A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains

Summary: Bovine immunoglobulins are made from genes belonging to a small family of closely related Vh, genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen Independent. Diversity seems to be generated by hypermutation, although other mechanistns cannot be discomited at this time. Contrary to humans and mice, which have several Vh gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.     

Histologic Classification of Endoscopically Removed Flat Colorectal Polyps: A Multicentric Study

A total of 594 flat colorectal polyps, removed at endoscopy, were histologically classified into non-neoplastic (n=49) and neoplastic (n=545) polyps. Non-neoplastic polyps were subdivided into metaplastic (n=45) and hyperplastic (n=4), whereas neoplastic polyps were subdivided into adenomas (n=481), intramucosal carcinomas (n=28) and invasive adenocarcinomas (n=36). Several adenoma phenotypes were discerned: tubular (n=375), serrated (n=59), villous (n=39), mixed (n=7) and fenestrated (n=1). Intramucosal carcinomas were subdivided into tubular (n=26) and serrated (n=2), and invasive adenocarcinomas into tubular (n=32), serrated (n=3) and fenestrated (n=1). The microscopic characteristics of each histologic phenotype described in this communication are defined and illustrated.     

Successful management of laryngotracheosophageal cleft through an anterior approach

Laryngotracheoesophageal cleft is an uncommon disease that is difficult to diagnose and treat. Repair of the cleft depends on length and localization of the defect as well as the associated anomalies. A successful repair of a type II cleft is reported in this paper. An anterior split of the larynx and trachea was used and provided excellent exposure and safe repair without injury to the neurovascular structures. This is the best approach and should be used to correct all type II defects.     

Drug conditioning induced by intrastriatal apomorphine administration

The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either apomorphine (2 μg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (apomorphine-paired group and vehicle group) or 30 min following (apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal apomorphine, since the locomotor response in the apomorphine-paired group did not increase, but rather decreased with daily repeated injections of apomorphine. Furthermore, only the apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.     

Untersuchung zur Morbidität der indigenen Volksgruppen der Chiquitanos im südlichen Amazonasgebiet

The Chiquitano-tribe lives in the southern Amazonas region in Bolivia, remote from larger towns. A study (n=1514) on morbidity over an one year period (April 1995 till March 1996) and its relation to general and social medicine is given. Most frequently, childreh under 15 years and women in parity age (15–45 years) sought consultation (34,1 %, 42,7 %). Gastrointestinal, respiratoral and gynecological-obstetric diseases were predominant (22,4 %, 16,2 % and 15,7 %). In the dry season, common colds and respiratoral infections represented the major health problem. In the rainy season, infectious diarrhea diseases caused by polluted water as a consequence of extended floods were most frequent. Typical tropical diseases (malaria, Dengue fever, Chagas’ disease, leprosy a.o.) and socially caused diseases (AIDS, dependencies on drugs and alcohol, consequencies of crime) were rarely seen. With respect to severity, 55,8 % of the patients showed mild disorders. More serious diseases were observed in 39, 8 %. 4,6 % of the patients were diagnosed severly ill and needed hospitalization. Epidemiological data on general and social medicine of minorities in developing countries and their actual degree of medical care are important in a shrinking world. The data are useful to estimate medical needs and plan improvements to the health care system especially in rural areas.     

Periodontal disease in adolescents: some clinical and microbiologic correlates of attachment loss

The influence of several clinical and microbiological variables on the site-specific risk of attachment loss was studied in Navajo Indian adolescents aged 14-19. Diagnoses were made at mesio-buccal sites of the four first permanent molars. Case-control analytical methods were used, with A. actinomycetemcomitans, B. gingivalis, and B. intermedius considered the "risk" variables, and with calculus, gingival bleeding, age, and gender treated as possible confounders. The presence of B. intermedius significantly increased the likelihood that attachment loss would be diagnosed at a site (odds ratio = 2.86). However, this association was confounded by calculus and gingival bleeding; when either or both were present, the effect of B. intermedius was markedly weaker. Step-wise multiple logistic regression analyses showed that, of the variables considered, the combination of calculus, gingival bleeding, and B. intermedius gave the most parsimonious explanation of the presence of attachment loss. The chance that attachment loss would be diagnosed was increased five times when calculus was present, 16.5 times in the presence of both calculus and gingival bleeding, and 37 times when these variables plus B. intermedius were observed at a particular site.     

Modulation of cutaneous reflexes in arm muscles during walking: further evidence of similar control mechanisms for rhythmic human arm and leg movements

Stimulation of cutaneous nerves innervating the hand evokes prominent reflexes in many arm muscles during arm cycling. We hypothesized that the mechanisms controlling reflex modulation during the rhythmic arm swing of walking would be similar to that documented during arm cycling. Thus, we expected cutaneous reflexes to be modulated by position in the walking cycle (phase dependence) and be different when walking compared to contraction while standing (task dependence). Subjects performed static postures similar to those occurring during walking and also walked on a treadmill while the superficial radial nerve was electrically stimulated pseudorandomly throughout the step cycle. EMG was recorded bilaterally from upper limb muscles and kinematic recordings were obtained from the elbow and shoulder joints. Step cycle information was obtained from force-sensing insoles. Analysis was conducted after averaging contingent upon the occurrence of stimulation in the step cycle. Phase-dependent modulation of cutaneous reflexes at early (~50–80 ms) and middle (~80–120 ms) latencies was observed. Coordinated bilateral reflexes were seen in posterior deltoid and triceps brachii muscles. Task dependency was seen in that reflex amplitude was only correlated with background EMG during static contraction (75% of comparisons for both early and middle latency reflexes). During walking, no significant relationship between reflex amplitude and background EMG level was found. The results show that cutaneous reflex modulation during rhythmic upper limb movement is similar to that seen during arm cycling and to that observed in leg muscles during locomotion. These results add to the evidence that, during cyclical movements of the arms and legs, similar neural mechanisms observed only during movement (e.g. central pattern generators) control reflex output. Electronic Publication     

Postnatal changes in membrane properties of mice trigeminal ganglion neurons

Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0-P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Adelta and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance (R(in)), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Adelta, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Adelta neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca(2+) or substitution with Co(2+) during the process of maturation.