Search PubMed⌕ Search

Biomedical subjects

A Gruber

Publications and source records attributed to A Gruber.

At least 145 records · Page 8Linked to original sources
PubMed1995

Multidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.

The clinical relevance of multidrug resistance gene (mdr1) expression in tumor cells remains largely unclear. Conflicting results regarding mdr1 gene expression and clinical outcome have been obtained. Little is known about regulation of mdr1 gene expression, and the conflicting results might be explained by the fact that mdr1 RNA levels do not reflect expression at the protein level. The aim of the present study was to investigate the relationship between mdr1 RNA levels and P-glycoprotein (Pgp) content of leukemic cells from patients with acute myelogenous or lymphocytic leukemia. Mdr1 RNA levels were determined by a quantitative RNA-RNA solution hybridization method, and Pgp by Western blot technique with enhanced chemiluminescence for immunodetection. Pgp was detected in 14/14 leukemic cell samples while mdr1 RNA was detectable (> 0.15 copies/cell) in cells from only six out of the 14 patients. Mdr1 RNA levels did not correlate with the Pgp content of leukemic cells (r = 0.284, p = 0.306). Relapsed leukemias had significantly (p = 0.016) higher levels of Pgp than de novo untreated leukemias (the mean and SD optical density units were 0.56 +/- 0.18 and 0.25 +/- 0.17 respectively) while no difference was found in RNA levels. The findings support post-transcriptional level regulation of mdr1 gene expression and stress the importance of accurate determinations of the Pgp content of tumor cells in studies of the relationship between mdr1 gene expression and clinical outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Pharmacokinetics of mitoxantrone, etoposide and cytosine arabinoside in leukemic cells during treatment of acute myelogenous leukemia--relationship to treatment outcome and bone marrow toxicity.

Twenty-seven patients with acute myelogenous leukemia (AML) were given remission induction treatment with mitoxantrone, etoposide and cytosine arabinoside (ara-C). The pharmacokinetics in leukemic blood cells of mitoxantrone, etoposide and the active metabolite of ara-C, ara-CTP, were determined during the first day of treatment. There was a large interpatient variability of the area under the time versus concentration curve (AUC) for all three drugs. On the individual level, there was no correlation between the AUCs of the different drugs. Neither did the AUC of any individual drug nor the calculated total intracellular drug exposure have any association with the outcome of treatment or hematological toxicity, measured as duration of leukopenia/thrombocytopenia. In conclusion, when combination chemotherapy with mitoxantrone, etoposide and ara-C is given to patients with AML, intracellular drug concentrations, achieved after the first dose of each drug, do not seem to be predictive for treatment response or hematological toxicity.

Adult↗
PubMed1995

Effects of intrapleural mitoxantrone and mepacrine on malignant pleural effusion--a randomised study.

30 patients with malignant pleuritis were randomised to be treated, either with intrapleural instillation of mepacrine chloride or with mitoxantrone. The patients were evaluated with chest X-ray and a symptom questionnaire during a follow-up period of 12 weeks. Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients. High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low, giving a plasma/intracavity ratio generally of less than 1:60. The chest X-rays showed excellent results for both treatment modalities. However, the patients treated with mepacrine chloride experienced greater discomfort with fever and pain, and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks. We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion. However, mitoxantrone seems to have further advantages when it comes to improving the quality of life.

Adult↗
PubMed1995

Mitoxantrone, etoposide and ara-C vs doxorubicin-DNA, ara-C, thioguanine, vincristine and prednisolone in the treatment of patients with acute myelocytic leukaemia. A randomized comparison.

Complex-binding of anthracyclines to DNA may increase their therapeutic efficacy. In a previous randomized trial patients with acute myelocytic leukaemia (AML) receiving combination chemotherapy including a DNA-bound doxorubicin preparation had a longer duration of first complete remission (CR) and survival than patients receiving free doxorubicin. In a parallel phase I/II study a combination of mitoxantrone, activity. In this randomized study of AML patients (15-60 years) induction treatment with MEA was compared to a combination of doxorubicin/DNA conjugate ara-C, thioguanine, vincristine and prednisolone (POCAL-DNA). The study was closed after an interim analysis of 86 patients. Thirty-five/42 (83%) and 20/44 (45%) patients entered CR in the MEA and POCAL-DNA groups, respectively (p < 0.001). With rescue therapy the corresponding figures were 88 and 64% (p < 0.02). Median survival was 27.8 and 13.1 months for MEA and POCAL-DNA patients, respectively (p < 0.03). In conclusion, the MEA regimen has a very high antileukaemic activity in good accordance with our previous experience. Since we could not reproduce our earlier clinical results using DNA-bound anthracyclines, the source and preparation of DNA seem to be of major importance.

