Search Results - (Author, Cooperation:R. Axel)

2014-11-11

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amygdala/cytology/*physiology ; Animals ; Behavior/*physiology ; Learning/physiology ; Mice ; Neurons/physiology ; Odors/*analysis ; Olfactory Bulb/cytology/physiology ; Olfactory Pathways/cytology/physiology ; Olfactory Perception/*physiology

2011-04-01

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amygdala/anatomy & histology/cytology/physiology ; Animals ; Axons/physiology ; Brain Mapping ; Mice ; Neuroanatomical Tract-Tracing Techniques ; Olfactory Bulb/anatomy & histology/cytology/physiology ; Olfactory Pathways/*anatomy & histology/cytology/*physiology ; Olfactory Perception/*physiology

2013-04-26

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Arthropod Antennae/anatomy & histology/innervation/physiology ; Coloring Agents ; Drosophila melanogaster/anatomy & histology/cytology/*physiology ; Female ; Learning/physiology ; Male ; Models, Neurological ; Mushroom Bodies/anatomy & histology/cytology/*physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons/physiology ; Odors/analysis ; Olfactory Pathways/cytology/*physiology ; Smell/*physiology ; Staining and Labeling

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] DARWIN'S theory of the origin of species presupposes the occurrence of occasional variants from the parent stock, of which some are preserved and fostered by natural selection. The cause of this natural variation has been sought in various quarters; and indeed it is to be presumed that it is ...

Electronic Resource

0012-1606

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Electronic Resource

0888-7543

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Medicine

Electronic Resource

1432-0843

Key words Carzelesin ; Lymphoma ; Solid tumors ; Toxicity

Springer Online Journal Archives 1860-2000

Medicine

Abstract Purpose: In a phase II trial, the activity of carzelesin, a cyclopropylpyrroloindole prodrug analog, was assessed. Patients and methods: Carzelesin was used as second- or third-line chemotherapy in patients with breast, ovarian, head and neck cancer and non-Hodgkin's lymphoma, and as first-line chemotherapy in patients with colorectal and gastric cancer and melanoma. The drug was given as a bolus infusion at a 4-weekly dose of 150 μg/m2. A total of 140 patients were entered and a total of 285 courses were administered. Results: In general, the compound was well tolerated. Myelotoxicity was the most common toxicity. Grade 3 and 4 leukopenia was observed in 18.6% of the courses, neutropenia in 20.3%, thrombocytopenia in 16.2% and anemia in 8.7%. Double nadirs were seen in a total of 41 courses for neutrophils, in 40 for leukocytes and in 3 for platelets. Non-hematological toxicity was very mild. Only one partial response in a patient with melanoma was seen. Conclusions: At this dose and schedule carzelesin did not yield activity in the types of tumors studied.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Molecular hybridization has been used to detect within human tumours RNA sequences that are homologous to the RNA of oncogenic viruses known to cause similar tumours in ...

Electronic Resource

1432-0711

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-0711

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-0711

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1335

Micrometastases ; Minimal residual disease ; RT-PCR ; Breast cancer

Springer Online Journal Archives 1860-2000

Medicine

Abstract A two-step reverse-transcriptase-based polymerase chain reaction (PCR) with nested primer pairs was developed to amplify sensitive and specific cytokeratin-19 (CK-19) mRNA sequences from human breast cancer cells. No CK-19 pseudogene interference was seen. The larger DNA-derived amplification products could be clearly discriminated from mRNA-derived products. The CK-19 message was not amplified from bone marrow or blood of healthy volunteers and patients with haematological malignancies nor from myeloid and lymphoid cell lines. Breast cancer cells were diluted in buffy coat cells up to 10−6 and CK-19 mRNA sought by PCR. The CK-19 message was detected in 14 of 26 blood samples and 14 of 24 marrow samples but in neither of two peripheral blood stem cell samples taken from 35 breast cancer patients. By sequence-analysis control of two of these samples and two cell lines, the amplified DNA fragments were confirmed to be homologous with the CK-19 sequence. The CK-19 message was further sought in matched blood/marrow samples taken from 13 untreated women in the same cohort at the time of diagnosis. In 3 of these, CK-19 RNA was detected in blood and marrow and, in 3 others, only in blood, but never in marrow alone. The results show that CK-19 assay by reverse transcriptase/PCR is a sensitive and specific technique for the detection of cancer cells in bone marrow and blood. It could be helpful in diagnosis and monitoring of metastatic breast cancer and detection of micrometastases. This should be evaluated on larger numbers of patients, with different clinical samples and epithelial malignancies.

