Perinatal psychiatry: infant mental health interventions during pregnancy

The authors focus on infant mental health interventions during pregnancy in response to stressors, behaviors, and difficulties experienced by the mother-to-be (as well as by the father-to-be and surrounding family or support system) that are likely to have a negative impact on the growth, development, behavior, and psychological environment of the baby. After summarizing normal tensions and psychological tasks, the authors focus on difficulties during pregnancy: "pathology of destiny," excessive anxiety, domestic violence, fear of becoming a mother, denial of pregnancy, somatic complaints, inadequate weight gain and eating disorders, and depression. The effects of these difficulties on the baby, as well as intervention techniques (including a psychosocial support group), are highlighted.     

Extended-spectrum beta-lactamases of the CTX-M type now in Switzerland

The epidemiology of clavulanic acid-inhibited extended-spectrum beta-lactamases (ESBLs) was investigated among infection-associated enterobacterial isolates at the University Hospital in Lausanne, Switzerland, from January 2004 to June 2005. Out of 57 nonrepetitive ESBL producers (prevalence rate of 0.7%), 45 produced CTX-M-like ESBLs. CTX-M enzymes were mostly from clonally nonrelated Escherichia coli isolates, from urinary infections and community-acquired infections. Pediatric patients (20 out of 57) accounted for a large number of CTX-M producers. CTX-M-15 was the most frequent CTX-M-type enzyme. The plasmid-located bla(CTX-M) genes were associated with either ISEcp1 or ISCR1 insertion sequences. This study is the first published report of CTX-M-type beta-lactamases in Switzerland.     

Relationship between responsiveness of cancer cells to Oncostatin M and/or IL-6 and survival of stage III melanoma patients treated with tumour-infiltrating lymphocytes

Immunotherapy by adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) shows promising clinical results for stage III (lymph nodes metastasis) melanoma patients, but some of them remain unresponsive. Here we analysed retrospectively the impact of resistance of melanoma cells to anti-proliferative cytokines on the clinical outcome of 24 TIL-treated metastatic melanoma patients. Patient relapse-free survival correlated significantly with Oncostatin M (OSM) and/or IL-6 sensitivity of melanoma cells, but not with interferon (IFN) gamma or tumour necrosis factor (TNF) alpha sensitivity. However, OSM/IL-6 sensitivity did not correlate with other known prognostic factors. Moreover, OSM and IL-6 were produced by TIL just before their injection to patients. In immunodeficient mice, OSM reduced human melanoma xenograft tumour growth, this effect being directly through inhibition of tumour cell proliferation rather than induction of apoptosis or necrosis. Thus, OSM/IL-6 resistance of melanoma cells appears to be a new escape mechanism to TIL treatment that could be added to the existing prognostic factors for early stage melanoma patients. This mechanism of action could be also relevant in other immunotherapy protocols, and could lead to better prognosis and anti-cancer treatments.     

Isotopic effect study of propofol deuteration on the metabolism,activity, and toxicity of the anesthetic

The use of isotopic substitution to delay the oxidative metabolism of the anesthetic propofol 1 was studied. The aromatic hydrogens of propofol 1 were replaced by deuterium to produce the mono- and trideuterated derivatives 4 and 5. In vitro metabolic studies on human hepatic microsomes showed no isotopic effect in the para hydroxylation of propofol, and 1, 4, and 5 display similar hypnotic activity and toxicity in mice.     

Novel genetic structure associated with an extended-spectrum beta-lactamase blaVEB gene in a Providencia stuartii clinical isolate from Algeria

A ceftazidime-resistant Providencia stuartii isolate from Algeria harbored a ca. 160-kb conjugative plasmid that contained a truncated bla(VEB-1b) gene flanked by three 135-bp repeated elements. This work gives further evidence of the worldwide spread of bla(VEB) genes that are associated with genetic structures other than class 1 integrons.     

Promoters P3, Pa/Pb,P4, and P5 upstream from bla(TEM) genes and their relationship to beta-lactam resistance

Using an isogenic system, we have determined the impact that the four promoters known to control bla(TEM) gene expression have on beta-lactamase activity. For both TEM-1 and TEM-30, this activity gradually increased in relation to the presence of promoters P3, Pa/Pb, and P4 upstream of the corresponding gene. Promoter P5, only found upstream of the bla(TEM-1B) gene, was related to the highest expression of this gene.     

Chromosome-borne class A BOR-1 beta-Lactamase of Bordetella bronchiseptica and Bordetella parapertussis

A narrow-spectrum clavulanic acid-inhibited class A beta-lactamase, BOR-1, was identified in a Bordetella bronchiseptica clinical isolate. It shared 45% amino acid identity with L-2 from Stenotrophomonas maltophilia. An identical beta-lactamase gene was found in B. bronchiseptica and Bordetella parapertussis reference strains that may contribute only in part to their resistance phenotype.     

Moth chemosensory protein exhibits drastic conformational changes and cooperativity on ligand binding

Chemosensory proteins (CSPs) have been proposed to transport hydrophobic chemicals from air to olfactory or taste receptors. They have been isolated from several sensory organs of a wide range of insect species. The x-ray structure of CSPMbraA6, a 112-aa antennal protein from the moth Mamestra brassicae (Mbra), was shown to exhibit a novel type of alpha-helical fold. We have performed a structural and binding study of CSPMbraA6 to get some insights into its possible molecular function. Tryptophan fluorescence quenching demonstrates the ability of CSPMbraA6 to bind several types of semio-chemicals or surrogate ligands with microM K(d). Its crystal structure in complex with one of these compounds, 12-bromo-dodecanol, reveals extensive conformational changes on binding, resulting in the formation of a large cavity filled by three ligand molecules. Furthermore, binding cooperativity was demonstrated for some ligands, suggesting a stepwise binding. The peculiar rearrangement of CSPMbraA6 conformation and the cooperativity phenomenon might trigger the recognition of chemicals by receptors and induce subsequent signal transduction.