Identification of a new Lesch-Nyhan syndrome mutation (HPRTBrasil) and analysis of potentially heterozygous females

The mutation in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene has been determined in two brothers affected with Lesch-Nyhan syndrome. Female members of the family who are at risk for being heterozygous carriers of the HPRT mutation were also studied to determine whether they carry the mutation. DNA sequencing revealed that the boys' mother is heterozygous for the mutation in her somatic cells, but that three maternal aunts are not heterozygous. Such carrier information is important for the future pregnancy plans of at-risk females. The mutation, an A-->T transversion at cDNA base 590 (590A-->T), results in an amino acid change of glutamic acid to valine at codon 197, and has not been reported previously in a Lesch-Nyhan syndrome male. This mutation is designated HPRTBrasil.     

Decreased Cyclosporin A requirement with anti-ICAM-1 and anti-LFA-1 in a peripheral nerve allotransplantation model

OBJECT: This study evaluated the dose related effects of Cyclosporin A (CsA) alone and in combination with monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1) and the alpha subunit of leukocyte function-associated antigen (LFA-1 ) on peripheral nerve allograft rejection in a rat model. METHODS: Nerve regeneration was assessed using gait analysis of returning hind limb function, histology, and morphometry. RESULTS: Regeneration comparable to isograft controls and high dose CsA treatment groups was observed when mAbs were used in combi-nation with intermediate dose CsA. Intermediate dose CsA therapy without additional mAbs was insufficient to support this level of regeneration. Nerve allografts treated with high and low dose CsA demonstrated no increased benefit with the addition of mAb therapy. CONCLUSIONS: Thus, mAbs seem to have a dose dependent effect on immunosuppression when used in combination with CsA, and may have therapeutic promise as a rescue therapy when CsA levels fall or issues of toxicity become important.     

CART: from gene to function

CART was identified as a novel mRNA regulated by psychostimulant drugs. CART peptides appear to be neurotransmitters involved in a variety of functions such as feeding. The mouse gene has been characterized and localized to Chromosome 13. The processing of CART peptides is evident in Western blotting studies.     

Public policy and state psychiatric hospitals

Professionals who operate from a clinical rather than a political ethic must be prepared to reclaim and accept leadership roles and responsibilities, which have shifted to the political arena.     

Complications of Penile Lengthening and Augmentation Seen at 1 Referral Center

Purpose

Complications of the recent cosmetic technique of penile lengthening and girth enhancement are reviewed.

Materials and Methods

During a 16-month period 12 men presented with complications of penile augmentation performed elsewhere. All 12 patients had undergone release of the suspensory ligament and 10 had received autologous fat injection.

Results

the chief complaint was poor cosmetic appearance (irregular residual fat nodules in 7 men, skin deformity and scarring in 4 and scrotalization in 4). Reoperation was necessary in 6 patients, wound complications occurred in 6 and sexual dysfunction was reported by 4. Only 1 patient reported a subjective increase in penile length.

Conclusions

Although a verifiable complication rate may never by available, the morbidity of elective penile lengthening and girth enhancement is noteworthy. These cosmetic techniques should be regarded as experimental.     

Heavy-ion-induced cataractogenesis.

Cataract formation following heavy ion exposure (O+8) was noted in three rhesus monkeys secondary to a study of retinal effects. The pathogenesis of these lens changes follows many, but not all, of the characteristics for "radiation cataracts." The ring-shaped opacity was not noted to occur. Posterior capsular changes were noted initially and followed through the formation of a mature cataract.     

Prostaglandins and cannabis. XII. The effect of cannabinoid structure on the synthesis of prostaglandins by human lung fibroblasts

Earlier findings indicated that several other cannabinoids in addition to delta 1-tetrahydro-cannabinol (THC) were able to stimulate the synthesis of prostaglandins in cell culture systems. The present study was initiated to delineate the structural requirements for this effect within the cannabinoid series. Among the primary cannabinoids, we found that the trend was for more planar structures to show greater activity. In the case of THC metabolites, the order of activity was delta 1-THC greater than 7-oxo-delta 1, 6-THC greater than 7-OH-delta 1-THC greater than 3"-OH-delta 1-THC = 6 beta-OH-delta 1-THC = 6 alpha-OH-delta 1-THC greater than delta 1, 6-THC-7-oic acid. The latter sequence compares favorably with the available data on the behavioral assay in the rhesus monkey and the subjective "high" in humans. We also observed a good correlation between the release of arachidonic acid and the production of prostaglandin E, over a series of eight cannabinoids. This gives further support that the site of action in this effect is the elevation of activity of the phospholipase(s) responsible for supplying precursor arachidonic acid for prostaglandin synthesis.