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Biomedical subjects

E Küng

Publications and source records attributed to E Küng.

8 recordsLinked to original sources
PubMed1995

Interleukin 2-induced increase of vascular permeability without decrease of the intravascular albumin pool.

Interleukin 2 (IL-2) exhibits anti-tumour activity. High-dose IL-2 regimens are limited by side-effects such as pulmonary oedema and a systemic vascular leak. The mechanisms by which IL-2 mediates transvascular fluid and protein losses in humans are largely unknown. We have, therefore, measured the transcapillary escape rate (TER) of albumin as a reflection of the vascular permeability by injecting [125I]albumin (5 microCi i.v.). In ten melanoma patients pretreated with interferon alpha (IFN-alpha) TER of albumin was measured before and after IL-2 injections (1.5 x 10(6) Cetus-U. s.c. daily for 4 days). The TER of albumin increased from 9.4 +/- 2.7% h-1 before to 14.9 +/- 3.3% h-1 (P < 0.001) after IL-2 injections and the absolute outflux of albumin (Jalb) from 159 +/- 28 mg kg-1 h-1 to 261 +/- 44 mg kg-1 h-1 (P < 0.001), whereas the intravascular albumin pool remained stable (136 +/- 19 g vs 136 +/- 18 g). IL-2 and IL-6 were not detectable in the plasma prior to IL-2 injections and increased to 549 +/- 315 U ml-1 (P < 0.001) and 7 +/- 6 pg ml-1 (P < 0.01), respectively, after IL-2 administration. In conclusion, IL-2 increases the vascular permeability in humans, without affecting the intravascular albumin pool. This suggests that mechanisms such as the lymphatic return can compensate for the severe transendothelial fluid/albumin losses.

Adult↗
PubMed1994

Chemical synthesis of O-thiophosphotyrosyl peptides.

The synthon for O-thiophosphotyrosine, Fmoc-Tyr[PS(OBzl)2]-OH (1c), was prepared in 63% yield from Fmoc-Tyr-OH by first transient protection as the tBuMe2Si-ester and phosphinylation with (BzlO)2PNiPr2/tetrazole followed by oxidation of P(III) to P(V) with S8 in CS2. Building block 1c was incorporated in the Fmoc solid-phase synthesis of two O-thiophosphotyrosine-containing peptides H-Thr-Glu-Pro-Gln-Tyr(PS)-Gln-Pro-Gly-Glu-OH (2) and H-Thr-Arg-Asp-Ile-Tyr(PS)-Glu-Thr-Asp-Phe-Phe-Arg-Lys-OH (3), corresponding to sequences of the p60src (523-531) protein and an insulin receptor (IR) (1142-1153) analogue, respectively. An alternative approach of synthesis, the global phosphorylation of a resin-bound peptide, also proved useful. Thus, the free tyrosyl side-chain containing-peptide IR (1142-1153) on support was phosphinylated with the above phosphoramidite reagent followed by oxidation with either S8/CS2 or tetraethylthiuram disulfide/CH3CN solutions. Deprotection and peptide-resin cleavage was performed with a TFA/thiophenol (H2O) mixture. Crude peptides 2 and 3 were stable to the acidolytic deprotection. Preparative RP(C18)HPLC was initially performed using 0.1% TFA(aq)/EtOH solvents. However, analyses of fractions resulting from the purification step indicated significant decomposition of thiophosphopeptide in solution. Stability measurements both as a function of time and pH, further confirmed this initial finding. Purifications performed at intermediate pH using a triethylammonium acetate (pH 7.5)/CH3CN solvent system overcame this problem.

Amino Acid Sequence↗
PubMed1994

Semimalignant ("pseudolymphomatous") cutaneous B-cell lymphomas.

Almost 50% of cutaneous B-cell lymphoproliferative infiltrates are derived from follicular center cells. Among these, about 25% show a rapidly progressive course, whereas about 75% account for flattening of the survival curve after about 7 years. This group is referred to as semimalignant ("pseudolymphomatous") cutaneous B-cell lymphoma (SM-CBCL). Clinical, histologic, and phenotypical criteria for their differentiation from B-cell pseudolymphoma and from CBCL have been investigated in 60 patients (11 CBCL, 30 SM-CBCL, 19 PSL). Semimalignant CBCL are different from malignant CBCL because they do not tend to disseminate to extracutaneous sites or to transform into high-grade malignant blast-type lymphomas; follicular center cell formation with CD21 positive dendritic reticulum cells is usually present; and normal survival time is not affected. On the other hand, SM-CBCL differ from PSL in that complete cure of the usually multiple and disseminated skin manifestations is not possible and that follicular center formation and the network of CD21-positive cells in conjunction with a kappa or lambda light chain restriction of cellular surface immunoglobulins is seen. If these and other criteria are taken together, differentiation of these various nosologic entities demanding different therapeutic approaches can be achieved with significant reliability.

