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Biomedical subjects

R Maurer

Publications and source records attributed to R Maurer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Myeloma and severe cholestasis.

Amyloidosis is a frequent complication of multiple myeloma. Liver involvement is common in amyloidosis. Hepatic dysfunction and liver chemistry abnormalities are often mild or absent and obstructive jaundice is rare. We report on a 44-year-old patient with multiple myeloma and rapidly deteriorating liver involvement with severe intrahepatic cholestasis. Autopsy showed widespread amyloidosis primarily involving the liver. This unusual cholestatic manifestation of hepatic amyloidosis has an uniformly poor prognosis, with death occurring within a few months. We discuss the clinical and pathologic aspects.

Adult↗
PubMed1999

Cyclin D1 overexpression lacks prognostic significance in superficial urinary bladder cancer.

The biological behaviour of urinary bladder neoplasms cannot be adequately predicted by histological criteria alone. Cyclin D1 is a cell-cycle regulating protein known to be overexpressed in a proportion of bladder carcinomas. To evaluate the prognostic significance of cyclin D1 expression and its relationship with tumour phenotype, 392 bladder carcinomas were analysed by immunohistochemistry. Clinical follow-up information was available in 337 patients with superficial bladder tumours (stages pTa/pT1). Cyclin D1 positivity was seen in 176 of 392 carcinomas. Cyclin D1 overexpression was strongly linked to papillary tumour growth, low stage, and low histological grade (p<0.005 each). Multivariate analysis showed that papillary tumour growth was the only parameter which was independently linked to cyclin D1 positivity. There was no significant difference in proliferative activity (Ki67 labelling index) between cyclin D1-negative and -positive tumours. Cyclin D1 positivity was not linked to the risk of recurrence or tumour progression, either in pTa or in pT1 carcinomas. It is concluded that cyclin D1 positivity distinguishes a large subgroup of papillary bladder tumours, but there is no evidence of prognostic significance for increased cyclin D1 expression.

Analysis of Variance↗
PubMed1999

Chromosomal imbalances in small cell carcinomas of the urinary bladder.

Small cell carcinomas (SCCs) represent a rare histological subtype of urinary bladder cancer. Little is known abut the genetic alterations in these tumours. To identify chromosomal aberrations that are typically present in SCC of the urinary bladder, ten tumours were analysed by comparative genomic hybridization (CGH). CGH allows screening for all relative DNA copy number gains and losses present in a tumour. SCCs of the bladder were characterized by a high number of genomic alterations (mean: 11.3 per tumour). Deletions were most frequent at 10q (7 of 10 tumours deleted), 4q, 5q (5/10 each), and 13q (4/10). These regions may carry tumour suppressor genes with relevance for this particular tumour type. Gains of DNA sequences were most prevalent at 8q (5/10), 5p, 6p, and 20q (4/10 each). High level amplifications were found at 1p22-32, 3q26.3, 8q24, and 12q14-21. These loci may pinpoint the localization of oncogenes with relevance for small cell bladder cancer. The analysis of one tumour having areas of both SCC and transitional cell carcinoma strongly suggests that SCC can develop from TCC through the acquisition of additional genetic alterations.

Carcinoma, Small Cell↗
PubMed1999

Focal loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma.

The majority of papillary transitional cell carcinomas of the bladder are localized tumors at initial diagnosis; identification of those developing recurrence and an aggressive behavior is important. CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors. Here, the usefulness of conventional CD44 protein immunohistochemistry as a prognostic parameter for recurrence of superficial transitional cell carcinomas was assessed in paraffin sections of 241 tumors with long-term follow-up. A highly significant association was found between focal loss of CD44v3 and -v6 immunostaining and short recurrence-free interval in noninvasive (pTa) transitional cell carcinomas (P = 0.005), but not in minimally invasive (pT1) carcinomas (P = 0.78). Our results indicate the value of conventional CD44 immunohistochemistry as an additional tool for identifying patients at high risk for recurrence of pTa transitional cell carcinomas. They also point to biological differences between noninvasive and minimally invasive transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗
PubMed1999

Polysomies but not Y chromosome losses have prognostic significance in pTa/pT1 urinary bladder cancer.

