Convergent in vivo and in vitro selection of ceftazidime resistance mutations at position 167 of CTX-M-3 beta-lactamase in hypermutable Escherichia coli strains

We report on a novel CTX-M extended-spectrum beta-lactamase (ESBL), designated CTX-M-42, with enhanced activity toward ceftazidime. CTX-M-42 was identified in a hypermutable Escherichia coli nosocomial isolate (isolate Irk2320) and is a Pro167Thr amino acid substitution variant of CTX-M-3. By molecular typing of ESBL-producing E. coli strains previously isolated in the same hospital ward, we were able to identify a putative progenitor (strain Irk1224) of Irk2320, which had a mutator phenotype and harbored the CTX-M-3 beta-lactamase. To reproduce the natural evolution of CTX-M-3, we selected for ceftazidime resistance mutations in bla CTX-M-3 gene in vitro both in clinical isolate Irk1224 and in laboratory-derived hypermutable (mutD5) strain GM2995. These experiments yielded CTX-M-3 Pro167Ser and CTX-M-3 Asn136Lys mutants which conferred higher levels of resistance to ceftazidime than to cefotaxime. CTX-M-3 Asn136Lys had a level of low activity toward ampicillin, which may explain its absence from clinical isolates. We conclude that the selection of CTX-M-42 could have occurred in vivo following treatment with ceftazidime and was likely facilitated by the hypermutable background.     

Task-related differential dynamics of EEG alpha- and beta-band synchronization in cortico-basal motor structures

Movement-related processing results in the modulation of neuronal synchronization over several electroencephalography (EEG) frequency ranges, including alpha- (8–12 Hz) and beta-band (14–30 Hz). Whether modulation patterns differ across sites within the motor system remains unclear, but could denote how information is conveyed across the cortico-basal network. We therefore compared the event-related synchronization/desynchronization (ERS/ERD) in recordings from the scalp, basal ganglia and thalamic structures during a motor task.
Simultaneous depth and scalp EEG were recorded in 13 patients, undergoing deep brain stimulation of the thalamic ventral intermediate nucleus (VIM) or the subthalamic nucleus (STN). They performed a choice-reaction task with pre-cued Go-signals, instructive for either left- or right-sided button presses.
In the beta-band, pre-cues and Go-signals were followed by ERD starting well before and peaking at task execution, uniformly in all cortical and subcortical recordings. In contrast, a comparable alpha-band ERD was only seen at the scalp, whereas mirror-like ERS were observed in the motor-inhibitory STN. In VIM, which receives strong somatosensory afferences, a major alpha-ERD upon the Go-signal did not start until the motor response.
These dissociations of task-related Alpha- and Beta-band dynamics tag a functional diversity in cortico-basal networks, which are simultaneously active in motor processing. Whereas the uniform downregulation of Beta-activity points to an anti-kinetic operation mode throughout the motor system, site-dependent courses of Alpha-synchronization rather reflect the coordination of activity levels in functionally divergent motor structures during the preparation and execution of movements.     

Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro

Trimetoquinol (1, TMQ) is a potent nonselective beta-adrenergic receptor (AR) agonist and a thromboxane A(2)/prostaglandin endoperoxide (TP) receptor antagonist, while 3',5'-diiodo-TMQ (2) exhibits beta(3)-AR selectivity. In search of selective beta(3)-AR agonists as potential drugs for the treatment of human obesity and type II diabetes mellitus, a series of 1-(3, 5-diiodo-4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ols has been prepared and evaluated for their biological activities at human beta(1)-, beta(2)-, and beta(3)-ARs expressed in Chinese hamster ovary (CHO) cells. The compounds have been synthesized by the Bischler-Napieralski cyclization of corresponding amides followed by NaBH(4) reduction, and the halogens in the aromatic ring A were introduced by direct halogenation of protected compound 11. Whereas halogen substitution in ring A reduced either potency or intrinsic activity on beta(3)-AR, the non-halogen-substituted compounds 8 and 10 were potent, selective, nearly full agonists for beta(3)-AR.     

