HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world. We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7. This was done by clearly distinguishing DR7, DQ2 haplotypes from DR7, DQ9 haplotypes, and by "subtraction analysis" of haplotype frequencies. As reported in other populations, most of the patients without DR3 were heterozygous for DR7 and DR11 or 12 (DR5), or had DR4. We used PCR-RFLP and direct sequencing of amplified DNA to examine HLA-DR4 subtypes. The frequency of HLA-DR4 was markedly decreased in patients compared with controls (p=0.000001) and there was a significant alteration of DR4 subtypes of the patients compared with controls (p=0.0227). Moreover, all of the CD patients (5 of 5) with DR4 had a haplotype associated with the DQB1*0302 allele compared with only 11 of 23 control subjects with DR4. Our results in this population with exceptionally high risk of CD strongly support the DQ heterodimer hypothesis and suggest that the recently described sequence difference between the DQB1*02 alleles of DR3 and DR7 may contribute to a synergistic increased risk when these haplotypes are inherited together. In addition, our findings suggest a role for HLA-DQ in DR4-associated CD.     

The relation between conduction velocity and axonal length

Motor evoked potentials (MEPs) obtained by electrical root stimulation and F waves were used to examine the proximal nerve conduction velocity (CV) to tibialis anterior (TA), extensor digitorum brevis (EDB), flexor carpi radialis (FCR), and abductor pollicis brevis (APB) muscles in 40 humans. By subtracting motor latencies obtained by stimulating the peripheral nerve at the same point from the F-wave and MEP latencies, we could measure the CV over identical proximal segments. It was found that proximal CV to TA and FCR was significantly higher than to EDB and APB, respectively. Combining the data of the proximal CV to all four muscles in relation with axonal length resulted in a highly significant inverse relationship (r² = 0.77). Thus the axonal length explained to a large extent the higher CV of the arm nerves and also the inverse relation between body height and CV. The distal CV was always lower than proximal CV; however, there was no support for an additional effect of this gradient in explaining the relationship between CV and height since it was constant for all body heights. © John Wiley & Sons, Inc.     

Work at sea: a study of sleep,and of circadian rhythms in physiological and psychological functions,in watchkeepers on merchant vessels

Summary Sleep length and sleep quality scores were collected on board ships over periods of up to two weeks from 38 watchkeepers working a 4-on/8-off routine and 29 dayworkers. All watchkeepers exhibited fragmented sleeping patterns, which indicated a lack of adaptation of the sleep/wakefulness cycle to the hours of work. There were only slight differences in total sleep length between watchkeepers and dayworkers, however, both groups did not obtain an adequate amount of sleep. Within the watchkeeping crews the 3rd Officers had by far the shortest sleep length. Concerning sleep quality, daytime sleep was generally given the lowest ratings, whereas sleep starting before midnight was on average evaluated as the best, both by watchkeepers and dayworkers. Watchkeeping personnel do not normally have any days off during a voyage so that missed sleep might even amount to a sleep deficit. A solution for this problem could perhaps be a new, stabilized system that allows a single uninterrupted sleep, which is required for full recuperation, to be taken each day.Dedicated to Professor J. Aschoff on the occasion of his 75th birthdayPartly supported by a grant from the Ministry for Technology and Research, Federal Republic of Germany, Project Schiff der Zukunft, Part ET83b     

Frequency and Output-Dependent Change in Conduction Over Slow Pathways in a Patient with Sustained Ventricular Tachycardia Unrelated to Coronary Artery Disease

In a patient with sustained ventricular tachycardia, we obtained two different paced QRS morphologies from a single pacing site. In one QRS morphology the stimulus to the QRS complex was long, 150 msec, and in the other it was 100 msec. At the paced cycle length of 600 msec and the stimulus output of 4 V, one QRS morphology with the stimulus to the onset of QRS activation (St-QRS) interval of 150 msec was observed. At the paced cycle length of 400 msec, the other QRS morphology with a St-QRS interval of 100 msec was observed alternatively with the former. At the paced cycle length of 353 msec or 316 msec, the latter with a shorter St-QRS interval was exclusively observed. When the stimulus output was increased from 4 to 10 V, keeping with the paced cycle length at 400 msec, the St-QRS interval was shortened from 100 to 80 msec. For the two QRS morphologies with two St-QRS intervals, two slowly conducting pathways would be responsible. The site of the block in the faster pathway must be located at the proximity of the pacing site and the conduction at a shorter paced cycle length would be explained by "supernormal conduction."     

抗乙酰胆碱受体单链抗体对致病性抗体结合活性的抑制作用

为探讨单链抗体 (ScFv )对重症肌无力 (MG )的特异性免疫治疗作用 ,从分离自MG患者胸腺的抗乙酰胆碱受体(AchR )抗原结合片段Fab6 37构建单链抗体ScFv6 37。应用放射免疫测定法测定了ScFv6 37与刺激抗原人AchR的特异性结合活性以及与相关抗原大鼠AchR和电鳐AchR的交叉反应 ,应用竞争性ELISA测定抑制致病性抗AchR完整抗体IgG6 37与人AchR结合活性。结果发现ScFv6 37只能与人AchR结合 ,不能与大鼠和电鳐的AchR结合。对IgG6 37与人AchR结合的抑制率为 17 5 %～ 32 9%。表明单链抗体对AchR具有一定的“保护”作用。     

Elastic strain energy in the low back muscles during human walking

Summary A simple model of the thorax, pelvis and three columns of the intrinsic lumbar back muscles (=ILBM) was constructed. The model was used to study the length of the ILBM during the different stages of the walking cycle. The length of the right ILBM (especially the lateral column) was largest at right toe off, exactly the stage of the walking cycle in which most force was needed to prevent the torso from falling forwards and laterally.     

