Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice

To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a model of Down Syndrome (DS, trisomy 21), we assessed spatial working and reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater number of reference memory errors across trials compared to control mice. Both genotypes showed improvement across trials, although improvement was slower in Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on the RAM, and in contrast to control mice, did not improve across trials, always performing at near-chance levels. These results provide evidence for both spatial working and reference memory deficits in Ts65Dn mice, characteristics of cognitive dysfunction.     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Immunoregulatory Effect of Substance P in Human Eosinophil Migratory Function

Substance P (SP) is a tachykinin involved in the regulation of inflammatory processes. To investigate a modulatory role of the neuropeptide SP in allergic inflammation, we studied its priming effect on human eosinophil chemotaxis and kinetic responses towards platelet activating factor (PAF) and recombinant human interleukin 5 (rhlL-5). Blood was obtained from normal subjects and eosinophils were separated by Percoll discontinuous density gradient centrifugation. High purification was obtained by negative selection procedure (CD16-beads) and the experiments were performed in a 48-well microchemotaxis Boyden chamber. In the present study we demonstrate a potent synergistic effect of 100nM dose of SP on the migratory function of human eosinophils stimulated by PAF and rhIL-5. This synergism was chemotaxis specific and was abolished by NK-1 receptor antagonist (FK888). The results suggest that neurogenic stimuli may play a significant role in eosinophil infiltration via its priming effect on the cell.     

In vivo 31P NMR studies of paraplegics' muscles activated by functional electrical stimulation

The bioenergetics of paralyzed muscles of spastic paraplegic patients under functional electrical stimulation (FES) was studied in vivo using ³¹P NMR. The protocol included rest, 3 min of induced tetanic isometric contraction through surface electrodes and 40 min of recovery. The continuous stimulation, the force recording and the ³¹P NMR measurements were sampled simultaneously inside the whole body imager. Normal values were found for the phosphorous metabolite ratios at rest. During contraction, prominent changes were detected including: a) accumulation of inorganic phosphate (P) accompanied by an unusually strong signal in the phosphomonoester (PME) region, b) phosphocreatine (PCr) decline, and c) a decrease in the intracellular pH. In the following recovery period the physiological state of the muscle was monitored and quantitated by ³¹P NMR. No metabolic and mechanical irreversible damage was detected in the paraplegics' muscles activated by FES under our experimental conditions.     

Characteristics of β-endorphin-induced histamine release from rat serosal mast cells Comparison with neurotensin,dynorphin and compound 48/80

Summary Rat peritoneal mast cells were exposed to the neurohormone and basic opioid peptide -endorphin. -Endorphin induced a dose-dependent release of histamine from the mast cells. A significant histamine release was found at 5 mol/l of -endorphin and maximal release (35% of total) at 20 mol/l. The histamine release process was very rapid and terminated within 30 s at 37°C, and in this sense is very similar to the histamine release induced by compound 48/80 or neurotensin. The histamine release was temperature-dependent showing an optimum release around 30°C, and it was independent of available extracellular calcium, but was inhibited in the presence of high extracellular calcium concentrations. Naloxone, only in very high concentrations (10 mmol/l), inhibited the release, and the very same concentration also inhibited the neurotensin — as well as the compound 48/80-induced histamine release. Cromoglycate and benzalkoniumchloride, a 48/80 antagonist, both produced a progressive dose-dependent inhibition of -endorphin-, neurotensin- as well as compound 48/80-induced histamine release. Taken together, the findings indicate that the opioid peptide -endorphin induces a selective, energy-dependent release of histamine from peritoneal rat mast cells. The pattern of release has much in common with that of compound 48/80 and other basic peptides, such as neurotensin and substance P. In addition this pattern of release is similar to that induced by dynorphin. Send offprint requests to Anita Sydbom at the above address     

宫颈粘液过氧化物酶在月经周期中的变化规律

本文对29例月经周期正常妇女的宫颈粘液过氧化物酶进行了30个周期的研究。在月经周期不同时间测定宫颈粘液过氧化物酶(CMPx)活性及血清促黄体生成素(LH)、雌二醇(E_2)和孕酮(P)。结果表明:在排卵前三天酶活性明显下降,至排卵后一天开始上升。卵泡期,酶活性与E_2呈负相关(r=-0.67);黄体期,酶活性与P呈正相关(r=0.79)。本研究提示:1.CMPx在排卵周期具有特定的变化规律,其变化受体内激素水平影响,可作为预告排卵的指标。2.如简化测定方法,可为自然避孕提供新途径。     

Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs

Summary The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F₂ (PGF₂). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr¹, D-Phe²)-growth hormone-releasing factor(1–29)-NH₂ or (D-Pro², D-Trp^7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A₂ (STXA₂). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF₂-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.     

Complex Ph1 translocation in chronic myeloid leukemia

This report describes a new case of chronic myeloid leukemia with an unusual Philadelphia chromosome translocation involving chromosomes No. 4,9, and 22; t(4,9,22) (q31;q34;q11).     

Differential regulation of cytokine genes in gingival epithelial cells challenged by Fusobacterium nucleatum and Porphyromonas gingivalis

IL-8 mRNA in human gingival epithelial cells (HGECs) is up-regulated by Fusobacterium nucleatum, and up-/down-regulated by Porphyromonas gingivalis in a complex interaction in the early stages (< or = 4 h) after infection. The mechanisms involved in this regulation in response to F. nucleatum and/or P. gingivalis infection, and identification of co-regulated cytokine genes, are the focus of this investigation. Heat, formalin or protease treatment of F. nucleatum cells attenuated the IL-8 mRNA up-regulation. NF-kappaB, mitogen-activated protein kinase (MAPK) p38 and MAPK kinase/extracellular signal-regulated kinase (MEK/ERK) pathways were involved in IL-8 mRNA induction by F. nucleatum. Pretreatment of P. gingivalis with heat, formalin or protease enhanced IL-8 mRNA induction. NF-kappaB, MARK p38, and MEK/ERK pathways were also involved in this induction. In contrast, down-regulation of IL-8 mRNA by P. gingivalis involved MEK/ERK, but not NF-kappaB or MAPK p38 pathways. cDNA arrays analysis revealed that mRNA down-regulation by P. gingivalis is a specific reaction that only a number of genes, e.g. IL-1beta, IL-8, macrophage inflammatory protein-2alpha, and migration inhibitory factor-related protein-14, are affected based on examination of 278 cytokine/receptor genes. These data indicate that F. nucleatum and P. gingivalis trigger specific and differential gene regulation pathways in HGECs.     

Abnormality of chromosome 16 and its phenotypic expression

An abnormality of chromosome 16 in which there is extra genetic material present on the short arm (46, XY, 16p+) has been identified. This chromosomal aberration was associated with multiple congenital anomalies, including mid-facial hypoplasia, arthrogryposis, and mental retardation. On the basis of the cytogenetic appearance and the phenotype of the patient, this may represent a partial 16 trisomy. Unlike most abnormalities of chromosome 16, this syndrome was compatible with life.