Low-intensity resistance training after high-intensity resistance training can prevent the increase of central arterial stiffness.

Although high-intensity resistance training increases arterial stiffness, low-intensity resistance training reduces arterial stiffness. The present study investigates the effect of low-intensity resistance training before and after high-intensity resistance training on arterial stiffness. 30 young healthy subjects were randomly assigned to a group that performed low-intensity resistance training before high-intensity resistance training (BLRT, n=10), a group that performed low-intensity resistance training after high-intensity resistance training (ALRT, n=10) and a sedentary control group (n=10). The BLRT and ALRT groups performed resistance training at 80% and 50% of one repetition maximum twice each week for 10 wk. Arterial stiffness was measured using carotid-femoral and femoral-ankle pulse wave velocity (PWV). One-repetition maximum strength in the both ALRT and BLRT significantly increased after the intervention (P<0.05 to P<0.01). Both carotid-femoral PWV and femoral-ankle PWV after combined training in the ALRT group did not change from before training. In contrast, carotid-femoral PWV after combined training in the BLRT group increased from before training (P <0.05). Femoral-ankle PWV after combined training in the both BLRT and ALRT groups did not change from before training. These results suggest that although arterial stiffness is increased by low-intensity resistance training before high-intensity resistance training, performing low-intensity resistance training thereafter can prevent the increase of arterial stiffness.

Effects of eccentric and concentric resistance training on arterial stiffness.

It has been suggested that resistance training (RT) increases arterial stiffness. The purpose of the present study was to clarify the effect of eccentric RT (ERT) and concentric RT (CRT) on arterial stiffness in female adults by an interventional study. In total, 29 healthy female subjects were randomly assigned to either the ERT group (n=10), CRT group (n=10) or sedentary (SED) group (n=9). The ERT and CRT groups performed resistance training three times a week for 8 weeks. We determined brachial blood pressure, brachial-ankle pulse wave velocity (baPWV), carotid artery intimamedial thickness (IMT) and carotid arterial lumen diameter before and after training and after detraining. The before-training baPWV did not differ significantly among the three groups. After 8 weeks of RT, arterial stiffness in the CRT group was increased compared with the ERT and SED group (P<0.05). However, brachial blood pressure, baPWV, carotid IMT and carotid lumen diameter in the ERT and CRT groups were unchanged by RT for 8 weeks. Consequently, it was clarified that arterial stiffness was not changed by ERT for 8 weeks. This suggests that ERT may be effective as an exercise prescription for middle-aged and elderly adults.

Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation.

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation of a number of proteins, which leads to a cascade of biochemical changes that initiates B cell proliferation and differentiation or growth inhibition. A novel cDNA, designed APS, encoding an adaptor protein with a Pleckstrin homology (PH) domain, Src homology 2 (SH2) domain, and a tyrosine phosphorylation site was cloned from a B cell cDNA library using a yeast two hybrid system. APS is structurally similar to SH2-B, an SH2 protein that potentially binds to the immunoreceptor tyrosine-based activation motif (ITAM) as well as Lnk which is postulated to be a signal transducer that links T-cell receptor to phospholipase Cgamma, Grb2 and phosphatidylinositol 3-kinase. APS expressed only in human Burkitt's lymphoma cells among cell lines we examined and tyrosine phosphorylated in response to BCR stimulation. APS bound to Shc irrespective of stimulation and bound to Grb2 after stimulation, suggesting that it plays a role in linkage from BCR to Shc/Grb2 pathway. These results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune receptors to signaling pathways involved in tyrosine-phosphorylation.

CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells.

We have reported JAK-signaling modulators, CIS1 (cytokine-inducible SH2 protein-1), CIS3 and JAB (JAK2 binding protein), which are structurally related. In M1 myeloid leukemia cells, CIS3 was induced by neither interleukin 6 (IL6) nor interferon gamma (IFNgamma), while JAB was induced strongly by IFNgamma and slightly by IL6 and leukemia inhibitory factor (ILF). Forced expression of CIS3 and JAB in M1 cells prevented IL6- or LIF-induced growth arrest and differentiation, even when their expression levels were comparable to endogenous ones in several cell lines such as HEL, UT-7, IFNgamma-treated M1, and CTLL2 cells. Pretreatment of parental M1 cells with IFNgamma but not IFNbeta resulted in suppression of LIF-induced STAT3 activation and differentiation, further supporting that physiological level of JAB is sufficient to inhibit LIF-signaling. However, unlike JAB, CIS3 did not inhibit IFNgamma-induced growth arrest, suggesting a difference in cytokine specificity between CIS3 and JAB. CIS3 inhibited STAT3 activation with slower kinetics than JAB and allowed rapid c-fos induction and partial FcgammaRI expression in response to IL6. In 293 cells, CIS3 as well as JAB bound to JAK2 tyrosine kinase domain (JH1), and inhibited its kinase activity, however, the effect of CIS3 on tyrosine kinase activity was weaker than that of JAB, indicating that CIS3 possesses lower affinity to JAK kinases than JAB. These findings suggest that CIS3 is a weaker inhibitor than JAB against JAK signaling, and JAB and CIS3 possess different regulatory roles in cytokine signaling.

