenged by antioxidants. OBJECTIVE: We wanted to know whether the total antioxidative capacity or single antioxidative components in sera from psoriasis patients are decreased. MATERIAL AND METHODS: Well-known antioxidants of the serum were measured using commercial kits or determined by HPLC in the sera of 33 inpatients with severe psoriasis and in 36 healthy control persons. The total antioxidative capacity was measured using the ability of endogenous antioxidants to scavenge the 2, 2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation. RESULTS: Several single antioxidative components were slightly elevated when considered groupwise, namely tocopherol (p = 0.001), bilirubin (p = 0.001) and urate which was increased over controls by about 33% (p= 0.01). Other parameters such as total protein and thiol content and ascorbic acid did not differ from controls. CONCLUSION: To our surprise the total antioxidative activity was normal in sera from psoriasis patients although some components such as urate were even elevated.

Antioxidants↗
PubMed1999

Masking of complex sound--technical notes for realization of constant signal-noise-ratio.

Based on findings regarding unconscious semantic information-processing for meaningful visual stimuli, this paper describes a standardized procedure for the construction of constant signal to noise ratio for the masking of complex sounds. The proposed algorithm is derived from psychoacoustical laws concerning frequency and time-weighting of sound. Spectral characteristics are taken into account by mixing signal and white noise within frequency ranges defined through critical bandwidth ("narrow-band masking"). Furthermore, time-weighting is taken into account using sound-pressure patterns generated through low pass filters which follow the international specification DIN IEC 651 which provides specification for sound-level meters. Hardware and software circuits are described in detail. This proposal overcomes recognized lack of standardized methods in studies addressing unconscious semantic processing of auditory stimuli.

Acoustic Stimulation↗
PubMed1998

Functional interactions among the subunits of replication factor C potentiate and modulate its ATPase activity.

Replication factor C (RF-C), a complex of five subunits, and several subassemblies of RF-C, representing intermediates along the proposed protein assembly pathway (Podust, V. N., and Fanning, E. (1997) J. Biol. Chem. 272, 6303-6310), were expressed in insect cells using baculoviruses encoding individual subunits (p140, p40, p38, p37, and p36). Purified proteins were analyzed for ATPase activity to assess the role of individual subunits in ATP hydrolysis. His-tagged p40 contained low ATPase activity, but tagged p37 and p36 did not. Complexes of p40.p37.p36 bearing a His tag on any subunit displayed DNA-stimulated ATPase activity, in agreement with a recent report (Cai, J., Gibbs, E., Uhlmann, F., Philips, B., Yao, N., O'Donnell, M. , and Hurwitz, J. (1997) J. Biol. Chem. 272, 18974-18981). In contrast, complex p38.p37.p36-his displayed no ATPase, suggesting that p40 is essential for ATPase activity. Although p38 was not required for ATPase activity, the activity of the p40-his.p38.p37. p36 complex was more salt-resistant than that of the p40-his.p37.p36 complex. The p140 subunit further increased the specific ATPase activity of RF-C complex by enhancing its stimulation by DNA. Taken together, the data indicate that all five RF-C subunits constitute ATPase activity, although the contributions of the individual subunits differ. Predicted ATP-binding domains of all five subunits were mutated to assess the importance of multiple ATP-binding sites of RF-C. In each case, the Lys of the conserved P-loop motif was replaced by Glu. The ATP-binding domain of p38 was found to be dispensable for the activity of the five-subunit RF-C in polymerase delta DNA synthesis. In contrast, mutation of the ATP-binding domains in other RF-C subunits impaired RF-C assembly, function, or both.

Adenosine Triphosphatases↗
PubMed1998

Plasma separation and bilirubin adsorption after complicated liver transplantation: a therapeutic approach to excessive hyperbilirubinemia.

