EMG power spectra of elbow extensors during ramp and step isometric contractions

Summary The goal of the present study was to compare electromyogram (EMG) power spectra obtained from step (constant force level) and ramp (progressive increase in the force level) isometric contractions. Data windows of different durations were also analysed for the step contractions, in order to evaluate the stability of EMG power spectrum statistics. Fourteen normal subjects performed (1) five ramp elbow extensions ranging from 0 to 100% of the maximum voluntary contraction (MVC) and (2) three stepwise elbow extensions maintained at five different levels of MVC. Spectral analysis of surface EMG signals obtained from triceps brachii and anconeus was performed. The mean power frequency (MPF) and the median frequency (MF) of each power spectrum were obtained from 256-ms windows taken at 10, 20, 40, 60 and 80% MVC for each type of contraction and in addition on 512-, 1024-and 2048-ms windows for the step contractions. No significant differences (P>0.05) were found in the values of both spectral statistics between the different window lengths. Even though no significant differences (P>0.05) were found between the ramp and the step contractions, significant interactions (P<0.05) between these two types of contraction and the force level were found for both the MPF and the MF data. These interactions point out the existence of different behaviours for both the MPF and the MF across force levels between the two types of contraction.     

Classification and subtype prediction of adult soft tissue sarcoma by functional genomics

Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.     

Bilateral cataract and high serum ferritin: a new dominant genetic disorder?

This paper reports the cosegregation in a three generation pedigree of dominantly inherited cataract with an abnormally high level of serum ferritin. In this family, circulating L ferritin was raised in all subjects affected by cataract independently of iron overload. We suggest that a disorder of ferritin metabolism could be a new genetic disorder leading to lens opacity. Cataract-hyperferritaemia syndrome could also be a new contiguous gene syndrome involving the L ferritin gene and the gene coding for the lens membrane protein (MP19), which both map to the same region of chromosome 19q.     

Comparison of leukocyte count and function in smoking and nonsmoking young men.

Leukocyte function and other hematological measurements were tested in 14 smoking and 13 nonsmoking young men free of intercurrent or chronic diseases. Leukocyte chemotaxis was depressed in smoking subjects when compared to the same subjects abstaining from cigarettes or to the nonsmokers. Smoking did not affect the whole blood bactericidal capacity of leukocytes and serum for Staphyloccus aureus or Klebsiella pneumoniae. Total leukocyte counts, hematocritis, and monocyte counts were higher in the smoking subjects when compared to the nonsmokers.     

Mononuclear cells in glomeruli and cytokines in urine reflect the severity of experimental proliferative immune complex glomerulonephritis.

Immunohistochemical methods were used to investigate the role of macrophages in the progression of proliferative immune complex glomerulonephritis. The mononuclear cell component of glomerular inflammation was analysed in three different stages of chronic serum sickness, each of which was clearly distinguished by criteria of kidney function. Urinary excretion of the macrophage secretory products interleukin-1 and tumour necrosis factor was also evaluated in relation to the functional severity of kidney disease. T lymphocytes and macrophages began to accumulate in glomeruli at the onset of proteinuria, but not before. Urinary excretion of interleukin-1 also began with proteinuria. Proteinuria increased in direct correlation with increases in the number of glomerular macrophages. Development of the most severe stage of glomerulonephritis, characterized by cachexia, declining kidney function, and necrotizing glomerular pathology, was accompanied by the disappearance of T cells from glomeruli and the expression of highly abnormal phenotypes by most macrophages. In addition, there was a switch from urinary excretion of interleukin-1 to excretion of tumour necrosis factor. The progression of proliferative immune complex glomerulonephritis was associated with qualitative as well as quantitative changes in glomerular macrophage populations. Differentiation and/or activation of those glomerular macrophages may have resulted from local T cell-mediated immunoregulation. Measurements of urinary cytokine excretion provided a reliable means of monitoring disease progression. The local action of tumour necrosis factor probably contributed to declining kidney function in the most severe stage of disease.     

A quantitative analysis of the slow component of delayed rectification in frog atrium

1. The slow component of delayed rectification in the atrial muscle membrane of Rana ridibunda has been analysed quantitatively using a voltage-clamp technique.2. It is shown that the current is proportional to a variable which obeys first-order kinetics. At negative potentials the time constant of this process is very long (tau = 3 sec at -55 mV) but it becomes faster at positive potentials (tau = 1.85 sec at +25 mV).3. In the steady state the degree of activation is a sigmoid function of potential. The activation threshold varies substantially between preparations but is usually negative to -30 mV.4. The instantaneous current-voltage relation is nearly linear and its reversal potential most frequently lies between zero and -30 mV.5. The properties of this current system resemble those of the current system i(x2) found in mammalian Purkinje fibres.     

Cellular content of amniotic fluid as predictor of central nervous system malformations.

Prospective observations on 442 consecutive samples have confirmed that pregnancies with CNS malformations are regularly associated with an abnormal cellular content of amniotic fluid. A crude semiquantitative test of the cell content can give valuable clinical information in relation to borderline amniotic fluid alpha-fetoprotein values, and help to detect false positive AFP's.     

A 1463 gene cattle-human comparative map with anchor points defined by human genome sequence coordinates

A second-generation 5000 rad radiation hybrid (RH) map of the cattle genome was constructed primarily using cattle ESTs that were targeted to gaps in the existing cattle-human comparative map, as well as to sparsely populated map intervals. A total of 870 targeted markers were added, bringing the number of markers mapped on the RH(5000) panel to 1913. Of these, 1463 have significant BLASTN hits (E < e(-5)) against the human genome sequence. A cattle-human comparative map was created using human genome sequence coordinates of the paired orthologs. One-hundred and ninety-five conserved segments (defined by two or more genes) were identified between the cattle and human genomes, of which 31 are newly discovered and 34 were extended singletons on the first-generation map. The new map represents an improvement of 20% genome-wide comparative coverage compared with the first-generation map. Analysis of gene content within human genome regions where there are gaps in the comparative map revealed gaps with both significantly greater and significantly lower gene content. The new, more detailed cattle-human comparative map provides an improved resource for the analysis of mammalian chromosome evolution, the identification of candidate genes for economically important traits, and for proper alignment of sequence contigs on cattle chromosomes.     

A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

BACKGROUND: INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression. METHODS: Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS. RESULTS: Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group. Limitations: This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies. CONCLUSIONS: INN 00835 appears to be a promising drug for the treatment of major depression.