A genetic algorithm for multiple molecular sequence alignment

MOTIVATION: Multiple molecular sequence alignment is among the most important and most challenging tasks in computational biology. The currently used alignment techniques are characterized by great computational complexity, which prevents their wider use. This research is aimed at developing a new technique for efficient multiple sequence alignment. APPROACH: The new method is based on genetic algorithms. Genetic algorithms are stochastic approaches for efficient and robust searching. By converting biomolecular sequence alignment into a problem of searching for optimal or near-optimal points in an 'alignment space', a genetic algorithm can be used to find good alignments very efficiently. RESULTS: Experiments on real data sets have shown that the average computing time of this technique may be two or three orders lower than that of a technique based on pairwise dynamic programming, while the alignment qualities are very similar. AVAILABILITY: A C program on UNIX has been written to implement the technique. It is available on request from the authors.     

Inflammatory myofibroblastic tumor in children

The authors presented the cases of two children with inflammatory myofibroblastic (IMF) tumor and reviewed the literature to facilitate the preoperative recognition, delineate the clinical features, and describe the natural history of this entity. The first child had IMF tumor arising from the mesentery of the small intestine. He presented with an abdominal mass associated with severe inflammatory response manifested by fever, impaired growth, thrombocytosis, and microcytic, hypochromic anemia. After surgical resection, his fever resolved and his growth rate and the laboratory abnormalities normalized. Five months after initial diagnosis, the fever, anemia, and thrombocytosis recurred along with two tumors arising from the omentum and the abdominal soft tissue. After the second surgery, he remains free of recurrent disease for 30 months. The second child presented with a lung mass that was radiologically indistinguishable from pulmonary sequestration. After surgical resection, she remains free of recurrent disease for 18 months. IMF tumor should be considered in any solid tumor that occurs in association with a chronic inflammatory response. IMF tumor should also be considered in the differential diagnosis of pulmonary sequestration.     

Alpha 1-adrenoceptors and calcium sources in adrenergic neurogenic contractions of rat vas deferens

1. The involvement of alpha 1-adrenoceptor subtypes in adrenergic neurogenic contractions of different type was studied in epididymal and prostatic portions of the rat vas deferens. 2. The adrenergic component of neurogenic contractions was isolated by suramin (300 microM). Twitch-like and tonic contractions were elicited by appropriate pulse patterns of electrical field stimulation, and contractions relying on intracellular calcium mobilization and calcium entry were isolated by means of nifedipine (10 microM) and ryanodine (20 microM), respectively. Increasing concentrations of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)- amino)-propyl)benzeneacetonitrile (HV 723), prazosin and 5-methylurapidil progressively, monophasically and with potency decreasing in that order reduced and finally abolished all types of contraction, with one exception: concentration-effect curves of 5-methylurapidil in epididymal segments in the presence of ryanodine levelled off at about 75% inhibition. In the presence of both nifedipine (10 microM) and ryanodine (20 microM), contractions were abolished. 3. Contractions elicited by exogenous noradrenaline were also studied in the presence of either nifedipine 10 microM (prostatic segments) or ryanodine 20 microM (epididymal segments). Increasing concentrations of tamsulosin, WB 4101, benoxathian, HV 723, prazosin, 5-methylurapidil and urapidil progressively, monophasically and with potency decreasing in that order reduced and eventually abolished both kinds of contraction, with two exceptions: in epididymal segments in the presence of ryanodine, the concentration-effect curve of 5-methylurapidil was biphasic and the curve of urapidil levelled off at only partial inhibition. 4. In slices prepared from the prostatic end and preincubated with [3H]-noradrenaline, WB 4101, HV 723, prazosin and 5-methylurapidil, at the highest concentrations tested against neurogenic contractions, increased only slightly the overflow of tritium elicited by trains of 50 pulses at 5 Hz. 5. It is concluded that two alpha l-adrenoceptor subtypes mediate adrenergic neurogenic contractions of rat vas deferens. The main one, pharmacologically alpha 1A, activates both calcium mobilization and entry. In addition there is a second receptor, not previously detected in the vas deferens and not corresponding to any named alpha l subtype, characterized by high and similar affinity for tamsulosin, WB 4101, benoxathian,HV 723 and prazosin and very low affinity for 5-methylurapidil and urapidil, and linked exclusively to calcium entry. Both subtypes and their respective transduction pathways also contribute to contractions elicited by exogenous noradrenaline. An alpha 1B-adrenoceptor-mediated contraction was not found under any experimental conditions.     

