Synthesis and thermodynamic studies of two new polymers carrying amido and amino groups in the side chains

Two linear vinyl polymers carrying amido and primary amino groups in the side chains were synthesized and characterized. Their behaviour in aqueous solution was investigated by potentiometric, viscometric and calorimetric techniques. In both cases, the basicity constants show a linear dependence on the degree of protonation α, while the enthalpy values of protonation do not. The thermodynamic results demonstrate the important role of hydrophobic interactions on the protonation process.     

Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal,intermediate, and premutation alleles

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.     

Control of locomotion in marine mollusc — Clione limacina. V. Photoinactivation of efferent neurons

Summary Efferent neurons in isolated pedal ganglia of the pteropodial mollusc Clione limacina were filled with Lucifer Yellow through the wing nerves. Then the ganglia were illuminated with intense blue light which resulted in the complete inactivation of these neurons. After inactivation of efferent neurons, interneurons of the pedal ganglia continued to generate the locomotor rhythm.     

Control of locomotion in the marine mollusc Clione limacina

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5×10^-7 to 1×10^-6 M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.     

Control of feeding movements in the freshwater snail Planorbis corneus

Isolated buccal ganglia of Planorbis corneus are capable of generating a feeding rhythm. In the present work, "rhythmic" neurons of different groups (see Arshavsky et al. 1988a) have been extracted, by means of an intracellular microelectrode, from the buccal ganglia. (1) After extraction, efferent neurons of groups 3, 5, 7, 9 and most group 4 neurons generated repeated spikes at a frequency controlled by a polarizing current. Any periodic oscillations, similar to those during feeding rhythm generation, were absent in these isolated neurons. It is concluded, therefore, that these neurons are "followers", that is, their rhythmic activity before extraction is determined by synaptic inputs from other neurons of the ganglia. (2) Isolated interneurons of groups 1 and 2 generated slow periodic oscillations similar to those observed in these neurons before their extraction. Subgroup 1e neurons generated smoothly growing depolarization accompanied by increasing spike activity; this depolarization was periodically interrupted by abrupt hyperpolarization, after which a new cycle started. Subgroup 1d neurons periodically generated short series of spikes. Group 2 neurons periodically generated a rectangular wave of depolarization with spike-like oscillations on its top. These results suggest that feeding rhythm generation in Planorbis is based on the endogenous rhythmic activity of group 1 and 2 neurons. (3) A pulse of hyperpolarizing current injected into an isolated neuron of subgroup 1e stopped the growth of depolarization in the neuron and reinitiated the process. This property as well as the character of the synaptic interactions of the interneurons (group 1 neurons excite those of group 2, while those of group 2 inhibit group 1 neurons; Arshavsky et al. 1988b) determine the alternating activity of groups 1 and 2.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors. Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R.