Search

The nucleotide sequences of three pseudogenes for the small nucleolar RNA, U13, were determined from three human DNA clones. The sequences are reported 50 bp 5' and 3' to each gene. These pseudogenes belong to class III because they contain dispersed mismatches when compared to the previously determined U13 RNA sequence, an adenine-rich region at the 3' end, and short imperfect repeats flanking the 5' end of the coding sequence and the 3' end of the adenine-rich region.

The mammalian U3 snRNP is one member of a recently described family of nucleolar snRNPs which also includes U8, U13, U14, X and Y. All of these snRNPs are immunoprecipitable by anti-fibrillarin autoantibodies, suggesting the existence of a common binding site for the 34 kDa fibrillarin (Fb) protein. Two short nucleotide sequences, called Boxes C and D, present in each of these RNAs are the most likely sites for fibrillarin binding. We have developed a HeLa in vitro assembly system for binding of fibrillarin to human U3 snRNA. Reconstitution of the input RNA is specific in our assay since four of the other nucleolar small RNAs (U8, U13, X and Y) which have Boxes C and D become immunoprecipitable by anti-fibrillarin whereas two RNAs which lack these sequences (5S and 5.8S) do not. Deletion analyses of the U3 snRNA demonstrate that the presence of Box C but not Box D is required for fibrillarin binding. Moreover, seven single or double site-specific mutations in the U3 Box C abolish binding. The role of the Box C-fibrillarin interaction in the biogenesis of the Fb snRNPs is discussed.

We have applied microelectrode technique to record 118 spontaneously firing units from the hypothalamus in rats. Detection of the recording sites showed that 84 were in the paraventricular nucleus (PVN) and 34 were near the PVN (near-PVN). After intracerebroventricular (i.c.v.) administration of atrial natriuretic polypeptide (ANP), 91% (P less than 0.005) of the PVN neurones and 71% (P greater than 0.05) of near-PVN neurones sensitive to ANP showed a significant decrease in spontaneously firing rate. After i.c.v. administration of hypertonic NaCl solution, 64.7% (P less than 0.005) of the PVN neurones and 61.1% (P greater than 0.05) of near-PVN neurones showed a significant increase in firing rate. The results indicate that i.c.v. administration of ANP profoundly inhibits the electrical activity of the PVN neurones, but hypertonic NaCl solution markedly stimulates the PVN neurones.

It has been demonstrated that atrial natriuretic polypeptide (ANP), or atriopeptin, is synthesized and stored not only in the cardiac atrial myocyte but also in the central nervous system, especially in the hypothalamus. ANP may play an important role in the regulation of fluid and electrolyte balance and blood pressure in the peripheral and central nervous systems. Some of the biological actions of ANP are opposite to those of angiotensin II and arginine vasopressin in the central nervous system. However, the mechanism of action of ANP remains, in a large part, to be defined.

Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described. Here we report that at mixed synapses between sensory afferents and an identified reticulospinal neuron, the electrotonic coupling potential can be potentiated, as well as the chemically mediated excitatory postsynaptic potential, for a prolonged time period using a stimulation paradigm like that which produces long-term potentiation in hippocampus. The effect on coupling is due to an increase in gap-junctional conductance. Our data indicate that the potentiation of both synaptic components requires an increase in intracellular calcium, involves activation of NMDA (N-methyl-D-aspartate) receptors, and is specific to the tetanized pathway.

Adjuvant arthritis induced by mycobacteria in rats is a widely used model of chronic arthritis. A previously described nonapeptide (Thr-Phe-Gly-Leu-Gln-Leu-Glu-Leu-Thr, amino acid sequence 180-188) from the recombinant 65 kDa heat shock protein of Mycobacterium bovis BCG, which was found to contain a T-cell epitope recognized by both arthritogenic and protective T-cell clones in vitro, has been investigated for its vaccination and therapeutic potential in adjuvant arthritis in rats. The nonapeptide was found not to be arthritogenic, although the T cells from nonapeptide immunized rats cross-react in vitro with mycobacterial antigens. Intraperitoneal administration of 0.1 mg nonapeptide in oil at day -20 or days -2, -1 and 0, resulted in a marked reduction of incidence and severity of adjuvant arthritis. The disease process and severity were also influenced by therapeutic treatment with 0.1 mg nonapeptide injected intraperitoneally at days 7 to 10. Interestingly, subplantar or intravenous application of the nonapeptide had no influence on the disease process. Deletion of the N-terminal threonine led to complete loss of in vivo activity of the nonapeptide.

