Hippocampal gene expression profiles in passive avoidance conditioning

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long‐term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, the collective behaviours of the genes is mostly unknown. We have used genome‐scale screening by microarray analysis to examine the hippocampal expression of more than 1200 genes relevant to neurobiology during instrumental conditioning. Training rats on a step‐through passive avoidance task led to unique patterns of gene expression when compared to naïve animals or those exposed to the conditioned or the unconditioned stimulus alone. The newly identified genes afford a quantitative view of the changes which accompany conditioning at the genomic level and enable deeper insights into the molecular basis underlying learning and memory.     

Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero

Charcot-Marie-Tooth disease type 1B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (P₀) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution in P₀ex. In both pedigrees, the mutation caused a late-onset, relatively mild CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the two index cases revealed an identical chronic demyelinating and remyelinating neuropathy dominated by focal foldings of the myelin sheath shaped either as tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P₀ex associated with focally folded myelin and provides strong evidence that such a structural alteration of the myelin sheath reflects a distinct pathogenetic mechanism in a subgroup of CMT1B. Received: 18 August 1999 / Revised, accepted: 22 November 1999     

Respiratory viral infection in lower airways of asymptomatic children

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty‐five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non‐bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one‐third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.     

Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype

Tardive dyskinesia (TD) is an important limiting factor in the use of typical antipsychotic drugs. Genetic variability in the serotonin 2A (5-HT(2A)) receptor may influence risk for TD but the results of prior studies are not confirmatory. The objective of this study was to determine association of T102C and His452Tyr polymorphisms in the 5-HT(2A) receptor gene (HTR(2A)) with TD in a large, multicentre patient sample. The design employed case-control analysis controlling for possible confounders using pooled, original data from published and available unpublished samples and employing logistic regression, analysis of variance and meta-analysis. The study sample consisted of 635 patients with schizophrenia or schizoaffective disorder (256 with TD and 379 without TD) drawn from five research centres, divided into six groups based on population origin. The main outcome measure was association of a categorical diagnosis of TD based on the Research Diagnostic Criteria for TD with HTR(2A) T102C and His452Tyr genotypes and haplotypes. The findings indicate significant association of TD with HTR(2A) T102C genotype (p=0.002) over and above the effect of population group, also when controlling for age and gender (p=0.0008), but not with His452Tyr genotype. The T102C genotype was significantly associated with TD in older (>median age 47 yr, p=0.002) but not younger patients and in patients with non-orofacial (limb-truncal) (p=0.001) but not orofacial TD. By meta-analysis the Mantel-Haenszel (M-H) pooled odds ratio (OR) across all the available data was 1.64. A T102C-His452Tyr haplotype was significantly associated with TD (p=0.0008). These findings confirm that genetic variability in HTR(2A) contributes a small but significant degree of risk for the expression of TD, particularly in older patients and specifically for the non-orofacial (limb-truncal) type. Together with other genetic variants associated with TD the findings could be used to assess risk in patients who are candidates for treatment with typical antipsychotic medications.     

N-cadherin as an invasion promoter: a novel target for antitumor therapy?

Cell adhesion molecules of the cadherin superfamily are frequently altered during tumor progression. The loss of E-cadherin, in particular, has long been described in various epithelial cancers where it correlates with malignancy and metastasis. In addition, a subset of tumors show de novo expression or upregulation of N-cadherin, a cadherin that promotes cell motility and invasion. In spite of the accumulating evidence supporting the relationship between N-cadherin levels and cancer progression, the causal role of N-cadherin in tumor development has not yet been clearly demonstrated. This review will address this issue at three different levels: (i) the expression pattern of N-cadherin in cancer; (ii) the cellular events that are modulated by N-cadherin and could account for its pro-invasive role in tumorigenesis; and (iii) the signaling properties of N-cadherin, with particular emphasis on its cross-talk with cell surface partners such as fibroblast growth factor receptor and with intracellular cascades such as the antiapoptotic machinery. Taken together, the topics discussed in this review point to N-cadherin as an important player in tumor development and, therefore, a potential target for novel therapeutic approaches.     

Solid Lipid Nanoparticles Containing Tamoxifen Characterization and In Vitro Antitumoral Activity

Solid lipid nanoparticles (SLNs) containing tamoxifen, a nonsteroidal antiestrogen used in breast cancer therapy, were prepared by microemulsion and precipitation techniques. Tamoxifen loaded SLNs seem to have dimensional properties useful for parenteral administration, and in vitro plasmatic drug release studies demonstrated that these systems are able to give a prolonged release of the drug in the intact form. Preliminary study of antiproliferative activity in vitro, carried out on MCF-7 cell line (human breast cancer cells), demonstrated that SLNs, containing tamoxifen showed an antitumoral activity comparable to free drug. The results of characterization studies and of in vitro antiproliferative activity strongly support the potential application of tamoxifen-loaded SLNs as a carrier system at prolonged release useful for intravenous administration in breast cancer therapy.     

Bovine lactoferrin for Helicobacter pylori eradication: an open, randomized, multicentre study

BACKGROUND: Cure rates for eradication of Helicobacter pylori appear to be decreasing, thus more effective therapies must be identified. AIM: To evaluate the efficacy of bovine lactoferrin in the treatment of H. pylori infection. METHODS: In a multicentered prospective study, 402 (mean age 52.4, range 19-84 years) H. pylori-positive patients were assigned to one of three regimens: group A - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for 7 days; group B - lactoferrin 200 mg b.d. for 7 days followed by the same schedule of group A; group C - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. plus lactoferrin 200 mg b.d. for 7 days. RESULTS: Of the 402 patients, 389 completed the study. Six patients were discontinued due to side effects, one patient in group B died and six patients were lost to follow up. The eradication rate (intention-to-treat analysis) was 77% in group A (105/136), 73% in group B (97/132) and 90% in group C (120/134) (chi(2)-test P < 0.01). The incidence of side effects was 9.5% in group A, 9% in group B and 8.2% in group C (chi(2)-test P = 0.1). CONCLUSION: This study demonstrates that bovine lactoferrin is an effective adjuvant to 7-day triple therapy for eradication of H. pylori infection.     

垂全催乳素瘤的诊断和治疗指南

3.男性:高催乳素血症通常导致阳痿、不孕和性功能低下.男性患者通常为大腺瘤,有神经系统症状.其原因可能是对症状认识的延误或者肿瘤生物学行为的差异.     

Kooperationsverträge zwischen Krankenhäusern und Vertragsärzten – Schnittstellenoptimierung oder Zuweisungsprovision?

Abstrakt  1. Eine Vereinbarung zwischen einem Krankenhaustr?ger und niedergelassenen ?rzten als potentiellen Zuweisern, die diesen ein Entgelt für Leistungen verspricht, die sie ohnehin im Rahmen ihrer (vertrags?rztlichen) Versorgung erbringen würden, ist rechts- und wettbewerbswidrig. 2. Eine in der Sache unzutreffende Bezeichnung dieser Zusammenarbeit als “sektorübergreifend” oder “pr?-/post” ?ndert an dieser Bewertung nichts, sondern verst?rkt eher den Verschleierungscharakter derartiger Vertr?ge. 3. Derartige Vertr?ge leisten in verantwortungsloser Weise sachwidrigen Erw?gungen bei der Wahl des geeigneten Arztes oder Krankenhauses Vorschub. (Leits?tze des Bearbeiters)