Electronic Resource

1432-2013

Microcirculation ; Rat mesentery ; Propagated dilation ; Propagated constriction ; Metabolic regulation

Springer Online Journal Archives 1860-2000

Medicine

Abstract The effect of microinjection of norepinephrine (10−5 M) into precapillary microvessels of the rat mesentery was studied using intravital microscopy. Upon application, in 29 out of 40 cases (73%) flow ceased at the site of drug application, although in most cases the precapillary microvessels themselves did not show a diameter change due to a lack of smooth muscle cells as confirmed by transmission electron microscopy. In 17 out of the 29 cases with flow cessation (59%), an intimate contact between the venule draining the site of application and the supplying arteriole was found. Initial constriction was seen at the site where the venule crossed the arteriole. Constriction propagated both up- and downstream along the arteriole, and also across arteriolo-arteriolar arcades. Arteriolar constriction could be abolished by intentionally occluding the venule draining the norepinephrine solution. It is proposed that venuloarteriolar contacts and propagated vasomotor response may contribute to local blood flow regulation by providing a feedback loop between tissue capillaries and resistance arterioles. In three complete mesenteric microvessel networks, the arterioles (n=34) supplying 273 out of 401 capillaries (68%) were in close proximity to venules draining these same capillaries. Each of these arterioles served, on average, 43 capillaries, showing a bimodal distribution with peaks at 4 to 16 and at 64 to 256 capillaries. On average, 62% of all capillaries drained by a given venule crossing an arteriole originated from this very arteriole, indicating a reasonably effective feedback.

Electronic Resource

1439-6327

Anterior cruciate ligament ; Quadriceps muscle ; Mechanical output ; Electromyography nervous

Springer Online Journal Archives 1860-2000

Medicine

Summary Integrated surface electromyograms of the three superficial parts of the quadriceps and isokinetic knee extensor maximum torque and power production were recorded simultaneously and at different angular velocities in both legs in 11 male subjects with unilateral tear of the anterior cruciate ligament. The cross-sectional area (CSA) of the thigh and its muscular components were measured by computerized tomography. The principal findings were a small but significant decrease in quadriceps CSA on the affected side; a decreased active, but not passive, range of movement; decreased mechanical output, whether or not corrected for differences in CSA; and decreased electrornyographic activity — particularly in rectus femoris. These findings suggest that the reason for the decreased maximum and total knee extensor performance seen in these patients is a change in knee joint receptor afferent inflow.

Electronic Resource

1439-6327

Human ; Skeletal muscle ; Biomechanics ; Isokinetic ; Electromyography ; Ergonomics

Springer Online Journal Archives 1860-2000

Medicine

Summary Isokinetic ankle plantar- and dorsal-flexion torques, IPF and IDF, respectively, were measured in twenty-five physically healthy athletes, fifteen males and ten females, with simultaneous recording of rectified, linearly enveloped surface electromyograms, and peak electromyographic tensions (PEMG). Angular delays from the start of motion to occurrence of peak torques were also registered. Manoeuvres were performed in two knee positions. For comparison of strength 30 non-athletic (untrained) controls were included. IPF, but not IDF, was greater in the trained than in the untrained subjects. Formulae for estimation of IPF at 30

Electronic Resource

1439-6327

Human ; Isokinetic ; Plantarflexion ; Work ; Torque ; Prediction

Springer Online Journal Archives 1860-2000

Medicine

Summary Contraction work (CW) and peak torque (PT) of maximum isokinetic plantar flexions were measured in clinically healthy subjects randomly chosen from the official census list of Umeå, Sweden, in three groups: 40–44, 50–54 and 60–64 years of age, with similar proportions of men and women. Maximum isokinetic plantarflexions were performed at angular velocities of 30, 60, 120 and 180

