Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test

Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 microl injections of saline, (+/-)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 microg) or 2,3 dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5, or 1 microg) 15 min before testing. Time spent in open arm, time per entry, end arrivals, open, closed, and total arm entries, relationship between open-, closed-, and total arm entries, rearing, face-, head-, and body grooming, and number of fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5 and 1 microg; P<.01) and NBQX (1 microg; P<.05) treatment, whereas time per entry was increased only with AP-7 (1 microg; P<.05). Open arm entries were increased by the intermediate doses of AP-7 (0.5 microg; P<.01) and NBQX (0.5 microg; P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5 microg/1 microl, P<.05). The frequency of rearing, grooming, and closed arm entries was not affected by the treatment. We conclude that NMDA and non-NMDA-glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical influences with the median doses, but that at higher doses the blockers have an anxiolytic-like effect.     

Characterization and partial purification of a lectin from the hemolymph of the white shrimp Litopenaeus schmitti

The agglutinating activity of the hemolymph of Litopenaeus schmitti is insensitive to calcium and specific for acetylated sugars, particularly sialic acid (Neu5Ac) and O-sialoglycoconjugates (bovine submaxillary mucin) and has varying specificity for different LPS, which may suggest a putative role in microorganism recognition. Affinity chromatography on fetuin-agarose of the agglutinin resulted in a 220 kDa band (lectin), and a 82.5 kDa band, which probably is hemocyanin. The 220 kDa protein consists of 31 and 34 kDa subunits, suggesting that this lectin is multimeric. The lectin molecular mass was estimated by gel filtration to be 153+/-10 kDa. The hemolymph of L. schmitti comprises at least another soluble lectin, with distinct chemical and carbohydrate specificity than the 220 kDa lectin.     

Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study.

BACKGROUND: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study is a worldwide, randomized, prospective study to investigate early intervention with inhaled corticosteroids in recent-onset mild persistent asthma. OBJECTIVE: To evaluate the safety and tolerability of long-term treatment with once-daily budesonide therapy in patients with mild persistent asthma. METHODS: Patients aged 5 to 66 years with mild persistent asthma for fewer than 2 years and no previous regular corticosteroid treatment received budesonide or placebo once daily for 3 years, in addition to their usual asthma therapy. The daily budesonide dose was 200 microg for children younger than 11 years and 400 microg for those 11 years or older. RESULTS: Overall, 7,221 patients were included in the safety analysis, and a total of 21,520 adverse events were reported (10,850 in the budesonide group and 10,670 in the placebo group). The most commonly reported events included respiratory infections, rhinitis, pharyngitis, bronchitis, viral infections, and sinusitis. The number of deaths and serious adverse events were similar for children and adults in both treatment groups. Fewer asthma-related serious adverse events were reported with budesonide (162) compared with placebo (276). Oral candidiasis was reported more frequently with budesonide (1.2%) than with placebo (0.5%); the frequencies of other adverse effects previously reported to be associated with inhaled corticosteroids (psychiatric disorders, skin disorders, and allergic reactions) were similar. CONCLUSIONS: Three-year treatment with budesonide once daily (200 or 400 microg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.     

Viral etiopathogenesis of Sjögren's syndrome: role of the hepatitis C virus

Patients with hepatitis C virus (HCV) chronic infection present some extrahepatic manifestations that may mimic the clinical, immunologic and histological manifestations of primary Sj?gren's syndrome (SS). Thus, HCV patients with sicca symptomatology and positive autoantibodies could be misdiagnosed as a 'primary' SS. Nevertheless, there are several clinical and immunologic features that could help us differentiate both processes.     

Transition between two forms of heterochromatin at plant subtelomeres

The manner of packing of the terminal DNA loci into nucleosomes and higher order structures may strongly influence their functional interactions. Besides the structural flexibility of telomeric DNA sequences, conserved features of their chromatin including short nucleosome phasing (157 bp) and nucleosome sliding have been described previously. To gain a complementary knowledge of subtelomeres, we have analysed the chromatin structure of two subtelomeric tandem repeats from the plant Silene latifolia: X43.1 and 15Ssp. X43.1 shows two distinct nucleosome periodicities – 157 and 188 bp. Preferred positions of its two nucleosomes have been mapped at both low and high resolution and the experimental results correspond to computer-predicted positions. 15Ssp is a newly-discovered sequence showing a telomere-associated position by PCR and a subtelomeric location by pulsed-field gel electrophoresis and fluorescence in situ hybridisation. Its 159 bp sequence unit shows a tandem arrangement and the presence of micrococcal nuclease-hypersensitive sites when either naked DNA or chromatin is digested. Use of a chemical nuclease results in a regular nucleosome ladder of 157 bp periodicity. Moreover, 15Ssp mononucleosomes show instability and absence of specific positioning, features typical for telomeric chromatin. This revised version was published online in July 2006 with corrections to the Cover Date.     

Helicobacter heilmanii, a spiral bacterium, in gastric mucosa biopsies

Interest in possible microbiological causes of gastritis has increased significantly since the discovery of Helicobacter pylori (Hp). Recently a spiral bacterium named Helicobacter heilmannii (Hh) was described in association with chronic gastritis in adult and pediatric patients. Comparisons between these two organisms, as well as the literature on Hh, have also been reviewed. The incidence of Hh gastritis is far lower than that of Hp gastritis. Concomitant infections by Hh and Hp are very rare. It is very probable that Hh gastritis is transmitted from domestic animals or pets to humans. The frequency of Hh gastritis (11/6059 cases, 0.18%) in authors' material was similar to that reported in Western Europe. The role of touch cytology has been becoming more and more significant recently in the diagnosis of mucosal infections of the GIT.     

Cross-reactivity among five major pollen allergens

We have studied the cross-reactivity between L. perenne, S. cereale, P. pratense, C. dactylon, and Ph. communis. The results obtained demonstrate that L. perenne, S. cereale, and P. pratense have strong cross-reactivity. C. dactylon has a number of allergens that cross-react with the rest of the grasses studied but they are minor allergens. Ph. communis possesses a moderate cross-reactivity with the species of the group but it has, as well, individual allergens.     

Latent infection of monkeys with oncogenic herpes viruses

Herpesvirus saimiri induced a latent infection in monkeys (Callithrix jacchus, Aotus trivirgatus) without development of a clinical disease. The animals are now under observation for one year. The virus can be isolated from the peripheral white blood cells after in vitro cultivation or after cocultivation with permissive indicator cells. The virus genome was transmitted with lymphocytes from a latent infected owl monkey (Aotus trivirgatus) to a CT-marmoset (S. oedipus) and to another owl monkey. Both recipients died of malignant lymphoma. Two Callithrix jacchus monkeys developed a latent infection withH. ateles after transplantation of tumor cells. The virus isolated from the peripheral white blood cells proved to be oncogenic in a CT-marmoset. The malignant lymphomas which may develop in the investigated species seem to require in their etiology a certain cofactor in addition to the herpesvirus. This cofactor is not species dependent.

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Zusammenfassung Die Inoculation vonHerpesvirus saimiri induzierte eine latente Infektion in Affen (Callithrix jacchus, Aotus trivirgatus), ohne daß eine Erkrankung klinisch bemerkbar wurde. Die Tiere sind nunmehr seit 1 Jahr unter Beobachtung. Das Virus kann aus den peripheren weißen Blutzellen nach deren Kultivationin vitro oder aber nach deren Kokultivation mit permissiven Indicatorzellen isoliert werden. Das Virusgenom wurde mit Lymphocyten von einem latent infizierten Eulenaffen (Aotus trivirgatus) in einen Marmoset-Affen (S. oedipus) und in einen weiteren Eulenaffen übertragen. Beide Empfängertiere starben an einem malignen Lymphom. Zwei Callithrix jacchus-Affen entwickelten eine latente Infektion mitH. ateles nach Tumorzelltransplantation. Das von den peripheren Blutzellen isolierte Virus erwies sich als onkogen in einem Marmoset-Affen. Für die Induktion eines malignen Lymphoms scheint bei den genannten Affenspecies ein Kofaktor zusätzlich zum Herpesvirus erforderlich zu sein. Der Kofaktor ist nicht speciesspezifisch.

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This investigation was supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg.     

Structure-function relationship and immunochemical mapping of external and intracellular antigenic sites on the lymphocyte activation inducer molecule, AIM/CD69.

Human activation inducer molecule (AIM/CD69), a dimeric glycoprotein structure of 33 and 27 kDa, is the earliest inducible cell surface antigen expressed during lymphocyte activation and is implicated in the induction of T and B cell proliferative responses. Cross-competition monoclonal antibodies (mAb) binding assays have allowed the definition of four antigenic epitopes. Three of them (antigenic sites E1-3) are extracellular while the fourth (site I) is a sequential epitope localized intracellularly and highly conserved interspecies. Site E1 is shown to be an immunodominant antigenic determinant closely related to a functional domain of AIM important for triggering of T cell proliferation. Studies of peptide fragmentation of the two isolated AIM subunits with different proteases have demonstrated that both AIM chains are differentially glycosylated forms of a single 24-kDa core protein. Moreover, the two denatured and isolated AIM chains share common epitope(s) as demonstrated by their reactivity with an mAb by both Western blot analysis and immunoprecipitation of the separated AIM subunits. Biosynthesis studies revealed the rapid appearance of two intermediate precursor forms of 29 and 26 kDa which arise from the 24-kDa unglycosylated AIM polypeptide. This 24-kDa unglycosylated form could be also precipitated from iodinated cells pretreated with tunicamycin, indicating that glycosylation of the protein was neither required for AIM cell surface expression nor for acquisition of external epitopes E1-E3. Cell treatment with pronase resulted in the loss of the external epitopes E1-3 and the generation of a proteolytic peptide of 16 kDa that could be precipitated by the anti-AIM mAb specific for the internal site I. This proteolytic fragment retained the transmembrane and cytoplasmic regions of the molecule where both epitope I and phosphorylation sites reside. These results demonstrate that AIM is an integral membrane homodimeric glycoprotein with a large cytoplasmic domain probably involved in the activation signals transduced through this molecule to lymphocytes.     

Prolactin and propranolol prevent the suckling-induced inhibition of lactation in rabbits

The normal once-a-day frequency of suckling in the rabbit was increased on day 31 (late lactation) by the addition of two extra sucklings (8 and 16 hr after) the daily suckling. In confirmation of previous data, two additional sucklings significantly decreased milk yield acutely on day 31 in comparison with the average 4-day milk yield before and after day 31. The decrease in milk secretion after the two additional sucklings was prevented by a single injection of 3 mg prolactin (given 24 hr before the two extra sucklings) and/or by injections of the beta-adrenergic-blocking drug, propranolol (100 micrograms/kg b. wt. given 30 min before each additional suckling). Since prolactin secretion is decreased in these species and the mammary gland is less responsive to the hormone during late lactation, the present results suggest that in addition to these factors, suckling-induced activation of sympathetic influences may contribute to the decline in milk production at this stage of lactation. Taken together, these results suggest that suckling may regulate lactation in the rabbit through antagonistic mechanisms at different stages of lactation.