BACKGROUND: Severe hyperbilirubinemia is known to exert multiple toxic effects. Thus, a reduction in bilirubin by use of various adsorbent columns has been reported for a variety of hepatic disorders, but no experience with liver transplant patients is available as yet. METHODS: Plasma separation and bilirubin adsorption by an anion-exchange adsorbent column (BR-350) were performed in two patients with severe jaundice (total serum bilirubin > 55 mg/dl) and multiple organ failure that had developed after orthotopic liver transplantation. RESULTS: The procedure resulted in an 18% to 35% reduction in total bilirubin after each session, accompanied by a remarkable clinical improvement. Both patients finally recovered and had a favorable outcome. No complications or side effects of bilirubin adsorption were observed during any of the six sessions. CONCLUSIONS: Bilirubin adsorption is a safe and effective treatment. It should be considered as supportive therapy for excessive hyperbilirubinemia after liver transplantation. In selected cases, retransplantation may thus be avoided.

Adsorption↗
PubMed1998

Apoptosis after injuries in the cerebellum of adult teleost fish.

In contrast to mammals, all teleost fish examined thus far exhibit an enormous potential to regenerate not only neuronal processes (axonal regeneration), but even whole neurons (neuronal regeneration) after injuries in the central nervous system. By application of lesions to one subdivision of the cerebellum, the corpus cerebelli, the role of apoptosis in neuronal regeneration was examined in the gymnotiform fish, Apteronotus leptorhynchus. Apoptotic cells were identified by examination of cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) reaction, an in situ technique employed for detection of nuclear DNA fragmentation. Additional evidence for the apoptotic nature of dying cells was obtained through analysis of morphologies displayed at both the light microscopic and the ultrastructural level. The first TUNEL-positive cells at the site of the lesion appeared as rapidly as 5 min following mechanical damage of the tissue. Thirty minutes after stab wound lesion, their number reached maximum levels. Starting with 2 days of postlesioning survival time, a gradual decline in the number of TUNEL-positive cells was evident, until this process reached background levels 20 days after the lesion. We hypothesize that apoptosis is used in A. leptorhynchus as an efficient mechanism for the removal of cells damaged through injury in the central nervous system. Since apoptosis is not accompanied by the side-effects known from necrosis (which is predominant after injuries in the mammalian central nervous system), this "clean" type of cell death may, at least partially, explain the tremendous regenerative capability of teleosts.

Animals↗
PubMed1998

Randomized study of intracorporeal laser lithotripsy versus extracorporeal shock-wave lithotripsy for difficult bile duct stones.

BACKGROUND: Endoscopic treatment modalities are well established for the removal of bile duct stones. For the small percentage of stones that are difficult or impossible to extract by conventional means, more sophisticated endoscopic techniques or associated modalities such as intracorporeal laser lithotripsy (ILL) and extracorporeal shock wave lithotripsy (ESWL) have to be applied. Little is known, however, about the relative value of these different techniques. We therefore compared endoscopic ILL with ESWL in patients with difficult bile duct stones in a prospective randomized study. METHODS: The study included 60 patients (35 women; mean age 70+/-15 years) with bile duct stones in whom standard extraction failed (n=33) or in whom the papilla was not accessible, thus requiring percutaneous access (n=27). They were randomized to receive ESWL under fluoroscopic targeting (maximum discharge number per session: 6000) or ILL using a pulsed dye laser with an automatic stone recognition system, which was mostly performed (28 of 30 cases) under cholangioscopic control. Endoscopic removal of fragments was attempted within the subsequent (ESWL) or the same (ILL) session. Failure was defined as failure to remove all ductal stones/fragments after a maximum of three lithotripsy sessions. RESULTS: There were no statistical differences in background variables between the two groups. Bile duct clearance was achieved in 22 of 30 patients (73%) in the ESWL group and in 29 of 30 patients (97%) in the ILL group (p < 0.05). The number of treatment sessions (ESWL 3.0+/-1.3; ILL 1.2+/-0.4; p < 0.001) and the duration of treatment (ESWL 3.9+/-3.5 days; ILL 0.9+/-2.3 days; p < 0.001) were also significantly different in favor of ILL. Two minor complications occurred in each group; there was no 30-day mortality. Crossover therapy to ILL led to stone removal in seven of the eight cases in which ESWL failed, whereas ESWL fragmented the stone in the single patient in whom ILL failed. CONCLUSIONS: ILL is more effective in the treatment of difficult bile duct stones than ESWL in terms of stone clearance rate and treatment duration.