Dimensional changes of proximal tubules and cortical capillaries in chronic obstructive renal disease

Summary The study was carried out to determine the proximal tubular length, surface area and length of peritubular capillaries and the nephron numbers in kidneys with chronic nephropathy and varying increase in the cortical interstitial volume. Kidneys of pigs with varying chronic obstructive nephropathy were used for the experiments. Two subgroups of ureterobstructed kidneys were defined arbitrarily according to the volume of cortical interstitium. One subgroup (I) comprised kidneys with a volume fraction of cortical interstitium less than 30% (mean 17.2%; mean of controls 9.7%). The other subgroup (II) consisted of kidneys with severe chronic nephropathy and with a volume fraction of interstitium more than 30% (mean 44.5%). Proximal tubular length and length and surface area of peritubular capillaries were assessed by conventional morphometric techniques on 1 m thick sections of plastic embedded material. Nephron numbers were determined by a stereological method for counting glomeruli.The results demonstrated that proximal tubular length and capillary dimensions were significantly reduced in subgroup II, whereas no significant changes were observed in subgroup I. The mean number of glomeruli was not significantly different from control values in any of the subgroups.The results are in line with observations from previous quantitative analyses of proximal tubular cross-sections indicating that proximal tubular dimensions become reduced mainly at advanced stages of chronic nephropathy. The results also indicate that shortening of individual tubules rather than loss of entire nephrons is responsible for the observed reduction in total length of proximal tubules. Finally, the present observations suggest that reduced dimensions of the cortical capillary network may have pathogenetic significance for ongoing proximal tubular atrophy in chronic renal desease.     

Effect of tissue fixatives on telomere length determination by quantitative PCR

Telomere length is a well established marker of cellular senescence and thus biological age. Quantitative PCR allows the determination even from very low amounts of tissue by using telomere specific and single copy gene primers. Comparing a directly processed tissue sample to a 4% formaldehyde fixed one showed a significantly reduced efficiency of PCR reactions (mainly in single copy gene experiments) in a storage time-dependent manner resulting in an artificial increase in reported relative telomere length. This effect was not seen when the tissue was stored in RNA later solution. In summary, telomere length determination from formaldehyde fixed material by quantitative PCR is not a reliable method. Unfortunately therefore, many easily accessible tissue samples from pathology laboratories are unsuitable for this technique.     

生物工程技术制备人源抗-HBs Fab 片段

目的：用生物工程技术制备人源性抗-HBsFab。方法：将从抗体文库中筛选出的人源抗-HBsFab基因克隆入pBAD/gⅢA载体，进而转化Tpo10大肠杆菌，对重组质粒菌发酵表达后，利用Ni-NTA-Agarose螯合层析柱纯化周质腔可溶性Fab蛋白。对所得包涵体依次变性，溶解，纯化后，利用透析进行复性，用Western blot检测Fab蛋白的特异性，Dot blot测定其生物学活性。结果：经Ni-NTA-Agarose柱纯化的周质腔可溶性Fab蛋白，有较好的生物学活性，并且总量达到80mg/L。对所获包涵体进行透析复性后，也可得到少量有活性的蛋白，但比例很小。结论；用pBAD/gⅢA-Top10表达系统表达人源抗-HBsFab片段，发酵培养后，经有效纯化可得到生物学活性较好的可溶性蛋白。为人源抗-HBsFab片段的大量制备提供了有效手段。     

Trimethylaminuria in a girl with Prader-Willi syndrome and del(15)(q11q13)

We report on an individual with trimethyl-aminuria, Prader-Willi syndrome, and del(15) (q11q13). To our knowledge, such an association has never been reported. Skin sores secondary to choline-rich foods and amenable to dietary control have not been described in trimethylaminuria, although they are seen in some patients with Prader-Willi syndrome. Pathogenesis, clinical diagnosis, and management of reported cases with trimethylaminuria are reviewed. Serious social and behavioral problems may result from strong body odor. Amelioration of the “fish odor” by dietary choline restriction makes trimethylaminuria detection important. Association of trimethylaminuria with Prader-Willi syndrome and del(15) (q11q13) in this patient is of particular interest. It may represent a contiguous gene syndrome, or deletion of the normal allele leading to expression of a single recessive trimethylaminuria gene, or an unrelated association, such as in Noonan syndrome. However, recent development of mapping of flavin-containing monooxygenase 2 (FMO2), the likely enzyme that is defective in fish odor syndrome, to chromosome 1q probably excludes pathogenetic association of fish odor syndrome with the Prader-Willi syndrome. © 1993 Wiley-Liss, Inc.