A disturbed cellular DNA content is of potential diagnostic and prognostic relevance in urinary bladder cancer. To evaluate the prognostic significance of individual chromosomal aberrations in superficial bladder cancer, specimens of 105 tumors (67 pTa, 38 pT1) were examined by fluorescence in situ hybridization (FISH). FISH allows quantitation of chromosomes on a cell by cell level. Centromere probes for the chromosomes Y, 1, and 17 were used. There was a strong association between polysomies of the chromosomes 1 (found in 46% of tumors) and 17 (40% of tumors, P < .0001). Polysomies (1 and 17) were significantly more frequent in pT1 than in pTa tumors (P < .0001 each). In pTa tumors, polysomies of both chromosomes were linked to a high risk of recurrences; polysomy 17 was associated with an increased risk of progression (P < .05 each). There was no significant association between polysomies and an unfavorable prognosis in pT1 carcinomas. Previous studies had suggested a prognostic role of Y losses in bladder cancer. However, Y losses were not linked to recurrences or tumor progression in pTa or pT1 tumors of 67 male patients. These data show that marked genetic differences exist between pTa and pT1 carcinomas. They also indicate that polysomies of different chromosomes may have prognostic relevance in pTa urinary bladder cancer.

Adult↗
PubMed1999

A prospective study of risk-adapted therapy for large cell non-Hodgkin's lymphoma with VACOP-B followed by high-dose CBV and autologous progenitor cell transplantation for high-risk patients in remission.

Several centres reported a favourable outcome after high-dose chemotherapy with autologous progenitor cell transplantation in selected patients with high-risk large cell non-Hodgkin's lymphoma in first remission. Based on these observations, we wanted to prospectively determine the outcome of a risk-adapted therapy for patients with large cell lymphoma. Patients aged 60 years or less received 12 weeks of VACOP-B chemotherapy. For high-risk patients in remission this was immediately followed by high-dose chemotherapy with cyclophosphamide, carmustine and etoposide and autologous progenitor cell transplantation. High-risk criteria were defined before the establishment of the International Index and included large cell lymphoma stage III or IV or mediastinal large lymphoma with sclerosis stage II or higher, and the presence of bulky tumours and/or an elevated LDH. 89 patients fulfilled the clinical selection criteria and were entered onto this multicentre study. 82 patients were evaluable after confirmation of large cell histology by pathology review. Of these, 51 were considered to be in the low-risk group and 31 in the high-risk group. The 3-year event-free survival for all patients was 68%. The 3-year event-free survival was 76% for the low-risk and 55% for the high-risk group (P = 0.061). Only 22/31 high-risk patients were able to receive the high-dose chemotherapy in first remission as intended. In conclusion, although our study demonstrated that a risk-adapted therapy for large cell lymphoma could be safely administered, the potential impact on outcome of the strategy chosen here is likely to be small.

Adult↗
PubMed1998

Navigation through vector addition.

During short foraging excursions away from their home, central place foragers update their position relative to their point of departure by processing signals generated by locomotion. They therefore can home along a self-generated vector without using learned references. In rodents and other mammals, this path integration process (dead reckoning) can occur on the basis of purely internal signals, such as vestibular or proprioceptive (re)afferences. We report here that hamsters are also capable of proceeding to a previously learned feeding site through vector information from locomotion only. The subjects compute the direction and distance to the goal by subtracting their current-position vector from the stored nest-to-goal vector. This computation pertains to locations per se and therefore occurs in absolute space, independently of landmark objects. If available, prominent visual cues merely serve to confirm the path planned through the addition of self-generated vectors, whereas visual as well as nonvisual references confirm that the subject has arrived at the goal site.

Animals↗
PubMed1998

Selection and immunomagnetic purging of peripheral blood CD34+ cells for autologous transplantation in B-cell non-Hodgkin's lymphomas.