Aged↗
PubMed1998

Long-term results of percutaneous transhepatic biliary drainage for benign and malignant bile duct strictures.

BACKGROUND: Long-term percutaneous transhepatic biliary drainage (PTBD) is a valid alternative to surgery in patients with benign or malignant bile duct strictures in whom endoscopic drainage has failed. However, few data are available on the long-term outcome with percutaneous drainage, specially when the application of Yamakawa-type prostheses is considered. METHODS: During 1996, 48 patients who were either treated with primary PTBD insertion followed by PTBD exchanges (n = 15) or who presented only for exchange of an earlier PTBD (n = 33) were included in the study. Thirty-one patients had malignant strictures, and 17 had benign ones. The PTBD catheters were scheduled for exchange every 3 months or earlier if signs and symptoms of obstruction or other problems were present. The data were collected prospectively during each follow-up visit and included both symptoms and the status and function of the PTBD at the time of exchange. RESULTS: Although PTBD was highly effective in relieving jaundice (progression of cholestasis was observed in only 2 cases), 73 of the 157 PTBD exchanges (47%) had to be carried out earlier than scheduled. Premature exchange was needed for clinical reasons, such as fever indicating PTBD dysfunction, in only 19% of these cases. The other reasons were related to the PTBD catheter and consisted of bile leakage alongside the drain (33%), PTBD disconnection or complete dislocation (30%), or occlusion suspected during regular flushing of the drain (15%). In most cases exchanging the drain was sufficient to solve the problem; in cases of complete dislocation, dilation of the same tract (n = 6) or fresh puncture and establishment of a new drainage site (n = 2) were necessary. Reducing the PTBD exchange interval from 3 to 2 months would have decreased the number of premature stent exchanges by 26%. CONCLUSIONS: Although PTBD is an effective method of biliary drainage, there are frequently minor problems-mostly catheter-related-which require premature exchange of the drain in almost half of the cases, and this may affect the patients' quality of life. Improvements in PTBD materials and catheter design are therefore needed. The effectiveness of reducing the intervals between PTBD exchanges should also be examined.

Adult↗
PubMed1998

[Focal nodular hyperplasia and liver cell adenoma: operation or observation?].

PATIENTS: In a 15-year period a total of 146 patients underwent surgery for benign hepatic tumors, including 54 focal nodular hyperplasias (FNH) and 23 hepatic cell adenomas (65 hemangioma and 4 cholangioma). METHODS: The medical records of these patients were retrospectively analyzed with respect to tumor-related symptoms, surgical procedures and postoperative complications. RESULTS: Regardless of the type of the tumor, 70% of the patients had no or only non-specific symptoms. Most frequently, surgery was indicated due to questionable dignity of the lesion (adenoma 70%, FNH 41%). In hepatic cell adenomas (HCA) also perforation or bleeding of the tumor (17%) and severe symptoms (13%) required urgent operation. In two of three cases local excision of the lesion or segmental hepatic resection were performed, whereas extended resection procedures became necessary only in 20 (FNH) to 34% (HCA). The mean duration of postoperative intensive care treatment was significantly shorter in FNH and HCA than in other benign hepatic tumors (1.0 vs. 2.0 days, p < 0.01). After resection of FNH no fatalities or significant complications were observed. In HCA morbidity was 13% without related mortality (hemangioma: 3% mortality; 11% morbidity). CONCLUSION: The elective resection of benign hepatic tumors can be achieved with very low mortality and morbidity, and usually provides longterm relief of annoying symptoms. Whenever HCA is suspected surgery should be performed, since severe symptoms and spontaneous hemorrhage (30%) are common in this tumor. Also hepatocellular carcinoma can be excluded only by histologic work-up of the operative specimen. In focal nodular hyperplasia (FNH), complications are rare and malignant transformation does not occur even when observation is employed only. Resection should be restricted to symptomatic or growing tumors with subsequent cholestasis or to cases with uncertain diagnosis.

Adenoma, Liver Cell↗
PubMed1998

[Plasma separation and bilirubin adsorption therapy in excessive hyperbilirubinemia after liver transplantation].

