Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia

Summary A murine anti-idiotypic monoclonal antibody (mAb), F1, (IgG_2a) was produced against the variable part of the T-cell receptor for antigen (T_i, /) on the tumor cells of a patient with T-cell chronic lymphatic leukemia (CD3⁺, 8⁺, 4^–). The molecular weight of the protein reactive with mAb F1, comodulation and coprecipitation with anti-CD3 antibody, and the restricted tumor-cell reactivity strongly support the anti-idiotypic nature of mAb F1. MAb F1 also stained 4% of peripheral blood lymphocytes of healthy donors. MAb F1 did not stimulate the tumor cells to DNA synthesis, but stimulated a fraction of the normal peripheral blood lymphocytes, mAb F1 did not mediate antibody-dependent cellular cytotoxicity or complement lysis to any significant degree in vitro. Three infusions of 1–10 mg anti-idiotypic mAb were given over a period of 4 weeks. The plasma half-life for mAb F1 was 3 h in the first 2 h after infusion and 44 h from 2 h to 120 h after infusion. After each treatment a rapid decrease of circulating tumor cells was seen. During the observation period an 80% reduction of the total circulating tumor cells was noted. After the second infusion, IgM and IgG antimouse antibodies were detected. Side-effects from therapy were fever, chills, nausea, vomiting, diarrhea, tachycardia, increase in systolic blood pressure and shortness of breath. Thus, in T-cell malignancies a major reduction of circulating tumor cells can be accomplished by low doses of anti-idiotypic mAb. Anti-idiotypic mAb might be a therapeutic agent of significant importance.     

Selenium concentrations in the human thyroid gland

Recently, we found that prediagnostic serum selenium concentration was significantly lower for cases developing thyroid cancer (n=43) than for controls. We assumed that redistribution of serum selenium into the affected tissue took place in the prediagnostic period. The present study was carried out to determine the physiological concentration of selenium in the thyroid, since very few data are available in the literature. The concentrations of selenium in the thyroid (n=45) and liver samples from Norwegians who had died because of acute illness or accidents were determined by hydride generation atomic absorption spectrometry. The mean selenium concentration was found to be 0.72±0.44 μg/g in the thyroid and 0.45±0.11 μg/g in the liver tissue. The surprisingly high concentration of selenium in apparently normal thyroids indicates that selenium has important functions in this organ. The remarkably broad range, together with the observation that no significant correlation exists between thyroid and liver concentrations, suggest that factors other than the selenium status are important determinants for the selenium concentration in the thyroid gland. This observation is consistent with our hypothesis that in carcinogenesis, prediagnostic processes influence the serum-/thyroid-ratio of selenium.     

Molecular evolution of pteridophytes and their relationship to seed plants: Evidence from complete 18S rRNA gene sequences

Complete 18S ribosomal RNA sequence data from representatives of all extant pteridophyte lineages together with RNA sequences from different seed plants were used to infer a molecular phylogeny of vascular plants that included all major land plant lineages. The molecular data indicate that lycopsids are monophyletic and are the earliest diverging group within the vascular land plants, whereasPsilotum nudum is more closely related to the seed plants than to other pteridophyte lineages. The phylogenetic trees based on maximum likelihood, parsimony and distance analyses show substantial agreement with the evolutionary relationships of land plants as interpreted from the fossil record.     

Rapid reactions of spruce cells to elicitors released from the ectomycorrhizal fungus Hebeloma crustuliniforme, and inactivation of these elicitors by extracellular spruce cell enzymes