Murine monoclonal antibodies which recognize similar epitopes as the naturally occurring human IgG anti-IgE antibodies were used to study their role in interfering with the effector functions of IgE. Two types of antibodies were found which were either anaphylactogenic or did not release histamine from human basophils. However, both types of antibodies were capable of inhibiting binding of IgE to Fc epsilon RII. Furthermore, the nonanaphylactic antibody was capable of removing IgE from Fc epsilon RII+ cells, but no antibodies were found which removed IgE from Fc epsilon RI+ cells. Thus, anti-IgE antibodies may interfere with the pathophysiological role of IgE.

A human T hybridoma was generated lacking demonstrable low-affinity IgE surface receptors. This cell line produces spontaneously immunoglobulin-binding factors. The factors have an affinity for human IgE and IgG as well as for IgG from other species. The binding factors were purified by concanavalin A affinity chromatography, an IgE immunoaffinity column and SDS-PAGE. This purification procedure resulted in five major proteins bands at 13, 15, 30, 60 and less than 150 kilodaltons. As judged by Western blot analysis, all bands were variably glycosylated and were capable of binding IgE. Biological activity resided even within the small molecular weight (13 kilodaltons) peptide in terms of inhibiting IgE synthesis of the U266 B cell line and net IgE synthesis of B cells from atopic blood donors. Additionally, semipurified binding factor preparations also inhibited the Pokeweed mitogen-induced IgG synthesis while stimulating IgE synthesis at the same time. At present it is not clear whether the different molecular entities are dimers or polymers of the same protein, or are all derived from one larger protein (proteolytically cleaved), or whether they are completely different peptides mediating similar immunoglobulin-binding capacities as well as similar biological activities. Glycosylation of binding factors is not responsible for binding to immunoglobulins, but might be important for its biological activity.

This paper analyses 240 cases of burn patients with pseudomonas (Ps) aeruginosa septicemia. They were admitted to our hospital from 1959 to 1988. The morbidity, time of episode of septicemia, mortality and relationship between the mortality and burned surface area are surveyed. The author considers that Ps. aeruginosa septicemia is a significant factor which burned patient dies of.

Recombinant human interleukin 4 (IL 4) alone enhanced the spontaneous IgE synthesis in cultures of peripheral blood leukocytes (PBL) from atopic patients as well as from nonatopic individuals, suggesting the existence of preactivated PBL sensitive for IL 4. Preactivated cells were also obtained by stimulation with Staphylococcus aureus strain Cowan I (SAC). However, co-stimulation of PBL by IL 4 with SAC or anti-IgM antibody and pokeweed mitogen did not result in an enhanced IgE synthesis. Optimal IL 4 concentrations for the induction of IgE synthesis coincided with optimal proliferative responses in PBL. The effect of IL 4 was not isotype specific, and in terms of protein even more IgG and IgM antibodies were formed. The effect of IL 4 on IgE synthesis was counteracted by very low concentrations of interferon-gamma (IFN-gamma), suggesting that both IL 4 and IFN-gamma might be decisive cytokines for the human in vitro IgE synthesis.

We report the case of a 6-year-old boy who developed diabetes insipidus caused by an epidural hematoma as a complication of extracorporeal circulation.

A case of patent ductus arteriosus coinciding with ocular hypertelorism (Greig's syndrome) is reported for the first time. The literature regarding association of congenital cardiac malformations and ocular hypertelorism is reviewed.

Mitogens such as pokeweed mitogen, Staphylococcus aureus Cowan I, concanavalin A and phytohemagglutinin and monoclonal anti-CD antibodies were examined for their capacity to induce IgE synthesis by peripheral blood leukocytes obtained from both atopic and nonatopic individuals. While lectins failed to induce IgE synthesis, monoclonal anti-CD3 antibodies were very potent stimuli for the induction of human in vitro IgE synthesis, possibly due to the activation of T cells. Activation via CD4 or CD8 molecules by OKT4 or OKT8 antibodies did not lead to a T cell-dependent modulation of IgE synthesis. PWM acted in synergy with the enhancing effect of anti-CD3 antibodies for IgE synthesis. In vitro IgG production was less affected. These results indicate that activation of T cell via CD3 molecules may be important in the regulation of IgE immune responses in man. Furthermore, the successful induction of IgE synthesis by anti-CD3 antibody in unfractionated peripheral blood leukocytes culture provides a simple model for investigation of human IgE regulatory mechanism in vitro.

There are facts suggesting that the changes of excitability of neurons and conductance of synapses are responsible for learning and memory. In accordance with the idea, the author proposed a neuronal network model of associative memory, which can learn conditioned reflexes repeatedly together with its adaptive properties, without much interference with the previously existing memories. Further, a modified model can memorize dynamic images and establish motor patterns. An analysis of the structure of the model is presented, and some conclusions about this sort of model are drawn. A theory of memory and learning suggesting that the brain works by means of a mechanism similar to that of the model is proposed, as well as the explanations for some behavioral and clinical findings from the viewpoint of the model.