Adolescent↗
PubMed1995

Increase of monocytes predicts mobilization of peripheral stem and progenitor cells after chemotherapy followed by G-CSF administration.

Mobilization of primitive haematopoietic cells to the peripheral blood was studied in 25 patients with haematological malignancies. The optimal level of peripheral stem cells (PSC), defined by their surface expression of CD34, was significantly higher after mobilization with G-CSF, either following chemotherapy or alone (median: 123 x 10(6)/l and 143 x 10(6)/l of CD34+ cells respectively) than without administration of G-CSF subsequent to chemotherapy (median: 27 x 10(6)/l of CD34+ cells). An individual variation in when optimal mobilization of CD34+ cells and myeloid progenitors occurs after chemotherapy and G-CSF administration was noted (median: day 12, range 7-24 days), which makes it difficult to predict when PSC collections in a given patient should be performed. In this study, chemotherapy followed by G-CSF administration resulted in a short lasting (2-3 days) peak appearance of CD34+ cells that could predicted by a 2-fold increase in absolute numbers of monocytes, as compared to the previous day. After the peak level of CD34+ cells in the blood was reached, no further increase in monocytes was seen. The identification of an increase in monocytes, to be used as a predictive variable for when optimal mobilization of PSC will occur in a given patient, may be particularly useful in the individual timing of PSC collections from non-hospitalized patients.

Adolescent↗
PubMed1995

Subendometrial myometrial contractions associated with transcervical chorionic villous sampling.

Thirty-two consecutive patients, referred for prenatal diagnosis by chorionic villous sampling, were examined by transvaginal ultrasound for the presence of myometrial contractions before and after the procedure. Increased myometrial activity was observed in 78% of patients. The mean frequency increased by 3.5 times and the amplitude increased by 4.2 times compared to the preprocedure condition. Cramping was associated with the increased amplitude and/or frequency of contractions. No significant correlation was found between the direction of propagation of the contraction wave and its frequency or amplitude. The sensitivity of ultrasonographically detected myometrial contractions in predicting cramping is 70%, but only 31% in predicting vaginal bleeding or spotting. Further studies are required to elucidate the prognostic significance of this uterine activity.

Adult↗
PubMed1995

Multidrug resistance (Mdr1) gene expression in peripheral blasts from patients with acute leukemia only rarely increases during disease progression after combination chemotherapy.

Multidrug resistance gene (mdr1) RNA levels were determined in 55, and P-glycoprotein expression in 37 samples of peripheral leukemic cells from 17 patients with acute myeloblastic leukemia (AML) and 7 patients with acute lymphocytic leukemia (ALL). Between sample collections, patients were treated with various chemotherapy regimens. Mdr1 RNA levels were quantified by a RNA-RNA solution hybridization assay. P-glycoprotein was determined by Western blot analysis. Samples from 14 patients (9 AML, 5 ALL) had undetectable mdr1 RNA levels at initial analysis. Only two of these had detectable levels after chemotherapy. Ten patients (8 AML, 2 ALL) had detectable mdr1 RNA levels at initial analysis (median 1.0 transcript per cell, range 0.2-1.4). Increase of mdr1 RNA levels after chemotherapy were observed in cells from 3 patients, one patient had a lower level after chemotherapy and the 6 remaining patients had essentially unchanged mdr1 RNA levels in their leukemic cells. Samples from 13 patients were sequentially analysed for P-glycoprotein expression. In one patient, no P-glycoprotein was detectable at initial analysis but was weakly positive after chemotherapy. In the remaining 12 patients, P-glycoprotein levels stayed stable during disease progression. In conclusion, combination chemotherapy seems only rarely to be associated with an increase of mdr1 gene expression in residual leukemic cells. The addition of resistance modifiers to chemotherapy in order to overcome P-glycoprotein mediated resistance might therefore be more effective in chemotherapy naive patients since it is possible that during later disease progression additional mechanisms of resistance may be more operative.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Classical swine fever in wild boar (Sus scrofa)--experimental infections and viral persistence.

A pregnant wild boar and two wild boar weaners were inoculated intranasally with a field isolate of classical swine fever virus (CSFV) recently derived from a diseased domestic pig. The clinical, pathological and haematological findings noted in the young wild boars were comparable to those in domestic weaner pigs inoculated with the same virus isolate. Both wild boars showed the acute haemorrhagic form of CSF, one animal died 18 days post inoculation (p. i.) and the second one had to be euthanized when moribund two days later. The wild boar sow did not show any signs of illness p. i. but seroconversion was noticed. Twenty-eight days p. i. birth was given to six clinically healthy offsprings. One of the newborn proved to be viraemic until death when 39 days of age. Except for poor growth no other symptoms were noticed in this piglet. The non-viraemic litter mates remained healthy, although they had close contact to the persistently infected piglet. High titres of neutralizing antibodies against CSFV were measured in the serum samples of these offsprings. All findings were more or less in accordance with observations previously made in domestic pigs when infected with CSFV around 85 to 90 days of gestation. The wild boar was calculated to have been inoculated at about 87 to 92 days of gestation.

