Cooperation of B- and T-lymphocytes of the human in vitro and in vivo

It is reported on the experimental proofs for the existence of a cooperation of different populations of lymphocytes in man. Regulatory lymphocytes play a part in the regulation of the synthesis of immunoglobulins by polyclonally stimulated B-lymphocytes, in the generation of killer-T-cells and in the regulation of the DNA-synthesis by mitogenically stimulated T- and B-cells. Typical helper- and suppressor-effects may be proved. Disturbances of lymphocytic interactions may be a cause for the development of immune deficiency diseases. It is very probable that also in several chronic infections a dysfunction of regulatory T-lymphocytes is present.     

Chemotherapy for advanced (stage IIIB and stage IV) non-small cell lung cancer: The Hong Kong perspective

Abstract Non-small cell lung cancer (NSCLC) accounts for about 80% of all primary lung cancers, and 60% of cases present as advanced stages IIIB and IV disease. Traditionally, treatment of stages IIIB and IV disease was only symptomatic (including radiotherapy) and supportive care, and cytotoxic chemotherapy was relatively ineffective. Our initial clinical trials, using MACC, FuAM, FAM, Hi-FAM and cisplatin-VP16, gave response rates of 5–20% and a stabilization rate of 7–25%, with no impact on median survival. Our most recent chemotherapy regimen MIP (mitomycin-C, ifosfamide and cisplatin) proved to be more effective with a 44% response rate and a 28% stabilzation rate, and produced a significantly longer median survival (32 weeks) than best supportive care alone (19.5 weeks, P < 0.05). The response rate further increased to 62.5% with dose intensification and GM-CSF support. Chemotherapy can now be recommended to motivated, well-informed patients with good performance status in institutions with experience in cancer chemotherapy on a protocol basis. The most recent addition of new effective cytotoxic agents such as paclitaxel, docetaxel, gemitabine and vinorelbine gave promising results in NSCLC, and optimal combinations and dose schedules are being defined by multicentred studies.     

Casein kinase 1γ acts as a molecular switch for cell polarization through phosphorylation of the polarity factor Tea1 in fission yeast

Fission yeast undergoes growth polarity transition from monopolar to bipolar during G2 phase, designated NETO (New End Take Off). It is known that NETO onset involves two prerequisites, the completion of DNA replication and attainment of a certain cell size. However, the molecular mechanism remains unexplored. Here, we show that casein kinase 1γ, Cki3 is a critical determinant of NETO onset. Not only did cki3? cells undergo NETO during G1‐ or S‐phase, but they also displayed premature NETO under unperturbed conditions with a smaller cell size, leading to cell integrity defects. Cki3 interacted with the polarity factor Tea1, of which phosphorylation was dependent on Cki3 kinase activity. GFP nanotrap of Tea1 by Cki3 led to Tea1 hyperphosphorylation with monopolar growth, whereas the same entrapment by kinase‐dead Cki3 resulted in converse bipolar growth. Intriguingly, the Tea1 interactor Tea4 was dissociated from Tea1 by Cki3 entrapment. Mass spectrometry identified four phosphoserine residues within Tea1 that were hypophosphorylated in cki3? cells. Phosphomimetic Tea1 mutants showed compromised binding to Tea4 and NETO defects, indicating that these serine residues are critical for protein–protein interaction and NETO onset. Our findings provide significant insight into the mechanism by which cell polarization is regulated in a spatiotemporal manner.     

Anti-inflammatory cytokines in subclinical carotid atherosclerosis

Some studies have shown correlations between selected proinflammatory factors and carotid atherosclerosis. It has not been established whether anti-inflammatory cytokines are associated with carotid intima-media thickness (IMT), an ultrasound surrogate marker of atherosclerosis. Therefore, the authors studied the relationship between the carotid IMT and serum levels of interleukin (IL)-10 and transforming growth factor-beta1 in 76 subjects. They discovered that lower IL-10 levels were associated with increased mean IMT in common carotid arteries.     

Genetics of rapid eye movement sleep in humans

The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases.