Neuroanatomical evidence for participation of the hypothalamic dorsomedial nucleus (DMN) in regulation of the hypothalamic paraventricular nucleus (PVN) by alpha-melanocyte stimulating hormone

To test the hypothesis that neurons in the hypothalamic paraventricular nucleus (PVN) may be under both direct and indirect regulation by alpha melanocyte-stimulating hormone (alpha-MSH)-synthesizing neurons of the arcuate nucleus, we determined whether the retrogradely transported marker substance, cholera toxin beta-subunit (CtB), when injected into the PVN, labels distinct populations of neurons in the hypothalamic dorsomedial nucleus (DMN) that are innervated by axon terminals containing alpha-MSH. Following iontophoresis of CtB into the PVN, retrogradely labeled neurons were identified in the DMN primarily on the same side as the injection, although a few neurons were also identified in the opposite side of the DMN. The greatest percentage of retrogradely labeled DMN neurons were located in the medial portion of the ventral subdivision of the DMN (DMNv), accounting for approximately 64.8 +/- 1.1% of all CtB-labeled cells in the DMN. The second largest population, comprising 25.9 +/- 1.6% of the total number of CtB cells in the DMN, was diffusely distributed in the dorsal subdivision of the DMN (DMNd). Only 9.4 +/- 0.3% of the CtB-labeled cells were located in the compact zone of the DMN (DMNc). In double-labeling immunofluorescent preparations, 61.1 +/- 1.0% of the CtB cells in the DMNv, 38.6 +/- 0.9% of the CtB cells in the DMNd, and 13.1 +/- 1.3% of the CtB cells in the DMNc were contacted by axon terminals containing alpha-MSH. These data establish that neurons in discrete regions in the DMN may be influenced by the melanocortin signaling system and thereby, could serve as important relay sites to the PVN.     

Low levels of antibodies against <Emphasis Type="Italic">E. coli</Emphasis> and mycobacterial 65kDa heat shock proteins in patients with inflammatory bowel disease

Objective and design: The aim of the present study was to support and extend our initial observation, where we found low levels of antibodies against mycobacterial 65kD heat shock proteins in patients with inflammatory bowel disease (IBD). For this purpose we tested a new group of 124 patients with IBD, and beside measuring antibodies to Mycobacterium bovis 65kD heat shock protein (Hsp65) and human 60kD heat shock protein (Hsp60) as described previously, we also determined IgG antibody levels to Hsp65 from E. coli, called GroEL.Patients and control subjects: seventy-four patients with Crohns disease (CD) (30 males, 44 females, 33 (27–45) years old, median (interquartile range)) and 50 patients with ulcerative colitis (UC) (22 males, 28 females, 38 (30–50) years old) were involved in the study. 110 healthy subjects (34 males, 76 females, 47 (37–53) years old) served as controls. Study subjects were consecutive patients referred to an IBD center for complex treatment of the disease.Methods and statistical analysis: The amounts of IgG-type antibodies reacting with proteins of the chaperonin 60 family were assessed by ELISA. Since the antibody levels to heat-shock proteins as variables were not normally distributed, non-parametric Mann-Whitney test and Dunn post hoc test were used for group comparisons.Results: Median levels of anti-GroEL (7,5 (3,5–18,3)) and anti-Hsp65 (4,8 (2,1–7,85)) were significantly (GroEL p = 0,008; and Hsp65 p < 0,001) lower in the IBD patients than in the healthy subjects (GroEL: 10,0 (5,4–31,0); Hsp65: 7,04 (4,66–12,77)). However this difference was found to be restricted to the CD patients (GroEL: 7,5 (3,7–14,2); p < 0,05; Hsp65: 4,35 (1,90–6,94); p < 0,001). We did not find difference in the concentration of anti-human Hsp60 IgG levels between patients (Hsp60: 45,5 (24,9–69,0)) and healthy controls (38,4 (21,6–69,4). Regarding the serum concentrations of each antibody tested there was no significant difference between the active and inactive stage of disease.Conclusion: Our present findings support conclusion of our previous work, antibody levels not only for Mycobacterium bovis hsp65 but for E. coli GroEl were found to be decreased as well. In contrast no changes in the concentrations of human anti-hsp60 antibodies were observed. These findings indicate that production of antibodies to 65 kDa bacterial heat shock proteins is selectively impaired in IBD.Received 9 March 2004; returned for revision 9 April 2004; accepted by A. Falus 18 May 2004     

Effect of a single mutation in neuraminidase on the properties of Influenza B virus isolates

Two strains of Influenza B virus were isolated in Vero cells. Subclones with improved efficiency of plaque formation were selected. The activity of the neuraminidase (NA) of the two subclones compared to their respective isolates dropped 20- and 100-fold, respectively. Both subclones had a common mutation in segment 6 leading to a change from Asp to Asn at position 457 in the NA. This mutation destroyed a salt bridge of the contact surface between the monomers, thereby causing the loss in enzymatic activity. The decreased NA activity caused improved plaque formation but had no significant impact on the replication in liquid culture.     

Effects of angiotensin II and AIII microinjections into the zona incerta after intra- and extracellular fluid loss

Our recent results showed that angiotensin II or III (AII, AIII) microinjected into the zona incerta (ZI) significantly increased water intake. The most effective doses of AII and AIII were also defined. The two neuropeptides had their effects differently on drinking via different receptors. AII bound to AT(1) that was blocked by AT(1) receptor antagonist Losartan and the effect of AIII was eliminated by prior application of AT(2) receptor antagonist PD 123319. After different hydrational challenges, the effects of AII and AIII in the ZI have never been experimented, however. In the present experiments, the previously defined effective doses of AII (100 ng) or AIII (200 ng) were microinjected into the ZI after different types of challenges: (1). lowered thirst motivation when animals ingested approximately 40% of their daily fluid need during the consequent 60-min-daily-drinking period before the injection, (2). 48-h water deprivation, (3). intracellular dehydration and (4). extracellular dehydration. In all of the cases, incertally injected AII increased the animals' water ingestion. While Losartan could block these effects, PD 123319 was ineffective. Experiments were repeated by AIII, but in none of the cases differences were experienced between the groups. The finding that following hydrational challenges water intake increased only after AII injections and it could be blocked only by Losartan suggests that AII and AT(1) receptor play a pivotal role in the ZI in maintaining the body water balance.     

Galanin- but not galanin-like peptide-containing axon terminals innervate hypophysiotropic TRH-synthesizing neurons in the hypothalamic paraventricular nucleus

Galanin and galanin-like peptide (GALP) are both orexigenic peptides involved in the regulation of food intake and energy metabolism. To determine whether these peptides may directly influence the hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons, double-labeling immunocytochemistry was performed at light and electron microscopic levels using antisera against proTRH, galanin and GALP. Galanin-IR axons densely innervated all of the major parvocellular subdivisions of the PVN where proTRH neurons were identified. The periventricular and anterior parvocellular subdivisions exhibited a prominent network of galaninergic nerve fibers, while the density of fibers was less intense in the medial parvocellular subdivision. Galanin-immunoreactive (IR) axon varicosities were juxtaposed to the majority of TRH-synthesizing neurons in the anterior, medial and periventricular subdivisions of the PVN. Ultrastucturally, galanin-IR nerve terminals established symmetric type synapses with the perikarya of proTRH-IR neurons, suggesting an inhibitory nature of these contacts. In contrast, GALP immunoreactive fibers and nerve terminals concentrated primarily in the anterior parvocellular subdivision of the PVN and were found in association with only few proTRH-IR neurons in the periventricular and medial parvocellular subdivisions. In conclusion, the dense innervation of TRH neurons in all subdivisions of the PVN by galanin-IR axons indicates that galanin may be involved in the central regulation of the hypothalamic-pituitary-thyroid axis. In contrast, the relative paucity of GALP-containing axons in juxtapsoition to TRH neurons in the medial and periventricular parvocellular subdivisions of the PVN, the origin of hypophysiotropic TRH neurons, makes it unlikely that GALP similarly exerts direct regulatory effects on hypophysiotropic TRH neurons.     

Association between heat shock protein 72 gene polymorphism and acute renal failure in premature neonates

Heat shock protein (HSP)70 plays an important role in the ischemic tolerance of fetal and neonatal kidney. We have investigated the association of genetic polymorphisms of the constitutive HSP70 (HSP73) and the inducible HSP70 (HSP72) encoding genes with the risk of acute renal failure (ARF) in very low birth weight (VLBW) neonates. Thirty-seven VLBW neonates with ARF and 93 VLBW neonates without ARF were enrolled in the study. The presence of HSP72 (1267)AG and HSP73 (190)GC polymorphism was analyzed from dried blood samples by PCR and restriction length fragment polymorphism. Allelic prevalence was related to reference values obtained in 131 healthy adults. Stepwise binary logistic regression was applied to determine the independent effect of the established risk factors to the development of ARF. Sixteen of 37 VLBW neonates with ARF and 18 of 93 VLBW neonates without ARF were homozygous for HSP72 (1267)G allele (p 相似文献   

Acute abdominal attack of hereditary angioneurotic oedema associated with ultrasound abnormalities suggestive of acute hepatitis

Hereditary angioneurotic oedema (HANO) is an autosomal dominant disorder caused by a deficiency of the inhibitor protein Cl-esterase. Recurrent subcutaneous and/or submucosal oedema formation is a hallmark of this disease. HANO is a rare, but potentially life-threatening disorder with a mortality around 20-30%. Acute oedematous abdominal attacks of HANO can mimic a surgical emergency; this is exemplified by the case of a 14-y-old male patient with HANO admitted for such clinical manifestations. Conclusion: Diagnostic clues include ascites and abnormalities of hepatic structure visible with ultrasound during the oedematous attack. The importance of appropriate treatment is emphasized.     

Coexistence of delusions of pregnancy and infestation in a male

The coexistent appearance of delusions of pregnancy and infestation is reported in a male patient with posttraumatic epilepsy. While published organic cases of delusions of pregnancy have involved patients with severe or mild mental retardation, our reported patient had a higher than average IQ. The interpretative role of these delusions in a probable perceptual symptomatology cannot be excluded, as both delusions can be based on sensations in the abdomen or on the skin.