Uroporphyria induced by 5-aminolaevulinic acid alone in Ahrd SWR mice

In mice, depression of hepatic uroporphyrinogen decarboxylase (UROD) leading to porphyrin accumulation (uroporphyria) occurs with chlorinated ligands of the aryl hydrocarbon (AH) receptor especially after iron overload. However, in the absence of chlorinated ligands, iron itself will eventually cause uroporphyria, but this response is not associated with the Ahr genotype. These effects are potentiated by administration of the haem precursor 5-aminolaevulinate (ALA). The aim of this study was to investigate the effects of ALA alone. Prolonged administration of 2 mg ALA/mL in the drinking water to SWR mice also led to decarboxylase insufficiency (11% of control) and uroporphyria by 8 weeks, whereas DBA/2 mice did not show reduced enzyme activity. Both strains are considered AH nonresponsive and analysis of the Ahr gene using restriction fragment length polymorphism was consistent with SWR, like DBA/2, possessing the Ahrd allele. Exposure of isolated hepatocytes to ALA (150-500 microM) for up to 48 hr showed a significant accumulation of both uroporphyrin and coproporphyrin in the medium, which for uroporphyrin particularly was significantly greater with SWR than with DBA/2 cells. Basal in vivo CYP1A2 activity, measured as microsomal methoxyresorufin dealkylation, was significantly greater in SWR than in DBA/2 mice (1.3-fold), but it was unclear whether this was sufficient to explain the marked difference in sensitivities of the two strains. Despite SWR mice being AH nonresponsive, uroporphyria and decarboxylase depression after an initial iron overload and ALA for 3 weeks were greatly potentiated by a single dose (100 mg/kg) of hexachlorobenzene (a weak AH ligand). The results demonstrate that there is a genetic difference in mice independent of the Ahr genotype and response to iron, which influences the susceptibility to ALA-induced uroporphyria. Thus chemicals, iron and ALA can act independently, but also together, to cause porphyria in susceptible individuals.     

Delta codes for line drawings

A new class of chain codes for line drawings, named delta codes is introduced. Two specific types of fixed angle delta codes and ring delta codes are described. The area-of-error distortion and rate are calculated for two types of delta codes applied to straight and slowly curving lines, and it is shown that the delta outperforms other chain codes with the same set of link types. For rapidly curving lines, however, the delta codes introduce curvature overload distortion analogous to the slope overload distortion of traditional delta modulation for waveforms     

Comparison of 55% TFA/CH2Cl2 and 100% TFA for Boc group removal during solid-phase peptide synthesis

Much has been written about closure of large spina bifida defects. There is an increased demand to close these defects irrespective of the final outcome of the patient. Plastic surgeons may become involved in the closure of large defects. Perforator vessels of the back passing through the latissimus fascia can maintain viability of triangular island flaps. Therefore, such flaps can be used to close the large midline defects of spina bifida. This article reviews the literature and presents a simple technique based on anatomical properties of the region surrounding the defect.     

Memory for pain and affect in chronic pain patients

Radioligand binding studies were performed to determine the effect of various cations on the characteristics of [3H]glibenclamide binding to its high-affinity receptor in rat cerebral cortex membranes. Mg2+ was shown specifically to reduce radioligand binding to membranes pretreated with 5 mM EDTA. CaCl2 enhanced [3H]glibenclamide binding whilst MnCl2, KCl and NaCl were without significant effect. 2 mM MgCl2 induced a statistically significant rightward shift in the dissociation constant for glibenclamide obtained from both saturation and competition studies. These results suggest that Mg2+ may participate in the regulation of the sulphonylurea receptor in the rat cerebral cortex.     

Audit and its impact in the management of early prostatic cancer

An analysis was made of a prospective database of 614 men with newly diagnosed carcinoma of the prostate who presented between January 1978 and December 1990; 3-monthly updates were available on their clinical, haematological and biochemical parameters and 6-monthly updates on chest X-rays, bone scans and skeletal X-rays. It was found that 107 men (mean age 73.5 years) had early disease at presentation. Their management was based on regular surveillance and the treatment deferred until disease progression or development of symptoms. The audit of outcome measured various clinical events. Four patients (3.7%) developed local failure, 11 (10.3%) developed bone metastases, 3 (2.8%) died of cancer with a median survival of 6.3 years, and 34 (31.8%) died of intercurrent disease with a median survival of 2.6 years. The observed survival for 12 years of the whole group was similar to the expected survival for an age-matched population in Scotland. The standardised mortality ratio was 81 (95% confidence limits 57-112).     

Use of expected progeny differences for marbling in beef: II. Carcass and palatability traits

A 2-yr study was conducted to determine the effect of EPD for marbling on marbling score, palatability traits, and carcass fatness in beef. Steer (n = 122) and heifer (n = 123) carcasses were obtained by mating Angus bulls having a high ( > .4) or low ( < -.16) EPD for marbling to MARC II cows (1/4 Angus, 1/4 Hereford, 1/4 Simmental, and 1/4 Gelbvieh). Carcass traits, composition of primals, quarters, and sides, palatability, and shear force data were obtained and adjusted to the mean number of days on feed, equal marbling score (Small50), fat thickness (1.0 cm), and carcass weight (318 kg) end points. Steer carcasses from the high marbling EPD group, adjusted to the mean number of days on feed, had significantly more marbling (P < .01) and less subcutaneous fat in the side and the hindquarter (P < .10) than their low marbling EPD counterparts. Adjusting steers to Small50 marbling produced smaller longissimus muscle area (by 5 cm2), less fat thickness (1.15 vs 1.28 cm), and lighter side weights (306 vs 333 kg) for high marbling vs low marbling EPD groups, indicating a faster rate of marbling deposition. Similar relationships of a greater magnitude were found for heifers, perhaps because the heifers were older than the steers at slaughter. No differences in taste panel ratings or shear force values were noted among steer carcasses. Heifer carcasses from the high marbling EPD group had better (P < .05) ratings for juiciness, muscle fiber tenderness, and overall tenderness than the low marbling EPD group heifers. These results indicate that it is possible, using existing genetic resources, to maintain marbling score and decrease fat in other depots of the carcass without compromising palatability.     

Enhanced activity of an antisense oligonucleotide targeting murine protein kinase C-alpha by the incorporation of 2'-O-propyl modifications

We have previously described the characterization of a 20mer phosphorothioate oligodeoxynucleotide (ISIS 4189) which inhibits murine protein kinase C-alpha (PKC-alpha) gene expression, both in vitro and in vivo. In an effort to increase the antisense activity of this oligonucleotide, 2'-O-propyl modifications have been incorporated into the 5'- and 3'-ends of the oligonucleotide, with the eight central bases left as phosphorothioate oligodeoxynucleotides. Hybridization analysis demonstrated that these modifications increased affinity by approximately 8 and 6 degrees C per oligonucleotide for the phosphodiester (ISIS 7815) and phosphorothioate (ISIS 7817) respectively when hybridized to an RNA complement. In addition, 2'-O-propyl incorporation greatly enhanced the nuclease resistance of the oligonucleotides to snake venom phosphodiesterase or intracellular nucleases in vivo. The increase in affinity and nuclease stability of ISIS 7817 resulted in a 5-fold increase in the ability of the oligonucleotide to inhibit PKC-alpha gene expression in murine C127 cells, as compared with the parent phosphorothioate oligodeoxynucleotide. Thus an RNase H-dependent phosphorothioate oligodeoxynucleotide can be modified as a 2'-O-propyl 'chimeric' oligonucleotide to provide a significant increase in antisense activity in cell culture.