Differences in recruitment properties of the corticospinal pathway between lengthening and shortening contractions in human soleus muscle

The purpose of this study was to investigate how the recruitment properties of the corticospinal pathway are modulated in the soleus muscle of the lower limb during lengthening (LEN) and shortening (SHO) contractions by comparing the shape of the input-output (I/O) relation of the corticospinal pathway. To this end, we investigated the relationship between various stimulus intensities applied via transcranial magnetic stimulation and the size of motor-evoked potentials in 14 healthy subjects during voluntary plantarflexion and dorsiflexion (active lengthening) with a similar background activity (BGA) level. The shape of this relationship was sigmoidal and was characterized by a plateau value, maximum slope and threshold. The plateau value was clearly lower during LEN contractions than during SHO contractions. Likewise, the maximum slope was lower during LEN contractions. However, the threshold did not differ significantly between the two tasks. Since the plateau value and the maximum slope clearly differed between LEN and SHO contractions despite the similarity of their BGA levels, the central nervous system appears to have a different activation strategy for each of these tasks. Namely, the relative balance between excitatory and inhibitory components of the corticospinal volleys, as well as the subliminal fringe of the corticospinal pathway, were reduced during LEN contractions compared with SHO contractions. These strategies may help to avoid reflexive contractions brought about by higher discharge of muscle spindles and enable fine motor actions in voluntary lengthening contractions.     

Potassium-lowering effect of mineralocorticoid therapy in patients undergoing hemodialysis

The present study was conducted to examine potassium lowering effect of exogenous mineralocorticoid (fludrocortisone acetate; FCA) administration to the patients with chronic renal failure undergoing hemodialysis. Fifteen patients on hemodialysis receiving FCA with its dosage gradually increased from 0 to 0.20 mg/day were observed for five successive 4-week periods. The serum potassium concentration was significantly decreased after FCA administration concomitant with the decrease of the salivary sodium to potassium ratio. Such decrease in serum potassium concentration was more significant in patients with <150 pg/ml of plasma aldosterone concentration (PAC) (low PAC group) than in those with >/=150 pg/ml of PAC (high PAC group). 0.05 mg of FCA was sufficient to lower serum potassium in low PAC group, while 0.15 mg of FCA was required for high PAC group. FCA administration did not affect serum sodium, chloride and bicarbonate concentrations. Body weight and blood pressure were not increased during the experimental periods. There were no significant changes in plasma level of glucose, insulin, epinephrine and norepinephrine. These results suggested that FCA could be effective to treat hyperkalemia without any adverse effects in patients undergoing hemodialysis.     

Mortality of pulmonary artery banding in the current era: recent mortality of PA banding

BACKGROUND: The mortality of pulmonary artery banding improved significantly in the 1980s. However, we lack information on this procedure in the current era. METHODS: The results of pulmonary artery banding in 365 patients who had operations between 1966 and 2001 were reviewed. The patients were divided into three groups: (1) group 1 patients who had operations between 1966 and 1979, (2) group 2 patients who had operations between 1980 and 1989, and (3) group 3 patients who had operations between 1990 and 2001. RESULTS: Significantly younger and smaller patients have been operated on recently (mean age: group 1, 169.0 +/- 40 days; group 2, 101.8 +/- 11 days; and group 3, 69.7 +/- 8.9 days; and mean weight: 4.6 +/- 0.1, 4.1 +/- 0.1, and 3.2 +/- 0.1 kg, respectively). A decrease was found in the number of simple cardiac anomalies, such as isolated ventricular septal defects. The early mortality in the three groups was 38.3% for group 1 (65 of 187), 13.5% for group 2 (15 of 111), and 13.8% for group 3 (12 of 87). Although the mortality did not vary significantly between groups 2 and 3, it improved over time in patients weighing less than 3 kg. Multivariate analysis of group 3 demonstrated that no isolated variable, including sex, weight, and diagnosis was a significant risk factor. CONCLUSIONS: Despite the advances in perioperative management, we found no improvement in the early mortality of pulmonary artery banding during the last decade. These results will support the preference for primary repair of intracardiac anomalies in small infants. However, this operation can now be performed with the same risk even in smaller patients. We believe that pulmonary artery banding has a role in the treatment of congenital cardiac anomalies.     