Reduction of bilirubin levels by various means has been proposed as symptomatic therapy for excessive jaundice in various end-stage liver diseases, since it exerts multiple toxic effects and may thereby promote multiple organ failure. Plasma separation and bilirubin adsorption by an anion-exchange column (BR-350) performed in four patients with excessive hyperbilirubinemia after liver transplantation resulted in a 29%-70% reduction in total serum bilirubin, accompanied by significant improvement of multiple organ failure or encephalopathy in three patients. Bilirubin adsorption may be beneficial in complicated jaundice after hepatic transplantation and should further be evaluated for its clinical indications.

Hemoperfusion↗
PubMed1997

Long-term survival of postembryonically born cells in the cerebellum of gymnotiform fish, Apteronotus leptorhynchus.

The gymnotiform fish Apteronotus leptorhynchus is, like all teleosts examined thus far, distinguished by its enormous potential for the production of new neurons in the adult brain. In the cerebellum, cells are generated continuously and at high rate in discrete proliferation zones. From there, they migrate into specific target areas comprised of granule cell layers in the four cerebellar subdivisions. The long-term fate of these cells was followed through labelling with 5-bromo-2'-deoxyuridine. Employment of survival times of up to 440 days after the administration of this thymidine analogue revealed that the newborn cells survive for extremely long periods of time, spanning most of the fish's adult life, without exhibiting a decline in their number. This long-term survival, together with the permanent addition of new cells to the population of older cells, forms the basis for the continuous growth of the cerebellum during adulthood.

Animals↗
PubMed1997

[Illness experience and treatment seeking behavior of psoriasis patients].

We analyzed how psoriasis patients sought professional help and correlated it to their illness attitudes and feeling of stigmatization. Semi-structured interviews of 400 patients were reanalyzed to identify homogeneous groups concerning initial reactions at first manifestations of the disease. Four groups ("isolated", "stigmatized", "socially supported" and "non-stigmatized" patients) were found and cross-tabulated with five resulting groups of a second cluster-analysis concerning the "style" of the seeking behaviour of professional and paraprofessional help and medical measures against the psoriasis ("multi-users", "arranged mini-users", "waiting-room patients", "optimists" and "self-therapists"). We were able to describe typical courses of illness behaviour depending on the initial reaction. The results are discussed with regard to the desirable identification of problematic patients within professional care units.

Adaptation, Psychological↗
PubMed1997

Evolutionary origins of two tightly linked mutations in arylsulfatase-A pseudodeficiency.

Deficient arylsulfatase A activity causes the neurodegenerative disease metachromatic leukodystrophy. However, some individuals with deficient enzyme activity appear clinically normal. This "pseudodeficiency" allele commonly found among many reported populations (frequency approximately 0.10) is associated with two A-->G transitions in cis in the arylsulfatase A gene causing the simultaneous loss of an N-glycosylation and a polyadenylation signal. To understand the evolutionary relationship between such common and tightly linked mutations, we studied 400 individuals in the African, European, Indian and East Asian populations and found none carrying the polyadenylation mutation alone. However, the N-glycosylation mutation could occur independently. Its frequency varied from 0.01 in Indians, 0.06 in Europeans, 0.21 in East Asians to 0.32 in Africans. The frequencies of both mutations occurring together ranged from almost non-existent in the Africans and East Asians, to 0.075 in the Europeans and 0.125 in the Indians. These frequencies were significantly different among populations. Haplotype analysis among homozygous pseudodeficiency individuals and eight multi-generation families with six polymorphic enzymes showed that, of the five haplotypes found in the general population, only one was linked to the double mutations. Alleles among the four populations with only the N-glycosylation mutation also supported linkage to the same haplotype except in some Europeans whose alleles were discordant. These results are consistent with the hypothesis that the N-glycosylation mutation may be a recurrent event among the Europeans but first occurred in an ancestral allele before the emergence of modern Homo sapiens from Africa at approximately 100,000-200,000 years ago. Subsequently, the polyadenylation mutation occurred in this ancient allele with the N-glycosylation mutation, an event that likely took place after the divergence between the European and East Asian lineages.

Canada↗