Contralateral unaffected wrists from 41 males with Kienböck's disease were compared with wrists from 66 normal males. From X-rays, various features of the lunate and radius were measured. In patients with Kienböck's disease, the lunate tended to be smaller and inclined more radially than in normal subjects and the radial inclination was flatter. Discriminant analysis showed that 85% of the unaffected contralateral wrists in patients with Kienböck's disease and 74% of the wrists in normal subjects were accurately discriminated to their respective groups. It may be possible to identify subjects who are at risk for Kienböck's disease prior to onset using discriminant analysis.
Amebiasis is caused by infection with the protozoan parasite Entamoeba histolytica. Although metronidazole has been a drug of choice against amebiasis for decades, it shows side effects and low efficacy against asymptomatic cyst carriers. In addition, metronidazole resistance has been documented for bacteria and protozoa that share its targets, anaerobic energy metabolism. Therefore, drugs with new mode of action or targets are urgently needed. L-cysteine is the major thiol and an essential amino acid for proliferation and anti-oxidative defense of E. histolytica trophozoites. E. histolytica possesses the de novo L-cysteine biosynthetic pathway, consisting of two reactions catalyzed by serine acetyltransferase and cysteine synthase (CS, O-acetylserine sulfhydrylase). As the pathway is missing in humans, it is considered to be a rational drug target against amebiasis. In this study, we established a protocol to screen both a library of structurally known compounds and microbial culture extracts to discover compounds that target de novo cysteine biosynthesis of E. histolytica. The new screening system allowed us to identify the compounds that differentially affect the growth of the trophozoites in the cysteine-deprived medium compared to the cysteine-containing medium. A total of 431 structurally defined compounds of the Kitasato Natural Products Library and 6,900 microbial culture broth extracts were screened on the system described above. Five compounds, aspochalasin B, chaetoglobosin A, prochaetoglobosin III, cerulenin, and deoxyfrenolicin, from the Kitasato Natural Products Library, showed differential antiamebic activities in the cysteine-deprived medium when compared to the growth in the cysteine-containing medium. The selectivity of three cytochalasans apparently depends on their structural instability. Eleven microbial extracts showed selective antiamebic activities, and one fungal secondary metabolite, pencolide, was isolated. Pencolide showed cysteine deprivation-dependent antiamebic activity (7.6 times lower IC50 in the absence of cysteine than that in the presence of cysteine), although the IC50 value in the cysteine-deprived medium was rather high (283 μM). Pencolide also showed inhibitory activity against both CS1 and CS3 isoenzymes with comparable IC50 values (233 and 217 μM, respectively). These results indicated that antiamebic activity of pencolide is attributable to inhibition of CS. Cytotoxicity of pencolide was 6.7 times weaker against mammalian MRC-5 cell line than E. histotytica. Pencolide has the maleimide structure, which is easily attacked by Michael donors including the thiol moiety of cysteine. The cysteine-adducts of pencolide were detected by mass spectrometric analysis as predicted. As CS inhibition by the pencolide adducts was weak and their IC50 values to CS was comparable to that to the parasite in the cysteine-containing medium, the cysteine-adducts of pencolide likely contribute to toxicity of pencolide to the parasite in the cysteine-rich conditions. However, we cannot exclude a ...
To clarify whether or not scapho-lunate ligamentous injury is common in scaphoid non-union with D.I.S.I. deformity and whether ligamentous repair is required to treat scaphoid non-union with D.I.S.I. deformity, roentgenographic, arthrographic and arthroscopic findings were analysed and compared to those of scaphoid non-union without D.I.S.I. deformity. The carpal alignment of scaphoid non-union with D.I.S.I. deformity treated by reduction and anterior wedge grafting without ligamentous repair was also studied. No significant difference in the scapho-lunate gap was present between 26 patients with D.I.S.I. deformity and 20 without. No statistically significant difference was detected in the incidence of arthrographically-proved scapho-lunate ligamentous tears between the two groups. Arthroscopic examination carried out in 22 patients did not detect massive ligamentous injury, and carpal alignment was satisfactory in most patients who underwent anterior wedge grafting. These results show that ligamentous injury rarely causes D.I.S.I. deformity in scaphoid non-union, and anterior wedge grafting alone is sufficient to correct D.I.S.I. deformity in most cases.
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