Animals↗
PubMed1994

Alteration of fibrin network by activated protein C.

The antithrombotic plasma enzyme, activated protein C (APC), may play a role in thrombolysis. In vitro, acceleration of clot lysis by APC depends on its ability to inhibit the activation of prothrombin. The effect of APC on the assembly and dispersion of fibrin network was studied using turbidimetry, plasmin digestion of fibrin, and electron microscopy of plasma clots. The addition of APC before clotting but not after clotting accelerated clot lysis. The rate of increase in the turbidity of clotting plasma was reduced by APC. The turbidity of plasma clots containing APC was directly related to the clot lysis time. Fibrin from plasma clots that were formed in the presence of APC yielded less fibrin degradation products than fibrin from clots without added APC. Furthermore, APC reduced the diameter and relative number of fibrin fibers in plasma clots during gel assembly. We propose that APC may enhance the efficacy of thrombolysis by reducing the relative mass of fibrin within maturing thrombi.

Electrophoresis, Polyacrylamide Gel↗
PubMed1994

Polydnavirus of the parasitic wasp Chelonus inanitus (Braconidae): characterization, genome organization and time point of replication.

Ultrastructural analysis of the polydnavirus of the braconid wasp Chelonus inanitus revealed that virions consist of one cylindrical nucleocapsid enveloped by a single unit membrane. Nucleocapsids have a constant diameter of 33.7 +/- 1.4 nm and a variable length of between 8 and 46 nm. Spreading of viral DNA showed that the genome consists of circular dsDNA molecules of variable sizes and measurement of the contour lengths indicated sizes of between 7 and 31 kbp. When virions were exposed to osmotic shock conditions to release the DNA, only one circular molecule was released per particle suggesting that the various DNA molecules are singly encapsidated in this bracovirus. The viral genome was seen to consist of at least 10 different segments and the aggregate genome size is in the order of 200 kbp. By partial digestion of viral DNA with HindIII or EcoRI in the presence of ethidium bromide and subsequent ligation with HindIII-cut pSP65 or EcoRI-cut pSP64 and transfection into Escherichia coli, libraries of 103 HindIII and 23 EcoRI clones were obtained. Southern blots revealed that complete and unrearranged segments were cloned with this approach, and restriction maps for five segments were obtained. Part of a 16.8 kbp segment was sequenced, found to be AT-rich (73%) and to contain six copies of a 17 bp repeated sequence. The development of the female reproductive tract in the course of pupal-adult development of the wasp was investigated and seen to be strictly correlated with the pigmentation pattern. By the use of a semiquantitative PCR, replication of viral DNA was observed to initiate at a specific stage of pupal-adult development.

Animals↗
PubMed1994

Serum vitamin B12 levels and incidence of dementia in a healthy elderly population: a report from the Bronx Longitudinal Aging Study.

OBJECTIVE: To determine whether low serum B12 levels are associated with an increased incidence of dementing illness. DESIGN: Longitudinal cohort study, 5-year follow-up. PARTICIPANTS: Volunteer cohort of 410 nondemented ambulatory subjects aged 75 to 85 years. MEASUREMENTS: Annual serum B12 determinations and neuropsychological assessments including the Blessed Test of Information, Memory and Concentration (BIMC) and the Fuld Object Memory Evaluation (FOME). If subject met criteria for a major cognitive change (as defined by an increase of 4 or more points on the BIMC), a work-up that included CT, EEG, and neurologic assessment was performed. Clinical diagnoses were made according to established criteria. RESULTS: Mean serum B12 level of entire sample was 558 pg/mL. Twenty-two subjects had low B12 levels defined as values < 150 pg/mL. Three of these 22 subjects (13.6%) became demented, compared with 57 of 388 subjects (14.7%) with higher levels. The incidence of Alzheimer disease among the low B12 group was 4.5% compared with 7.5% in the higher B12 group. The mean B12 level at time of diagnosis in subjects who did develop Alzheimer disease was 551 pg/mL. There was no evidence of hematologic disorder among the 22 subjects with low B12. Of the 3 low B12 subjects who did become demented, none responded to monthly B12 injections. CONCLUSION: A low B12 level may not be a risk factor for dementia in general or Alzheimer disease in particular.

Aged↗