IgVH gene analysis suggests that peritoneal B cells do not contribute to the gut immune system in man

The contribution of peritoneal B cells to the intestinal lamina propria plasma cell population is well documented in mice, but unknown in humans. We have analyzed immunoglobulin (Ig) genes of human peritoneal B cells, because such genes show distinctive characteristics in mucosal B cells, particularly highly mutated variable regions. Here, we report the characteristics of variable region genes used by IgM, IgA and IgG in peritoneal cells. We focused on the properties of IgV(H)4-34 to allow comparisons of like-with-like between different isotypes and cells from different immune compartments. We observed that the IgM genes were mostly unmutated, and that the mutated subset had less mutations than would be expected in a mucosal B cell population. Likewise, the IgV(H)4-34 genes used by IgA and IgG from peritoneal B cells had significantly lower numbers of mutations than observed in the mucosal counterparts. Other trends observed, while not reaching statistical significance, followed the trend of peripheral B cells. The peritoneal B cell population had more IgA1 than IgA2 sequences, and there was no dominance of J(H)4 in the IgA from peritoneum or spleen, in contrast to the mucosal sequences. Overall, this study suggested that human peritoneal B cell are either peripheral or mixed in origin; they are unlikely to represent an inductive compartment for the mucosal B cell system.     

Early brain lesions and face-processing development

Studies of functional plasticity after pre- or perinatal brain damage can tell us whether the neural substrate normally involved in the development of a given ability is specific and, if so, when it becomes functionally specified and unique. Development of face processing was investigated in 5- to 17-year-old children who had a unilateral brain injury in the pre-, peri-, or postnatal period. In Studies 1 and 2, patients with a posterior injury involving the temporal regions exhibited a face-processing deficit that was independent of their age at test time. Even though differences were observed between the two hemispheres in face processing during infancy as well as in adults in cases of normal development, no clear differences between right and left injury were observed here in face-processing deficit. Poor postlesional face-processing plasticity seems to contrast with results of several studies on speech development after early unilateral injury. If the difference in the time window for postlesional plasticity between these two areas of competency is confirmed, it would suggest that the two kinds of abilities rely on neural cells which are sensitive to different plasticity factors.     

HLA Antigens in 16 Families with Xeroderma Pigmentosum

Xeroderma pigmentosum is an autosomal recessive disease. HLA-A and -B typing was performed on peripheral blood lymphocytes and platelets. Sixteen Tunisian families were typed with 37 patients and 108 relatives. Genetic transmission of the disease and of the HLA system seemed to be independent in this study. Comparison of HLA gene frequencies between (unrelated) parents of patients and a control population showed no difference, proving that there is no clear association in populations between deleterious XP genes and a particular HLA gene. However, an excess of identical HLA among pairs of diseased siblings would suggest that the disease is polymorphic and a form of the XP could be linked to HLA.     

Neural basis of visually guided head movements studied with fMRI

We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus. These areas have been previously observed in functional imaging studies of human eye movements, suggesting that a common set of brain areas subserves both oculomotor and head movement control in humans, consistent with data from single-unit recording and microstimulation studies in nonhuman primates that have described overlapping eye- and head-movement representations in oculomotor control areas. A second set of areas was active during head and gaze movements but not during eye movements. This set of areas included the posterior part of the planum temporale and the cortex at the temporoparietal junction, known as the parieto-insular vestibular cortex (PIVC). Activity in PIVC has been observed during imaging studies of invasive vestibular stimulation, and we confirm its role in processing the vestibular cues accompanying natural head movements. Our findings demonstrate that fMRI can be used to study the neural basis of head movements and show that areas that control eye movements also control head movements. In addition, we provide the first evidence for brain activity associated with vestibular input produced by natural head movements as opposed to invasive caloric or galvanic vestibular stimulation.     

Blood lactate response to overtraining in male endurance athletes

Many physiological markers vary similarly during training and overtraining. This is the case for the blood lactate concentration ([La⁻]_b), since a right shift of the lactate curve is to be expected in both conditions. We examined the possibility of separating the changes in training from those of overtraining by dividing [La⁻]_b by the rating of perceived exertion ([La⁻]_b/RPE) or by converting [La⁻]_b into a percentage of the peak blood lactate concentration ([La⁻]_b,peak). Ten experienced endurance athletes increased their usual amount of training by 100% within 4 weeks. An incremental test and a time trial were performed before (baseline) and after this period of overtraining, and after 2 weeks of recovery (REC). The [La⁻]_b and RPE were measured during the recovery of each stage of the incremental test. We diagnosed overtraining in seven athletes, using both physiological and psychological criteria. We found a decrease in mean [La⁻]_b,peak from baseline to REC [9.64 (SD 1.17), 8.16 (SD 1.31) and 7.69 (SD 1.84) mmol · l⁻¹, for the three tests, respectively; P < 0.05] and a right shift of the lactate curve. Above 90% of maximal aerobic speed (MAS) there was a decrease of mean [La⁻]_b/RPE from baseline to REC [at 100% of MAS of 105.41 (SD 17.48), 84.61 (SD 12.56) and 81.03 (SD 22.64) arbitrary units, in the three tests, respectively; P < 0.05), but no difference in RPE, its variability accounting for less than 25% of the variability of [La⁻]_b/RPE (r=0.49). Consequently, [La⁻]_b/RPE provides little additional information compared to [La⁻]_b alone. Expressing [La⁻]_b as a %[La⁻]_b,peak resulted in a suppression of the right shift of the lactate curve, suggesting it was primarily the consequence of a decreased production of lactate by the muscle. Since the right shift of the curve induced by optimal training is a result of improved lactate utilization, the main difference between the two conditions is the decrease of [La⁻]_b,peak during overtraining. We propose retaining it as a marker of overtraining for long duration events, and repeating its measurement after a sufficient period of rest to make the distinction with overreaching. Accepted: 26 September 2000     