Electronic Resource

1573-0646

phase I ; dextran-conjugated doxorubicin ; pharmacokinetics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21–28 days. Thirteen patients have received a total of 24 courses (median 2; range 1–3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 × WHO grade IV, 1 × WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 × WHO grade IV, 2 × WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 μg/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83–80.21 μg/ml*h with dose-dependent elimination half lives (t1/2α: 0.02–0.87 h;1/2β: 2.69–11.58 h;1/2γ: 41.44–136.58 h). We conclude that the maximal tolerated dose (MTD) of AD-70 using this schedule is 40 mg/m2 DOXeq. The recommended dose for clinical phase II studies is 12.5 mg/m2 DOXeq.

Electronic Resource

1573-0646

vinorelbine ; clonogenic growth ; human tumors

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Vinorelbine (5′-nor-anhydrovinblastine) is a semisynthetic vinca alkaloid currently undergoing extensive clinical evaluation. We have studied the antitumor effect of vinorelbine (final concentrations: 8.4–1000.0 ng/ml) against freshly explanted clonogenic cells from 102 human tumors using a capillary soft agar cloning system and have compared the compound's activity with vinblastine, vincristine, vindesine, paclitaxel, docetaxel, and other clinically used anticancer agents. Four specimens were excluded from further analyses (3 bacterial or fungal contamination, 1 benign histology). Fifty-one of the remaining 98 (52%) specimens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety of solid rumors. At clinically relevant concentrations (0.1 × peak plasma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate, and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and docetaxel (78% inhibition, p = 0.002) were significantly more active than vinorelbine. Moreover, vinorelbine showed antitumor activity against several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wide spectrum of in vitro activity against freshly explanted human tumors and that the clinical activity of this compound against breast cancer and non-small cell lung cancer is reflected in vitro.

Electronic Resource

1573-9686

Heterogeneity ; Vascular networks ; Mathematical simulations ; Vascular adaptation ; Structural autoregulation

Springer Online Journal Archives 1860-2000

Medicine

Technology

Abstract Terminal vascular beds exhibit a high degree of heterogeneity. Pertinent parameters are nonlinearly related, and their distributions are not independent. The classical “typical vessel” approach using averaged values for different vessel classes may not lead to a correct understanding of physiology and pathophysiology of terminal vascular beds. Such problems can be avoided by studying microcirculatory functions at the network level using a combination of experiments and theoretical models. In this approach, distributions and relationships of pertinent parameters are measured in vivo, leading to the development of comprehensive databases. Such databases can be analyzed and complemented by suitable mathematical models, permitting estimation of parameters that are difficult to measure, and critical assessment of quantitative theories and hypotheses for microvascular function. This collaborative process between experimentally and theoretically oriented investigators may be facilitated in the future by the development of web-based repositories of experimental data and theoretical models. © 2000 Biomedical Engineering Society. PAC00: 8719Tt, 8719Uv

Electronic Resource

1573-0646

recombinant human interleukin-4 ; tumor growth modulation ; human tumor cloning assay

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explanted human tumor specimens using anin vitro soft agar cloning system. Final concentrations of 0.1 to 10 ng/ml were used in continuous incubation experiments. Of 147 specimens, 73 (50%) were evaluable for the determination of tumor growth modulating activity. The most common tumor types recruited included breast, nonsmall cell lung, ovarian cancer and melanoma. Stimulation of tumor colony forming units (colony formation ≥1.5× controls) was observed in 0/73 tumors. Similarly, only 1/73 (1.3%) specimens (a non-small cell lung cancer) had a significant decrease in tumor colony forming units (colony formation ≤ 0.5× controls) at 1 ng/ml. We conclude that rhuIL-4 is not a direct modulator of tumor colony formationin vitro. However, antitumor effects could perhaps be achievedin vivo via the immune-modulating effects of Interleukin-4.

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