1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

AIRE deficiency leads to impaired iNKT cell development

Autoimmune Polyendocrine Syndrome type I (APS I) is caused by mutations in the Autoimmune Regulator gene (AIRE), and results in the immunological destruction of endocrine organs. Herein we have characterized the CD1d-restricted invariant NKT cells (iNKT) and NK cells in APS I patients and Aire^?/? mice, two cell populations known to play a role in the regulation of autoimmune disease. We show that the frequency of circulating iNKT cells is reduced in APS I patients compared to healthy controls. In accordance with this, iNKT cells are significantly reduced in the thymus and peripheral organs of Aire^?/? mice. Bone marrow transfer from wild type donors into lethally irradiated Aire^?/? recipients led to a decreased iNKT cell population in the liver, suggesting an impaired development of iNKT cells in the absence of Aire expression in radio-resistant cells. In contrast to the iNKT cells, both conventional NK cells and thymus-derived NK cells were unaffected by Aire deficiency and differentiated normally in Aire^?/? mice. Our results show that expression of Aire in radio-resistant cells is important for the development of iNKT cells, whereas NK cell development and function does not depend on Aire.     

Usefulness of chromosome 19 RFLP haplotypes in the diagnosis of myotonic dystrophy.

Three DNA probes (APOC2, PSC11, and LDR152) detecting RFLP polymorphisms were used to test the usefulness of the RFLP approach in myotonic dystrophy (MD) families from the isolated Finnish population. The informativeness of these polymorphisms did not differ from that reported in more mixed populations: in the 13 families of the study most of the 79 meiotic events studied were informative. One known recombinant is included in the study. The highest lod score obtained in the multilocus linkage analysis was z = 5.941 at recombination fraction theta = 0.02. The RFLP results significantly facilitated genetic counseling in problematic cases among the families studied. Although evidence could be found for linkage disequilibrium of the RFLP haplotypes formed in Finnish MD patients, our results do not exclude the possible existence of more than one ancient MD mutation in this population.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Reversible endoneurial changes after nerve injury

Summary Endoneurial changes in the rat sciatic nerve were studied during Wallerian degeneration and subsequent regeneration. After total axotomy two different experimental models were used. In the first the cut ends of the sciatic nerves were left free to allow reinnervation. In the second model the distal end of the transected nerve was sutured to the adjoining muscle to prevent regeneration. Within 2 weeks after the axomoty, a Wallerian type of degeneration was seen with axonal destruction and phagocytosis of myelin sheaths. After 4 weeks endoneurial fibroblastic cells formed circular structures around the Schwann cell columns, i.e., the bands of Buengner in both groups. These fascicle-like structures became more pronounced in the non-regenerating nerves up to 8 weeks, while during reinnervation the cellular reaction in the endoneurium nearly disappeared within this time. Ultrastructurally, the endoneurial fibroblast-like cells showed marked phagocytotic activity and also fragments of basement membrane on their surface. The appearance of thin (25–30 nm in diameter) collagen fibrils closely related to the basement membrane was noted around the bands of Buengner, as well as the appearance of an amorphous extracellular gap between the newly synthetized thin collagen fibrils and normal endoneurial collagen (50–60 nm). The reversible endoneurial compartmentation seems to be important for maintaining the nerve structure, serving as a support for axonal regeneration in addition to the bands of Buengner.Supported in part by grants from the Emil Aaltonen Foundation and from the Research and Science Foundation of Farmos (to V. S.) and institutional grants (to Dept. Med. Chem.) from the Sigrid Jusélius Foundation and the Turku University Foundation     

4p16.3 haplotype modifying age at onset of Huntington disease

Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish families in the study carrying this haplotype most likely have a common founder. Several of the polymorphic loci displayed alleles that may be specific to the late-onset haplotype, implicating that from this study we cannot determine which of the loci tested (or other polymorphic loci in this chromosomal area) do in fact contain genetic modifiers of age at onset.     

The knee joint in diastrophic dysplasia. A clinical and radiological study.

We examined clinically and radiologically the knees of 46 patients (27 females and 19 males) with diastrophic dysplasia. The age of the patients varied from newborn to 38 years. A total of 18 patients was followed during their growth until adolescence. The knees of two legally aborted fetuses appeared on examination to be macroscopically normal and congruous. Excessive valgus deformity of the tibiofemoral weight-bearing angle with a mean of 14 degrees was noted in infancy. Most of the patients had marked instability of the knees. The range of movement of the knee began to decrease before the age of five years. There were signs of early degeneration and deformation of the bony epiphyses before the age of six years. The patellofemoral joint was abnormal from an early age. A marked patella infera, often associated with a lateral position of the patella with bony fragmentation, was noted. The knee in diastrophic dysplasia is basically unstable, showing early deformation of the subchondral bone and degeneration of the joint.