Parental bonding and mental health in adolescence

Attachment between parent and child plays a crucial role in the healthy development of the child. Accordingly disturbances in parental bonding will be linked with the development of mental disorders later in life. The present study examines the relationship between parental bonding and mental health in healthy adolescents. Participants were 847 Israeli high school students who completed the Parental Bonding Instrument (PBI), the Brief Symptom Inventory (BSI), the General Well-Being (GWB), the Perceived Social Support (PSS), and the Social Desirability scale (SDS). In general, Israeli adolescents reported more parental care and less control than did Australian adolescents and adults. Female subjects reported more maternal care than did males. Subjects who reported high care and low control (optimal bonding) reported less distress, better general well-being and better social support that did all other groups. In contrast, those who reported low care and high control (affectionless control bonding) had the highest BSI scores and the lowest GWB and PSS scores. These results are in line with Bowlby's theory of attachment. They also show that specific configuration of parental bonding are linked with distress and isolation in adolescents.     

The relative contribution of selected carpal bones to global wrist motion during simulated planar and out-of-plane wrist motion

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.     

Discrepancies between thyrotropin (TSH) measurement by four sensitive immunometric assays

A comparison of four different commercial immunometric thyrotropin (TSH) assays (Amerlite R TSH-30 Ultrasensitive assay from Kodak, BeriLux R hTSH from Behring Werke, Delfia R hTSH Ultra from Wallac and IMX R Ultrasensitive hTSH from Abbott) was made by measuring serum TSH in 81 consecutive patients referred to hospital for various reasons with a serum TSH less than 0.8 mlU/l in the IMX assay. The analytical and functional assay sensitivities of each of the assays were analysed. Even though three of the methods had a sensitivity corresponding to third generation assays, we could only demonstrate an overall agreement of serum TSH when comparing two of the kits. The measurements in Delfia Ultra and Berilux showed good agreement (P = 0.7, paired t-test and bias = 0.003 mIU/l), while the comparisons between the other assays showed different measurements (P < 0.00001, paired t-test and bias more than 0.07 mIU/l). Differences in the calibrators used in the assays might explain some of the discrepancy, although all methods were calibrated according to the same international standard. Also, differences in the specificity of the TSH monoclonal antibodies used in the assays might be an evident explanation and further studies of the specificity of the monoclonal antibodies are needed. An international collaborative study to clarify reasons for the differences between the TSH assays and to standardize the measurements is recommended.     

Endoneurial localisation of microvascular damage in human diabetic neuropathy

Twenty diabetic patients with neuropathy underwent clinical and neurophysiological evaluation together with a detailed morphometric assessment of capillary pathology in endoneurial and epineurial microvascular beds of the sural nerve. Morphological data were compared with ten non-diabetic control subjects. There were no significant differences in control subjects between basement membrane area, endothelial cell area, endothelial cell profile number or luminal area of endoneurial when compared with epineurial capillaries. In contrast, when compared with epineurial capillaries, endoneurial capillaries from diabetic patients demonstrated a significant increase in basement membrane (p < 0.001) and endothelial cell (p < 0.001) area and a significant reduction in luminal area (p < 0.001). There was no significant difference in endothelial cell profile number between endoneurial and epineurial capillaries amongst diabetic patients. Previous studies have demonstrated a good correlation between the degree of microangiopathy and measures of neuropathic severity. In the present study increased endoneurial capillary basement membrane area was significantly related to reduced peroneal nerve conduction velocity (p < 0.001), myelinated fibre density (p < 0.001) and elevated vibration (p < 0.05) and thermal (p < 0.001) perception. Increased endothelial cell area and reduced luminal size were related to a reduced peroneal nerve conduction (p < 0.05, p < 0.01, respectively), reduced myelinated fibre density (p < 0.05, p < 0.01) and elevated thermal perception (p < 0.05, p < 0.001). Epineurial capillary basement membrane, endothelial cell and luminal area failed to relate to measures of neuropathic severity.(ABSTRACT TRUNCATED AT 250 WORDS)