Biomedical subjects

J Classen

Publications and source records attributed to J Classen.

59 records · Page 4Linked to original sources

PubMed1987

Gramicidin-induced enhancement of transbilayer reorientation of lipids in the erythrocyte membrane.

Incorporation of the channel-forming antibiotic gramicidin into the membrane of human erythrocytes highly (up to 30-fold) enhances rates of reorientation (flip) of lysophosphatidylcholine and palmitoylcarnitine to the inner membrane layer after their primary incorporation into the outer layer. Despite the high increase of flip rates by gramicidin, the asymmetric orientation of the inner membrane layer phospholipids phosphatidylethanolamine and phosphatidylserine is stable as demonstrated by the lack of accessibility of these lipids toward cleavage by exogenous phospholipase A2. On the other hand, gramicidin enhances the rate of cleavage of outer membrane layer phosphatidylcholine by phospholipase A2, which indicates changes in the packing of phosphatidylcholine following gramicidin binding. The increase of flip becomes detectable when about 10(5) copies of gramicidin per cell have been bound (gramicidin to membrane phospholipid ratio of 1:2000). This is a 1000-fold higher concentration than that required for an increase of K+ permeability mediated by the gramicidin channel. Acceleration of flip is thus not simply correlated with channel formation. The enhancement of flip is markedly dependent on structural details of gramicidin. Formylation of its four tryptophan residues abolishes the effect. Even at high concentrations of formylated gramicidin at which the extents of binding of native and of formylated gramicidin to the membrane are comparable, no flip acceleration is produced. Enhancement of flip by gramicidin occurs after a temperature-dependent lag phase. At 37 degrees C, flip rates begin to increase within a few minutes and at 25 degrees C, only after 3 h. This lag phase is most likely not due to limitations by the rate of binding of gramicidin to the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Membrane↗

PubMed1987

Formation of flip sites for phospholipids by introduction of channel-forming antibiotics into the membrane of human erythrocytes.

Incorporation into the erythrocyte membrane of channel-forming antibiotics, such as the polyene amphotericin B or the polypeptide gramicidin A, highly accelerates the transbilayer reorientation (flip) of exogenously incorporated lysolecithin. The first enhancement of flip is obtained when about 2 X 10(5) copies per cell are incorporated of each of the antibiotics. An up to 40-fold increase is obtained at about 2 X 10(6) copies per cell. Conversely, pimaricin, a polyene antibiotic which does not form channels probably because it cannot span the lipid bilayer, does not enhance flip. Moreover, the N-formylated analogue of gramicidin, which does not form channels either, does not enhance flip. The results clearly demonstrate the specificity of the flip enhancing effect and indicate a requirement of a focal perturbation of the outer and the inner membrane layer to induce flip by the channel formers. Besides flip enhancement antibiotics increase the rate of cleavage of outer membrane layer phosphatidylcholine by phospholipase A2. Moreover, amphotericin increases accessibility of inner membrane layer phosphatidylethanolamine to the lipase, whereas gramicidin does not enhance accessibility of this phospholipid. This indicates a more general perturbation of the inner membrane lipid domain by the polyenes.

Amphotericin B↗

PubMedDate not supplied

Somatosensory evoked potentials (SEPs) elicited by magnetic nerve stimulation.

Magnetic stimulation of peripheral nerves at distal and proximal sites of the upper and lower extremities and at the midlumbar level were used to elicit cortical somatosensory evoked potentials. Evidence is provided that peripheral nerve trunks, rather than distal receptor afferents, are the anatomical structures stimulated by the electromagnetic fields. Magnetic stimulation of peripheral nerves is considered to be useful for an evaluation of the integrity of proximal nerves, nerve roots and central conduction along sensory pathways. In contrast to electrical nerve stimulation, magnetic stimulation is painless and can be applied to proximal nerves and plexus. By means of proximal nerve stimulation central sensory conduction can be tested even in patients with peripheral nerve lesions or polyneuropathy.

Adult↗

PubMedDate not supplied

Thermoradiotherapy for locally recurrent breast cancer with skin involvement.

PURPOSE: This retrospective analysis investigated the effectiveness and side-effects of combined hyperthermia and radiation therapy in locally recurrent breast cancer after primary modified radical mastectomy. The aim of the thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall disease. MATERIALS AND METHODS: Between May 1995-August 1998, 39 extensively pre-treated women with progressive locoregional chest wall tumours were treated with local radiofrequency hyperthermia, given twice a week immediately before radiotherapy. Sixty-two per cent of the patients had received previous radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36% hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine patients were treated for microscopic residual disease after local tumour excision (R1-resection) and 30 patients for gross macroscopic nodular recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the ipsilateral chest wall to cover the whole irradiation area. Each field received a median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions) just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The monitored maximum(average) and average(average) epicutaneous temperatures were 42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C, respectively, were achieved in nine chest wall recurrences with intratumoural temperature probes. Concurrent hormonal therapy was administered in 48%, and concurrent chemotherapy in 10% of patients. RESULTS: Median overall survival time was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years after thermoradiotherapy. The median time to local failure has not been reached, local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour controls for microscopic residual disease were 89%, and for macroscopic nodular recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local tumour controls after treatment with a total dose of less than 60 Gy were 51% and 38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p = 0.01), respectively. Actuarial 1 year local tumour control was 92% after complete tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39 patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute thermoradiotherapy related erythema, dry desquamation and moist desquamation were seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis occurred in two patients with previous post-operative delayed wound healing, and in one patient above a silicon implant. CONCLUSION: This study showed that, in extensively pre-treated patients with locally recurrent breast cancer, local tumour control after thermoradiotherapy depended on tumour resectability, response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.

Adult↗

PubMedDate not supplied

Future strategies in external radiation therapy of renal cell carcinoma.

The advantage of external radiation therapy in renal cell carcinoma is controversial. High complication rates reported in previous trials of postoperative radiation therapy can now be avoided by using contemporary modern treatment techniques. Based on both prospective and retrospective data the following indications for adjuvant radiation therapy should be considered and tested in phase III trials: a) unresectable non-metastatic tumours (preoperative irradiation), b) incomplete resection with gross or macroscopically positive margins, c) locally advanced tumour with perinephric fat extension or adrenal invasion.

Carcinoma, Renal Cell↗