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Biomedical subjects

R Maurer

Publications and source records attributed to R Maurer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients.

BACKGROUND: Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation. PATIENTS AND METHODS: Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission. RESULTS: Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival. CONCLUSION: Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.

Adolescent↗
PubMed1995

Urease-specific monoclonal antibodies prevent Helicobacter felis infection in mice.

Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgA] 71) previously demonstrated to neutralize the ability of Helicobacter felis to colonize mice. Immunoprecipitation of radiolabeled H. felis outer membrane proteins with IgA 71 revealed specificity for a 62-kDa protein. Another of our monoclonal antibodies, IgG 40, precipitated a protein of similar molecular weight. IgA 71 but not IgG 40 also precipitated purified recombinant H. pylori urease. The antigenic specificity of both antibodies was confirmed to be urease by the ability of each to select Escherichia coli clones expressing the H. felis urease genes. The two antibodies were shown to bind nonoverlapping epitopes in a competition enzyme-linked immunosorbent assay. Both IgA 71 and IgG 40 could effectively neutralize H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protection does not appear to be inhibition of urease activity, as IgA 71 does not inhibit the conversion of urea to ammonia by H. pylori urease in vitro. These results support a protective role for the secretory humoral immune response in Helicobacter immunity and provide further evidence that the urease enzyme can serve as a protective antigen.

Amino Acid Sequence↗
PubMed1995

[Experimental aortic aneurysm with endovascular technique].

We created a simple experimental aneurysm by a minimal operative trauma performing the balloon-dilatation and the rupture of the abdominal aorta of animals. The aorta of minipigs was dilated under angiographic control until the rupture became visible. The abdominal aorta and its branches were mapped out and measured. The angiographics were calculated using a planimetric device. The dilatation of the aorta was increased up to 3.5 times the initial diameter when rupture occurred. The microscopical examination showed lesions in all three layers of the vessel only at the rupture site and some focal lesions of the tunica intima. This one-step procedure of producing an experimental aneurysm is done using a low operative trauma and allows testing of endovascular systems using only one anaesthetic.

Aneurysm, Ruptured↗
PubMed1994

[Primary malignant melanoma of the male urethra. Case report and discussion of the literature].

We report the case of a 77-year-old man who presented with a polypoid tumor in the distal urethra. It was excised, and a histological diagnosis of malignant melanoma was made. The patient had no history of previous cutaneous biopsies or suspicious pigmented lesions; therefore, the melanoma was considered to be primary in the urethra. The patient declined therapy and died 28 months later with local tumor progression. The autopsy revealed a widespread metastatic disease. The male urethra is rarely the primary site of a malignant melanoma. This event has so far been described in about 45 patients. The case is discussed in view of the pertinent literature.

Aged↗
PubMed1994

[Low-grade MALT-type non-Hodgkin lymphoma of the stomach with local recurrence 14 years following resection. Demonstration of clonal identity using polymerase-chain-reaction (PCR)].

So-called low grade B-cell lymphomas of MALT type occurring mainly in the gastrointestinal tract but also in the salivary glands, the thyroid and the lungs are indolent neoplasms with a prolonged clinical course and persistent localized disease at the site of origin. This behaviour sets them apart from their nodal counterparts, which are frequently generalized from onset. Their recognition within and their separation from accompanying reactive processes (e.g. chronic gastritis) is important but may be difficult on morphology alone. In the immediate past there have been reports on regression of gastric MALT type lymphomas after eradication of Helicobacter pylori. We observed a 68-year-old male patient who underwent partial gastric resection for persistent ulcer disease in 1979. A histological diagnosis of pseudolymphoma was established at that time. In 1993 he again had gastrointestinal bleeding. Endoscopy revealed ulcerations at the anastomosis. Biopsies showed a monoclonal infiltrate of centrocytoid B-cells with typical lymphoepithelial lesions, suggesting the diagnosis of low grade B-cell lymphoma of MALT type which was seen focally in multiple biopsies randomly taken from the gastric remnant. Review of the 1979 specimen revealed identical lesions. Polymerase chain reaction (PCR) on both specimens demonstrated identical products of rearranged Ig-heavy chain genes, thus confirming the monoclonality and establishing the clonal relationship of both lesions. Staging revealed no extragastric disease. Two courses of chemotherapy did not affect the mucosal infiltrates. Although the patient had been under antacid medication and the presence of Helicobacter pylori could not be demonstrated, antimicrobial treatment was given, after which follow-up biopsies were free of tumor and bacteria after 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

The value of inferior petrosal sinus sampling in diagnosis and treatment of Cushing's disease.