BACKGROUND: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. PATIENTS AND METHODS: We examined the feasibility and safety of a CD34-selection followed by purging with anti B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophosphamide, BCNU and etoposide with retransfusion of autologous HPC's. RESULTS: A mean number of 340 x 10(8) mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2 x 10(6)/kg (range 0.6-2.2 x 10(6)/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5 x 10(9)/l and 17 days (range 13-25 days) to platelet recovery of 50 x 10(9)/l. Mean number of intravenous antibodies and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. CONCLUSIONS: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphomas.

Antibodies, Monoclonal↗
PubMed1997

Pharmacodynamic and safety results of PEG-Hirudin in healthy volunteers.

PEG-Hirudin, a chemically defined conjugate of recombinant hirudin and two molecules of polyethylene glycol (PEG)-5000 is a highly selective direct thrombin inhibitor with a significantly longer duration of action than non-conjugated recombinant hirudin permitting once daily subcutaneous administration. A series of placebo-controlled, randomized, Phase I clinical trials were conducted in 75 healthy volunteers to investigate the anticoagulant effects, safety and pharmacodynamics of PEG-Hirudin when administered intravenously as a bolus injection, infusion, and subcutaneously. After single i.v. injections of various doses of PEG-Hirudin (0.03-0.3 mg/kg) dose-dependent increases in anti-IIa activity and APTT were observed. Four hours after injection of 0.3 mg/kg, mean plasma concentration expressed in terms of anti-IIa activity was still 0.89 micrograms/ml, corresponding to a 1.8-fold prolongation of APTT. Continuous intravenous infusions of 0.01 and 0.02 mg/kg/h PEG-Hirudin resulted in maximum anti-IIa activities of 0.42 micrograms/ml and 0.77 micrograms/ml, respectively, at the end of a six-hour infusion period without having reached steady state at this time. After termination of the infusion, anticoagulant activity displayed an immediate exponential decrease. The anticoagulant activities of single subcutaneous doses of 0.05 to 0.6 mg/kg were studied in a further series of investigations and slow increases and prolonged durations of anti-IIa activity and APTT prolongation were found. Repeated, once daily subcutaneous administrations of 0.2 to 0.4 mg/kg for five days resulted in dose-dependent prolongations of APTT and increases in anti-IIa activity without completely reaching steady state conditions. In a further study, 0.3 mg/kg of PEG-Hirudin was given as an i.v. bolus injection followed by three repeated single daily s.c. injections. In this trial, the APTT was shorter than expected from previous studies; therefore, a direct comparison of various APTT reagents was made in the intravenous infusion trial. Of the APTT reagents tested, BioMérieux Silimat and IL-ellagic acid proved to be the most sensitive to PEG-Hirudin. The hirudin derivative PEG-Hirudin was tolerated very well without immuno-allergic side effects. In view of the significantly prolonged anticoagulant efficacy in comparison to non-conjugated r-hirudin, PEG-Hirudin is a promising compound especially for repeated once daily subcutaneous administration.

Adult↗
PubMed1996

Cloning and characterization of dnaE, encoding the catalytic subunit of replicative DNA polymerase III, from Vibrio cholerae strain C6706.

We report that Vibrio cholerae (Vc) contains a gene homologous to Escherichia coli dnaE, the structural gene for the alpha (catalytic) subunit of replicative DNA polymerase III (PolIII). Despite 24% amino acid (aa) differences in the encoded proteins, the Vc gene strongly complements an E. coli dnaE temperature sensitive (ts) mutant, indicating that all functional features essential for replication are conserved.

Amino Acid Sequence↗
PubMed1996

The storm before the qualm.

More than half of all changes in organizations fail. But there is hope, suggests Rick Maurer, author of ¿Beyond the Wall of Resistance.¿ He says that it isn't resistance itself--since resistance is nothing more than people's need to protect themselves from harm--but how you handle it that creates the problem. Here in this exclusive excerpt, he argues that you shouldn't try to overcome resistance, but embrace it.