Adequate evaluation of HSL mass and activity in rat adipose tissue in fasting and aging-related obesity

Adipose tissue is a unique tissue because its mass is readily changed by altering nutritional conditions. Therefore the activity and content of enzyme in the adipose tissue is significantly differed according to the way of their presentation: per g tissue, per whole tissue, or per cell number. In the present study, the effects of the ways of expressing the hormone sensitive lipase (HSL) activity and content were studied in rat by decreasing or increasing adipose tissue. Fasting caused a progressive decline in body weight and in the weight of the epididymal fat pad. When the HSL content was expressed per g of adipose tissue, the lipase activity and immunoreactive HSL protein content in fasting rats were higher than those in fed rats. On the other hand, when they were expressed as per fat pad, the lipase activity and immunoreactive HSL protein in fasting rats were lower than those in fed rats. The opposite results were observed in obesity. When the HSL content was expressed per g of adipose tissue, the lipase activity and immunoreactive HSL protein in obese rats were lower than in control rats. However, when the HSL content was expressed per fat pad, the lipase activity and immunoreactive HSL protein in the obese rats were higher than in the control rats. Therefore we must pay careful attention to the way of presentation of adipose tissue enzyme contents.     

Hepatocyte nuclear factor (HNF)-4alpha induces expression of endothelial Fas ligand (FasL) to prevent cancer cell transmigration: a novel defense mechanism of endothelium against cancer metastasis.

Endothelial Fas ligand (FasL) contributes to the "immune privilege" of tissues such as testis and eye, in which apoptosis is induced in infiltrating Fas-positive activated T cells and results in the inhibition of leukocyte extravasation. In this study, we examined the role of endothelial FasL in controlling cancer cell transmigration using rat lung endothelial (RLE) cell line bearing a doxycycline-inducible hepatocyte nuclear factor (HNF)-4alpha expression system. We showed that a detectable level of FasL was expressed in RLE cells and that this expression was markedly up-regulated and well correlated to the degree of HNF-4alpha expression in a time-dependent manner. When various cancer cells were overlaid on an RLE monolayer sheet, we examined the ability of endothelial FasL to induce massive apoptosis in Fas-expressing cancer cells and found a causal link to inhibition of the transmigration. Finally, we showed that FasL was expressed in capillaries of the rat brain by immunohistochemical staining, suggesting that FasL serves its functions not only in vitro, but also in vivo. These results raise the possibility that HNF-4alpha is involved in regulating cancer cell transmigration by modulating the Fas-FasL system.     

Oxidative nucleotide damage: consequences and prevention

8-Oxoguanine (8-oxo-7,8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides with an almost equal efficiency, then transversion mutation ensues. MutT protein of Escherichia coli and related mammalian protein MTH1 specifically degrade 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorporation of 8-oxoguanine into DNA. The bacterial and mammalian enzymes are close in their size and share a highly conserved region consisting of 23 residues with 14 identical amino acids. Following saturation mutagenesis of this region, most of these residues proved to be essential to exert 8-oxo-dGTPase activity. Gene targeting was done to establish MTH1-deficient cell lines and mice for study. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1(-/-) mice, as compared with findings in wild-type mice. These proteins protect genetic information from untoward effects of threats of endogenous oxygen.     

Combination chemotherapy with carboplatin and etoposide for elderly patients aged 76 years or older with small cell lung cancer

Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin (AUC = 4 mg/ml.min, i.v. day 1) and etoposide (70 mg/m2 i.v. day 1-3) and 17 patients were evaluable. The median age of the study population was 77 years (range: 76-81). Eight patients had limited disease (LD) and nine did extensive disease (ED). The overall response rate was 88% for LD patients and 67% for ED patients. Median survival time was 219 days for LD patients and 158 days for ED patients. Grade 3 and 4 leukopenia, neutropenia, thrombocytopenia and anemia occurred in 41%, 76%, 24% and 6% of patients, respectively. There was one treatment-related death due to pneumonitis.