Autoreactivity in human IgG+ memory B cells

More than half of the nascent B cells in humans initially express autoreactive antibodies. However, most of these autoantibodies are removed from the repertoire at two checkpoints before maturation into naive B cells. A third checkpoint excludes remaining autoantibodies from the antigen-experienced IgM(+) memory B cell pool. Nevertheless, low-affinity self-reactive antibodies are frequently found in the serum of normal humans. To determine the source of these antibodies, we cloned and expressed antibodies from circulating human IgG(+) memory B cells. Surprisingly, we found that self-reactive antibodies including anti-nuclear antibodies were frequently expressed by IgG(+) memory B cells in healthy donors. Most of these antibodies were created de novo by somatic hypermutation during the transition between mature naive and IgG(+) memory B cells. We conclude that deregulation of self-reactive IgG(+) memory B cells may be associated with autoimmunity.     

IMPAIRMENT OF ANTIBODY RESPONSE IN PYRIDOXINE-DEFICIENT RATS

Striking impairment of the antibody response to sheep erythrocytes was found in pyridoxine-deficient rats. Deficiencies in the three other B factors required by the rat, and low protein feeding, having effects on body weight comparable to pyridoxine deficiency, failed to influence the antibody response studied. Confirming previous observations, a striking loss of thymic and lymphoid tissue occurred in the pyridoxine-deficient animals. A marked deficit in thymus weight also resulted from the feeding of a diet low in thiamin. Histologically, however, lymphoid atrophy was less pronounced in thiamin-deficient rats than in those deprived of pyridoxine.     

Peripheral development of B cells in mouse and man

Summary:  In man and in mouse, B-cell maturation occurs in steps, first in the bone marrow from hematopoietic precursors to immature/transitional B cells, then in the periphery from transitional to fully mature B cells. Each developmental step is tightly controlled by the expression and function of the B-cell receptor (BCR) and by the ability to interact with the microenvironment. Mature B cells collaborate with T cells in the adaptive immune response, leading to the production of high-affinity antibodies. This response is very accurate, but slow. Immediately after pathogen entry, however, antibodies already present in the serum reinforce the innate immune response and contribute to the first-line defense against infection. Low-affinity natural antibodies are produced by B-1a B cells in the mouse and immunoglobulin M (IgM) memory cells in man. These antibodies represent an immediate protection against all microorganisms and the only one against encapsulated bacteria. B-1a and IgM memory B cells may function as a link between the innate and adaptive immune response and thus perform a primordial B-cell function.     

Wide geographic distribution of a unique methicillin-resistant Staphylococcus aureus clone in Hungarian hospitals

Objective: To determine the genetic relatedness of methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from six provincial hospitals in Hungary between 1993 and 1994.
Method: Molecular fingerprinting methods were used: hybridization with a mecA -specific DNA probe after Cla I restriction; hybridization with a probe for Tn 554 ; and pulsed-field gel electrophoresis after Sma I digestion of chromosomal DNA.
Results: All strains were resistant to penicillin, oxacillin, erythromycin, gentamicin, tetracycline, imipenem, and cephalosporins, and variably resistant to ofloxacin, clindamycin and tobramycin; all isolates were susceptible to vancomycin. Forty-eight of the 51 isolates carried the mecA gene as determined by Southern hybridization, using a mecA -specific DNA probe, indicating that the methodology used for initial identification may have been in error in three of the cases. Forty-seven of the 48 mecA -positive isolates showed very similar genetic backgrounds as defined by pulsed-field gel electrophoresis (PFGE) patterns after Sma I digestion of chromosomal DNAs: a unique PFGE pattern was seen in 32 isolates and minor variants of it in 15 additional isolates. All the 47 isolates carried the same mecA polymorph ( Cla I type III), as determined by DNA hybridization after Cla I digestion of chromosomal DNA. Only one of the MRSA isolates had a completely different PFGE pattern and a novel mecA polymorph.
Conclusions: The findings demonstrate the existence of a unique, epidemic MRSA clone, in both invasive and colonizing strains, which is widely dispersed in Hungarian hospitals hundreds of kilometers apart.     

Urinary tract anomalies and urinary tract dysfunction in children with Hirschsprung disease—Is follow-up indicated?

Background/PurposeUrinary tract function in children with Hirschsprung disease (HD) is rarely considered. Aim: to evaluate the prevalence of urinary tract anomalies and dysfunction in children with HD compared to controls.MethodsThis was an observational cross sectional case–control study. Children with HD who underwent transanal endorectal pull-through technique (TERPT) from 2005 to 2017 were invited to participate. Ultrasound of the urinary tract was performed postoperatively. Children > 4 years were asked to answer a urinary tract function questionnaire. Controls were age-matched healthy children. Ethical approval was obtained.ResultsSeventy two children with HD and TERPT were included. Ultrasound was performed in 58 children (83%) post-TERPT. Ten anomalies were diagnosed in six children (10%). Structural anomalies included abnormal kidney size (7%), renal agenesis (2%), prominent calyces (2%) and renal pelvis anomaly (25). Probable acquired anomalies included hydronephrosis (2%), hydroureter (2%) and parenchymal damage (2%). One child had a prior nephrectomy owing to a Wilms' tumor. All 37 children > 4 years (27 boys and 10 girls), median aged 8 years (range 4–12), answered the questionnaire as did 284 healthy controls (144 boys and 140 girls). Boys with HD reported a higher frequency of enuresis: 65% versus 9% (p = 0.001) and urinary tract infections: 18% versus 3% (p = 0.012). Girls with HD reported enuresis more frequently (60%) than healthy girls (7%) (p = 0.001). Children with HD with constipation reported enuresis more frequently (p = 0.038).ConclusionsUrinary tract anomalies and dysfunction deserve attention in the follow-up of children with HD. We suggest screening for urinary tract anomalies and urinary tract symptoms in follow-up of children with HD.Type of studyTreatment study.LevelIII.     

Hemispheric specialisation for imitation of hand-head positions and finger configurations: a controlled study in patients with complete callosotomy

Several studies of patients with unilateral brain damage and a patient with spontaneous callosal disconnection [Journal of Neurology, Neurosurgery, and Psychiatry 61 (1996) 176; Neuropsychologia 37 (1999) 559; Neuropsychologia 39 (2001) 1432] suggest that the imitation of positions of the hand relative to the head is a strongly lateralised left hemispheric function. In contrast, the imitation of finger configurations draws on resources of both hemispheres with a predominance of the right hemisphere. While these findings suggest a specific pattern of imitation impairment in split-brain patients, thus far, no imitation deficits have been reported in split-brain patients. Three patients with complete callosotomy and two control groups, four patients with partial callosotomy and 10 healthy subjects, imitated hand-head positions and finger configurations with non-lateralised and tachistoscopic stimulus presentation. In addition, the influence of visual control on the imitation performance was examined. One split-brain patient showed the predicted dissociation as she had severe right hemispheric deficit in imitating hand-head positions, while finger configuration imitation was preserved. The other two split-brain patients had no impairment in hand-head position imitation. Withdrawal of visual control significantly deteriorated imitation of finger configurations in the split-brain group, but not in the controls, demonstrating that the split-brain patients relied heavily on visual control as a compensatory strategy indicating an imitation deficit in the separate hemispheres. The findings question the previously held belief that in split-brain patients both hemispheres are perfectly capable of imitating gestures and that imitation is not dependent on hemispherically specialised functions.     

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.