Contractile behavior of the forelimb digital flexors during steady-state locomotion in horses (Equus caballus): an initial test of muscle architectural hypotheses about in vivo function

The forelimb digital flexors of the horse display remarkable diversity in muscle architecture despite each muscle-tendon unit having a similar mechanical advantage across the fetlock joint. We focus on two distinct muscles of the digital flexor system: short compartment deep digital flexor (DDF(sc)) and the superficial digital flexor (SDF). The objectives were to investigate force-length behavior and work performance of these two muscles in vivo during locomotion, and to determine how muscle architecture contributes to in vivo function in this system. We directly recorded muscle force (via tendon strain gauges) and muscle fascicle length (via sonomicrometry crystals) as horses walked (1.7 m s(-1)), trotted (4.1 m s(-1)) and cantered (7.0 m s(-1)) on a motorized treadmill. Over the range of gaits and speeds, DDF(sc) fascicles shortened while producing relatively low force, generating modest positive net work. In contrast, SDF fascicles initially shortened, then lengthened while producing high force, resulting in substantial negative net work. These findings suggest the long fibered, unipennate DDF(sc) supplements mechanical work during running, whereas the short fibered, multipennate SDF is specialized for economical high force and enhanced elastic energy storage. Apparent in vivo functions match well with the distinct architectural features of each muscle.     

Chronobiological evidence for an uncoupling of the Na,K-ATPase to aldosterone in normal renin hypertension

The Na,K-ATPase activity of erythrocyte membranes is markedly increased in normal-renin essential hypertensives. A temporal shift of the chronobiology of the erythrocyte-membrane-bound Na,K-ATPase in these patients is described. The disorder causes a loss of synchronism between the circadian rhythms of aldosterone and Na,K-ATPase. Such uncoupling phenomenon may explain the inversion of the day/night sodium excretion ratio and other disturbances of sodium metabolism found in essential hypertensives.     

Are we ready for therapeutic drug monitoring of biologic therapeutics?

In the previous issue of Arthritis Research & Therapy, Ducourau and colleagues report that they retrospectively detected anti-infliximab antibodies in 21% of patients with rheumatic diseases. Patients with anti-infliximab antibodies had lower serum drug concentrations. These findings contribute to the existing evidence of immunogenicity of biologicals and its clinical relevance. We argue for therapeutic drug monitoring to optimize treatment response.     

The influence, in normal subjects, of a high-protein normocaloric diet on the response of cortisol, ACTH, GH, and PRL to insulin hypoglycemia

A protein rich diet causes a remarkable increment of plasma cortisol, corticotropin and somatotropin concentration, but does not modify the plasma prolactin level; this diet, moreover, is followed by a more vivacious response to the Lysin-8-Vasopressin test. In 10 healthy voluntary subjects we have studied the hormonal behaviour during the insulin-induced hypoglycemia test in course of equilibrated diet and after 15 days of protein-rich diet. In these two experimental conditions the insulin-induced hypoglycemia test has promoted a similar increment of the four hormones. The different behaviour between the two tests -Lysin-8-Vasopressin and insulin-induced hypoglycemia- indicates that the increased hormonal levels which follow a protein-rich diet are not provoked by a generic stress effect, but by a direct stimulation of the hypothalamo-hypophyseal structures.     

Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction- site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.      

Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake

To examine the effects of reducing sodium intake upon the renin-angiotensin-aldosterone system (RAAS), 5 healthy men and 5 healthy women, 17-37 years old, living under standardized conditions, were sampled around the clock, once on habitual and once on restricted sodium intake. Plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) were determined by radioimmunoassay. All three variables were found to exhibit a statistically significant circadian rhythm, both on habitual and restricted salt intake. After salt restriction, an increase in midline-estimating statistic of rhythm (mesor) of PRA and PA, but not of PC, was observed. The acrophase (an estimate of the time of high values) for PC lagged behind that for PRA and PA. This difference in acrophase was of specially high statistical significance when subjects were on a sodium-restricted diet. These results demonstrate the importance of inferential statistical so-called rhythmometric methods: parameters such as the acrophase can also be used for the assessment of novel effects and for a quantification in time. The derivation of confidence intervals for each rhythm parameter allows one to verify that a given variable exhibits values bracketing an average not only between a higher and a lower, but also between an earlier and a later limit. Changes that may involve only the acrophase, such as a lead or lag, as here noted, are then detected and are of factual as well as methodological interest.     

Slipped-strand mispairing in a plastid gene: rpoC2 in grasses (Poaceae)

An exception to the generally conservative nature of plastid gene evolution is the gene coding for the beta" subunit of RNA polymerase, rpoC2. Previous work by others has shown that maize and rice have an insertion in the coding region of rpoC2, relative to spinach and tobacco. To assess the distribution of this extra coding sequence, we surveyed a broad phylogenetic sample comprising 55 species from 17 angiosperm families by using Southern hybridization. The extra coding sequence is restricted to the grasses (Poaceae). DNA sequence analysis of 11 species from all five subfamilies within the grass family demonstrates that the extra sequence in the coding region of rpoC2 is a repetitive array that exhibits more than a twofold increase in nucleotide substitution, as well as a large number of insertion/deletion events, relative to the adjacent flanking sequences. The structure of the array suggests that slipped-strand mispairing causes the repeated motifs and adds to the mechanisms through which the coding sequence of plastid genes are known to evolve. Phylogenetic analyses based on the sequence data from grass species support several relationships previously suggested by morphological work, but they are ambiguous about broad relationships within the family.      

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m² were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.