Chief Executive Officers, Hospital↗
PubMed1996

Defect in general priming conferred by linker region mutants of Escherichia coli dnaB.

The dnaB gene of Escherichia coli encodes a bifunctional primase accessory protein/helicase necessary for chromosomal replication. Monomers of DnaB comprise two trypsin-resistant domains connected by a 45-amino-acid linker. To investigate the role of the linker in the structure and function of DnaB, we have purified and characterized three DnaB mutant proteins having single amino acid substitutions in the linker. We find that the mutant proteins retain the two-domain structure and assemble into hexamers that may be less stable than hexamers formed by wild-type DnaB. These mutant hexamers have hydrodynamic properties slightly different from those of the wild type, suggestive of a more open structure. The mutant proteins had reduced or absent ability to stimulate primase and also exhibited slight alterations in ATPase activity compared with the wild type. We conclude that the linker region promotes primase-DnaB interaction, but this effect may be indirect. We propose a model involving repositioning of N-terminal domains to explain the properties of the mutant proteins.

Adenosine Triphosphatases↗
PubMed1996

Path integration in mammals and its interaction with visual landmarks.

During locomotion, mammals update their position with respect to a fixed point of reference, such as their point of departure, by processing inertial cues, proprioceptive feedback and stored motor commands generated during locomotion. This so-called path integration system (dead reckoning) allows the animal to return to its home, or to a familiar feeding place, even when external cues are absent or novel. However, without the use of external cues, the path integration process leads to rapid accumulation of errors involving both the direction and distance of the goal. Therefore, even nocturnal species such as hamsters and mice rely more on previously learned visual references than on the path integration system when the two types of information are in conflict. Recent studies investigate the extent to which path integration and familiar visual cues cooperate to optimize the navigational performance.

Animals↗
PubMed1996

Excretion and metabolism of remikiren, a potent orally active inhibitor of primate renin.

1. Following intravenous administration of 14C-remikiren to the male rat, 78% of the administered radioactivity was recovered in faeces, indicating high biliary elimination. Of the 25 +/- 0.1% of the dose recovered in urine, the majority (16.5% of dose) was intact drug. 2. After oral administration to the male rat the urinary recovery was markedly reduced (8.5 +/- 2.0% of dose), and virtually all of the material was excreted as an inactive hydrolysis product. Intact drug was non-detectable, suggesting extensive first-pass metabolism. 3. Perfusion of isolated rat liver confirmed high biliary elimination, coupled with extensive metabolism. Although intact remikiren was the major component in bile (20% of the 'dose'), the majority of the radioactivity was recovered as a series of mono- and di-hydroxylated metabolites. 4. When screened against human renin, only one of the metabolites in bile and urine (mono-hydroxylated in the t-butyl side chain, and synthesized as Ro 44-0444) showed comparable activity to remikiren. The remaining ten metabolites tested were at least one order of magnitude less active than the parent drug. 5. In comparative in vitro studies Ro 44-0444 was formed by rat, but not human or cynomolgus monkey, liver microsomes. The primate microsomes also produced more of the remaining mono- and di-hydroxy products, suggesting that metabolites make little contribution to the oral activity of remikiren which is observed in these species in vivo.

Administration, Oral↗
PubMed1995

Optimizing distal landmarks: horizontal versus vertical structures and relation to background.

During hoarding excursions, golden hamsters use distal landmarks and dead reckoning (updated signals derived from locomotion) to find their way back from a food source at the centre of a circular arena to their nest at the periphery. The preference for particular landmarks was assessed by setting landmark panoramas in conflict with dead reckoning. The hamsters tended to prefer horizontal landmarks to vertical ones when these landmarks were presented alone. However, in combination with a continuous background pattern including a single apex, vertical landmarks were more effective than horizontal ones. A panorama consisting of a vertical cylinder or bar and the background pattern was optimal provided the vertical landmark was aligned or superimposed on the apex of the background. The impact of a landmark panorama therefore depends on its particular components as well as on their mutual relationship.

Animals↗