Mechanoreceptors in human myotendinous junction

The sensory-nerve-ending system of 40 myotendinous junctions of human palmaris longus and plantaris muscles was studied histologically. All the known four types of nerve endings were identified. The Ruffini corpuscles could be found in equally small numbers (one to five) in both the muscular and tendineal sites of the junction. Also the free nerve endings were distributed equally on both sites. The Pacini corpuscles were frequent in the tendineal site (six to 14), but rare in the muscular site (one to three). The Golgi tendon organs were, in turn, frequent in the muscular site (nine to 12) but rare in the tendineal site (one to four), respectively. Within the muscle and tendon parts of the junction, the distance between two mechanoreceptors was always more than 250 m?m and the receptor distribution was homogeneous. Further studies are needed to give functional explanation for these anatomic findings. © 1993 John Wiley & Soncs, Inc.     

Prolonged intestinal mucosal acidosis is associated with multiple organ failure in human acute pancreatitis： Gastric tonometry revisited

AIM: To evaluate whether multiple determinations of intramucosal pH (pHi) in acute pancreatitis (AP) patients could provide additional information of the disease severity during early hospitalization. METHODS: Twenty-one patients suffering from acute pancreatitis were monitored by gastric tonometry in the first 72 h after hospital admission. RESULTS: In the survivor group (n = 15) the initially low pHi values returned to normal level (pHi≥7.32) within 48 h (median pHi: d 1: 7.21; d 2: 7.32; d 3: 7.33). In contrast, pHi values in the non-survivor group n = 6) were persistently either below or in the low normal range (median pHi 7.12; 7.12; 7.07 respectively), but pHi differences between the two groups reached significance only after 24 h (P < 0.01). Mucosal acidosis detected at any time during the monitored period was associated with the emergence of single or multiple organ dysfunction (P < 0.01). CONCLUSION: Prolonged gastric mucosal acidosis was associated with remote organ dysfunction and failure in Acute Pancreatitis, however, correlation with the fatal outcome became significant only 24 h after admission. Due to its non-invasive nature gastric tonometry may supplement the pro-inflammatory markers to achieve a multi-faceted monitoring of the disease.     

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin

PROBLEM: Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy. METHOD OF STUDY: A complex immunological panel assay was offered to patients with reproductive failure without any other known cause. We focused here on the cellular immunological parameters. RESULTS: High cytotoxic T lymphocyte precursor frequency and cell-mediated cytotoxic activity and a rather high natural killer cell activity were found in alloimmune RSA patients. Thirty-two patients were investigated by immunological assays and in 78% of the women an alloimmune background could be defined. The efficacy of IVIG treatment was 96% in this group. CONCLUSIONS: The novel cellular immunological assays proved to be favourable for the indication of RSA patients and showed the usefulness of this selection process for effective immunotherapy.     

Behaviour changes in a transgenic model of Huntington's disease

Huntington's disease is an autosomal dominant inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin with unknown function. Transgenic mice expressing the N-terminal of huntingtin, containing 82 glutamines, exhibit a progressive disorder, which resembles to the human disease. In this study, we tested the longitudinal behaviour changes in this transgenic line in open-field and elevated-plus-maze tests. The motor performance deteriorated at 12 weeks of age and the disease progressed as indicated by the decreased total distance covered, the decreased mean velocity and the decreased exploratory behaviour. The level of anxiety was unchanged in transgenic mice as compared with their littermate controls. The motor deterioration was similar to that in other Huntington's disease models, while the level of anxiety was different. These tests are suitable means of following the progression of the disease and useful for studies of the effects of therapeutic interventions.     

Excessive aggression as model of violence: a critical evaluation of current preclinical methods

Rationale

Preclinical experimental models of pathological aggressive behavior are a sorely understudied and difficult research area.

Objectives

How valid, reliable, productive, and informative are the most frequently used animal models of excessive aggressive behavior?

Methods

The rationale, key methodological features, supporting data, and arguments as well as their disadvantages and limitations of the most frequently used animal models for excessive aggressive behavior are summarized and their validity and reliability are evaluated.

Results

Excessive aggressive behavior is validly and reliably seen in (1) a proportion of feral-derived rats and selectively bred mice; (2) rats with compromised adrenal function resulting in a hypoglucocorticoid state; (3) a significant minority of mice, rats, and monkeys after consumption of a moderate dose of alcohol; and (4) resident animals of various species after social instigation. Limitations of these procedures include restrictive animal research regulations, the requirement of expertise in surgical, pharmacological, and behavioral techniques, and the behaviorally impoverished mouse strains that are used in molecular genetics research. Promising recent initiatives for novel experimental models include aggressive behaviors that are evoked by optogenetic stimulation and induced by the manipulation of early social experiences such as isolation rearing or social stress.

Conclusions

One of the most significant challenges for animal models of excessive, potentially abnormal aggressive behavior is the characterization of distinctive neurobiological mechanisms that differ from those governing species-typical aggressive behavior. Identifying novel targets for effective intervention requires increased understanding of the distinctive molecular, cellular, and circuit mechanisms for each type of abnormal aggressive behavior.     

A function for all posterior Hoxd genes during digit development?

Background: Four posterior Hoxd genes, from Hoxd13 to Hoxd10, are collectively regulated during the development of tetrapod digits. Besides the well‐documented role of Hoxd13, the function of the neighboring genes has been difficult to evaluate due to the close genetic linkage and potential regulatory interferences. We used a combination of five small nested deletions in cis, involving from two to four consecutive genes of the Hoxd13 to Hoxd9 loci, in mice, to evaluate their combined functional importance. Results: We show that deletions leading to a gain of function of Hoxd13, via regulatory re‐allocation, generate abnormal phenotypes, in agreement with the dominant negative role of this gene. We also show that Hoxd10, Hoxd11, and Hoxd12 all seem to play a genuine role in digit development, though less compelling than that of Hoxd13. In contrast, the nearby Hoxd9 contributed no measurable function in digits. Conclusions: We conclude that a slight and transient deregulation of Hoxd13 expression can readily affect the relative lengths of limb segments and that all posterior Hoxd genes likely contribute to the final limb morphology. We discuss the difficulty to clearly assess the functional share of individual genes within such a gene family, where closely located neighbors, coding for homologous proteins, are regulated by a unique circuitry and all contribute to shape the distal parts of our appendages. Developmental Dynamics 241:792–802, 2012. © 2012 Wiley Periodicals, Inc.     

Paired-pulse plasticity in the strength and latency of light-evoked lateral inhibition to retinal bipolar cell terminals

Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (～50-80 and ～70-150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1-2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABA(A)Rs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.