Evidence for the extranuclear localization of thymosins in thymus

A new radioimmunoassay has been developed for thymosin ₄ by generating rabbit polyclonal antibodies against the synthetic N-terminal peptide fragment 1–15 coupled to KLH. The synthetic analogue [Tyr¹²]-thymosin ₄ (1–15) was used as tracer. This radioimmunoassay, with a useful range of 10–1000 pmoles, showed cross-reactivity with the second homologous -thymosin of man and rat (thymosin ₁₀) but not of calf (thymosin ₉). This radioimmunoassay, together with an improved radioimmunoassay for the N-terminus of parathymosin , was employed for the measurement of the levels of thymosin ₄ and parathymosin in nuclear and extranuclear extracts of calf thymus. The bulk of these polypeptides was found in the extranuclear material whereas only traces were observed in the nuclear environment, which indicates the extranuclear localisation of - and -thymosins.     

Parental origin of chromosomes involved in the translocation t(9;22).

Functionally equivalent genetic maternal can be labelled by an epigenetic marking process and used differentially depending on whether its origin is maternal or paternal. This phenomenon is known as genomic imprinting and is manifested at either the chromosomal or gene level. Genomic imprinting seems to play an important role in cancer predisposition syndromes, and phenotypic consequences are evident in constitutional deletion syndromes and uniparental disomies. Moreover, there seems to be a preferential retention of paternal alleles in sporadic tumours such as Wilms' tumour, rhabdomyosarcoma, osteosarcoma and retinoblastoma. To investigate whether chromosomes involved in acquired abnormalities of haematologic neoplasms show a similar 'parent of origin' bias, we studied the inheritance of the translocated chromosomes 9 and 22 in cases of Philadelphia-chromosome-positive leukaemia, using unique specific chromosome band polymorphisms. Here we show that the translocated chromosome 9 was of paternal origin, whereas the translocated chromosomes 22 were derived exclusively from the maternal copy, in 11 cases with reliable polymorphisms. Our data therefore provide evidence that imprinting phenomena may play an important role in acquired tumour-specific chromosome rearrangements.     

Parents suppress reproduction and stimulate dispersal in opposite-sex juvenile white-footed mice.

Juvenile dispersal is sex-biased in many mammals and birds: one sex often disperses more often or farther than the other. Two hypotheses are generally presented for sex-biased dispersal. The first holds that juvenile dispersal reduces reproductive and/or resource competition between parents and same-sexed offspring. If so, presence of a parent on the natal home range should both promote dispersal of same-sex offspring and suppress reproduction of those that remain. The second is that juvenile dispersal reduces matings between parents and offspring, thus decreasing the likelihood of inbreeding depression. If so, presence of a parent should favour dispersal and reproductive suppression of offspring of the opposite sex. Here I present evidence that juvenile dispersal in white-footed mice, Peromyscus leucopus, is due to inbreeding avoidance. When population density was high, experimental removal of one parent delayed dispersal of opposite-sexed offspring and only the presence of the parents of opposite sex suppressed juvenile reproduction.     

Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix.

The primary sequence of two components of the dystrophin-glycoprotein complex has been established by complementary, DNA cloning. The transmembrane 43K and extracellular 156K dystrophin-associated glycoproteins (DAGs) are encoded by a single messenger RNA and the extracellular 156K DAG binds laminin. Thus, the 156K DAG is a new laminin-binding glycoprotein which may provide a linkage between the sarcolemma and extracellular matrix. These results support the hypothesis that the dramatic reduction in the 156K DAG in Duchenne muscular dystrophy leads to a loss of a linkage between the sarcolemma and extracellular matrix and that this may render muscle fibres more susceptible to necrosis.     

Perforin and its role in T lymphocyte-mediated cytolysis.

The killing mediated by cytotoxic T lymphocytes (CTL) represents an important mechanism in the immune defence against tumors and virus infections. The lytic mechanism has been proposed to consist of a polarized secretion of granule-stored molecules, occurring on effector-target cell contact. By electron microscopy, membrane deposited, pore-like lesions are detected on the target cell membrane during cytolysis by CTL. These structures resembled strikingly pores formed during complement attack. Granules of CTL isolated by nitrogen cavitation and Percoll gradient centrifugation were shown to retain cytotoxic activity. Further purification of proteins stored in these granules led to the discovery of a membranolytic protein named perforin which was capable of polymerizing into pore-like structures. In addition to this cytolytic protein, a set of serine esterases was found as well as lysosomal enzymes and proteoglycans, whose function are not yet clearly defined. The role of perforin in the cytotoxic process is currently being explored by ablating the active gene in mice.     

NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons.

The modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons possess low-threshold (T-type) Ca2+ channels and both L- and N-type high voltage-activated Ca2+ channels. N-type Ca2+ channels are blocked selectively by omega-conotoxin and adenosine. These substances both block excitatory synaptic transmission in the hippocampus, whereas dihydropyridines, which selectively block L-type channels, are ineffective. Excitatory synaptic transmission in the hippocampus displays a number of plasticity phenomena that are initiated by Ca2+ entry through ionic channels operated by N-methyl-D-aspartate (NMDA) receptors. Here we report that NMDA receptor agonists selectively and effectively depress N-type Ca2+ channels which are involved in neurotransmitter release from presynaptic sites. The inhibitory effect is eliminated by the competitive NMDA antagonist D-2-amino-5-phosphonovalerate, does not require Ca2+ entry into the cell, and is probably receptor-mediated. This phenomenon may provide a negative feedback between the liberation of excitatory transmitter and entry of Ca2+ into the cell, and could be important in presynaptic inhibition and in the regulation of synaptic plasticity.     

Cloned neuronal IK(A) channels reopen during recovery from inactivation

The kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (IK(A)) has been widely discussed. Activating in the subthreshold range of excitation, IK(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time-dependent manner. Here we report that IK(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting afterhyperpolarizations under current-clamp conditions. This implies an additional physiological role for IK(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N-terminal end of the IK(A) channel proteins. It was found to be a voltage-dependent release of the inactivation gate.     

Kininase and anti-inflammatory activities of acid carboxypeptidase from Penicillium janthinellum.

The acid carboxypeptidase from Penicillium janthinellum catalyzed the rapid release of arginine, and the slow release of phenylalanine, proline, serine and glycine from the carboxy-terminal of bradykinin at pH 4.15 to 4.8. Anti-inflammatory activity of the acid carboxypeptidase seems to suggest that the enzyme hydrolyzed bradykinin in vivo.     

Effect of Ftorafur on acid phosphatase activity in the liver of mice with transplanted lymphatic leukaemia

Zusammenfassung Nachweis, dass Ftorafur, N₁-(2-Furanidyl)-5-Fluorouracil das Überleben leukämischer Mäuse deutlich steigert und ausserdem als Lysosomen-Stabilisator wirken könnte, wobei die in vivo Stabilisierung der Lysosomen den antileukämischen Effekt dieses Zytostatikums unterstützen könnte.