OBJECTIVE: While microsurgical selective adenomectomy is the best method available at present for the treatment of Cushing's disease, its success depends to a large degree on precise preoperative intrapituitary microadenoma localization. This study compares the results of intrapituitary adenoma localization obtained with inferior petrosal sampling, computerized tomography and magnetic resonance imaging with the adenoma localization as found at surgery. DESIGN: The results of inferior petrosal sampling for intrapituitary localization of ACTH-producing pituitary adenomas were compared in a retrospective study with the results of computerized tomography, magnetic resonance imaging, surgical and pathological findings. Special attention was paid to the intersinus ACTH relation. PATIENTS: Thirty-eight patients (33 women and 5 men) of 11-68 years of age suffering from pituitary-dependent Cushing's disease were studied. Patients with ectopic ACTH-secreting tumours and recurrent pituitary adenomas were excluded. MEASUREMENTS: Blood samples were obtained simultaneously from both inferior petrosal sinuses and a peripheral vein before and 5, 10, 15 and 20 minutes after stimulation with 60 micrograms/m2 human corticotrophin-releasing hormone (hCRH). RESULTS: Of the adenomas in our series, 42% had a diameter of 3 mm or less. Only 6 of 20 adenomas examined by computerized tomography and 11 of 29 examined by magnetic resonance imaging were identified correctly. Inferior petrosal sinus sampling produced significantly better results, particularly when combined with a stimulation test with hCRH: for 29 of 38 adenomas examined, the location was predicted correctly with these techniques. Analysis of the intersinus adrenocorticotrophin concentration ratio showed that the best right-central-left discrimination was obtained with values of 1.3 and 1.4. CONCLUSIONS: We conclude that inferior petrosal sinus ACTH sampling after hCRH stimulation is the best method available for the intrapituitary localization of microadenomas causing Cushing's disease provided that the appropriate technique of blood sampling is used meticulously.

Adenoma↗
PubMed1994

holE, the gene coding for the theta subunit of DNA polymerase III of Escherichia coli: characterization of a holE mutant and comparison with a dnaQ (epsilon-subunit) mutant.

DNA polymerase III holoenzyme is a multiprotein complex responsible for the bulk of chromosomal replication in Escherichia coli and Salmonella typhimurium. The catalytic core of the holoenzyme is an alpha epsilon theta heterotrimer that incorporates both a polymerase subunit (alpha; dnaE) and a proofreading subunit (epsilon; dnaQ). The role of theta is unknown. Here, we describe a null mutation of holE, the gene for theta. A strain carrying this mutation was fully viable and displayed no mutant phenotype. In contrast, a dnaQ null mutant exhibited poor growth, chronic SOS induction, and an elevated spontaneous mutation rate, like dnaQ null mutants of S. typhimurium described previously. The poor growth was suppressible by a mutation affecting alpha which was identical to a suppressor mutation identified in S. typhimurium. A double mutant null for both holE and dnaQ was indistinguishable from the dnaQ single mutant. These results show that the theta subunit is dispensable in both dnaQ+ and mutant dnaQ backgrounds, and that the phenotype of epsilon mutants cannot be explained on the basis of interference with theta function.

DNA Polymerase III↗
PubMed1994

Golden hamsters on the eight-arm maze in light and darkness: the role of dead reckoning.

This paper examines whether golden hamsters can rely on dead reckoning (getting positional information from updated signals generated during locomotion) on an eight-arm maze. Two groups of hamsters were tested: Group L under ordinary room light, Group D in darkness. To enhance the role of dead reckoning, each subject could climb from its own home cage onto the central platform of the maze. In a first experimental phase (15 trials), the L subjects learned to master the maze through developing a locomotor rule (arm chaining) after three to four trials. The D subjects developed arm chaining less readily and fluctuated more in their performance than did the L subjects. In a second experimental phase (15 trials), four arms were blocked at the beginning of each trial. In both experimental groups the performance decreased, yet remained well above chance level. Success and arm chaining were positively correlated in Phase 1 and negatively correlated with success in Phase 2. We assume that in Phase 2 the L subjects switched to the predominant use of visual cues, and the D subjects to dead reckoning.

Animals↗
PubMed1993

[Suspected adult-onset Still's disease: unexpected manifestation of leprosy].

A 23-year old male from Sri Lanka was admitted to hospital with symmetrical inflammatory peripheral polyarthritis, fever of 39 degrees C and poly-lymphadenopathy. At first we suspected adult onset Still's disease. The histological findings from axillary lymph node biopsy strongly suggested the diagnosis of leprosy, for which we had had little evidence thus far. Typical skin lesions were absent, skin smears were negative and neurological symptoms only became obvious much later when fever and arthritis had subsided under anti-inflammatory treatment. At this time a right ulnar palsy developed, with atrophy of the interosseous muscles and thickening of the ulnar nerves at both medial epicondyles. Fite-stains of a sural nerve biopsy confirmed the diagnosis when mycobacteria were detected. Leprosy displays a clinico-pathological spectrum caused by variations in host resistance. A widely accepted classification is the five group system of Ridley and Jopling. At one extreme of this spectrum are patients with lepromatous or low resistance leprosy with numerous bacilli, and at the other those with high resistance or tuberculous leprosy where few or no bacilli are found. The numerous bacilli in the sural nerve biopsy classified the disease as lepromatous in our case. Of the various manifestations of the lepra reaction occurring in lepromatous leprosy, one is acute arthritis, but a more common one is erythema nodosum leprosum. Our patient's clinical presentation was interpreted to be a rheumatic manifestation of a type-2 reaction. This form of immunological response in leprosy is an immune complex syndrome and may mimic different rheumatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Dead reckoning in a small mammal: the evaluation of distance.

When hoarding food under infra-red light, golden hamsters Mesocricetus auratus W. return fairly directly from a feeding place to their nest site by evaluating and updating internal signals that they have generated during the previous outward journey to the feeding place. To test more specifically the animals' capacity to evaluate the linear components of the outward journey, the subjects were led from their (cone-shaped) nest to a feeding place along a detour which comprised either 2 (experiment 1) or 5 (experiment 2) segments; adjoining segments were at right angles to each other. In these conditions, the subjects remained significantly oriented towards the nest and therefore were capable of assessing translations as well as rotations during the outward journey. In experiment 3, the nest was removed after the hamsters had started the direct outward journey to the feeding place and the hamsters were rotated during the food uptake. The animals were no longer oriented towards the starting point of their journey, but nonetheless covered, along a fairly straight path, the correct homing distance, and then changed over to a circular search path. These results confirm that mammals can derive the linear components of an outward journey from self-generated signals and therefore are able to judge the homing distance without relying on cues from the environment. For a number of detour outward journeys, our data yield an unexpectedly good fit to Müller and Wehner's (1988) model of dead reckoning in ants. However, this is no longer the case when the outward journey contains an initial loop which brings the subject back to the starting point. These findings are discussed in terms of the biological significance and limitations of an approximate form of path integration.

Algorithms↗
PubMed1992

[Liposarcoma of the laryngeal region. Case report and literature review].

The case is reported of a 64-year-old man in whom a pedunculated tumor of the Vallecula epiglottica occurred and was excised. Histologically it proved to be a dedifferentiated liposarcoma. The patient is well and free of disease 18 months later. The literature is reviewed and 20 other cases of liposarcoma in the laryngeal region are discussed.

Epiglottis↗
PubMed1992

[Isolated massive adrenal hemorrhage--an insidious complication in anticoagulation].

Massive bilateral adrenal hemorrhages are a rare complication of anticoagulant therapy. Among over 34,000 autopsies of adults we found six patients with such hemorrhages. Two were women and four men with a mean age of 81 years. They had been hospitalized and anticoagulated for various reasons. The hemorrhage occurred within ten days of anticoagulation, was always bilateral and massive and destroyed the adrenal cortex, thus leading to acute adreno-cortical insufficiency. The diagnosis in all patients was made only at autopsy. Main symptoms are abdominal pain, progressive hypotension, electrolyte disorders and disturbances of consciousness. In patient on anticoagulant therapy, these symptoms justify the suspicion of adrenal hemorrhage and the institution of lifesaving substitution therapy. Pathogenetically these hemorrhages are attributed to the combined effects of stress-induced adrenocortical tissue damage and increased bleeding tendency. The findings in our patients are compared with those of 83 patients from the literature.

Adrenal Cortex Diseases↗
PubMed1992

[Large myelolipoma with reversible hypertension].

Myelolipomas are rare, benign, usually asymptomatic tumors of the adrenals consisting of fatty and hemopoietic tissue. New imaging techniques lead increasingly to incidental findings. Diagnosis of a myelolipoma is confirmed by fine needle aspiration yielding mature adipose tissue together with hematopoietic cells, in particular megakaryocytes. Pathophysiology is unclear, correlations to hormonal disturbances are discussed and increased incidence of hypertension associated with myelolipoma has been reported. We describe a female patient who was found at evaluation of hypertension to have a myelolipoma of more than 1 kg of weight. Liposarcoma was suspected and the tumor excised. After excision blood pressure returned to normal.