Elicitors released from hyphae or cell walls of the ectomycorrhizal fungus Hebeloma crustuliniforme (Bull. ex Fries.) Quél. induced in suspension-cultured cells of Picea abies (L.) Karst. a set of fast reactions: (i) an immediate efflux of Cl^– into the medium, followed by a K⁺ efflux; (ii) an influx of Ca²⁺ (measured as accumulation of ⁴⁵Ca²⁺ in the cells); (iii) a phosphorylation of a 63-kDa protein and dephosphorylation of a 65-kDa protein (detectable by 4 min after elicitor application); (iv) an alkalinization of the medium, and (v) a transient synthesis of H₂O₂. The removal of extracellular Ca²⁺ by EGTA delayed the elicitor-induced alkalinization. A further reduction of this response could be achieved by TMB-8 an inhibitor of Ca²⁺ release from intracellular stores. Moreover, the inhibition of protein kinase activity by staurosporine prevented the extracellular alkalinization completely. However, the effectiveness of the elicitors in inducing the extracellular alkalinization was strongly impaired by constitutively secreted enzymes of spruce cells which cleaved the elicitors to inactive fragments. It is suggested that in ectomycorrhizae the efficacy of elicitors released from fungal cell walls is controlled by apoplastic enzymes of the host; the plant itself is able to reduce the activity of fungal elicitors on their way through the plant cell wall. But those elicitors which finally reach the plasma membrane of host cells induce reactions that are similar to the early defense reactions in plant-pathogen interactions.Abbreviations DW dry weight - FW fresh weight - TMB-8 3,4,5 trimethoxybenzoic acid 8-(diethylamino)-octyl ester We thank Prof. M. Zenk (Universität München, Germany) for providing spruce cell cultures, and Dr. I. Kottke (Universität Tübingen, Germany) for isolates of Hebeloma crustuliniforme Tü 704. We are also thankful to Dr. W. Mayer (Universität Tübingen) for valuble discussions. This work was supported by Deutsche Forschungsgemeinschaft. B. Zitterell-Haid was financed by Graduiertenkolleg Interaktion in Waldökosystemen (supported by Deutsche Forschungsgemeinschaft) and G. Hebe by a scholarship of the Landesgraduiertenförderungsgesetz.     

The N-acylation-phosphodiesterase pathway and cell signalling

Long-chain N-acylethanolamines (NAEs) elicit a variety of biological and pharmacological effects, Anandamide (20:4n-6 NAE) and other polyunsaturated NAEs bind to the cannabinoid receptor and may thus serve as highly specific lipid mediators of cell signalling. NAEs can be formed by phospholipase D-catalyzed hydrolysis of N-acylethanolamine phospholipids or by direct condensation of ethanolamine and fatty acid, So far, most of the latter biosynthetic activity has been shown to be the reverse reaction of the NAE amidohydrolase that catalyzes NAE degradation. Thus, increasing evidence supports the hypothesis that the N-acylation-phosphodiesterase pathway yields not only saturated-monounsaturated NAEs, but polyunsaturated ones, including anandamide, as well.     

Does the energy equivalence rule apply to intertidal macrobenthic communities?

Energy equivalence assumes equal contribution of large and small species to production and energy flow in communities. As in a double logarithmic plot, physiological rates decline with body weight by –0.25, log biomass should increase by 0.25 and log abundance decline by –0.75 with log species weight, when this concept is valid. This was tested with annual data sets of the macrobenthos of 4 intertidal sites in the German Wadden Sea (Königshafen) and 3 sites in a south Portuguese lagoon (Ria Formosa). Only abundance data from two of these sites displayed significantly negative slopes with mean body size of the species. Biomass and secondary production data were significantly positively correlated with mean body size for all Ria Formosa sites and also for the biomass of a mussel bed in Königshafen. However, high variation in body size of the individuals of a species limits interpretation of these plots.It is preferable to test this concept by body weight classes regardless of its species composition. At Königshafen, biomass and production displayed two distinct peaks. One peak at small body size was caused by browsing species. The other peak at larger body size was caused by animals which potentially extract their food from the water column. This bimodality was only vaguely reflected at one station in the Ria Formosa, possibly because of a dominance of detritus feeding species. In a normalized form (log biomass or production / width of size classvs. log size class), these spectra imply a dominance of small individuals in biomass and production at all sites (except for a mussel bank at Königshafen). This is interpreted as a consequence of permanent disturbances.     

Oxidatively Modified Plasma Phospholipids Containing Reactive Carbonyl Functions Measured by HPLC: Evidence for Phosphatidylcholine-Bound Aldehydes in Plasma of Burn Patients

A HPLC method has been developed to measure phosphatidylcholine (PC) containing reactive carbonyl functions in the sn-acyl residue in order to study processes in which such reactive carbonyls can be formed due to e.g. oxidative fragmentation. The method has been applied to determine PC-bound carbonyls as 2, 4-dinitrophenylhydrazones (DNPH) in plasma of burn patients. Plasma from healthy volunteers served as controls. Additionally, in vitro oxidation experiments (A: plasma, buffer diluted; B: plasma + iron-EDTA complex and C: plasma + iron-EDTA complex + H₂O₂) have been performed to obtain and to identify 2, 4-dinitrophenylhydrazine derivatizable carbonyl functions in plasma PC. Both, the PC-aldehydes and PC-aldehyde DNPH derivatives were cleavable with phospholipase C. Quantification was based on thin-layer chromatography purified soybean phosphatidylcholine, which was identically oxidized and derivatized as the plasma lipids in vitro.     