Determination of grade and receptor status from the primary breast lesion by magnetic resonance spectroscopy

Magnetic resonance spectra (MRS) from fine needle aspiration biopsies (FNAB) from primary breast lesions were analysed using a pattern recognition method, Statistical Classification Strategy, to assess tumor grade and oestrogen receptor (ER) and progesterone receptor (PgR) status. Grade 1 and 2 breast cancers were separated from grade 3 cancers with a sensitivity and specificity of 96% and 95%, respectively. The ER status was predicted with a sensitivity of 91% and a specificity of 90%, and the PgR status with a sensitivity of 91% and a specificity of 86%. These classifiers provide rapid and reliable, computerized information and may offer an objective method for determining these prognostic indicators simultaneously with the diagnosis of primary pathology and lymph node involvement.     

Functional links between motor and language systems

Transcranial magnetic stimulation (TMS) was applied to motor areas in the left language-dominant hemisphere while right-handed human subjects made lexical decisions on words related to actions. Response times to words referring to leg actions (e.g. kick) were compared with those to words referring to movements involving the arms and hands (e.g. pick). TMS of hand and leg areas influenced the processing of arm and leg words differentially, as documented by a significant interaction of the factors Stimulation site and Word category. Arm area TMS led to faster arm than leg word responses and the reverse effect, faster lexical decisions on leg than arm words, was present when TMS was applied to leg areas. TMS-related differences between word categories were not seen in control conditions, when TMS was applied to hand and leg areas in the right hemisphere and during sham stimulation. Our results show that the left hemispheric cortical systems for language and action are linked to each other in a category-specific manner and that activation in motor and premotor areas can influence the processing of specific kinds of words semantically related to arm or leg actions. By demonstrating specific functional links between action and language systems during lexical processing, these results call into question modular theories of language and motor functions and provide evidence that the two systems interact in the processing of meaningful information about language and action.     

Reaction of the autonomic nervous system of children to a magnetic field

A study was made of some reactions of the child's body to the magnetic field action with the aid of thermography, investigation of the parameters of vegetative functions and determination of the changes in the amount of the formed elements of white blood in 20 normal children and 20 patients aged 6-15 years suffering from chronic gastroduodenal diseases. It has been established that the changes in infrared radiation on the surface of the anterior abdominal wall in the patients mirror the adequacy of the compensatory reactions of the vegetative nervous system to the magnetic field action. The parameters of the function of the vegetative nervous system, mainly those of its sympathetic part, are indicative of the effect of the magnetic field on the patient's body.     

Palmoplantar epidermal atrophy with hypokeratosis, dys- and hypotrichosis, hypodontia, enamel and dentin hypoplasia, isolated cleft palate with cleft uvula, strabismus cryptorchism and other anomalies--an undescribed ecto-mesodermal dysplasia?]

A 15-year-old boy had suffered burning of both palms and all fingers during his 2nd year of life. Epitheliazation of the lesions did not occur. In his 6th year, erythema, desquamation and erosion-like alterations appeared spontaneously on the soles of both feet and on the plantar sides of the toes. These alterations were similar to those on the hands. Histologically the lesion on the right sole was covered with a very thin horny layer and thin epidermis. The cells of the epidermis had clear cytoplasm and probably derived from the ductal epithelium of the sweat glands. Under the atrophic epidermis, granulation tissue consisting of lymphocytes, plasma cells, histiocytes, and a few polynuclear cells and eosinophils was seen. The following symptoms were still present in the boy: dys- and hypotrichosis, oligodontia, enamel and dentin hypoplasia, cleft palate and uvula, concomitants strabismus (left eye), and cryptorchidism. Transplantation of the patient's skin from the right thigh to the lesion on the right sole was tried. The authors postulate a previously unreported form of ecto-mesodermal dysplasia in this case.     

On validity of the term "chronic" rupture of abdominal aortic aneurysm

Treatment of patients with abdominal aortic aneurysms has been analyzed. From 506 patients (265 emergency and 241 elective cases) treated in the department of urent vascular surgery 36 had "chronic disruptions". Validity of this term is discussed. The authors consider the term "repeated disruption" as the most adequate.