Adrenal Gland Neoplasms↗
PubMed1992

Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors.

Eighty-three previously untreated patients with aggressive non-Hodgkin's lymphomas were treated with either MACOP-B (23 patients) or VACOP-B (60 patients) as originally described by Klimo and Conners [1, 2]. Their median age was 46 years. Thirty-seven patients had stage I or II and 46 stage III or IV disease. The tumor histopathology was reviewed in all cases. Sixty-five patients had intermediate grade and 18 high-grade non-Hodgkin's lymphomas according to the International Working Formulation. The rate of complete response was 74% for MACOP-B and 76% for VACOP-B. At the time of analysis the duration of follow-up was 50 months for the MACOP-B and 22 months for the VACOP-B group. The actuarial three-year progression-free survival was 35 +/- 10% for the MACOP-B group, 48 +/- 11% for the VACOP-B group, and 46 +/- 7% for all patients. Treatment mortality was 6%. A univariate and a multivariate analysis of selected pretreatment parameters and of regimen demonstrated that stage III or IV, high-grade lymphoma, and elevated serum LDH, but not the type of regimen, are significantly associated with poor progression-free survival in our patient population.

Adolescent↗
PubMed1992

DNA replication defect in Salmonella typhimurium mutants lacking the editing (epsilon) subunit of DNA polymerase III.

In Salmonella typhimurium, dnaQ null mutants (encoding the epsilon editing subunit of DNA polymerase III [Pol III]) exhibit a severe growth defect when the genetic background is otherwise wild type. Suppression of the growth defect requires both a mutation affecting the alpha (polymerase) subunit of DNA polymerase III and adequate levels of DNA polymerase I. In the present paper, we report on studies that clarify the nature of the physiological defect imposed by the loss of epsilon and the mechanism of its suppression. Unsuppressed dnaQ mutants exhibited chronic SOS induction, indicating exposure of single-stranded DNA in vivo, most likely as gaps in double-stranded DNA. Suppression of the growth defect was associated with suppression of SOS induction. Thus, Pol I and the mutant Pol III combined to reduce the formation of single-stranded DNA or accelerate its maturation to double-stranded DNA. Studies with mutants in major DNA repair pathways supported the view that the defect in DNA metabolism in dnaQ mutants was at the level of DNA replication rather than of repair. The requirement for Pol I was satisfied by alleles of the gene for Pol I encoding polymerase activity or by rat DNA polymerase beta (which exhibits polymerase activity only). Consequently, normal growth is restored to dnaQ mutants when sufficient polymerase activity is provided and this compensatory polymerase activity can function independently of Pol III. The high level of Pol I polymerase activity may be required to satisfy the increased demand for residual DNA synthesis at regions of single-stranded DNA generated by epsilon-minus pol III. The emphasis on adequate polymerase activity in dnaQ mutants is also observed in the purified alpha subunit containing the suppressor mutation, which exhibits a modestly elevated intrinsic polymerase activity relative to that of wild-type alpha.

Base Sequence↗
PubMed1992

Purification and characterization of a mutant DnaB protein specifically defective in ATP hydrolysis.

The dnaB gene of Escherichia coli encodes an essential DNA replication enzyme. Fueled by the energy derived from the hydrolysis of ATP to ADP+P(i), this enzyme unwinds double-stranded DNA in advance of the DNA polymerase. While doing so, it intermittently stimulates primase to synthesize an RNA primer for an Okazaki fragment. To better understand the structural basis of these and other aspects of DnaB function, we have initiated a study of mutant DnaB proteins. Here, we report the purification and characterization of a mutant DnaB protein (RC231) containing cysteine in place of arginine at residue 231. The mutant protein attains a stable, properly folded structure that allows association of six promoters to form a hexamer, as is also true for wild-type DnaB. Further, the mutant protein interacts with ATP, the nonhydrolyzable ATP analog adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), ADP, and poly(dT), and it stimulates primase action. It is, however, profoundly deficient in ATP hydrolysis, helicase activity, and replication activity at the chromosomal origin of replication. In addition, while general priming reactions with wild-type DnaB and ATP elicited the synthesis of short primers, reactions with DnaB and ATP gamma S or with RC231 and either ATP or ATP gamma S stimulated the synthesis of significantly longer primers. On the basis of these observations, we suggest that primase interacts directly with DnaB throughout primer synthesis during general priming, until dissociation of DnaB from DNA or ATP hydrolysis by DnaB disrupts the interaction and leads to primer termination.

Adenosine Triphosphate↗