The ontogenetic mouse brain model employed in the characterization of antibrain antibodies in multiple sclerosis

The complement-fixing antibrain antibodies which may be found in patients with multiple sclerosis (MS) belong to several specificities, of which only two are as yet identified. In order to study three of the incompletely characterized specificities, the ontogenetic evolution of the corresponding antigens in mouse brain was followed. MS serum containing antibodies to sulfatide, a relatively myelin-specific glycolipid, served as a control. The studied antigens were virtually absent at birth and accumulated at different rates during the postnatal period. The results give valuable clues for the further study of the antibrain antibodies in MS.     

Acute cholecystitis

Background: Most of the literature dealing with the surgical management of acute cholecystitis bases patient selection on pathological diagnosis, either exclusively or using it as a major selection criteria or as a confirmation of diagnosis. The purpose of this study was to examine the correlation between preoperative clinical findings, intraoperative gross findings, and postoperative pathological findings. Methods: A retrospective review of 493 consecutive laparoscopic cholecystectomies performed by a single surgeon (RJF) in a single institution was done. Four different sets of criteria were used to define four groups of patients as having acute cholecystitis: (1) preoperative acute cholecystitis based on defined criteria (PA); (2) intraoperative gross findings of acute or subacute cholecystitis based on surgeon assessment of inflammation (IA); (3) initial pathological evaluation by a staff pathologist (IP); and (4) expert pathological (EP) review using strictly defined histological criteria. Results: Of 41 patients, 40 (97.6%) were classified as having acute cholecystitis by IA, 21 (51.2%) by IP, and 17 (41.5%) by EP. Of the 75 patients classified as having acute cholecystitis by IA, 40 (53.0%) were classified acute by PA, 34 (45.0%) by IP, and 17 (22.7%) by EP. Of the 72 IP patients, 34 (47.2%) were classified as acute by IA, 15 (20.8%) by EP, and 24 (33.3%) were PA. Of the 32 EP patients, 21 (65.6%) were classified as acute by IA, 14 (43.8%) by IP, and 18 (56.3%) were PA. Conclusion: The correlation between the pathological diagnosis and intraoperative findings is poor. Preoperative clinical findings of acute cholecystitis are highly reliable for predicting intraoperative gross findings. However, intraoperative findings of acute cholecystitis are commonly found in the absence of preoperative clinical signs. Recommendations for surgical therapy should be based on studies which use either operative findings or the preoperative clinical findings as the basis for patient selection. Received: 29 March 1996/Accepted: 12 June 1996     

Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly.     

Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover

Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss‐of‐function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino‐terminal propeptide (P1NP), and cross‐linked C‐telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age‐ and gender‐matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. © 2011 American Society for Bone and Mineral Research     

急性淋巴细胞白血病(上)

急性淋巴细胞白血病是淋巴前体细胞异常引起的恶性疾病,儿童与成人均可能发生。儿童发病高峰2～5岁。有效治疗的稳步进展使本病在儿童中的治愈率80％以上,同时为新的治疗方案提供了良机,新方案将保留我们在白血病无病生存病例中获得的治疗经验,同时减轻当前强化治疗方案中的毒副作用。     

急性淋巴细胞白血病(下)

5 风险评估对病人的复发风险进行评估以确保只有高危病例才被施予极强治疗.研究表明采用成人方案治疗的青少年病人,其效果要显著差于使用儿童方案治疗的同年龄组.     

Rare alleles at different VNTR loci among lung-cancer patients with microsatellite instability in tumours

Work in our laboratory has shown a significantly higher frequency of microsatellite mutations in tumours from lung-cancer patients with rare alleles at the Hras1 VNTR locus compared with those with common alleles. In 137 lung-cancer patients, the association between microsatellite instability and rare alleles at the Hras1 VNTR locus was confirmed with 17 microsatellite markers. We found a significant association between LOH in lung tumours of marker D3s966 with microsatellite instability. In samples with LOH at marker D3s966 (3p21.3) 22% of loci tested showed instability, whereas 8% showed instability without LOH at D3s966. To investigate whether rare alleles at the Hras1 locus are linked to rare alleles at other loci, a second minisatellite (D17S4) was genotyped. In a population of 406, 4 individuals with D17S4 rare alleles were detected of whom 3 also had rare alleles at the Hras1 VNTR locus. The probability of this association to occur by chance is low. Thus, rare alleles at the Hras1 locus may be associated with rare alleles at other loci, and could be an indication of germline instability. The findings indicate that microsatellite instability in lung tumours is not strictly associated with features in the Hras1 proto-oncogene, but may be the result of the same mechanism(s) that generate(s) new alleles at the Hras1 and D17S4 loci. Int. J. Cancer, 70:412–415, 1997. © 1997 Wiley-Liss, Inc.     

Contact allergy to oxidized geraniol among Swedish dermatitis patients—A multicentre study by the Swedish Contact Dermatitis Research Group

Background

Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol‐7‐hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%.

Aim

To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting.

Methods

One thousand four hundred and seventy‐six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet.

Results

Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet.

Conclusions

Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series.