A novel, “hidden” penicillin-induced death of staphylococci at high drug concentration,occurring earlier than murosome-mediated killing processes

In log-phase cells of staphylococci, cultivated under high, non-lytic concentrations of penicillin G, there occurred a novel killing process hitherto hidden behind seemingly bacteriostatic effects. Two events are essential for the apprearance of this hidden death: (i) the failure of the dividing cell to deposit enough fibrillar cross-wall material to be welded together, and (ii) a premature ripping up of incomplete cross walls along their splitting system. Hidden death started as early as 10–15 min after drug addition, already during the first division cycle. It was the consequence of a loss of cytoplasmic constituents which erupted through peripheral slit-like openings in the incomplete cross walls. The loss resulted either in more or less empty cells or in cell shrinkage. These destructions could be prevented by raising the external osmotic pressure. In contrast, the conventional non-hidden death occurred only much later and exclusively during the second division cycle and mainly in those dividing cells, whose nascent cross walls of the first division plane had been welded together. These welding processes at nascent cross walls, resulting in tough connecting bridges between presumptive individual cells, were considered as a morphogenetic tool which protects the cells, so that they can resist the otherwise fatal penicillin-induced damages for at least an additional generation time (morphogenetic resistance system). Such welded cells, in the virtual absence of underlying cross-wall material, lost cytoplasm and were killed via ejection through pore-like wall openings or via explosions in the second division plane and after liberation of their murosomes, as it was the case in the presence of low, lytic concentrations of penicillin. Bacteriolysis did not cause any of the hitherto known penicillin-induced killing processes.Dedicated to Prof. Dr. Georg Henneberg on the occasion of his 85th birthday     

Different responses to changes in phosphorus,P, among lakes. A study of slopes in chl-a = f(P) graphs

The least squares estimator of a linear regression coefficient _L will give an overall expression for the change in with x. In fresh water ecology, however, subgroups, % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaamiuaSGaci% 4Aaaaa!37BE!\[P\operatorname{k}\], of a parent population may have slopes which differ from the overall slope, _L. By constructing frequency histograms for the set of angles: Arctang % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaci4uaSGaam% yAaiaadQgaaaa!38AE!\[\operatorname{S} ij\],% MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaci4uaSGaam% yAaiaadQgaaaa!38AE!\[\operatorname{S} ij\]= para sa y and x% MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaaiikaiaadM% faliaadMgakiabgkHiTiaadMfaliaadQgakiaacMcacaGGVaGaaiik% aiaadIhaliaadMgakiabgkHiTiaadIhaliaadQgakiaacMcaaaa!42F0!\[(Yi - Yj)/(xi - xj)\], i < j, % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaamiEaSGaam% yAaOGaeyiyIKRaamiEaSGaamOAaaaa!3BAB!\[xi \ne xj\], peaks in the distribution may be identified and related to ecological phenomenon. To identify peaks we fit Gaussian distributions to the frequency histograms. For a set consisting of 142 observations of chlorophyll-a and total phosphorus (nutrient) concentrations (TP) from 16 lakes we found four Gaussian peaks corresponding to four subgroups, % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaamiuaSGaci% 4Aaaaa!37BE!\[P\operatorname{k}\]k = 1,4. One group identified a response of chl-a to changes in TP which correspond approximately to the average slope found by least square regression (the slope was 0.49). The second group consisted of steeper response than the average (1.28). A third group showed that there is an enhanced proportion of cases where chl-a does not respond to TP (zero slope, all the three deep lakes > 10 m, included in the date set contributed to this group). The size of the last group, spanning a wide range of slopes, suggested that about 30% of the inter annual changes in chl-a is unrelated to TP. The results are compared to result obtained by simple least squares regression and to the Theil non-parametric slope estimator.