A dynamic pattern analysis of coordination between breathing and rhythmic arm movements in humans

An insertion (I)/deletion (D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene has, in some studies, been associated with increased risk for Alzheimer's disease (AD), and functionally the enzyme has been implicated in the degradation of amyloid beta protein (Abeta). We have investigated the frequency of the I/D polymorphism in a clinic-based and autopsy-confirmed series of cases of AD, and investigated what impact the I/D polymorphism in ACE gene might have on the extent of Abeta and tau pathology in the frontal cortex in the autopsy-confirmed series. We found no differences in I/D allele or genotype frequencies between the clinic-based and autopsy-confirmed AD cases, or between the pooled clinic-based and autopsy-confirmed AD cases and a series of normal control subjects. Moreover, Abeta (Abeta(40) and Abeta(42)) load, tau load or extent of amyloid angiopathy did not differ between D/D, I/D and I/I genotype groups, though Abeta(42) load tended to be higher in bearers of I/I genotype (compared to D/D genotype). Neither age at onset nor duration of illness differed according to genotype. We conclude therefore that the frequency of ACE I-allele is not increased in AD and, in autopsy-confirmed AD cases, possession of the ACE I allele has no impact upon the pathology of AD, at least in terms of the amount of Abeta or tau deposited in the brain.     

Immunologically silent autochthonous acute hepatitis E virus infection in France

Hepatitis E is an acute and self-limiting hepatitis, and the causative agent, hepatitis E virus, is excreted in feces and orally transmitted. The disease is common in Asia and Africa, causing outbreaks or sporadic cases. In Europe, the infection is generally observed after a history of travel in an area of endemicity. We report on an autochthonous case in southwestern France in which the diagnosis was based on molecular tools rather than serological testing.     

Cell-associated, non-replicating strand(+) hepatitis C virus-RNA shedding in cervicovaginal secretions from chronically HCV-infected women.

BACKGROUND: Lack of mucosal hepatitis C virus (HCV) transmission may be due to fairly low infectivity of body fluids in HCV-infected individuals in association with yet unknown innate or acquired resistance factors in individuals exposed to the virus. OBJECTIVE: To evaluate HCV excretion patterns in cervicovaginal secretions obtained from chronically HCV-infected women. STUDY DESIGN: Fifteen chronically HCV-infected women of childbearing age hospitalized for chronic hepatitis were prospectively recruited. Cervicovaginal secretions were obtained by vaginal washing with 3 ml phosphate-buffered saline (PBS). All cervicovaginal secretions were free of hemoglobin traces and also free of semen traces. Free HCV-RNA and cell-associated HCV-RNA were examined in acellular part and cellular part of the cervicovaginal secretions, respectively, by in-house qualitative PCR for 5'-HCV-non-coding region (NCR). Negative strand HCV-RNA, a marker of HCV replication, was searched by using tag-RT-nested PCR (tag-RT-NPCR). RESULTS: HCV-RNA could not be detected in the acellular fractions of the 15 evaluated cervicovaginal secretions. In contrast, HCV-RNA could be detected in the cellular fractions of four of 15 (27%) cervicovaginal secretions. None of the cervicovaginal secretions, including the four positive cell-associated HCV-RNA, contained negative strand, replicating HCV-RNA. CONCLUSIONS: Our results suggest that positive strand HCV-RNA may be present outside the menstruation periods as cell-associated virus in the cervicovaginal secretions of a minority of untreated HCV-seropositive, HCV-RNA-viremic women, and that the lower female genital tract does not constitute a reservoir where HCV replicates. These observations thus provide the basis for the low risk of female-to-male sexual transmission of HCV infection.     

Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia

The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 ± 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 μmol kg⁻¹) constant infusion (0.06 μmol kg⁻¹ min⁻¹) of l -[1-¹³C]phenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 ± 0.008 versus 0.053 ± 0.009% h⁻¹, respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.