Adolescent↗
PubMed1993

[Amyloidosis cutis nodularis atrophicans (Gottron)].

We report an exceptionally severe case of amyloidosis cutis nodularis atrophicans (Gottron) of the lower limbs in a 49-year-old female patient. The diagnosis was made on clinical and histological grounds and was confirmed by immunohistochemical evidence of amyloid of the A-lambda type. For the first time, cutaneous microcirculation in the region of the nodules was investigated by means of fluorescence video microscopy. Pronounced microangiopathy characterized by avascular fields, enlarged and tortuous capillaries and increased transcapillary diffusion of sodium fluorescein, was clearly demonstrable in the area of the nodules. The pathogenetic role of these vascular changes is discussed.

Amyloid↗
PubMed1988

The neurotensin analog xenopsin excites nigral dopamine neurons.

The electrophysiological effects of neurotensin (NT), its analog xenopsin, and the fragment NT-(1-8) on the activity of dopaminergic neurons in rat substantia nigra slices were compared. Xenopsin and NT produced a concentration-dependent increase in the firing rate. The mean firing rate was increased by 58.5% with xenopsin (0.1 microM) and 49.1% with NT (0.1 microM). NT-(1-8) was inactive at this concentration. Dopamine (100 microM) inhibited firing in these neurons by 54.7%. These data provide evidence that xenopsin mimics the physiological effects of NT.

Action Potentials↗
PubMed1988

Cutaneous T cell lymphoma: immunocytochemical study on activation/proliferation and differentiation associated antigens in lymph nodes, skin, and peripheral blood.

The expression of activation/proliferation antigens (CD 25, CD 30, Ki 67, transferrin receptor) in lymph nodes and skin were compared in nine patients with mycosis fungoides (MF) with patients with erythroderma not related to MF, and patients with reactive lymphofollicular hyperplasias (a total of 14 patients). A panel of differentiation antigens was analyzed in addition. Reactivities were revealed by the APAAP technique. Activation/proliferation antigen scores in lymph nodes were related to the clinical stages of MF in most instances (low scores in cases of MF stage I/II, high scores in 3/4 cases of MF stage III/IV). They differed markedly in cases of non-MF-erythrodermia with the exception of one patient, and in all cases of reactive lymphofollicular hyperplasia. Expression of activation/proliferation antigens in lymph nodes were different in most cases from those in skin and peripheral blood. For diagnostic use, the activation/proliferation antigen scores were superior to the cell differentiation antigen profiles. Among cellular differentiation antigens, only the extent of CD1+ cells provided some diagnostic information, since the number of these cells were markedly increased in all cases of dermatopathic lymphadenitis with/without MF when compared with reactive lymphofollicular hyperplasia. In the diagnosis of MF, immunohistochemistry of activation/proliferation or differentiation antigens cannot replace routine paraffin histology, but may provide supplement any data in equivocal cases.

Adult↗
PubMed1987

Cholinomimetics induce theta rhythm and reduce hippocampal pyramidal cell excitability.

The actions of cholinomimetics and of physostigmine were tested on two parameters reflecting hippocampal activity, namely theta activity and pyramidal cell excitability. In rats pretreated with methylscopolamine and anaesthetized with urethane i.v. administration of the cholinomimetics oxotremorine and arecoline and the cholinesterase blocker physostigmine evoked theta wave activity in the hippocampus, which was blocked by scopolamine. Spectral analysis demonstrated that the frequency of the theta waves induced was dose-related, ranging from about 3 Hz to between 5 and 6 Hz. theta Activity could not be induced by arecoline in animals with large septal lesions. Pyramidal cell excitability is known to be increased by endogenous acetylcholine released from cholinergic fibres. In the present study, however, i.v. injections of oxotremorine, arecoline and physostigmine in doses that induce theta activity diminished the excitability of CA1 pyramidal cells in a dose-dependent manner, as judged by the reduction in the amplitude of the population spike and the dendritic epsp. These depressant effects were attenuated by scopolamine but not by methylscopolamine. The depressant effect of arecoline was attenuated in rats with extensive lesions in the medial septal area. The present findings demonstrate that exogenously administered cholinomimetics only partly mimic the action of endogenous acetylcholine in the hippocampus. The central sites of action of exogenously administered cholinomimetics for mediation of theta activity and alteration of pyramidal cell excitability remain to be elucidated.

Acetylcholinesterase↗