Analysis of CFTR transcripts in nasal epithelial cells and lymphoblasts of a cystic fibrosis patient with 621 +1G->T and 711 +1G->T mutations

We have analyzed the CFTR mRNA populations in a cystic fibrosispatient heterozygous for the 621 +1G     

Mutagenesis studies of the major benzo[a]pyrene N2-dG adduct in a 5'-TG versus a 5'-UG sequence: removal of the methyl group causes a modest decrease in the [G->T/G->A] mutational ratio

The potent mutagen/carcinogen benzo[a]pyrene (B[a]P) is metabolically activated to (+)-anti-B[a]PDE, which induces a full spectrum of mutations primarily at the G:C base pairs (e.g. GC-->TA, GC-->AT, etc.). Each of these mutations can be induced by its major adduct [+ta]-B[a]P-N(2)-dG, where DNA sequence context appears to influence both the quantitative and qualitative pattern of mutagenesis. We noted previously that 5'-TG sequences tend to have a higher fraction of G-->T mutations for both [+ta]-B[a]P-N(2)-dG and (+)-anti-B[a]PDE in comparison with 5'-CG, 5'-GG or 5'-AG sequences. To investigate a possible structural element for this trend, the role (if any) of the methyl group on the 5'-T is considered. Using adduct site-specific means, the [G-->T/G-->A] mutational ratio for [+ta]-B[a]P-N(2)-dG is determined to be approximately 1.08 in a 5'-TGT sequence, and approximately 0.60 in a 5'-UGT sequence. (G-->C mutations are minor.) Although this modest approximately 1.8-fold decrease in [G-->T/G-->A] ratio is statistically significant (P = 0.03), it suggests that the methyl group on the 5'-T is not the main reason why a 5'-T tends to enhance G-->T mutations. This study was prompted by an adduct conformational hypothesis, which predicted that the removal of the methyl group in a 5'-TG sequence would lower the fraction of G-->T mutations; however, the approximately 1.8-fold decrease is too small to do additional experiments to assess whether this conformational hypothesis, or other hypotheses, are the true cause of the decrease, which is discussed in this paper.     

A polymorphism (80G->A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia

5-methyltetrahydrofolate is the predominant form of folate in plasma. It may be the preferred substrate for transport via the reduced-folate carrier (RFC). We isolated a cDNA for the reduced folate carrier (RFC-1) from human skin fibroblasts. A common polymorphism at position 80 in exon 2 of RFC-1 was identified. This polymorphism changes a guanine (G) to an adenine (A), abolishing a CfoI restriction site. Using genomic DNA samples from 169 healthy subjects, we identified 27.1% GG homozygotes, 21.9% AA homozygotes, and 50.9% GA heterozygotes. We explored the impact of this polymorphism, separately and in combination with the 677C->T polymorphism in the methylenetetrahydrofolate reductase gene, on folate status and total homocysteine levels. We found a moderate, but significant, increase in total homocysteine levels in doubly homozygous 80GG/677TT subjects as compared to 80GG/677CC (P = 0.01) or 80GG/677CT (P = 0.04) subjects. In addition, individuals who were 80AA/677CT had higher plasma folate levels than those who were 80GG/677CT (P = 0.02).     

Utilization of offender case information by “lenient” vs. “punitive” clinicians

Presentence evaluations conducted by psychologists and psychiatrists (clinicians) and correctional counselors (caseworkers) were subjected to multiple regression analyses in order to specify the relative contribution of inmate characteristics (offense severity and recidivism probability) and decision maker response biases to sentencing recommendations. Although both groups of decision-makers showed a response bias effect for cases that were difficult to discriminate, the effect was generally lerger for chnicians than for caseworkers. Response bias (lenient vs. punitive) was not associated with type of clinical judgment model (linear vs. configural) or predictability of recommendation, although it was associated with the degree of relative weighting of the two independent variables and, in the case of extremely punitive decision-makers, with the tendency to utilize only one evaluative dimension (offense severity) to the exclusion of the other. Furthermore, it was found that inmates who committed the most serious offenses were exposed selectively to those decision-makers most likely both to place exclusive emphasis on offense severity and to recommend relatively punitive case dispostions. The need for an accountability system designed to minimize the effects of the response biases of correctional decision-makers was discussed.     

11th IUPAC “International Symposium on Macromolecule‐Metal Complexes” (http://www.dcci.unipi.it/∼bea/mmc‐11/)

Conference Reports: This section contains reports on topical conferences. Reports are usually written at the request of the editorial office, but unsolicited contributions are also welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de.     

Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter

Sixty-three Arabic patients (16 males and 47 females) with thyroid toxic and nontoxic goiter who attended the endocrinologist in Nuclear Medicine Hospital and Al Yarmok Nuclear Medicine Department in Baghdad, Iraq were examined for thyroid peroxidase (TPO) gene mutations. A total of ten heterozygous mutations have been identified in the human TPO gene associated with thyroid toxic and nontoxic goiter. These mutations involved transition or transversion of cysteine either by thymine or guanine at the position 1708 of the exon 10 (c.1708C>T) and the position 1978 of the exon 11 (c.1978C>G). From a total of ten detected mutations, two c.1978C>G mutations were detected in nontoxic goiter patients and eight (two c.1708C>T and six c.1978C>G mutations) were detected in toxic goiter. In conclusion, this study identified ten TPO mutations associated with toxic and nontoxic goiter that have not been yet reported in Iraq, and most of them are detected among females (90 %) and adults age between 30 and 50 years old (80 %).     

Polycondensation-addition. II. Polyurethan-ureas from ω-isocyanatoalkyl chloroformates and diamines

5-Isocyanatopentyl chloroformate (I), 3-isocyanatopropyl chloroformate (II), and 2-isocyanatoethyl chloroformate (III) were prepared by treating corresponding amino alcohols with phosgene in dioxane. The preparations gave ω-Chloralkylisocyanate und 2-Oxazolidone. as by-products. I, II, and III were subjected to polycondensationsaddition with various diamines to obtain high molecular weight, film forming polyuretharr-ureas.     

Anionic copolymerization of ω-lactams with ω-lactones

Copolymerizations of ε-caprolactam, α-pyrrolidone or α-piperidone with ε-caprolactone or δ-valerolactone have been carried out in the presence of alkali metal. It has been shown that in copolymerizations of ε-caprolactam or α-pyrrolidone with ε-caprolactone and α-pyrrolidone with δ-valerolactone conversions of above 70 % and reduced viscosities of above 0.5 in m-cresol at 35°C for all compositions were obtained. In the case of copolymerization of ε-caprolactam with δ-valerolactone at 180°C a conversion of 25 % and a reduced viscosity of 0.5 were obtained, but the polymer was polycaproamide, while at 90°C the conversion was 50 % but the polymer was polyvalerolactone. In copolymerizations of α-piperidone with ε-caprolactone or δ-valerolactone the copolymer contained only polyester. A mechanism is proposed for the copolymerization of ω-lactams with ω-lactones with alkali metal, which involves chain propagation by the stepwise addition of the lactam ring at an end of the chain molecule and by the stepwise addition of the lactone ring at the other end of the chain molecule, resulting to a certain extent in the formation of polyester and polyamide segments. This mechanism is supported by experimental results obtained through the reaction in the presence of alkali metal salts of ω-lactam, data on infrared analyses and elementary analyses, and by experimental results obtained through measurements of physical properties of these copolymers.     

Computer-aided tracking of body motions using a c.c.d.-image sensor

A c.c.d-image sensor has been used to obtain virtually online trajectories of moving objects in one plane. The image data acquired are stored and processed by several programs to yield displays which enable interpretation and measurement to be effected. Our major concern is in regard to kinesiological data allied with human locomotor function.

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Zusammenfassung Ein c.c.d.-Image-Sensor (Sensor mit ladungsgekoppelter Vorrichtung) wurde verwendet, um die Bahnen sich bewegender Objekte praktisch unmittelbar zu bestimmen. Die erhaltenen Bilddaten werden mittels mehrerer Programme gespeichert und verarbeitet und liefern Anzeigen, die Auswertung und Messung gestatten. Vor allem befassen wir uns mit kinesiologischen Daten in verbindung mit den Bewegungsfunktionen beim Menschen.

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Sommaire C'est un détecteur d'image combiné à une charge (c.c.d.), qui servit à obtenir la trajectoire pratiquement droite des objects en déplacement sur un plan unique. Les données de l'image acquise sont enregistrées, puis traitées par différents programmes. Les résultats permettent ensuite d'effectuer une interprétation et des mesures. Le problème abordé par la thèse est celui des données kinésiologiques, alliées à la fonction locomotrice de l'être humain.

     

Bone “mass” and the “mechanostat”: A proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500–3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100–300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate “setpoints” of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.