Expression of hepatocyte growth factor and transforming growth factor beta 1 mRNA in P. acnes and lipopolysaccharide-treated rats.

Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, triggers hepatocyte regeneration after partial hepatectomy and acute liver cell necrosis induced by chemicals. In contrast, transforming growth factor beta 1 inhibits hepatocyte proliferation in vitro and suppresses liver regeneration in vivo. We assessed the expression of HGF and TGF beta 1 mRNA in an endotoxin-related hepatic cell necrosis model. Intravenous injection of Gram-negative lipopolysaccharide (LPS) into rats previously given heat-killed Propionibacterium acnes induced endotoxin-related hepatic cell necrosis. In this model, serum ALT began to rise to more than 100IU as early as 3 h after LPS injection, reaching 300IU 12h after injection. HGF mRNA levels in the liver did not increase significantly until 5h after LPS injection; at 12h, they had increased about threefold compared with controls. TGF beta 1 mRNA expression increased threefold after P. acnes treatment alone and increased further after LPS injection. In the spleen, HGF mRNA levels increased within 3h, but in the lung no increase in HGF mRNA was observed. Early elevation of liver TGF beta 1 mRNA levels and delayed elevation of HGF mRNA levels, with low expression of HGF in the lung, may play a role in the pathogenesis of endotoxin-related hepatic necrosis.

Augmenter of liver regeneration (ALR) may promote liver regeneration by reducing natural killer (NK) cell activity in human liver diseases.

Cytotoxicity of liver natural killer cells against regenerating hepatocytes has been reported as a possible mechanism of regeneration failure in fulminant hepatitis. An augmenter of liver regeneration (ALR) inhibits liver natural killer cell activity in rats. In this study, we measured hepatic expression of ALR mRNA, blood levels of ALR, and peripheral blood natural killer cell activity in patients with various types of acute liver disease to investigate the relationship between failure of liver regeneration and hepatic natural killer cells. Hepatic ALR mRNA expression was higher in liver disease patients than in non-liver disease controls, and a correlation was found between serum ALR values and hepatic levels of ALR mRNA. In acute liver injury, the serum ALR level also showed a negative correlation with NK activity. ALR was produced by and released from the liver at the time of hepatic injury. Our findings suggest that ALR may protect against failure of regeneration by inhibition of hepatic natural killer cell activity in acute liver injury.

Fulminant hepatitis complicated by small intestine infection and massive hemorrhage.

A 34-year-old man diagnosed with fulminant hepatitis, caused by hepatitis B virus, and acute renal failure was referred to our hospital. After admission to the intensive care unit, the liver and renal failure were ameliorated. Melena requiring transfusion occurred during the course of his illness. Endoscopic examination demonstrated pseudomembranes, erosions, ulcers, and hemorrhage in the duodenum, the upper jejunum, and the terminal ileum, suggesting widespread lesions throughout the small intestine. Pseudomonas putida, Xanthomonas maltophilia, and Candida glabrata were cultured from ileal fluid. Candida glabrata was also detected in sputum, feces, and on an intravenous catheter tip. The patient was treated with amphotericin B and miconazole. The melena was ameliorated, but inflammation of the small intestine persisted. Although we had difficulty in treating the enteritis, the patient survived, and 1 year later colonoscopic examination demonstrated no abnormalities. The small intestine is a difficult site to examine, but endoscopic examination of this site is important when massive hemorrhage develops.

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation.

Fulminant hepatic failure (FHF) usually has a fatal prognosis without liver transplantation. We describe the case of a woman who developed FHF, and was evaluated as a candidate for liver transplantation, but who was cured without transplantation through intensive medical care that included glucagon-insulin therapy, methylprednisolone pulse therapy, interferon beta and lamivudine administration, cyclosporine administration, and high-volume hemodiafiltration and plasma exchange. In a patient with FHF who is a candidate for liver transplantation but for whom the transplantation cannot be performed for some reason, intensive medical therapy, including regeneration-promoting therapy, immunosuppressive therapy, antiviral therapy, and vigorous hepatic support, should be carried out.

Changes of vinculin and extracellular matrix components following blunt trauma to rat skeletal muscle.

The purpose of the present study was to determine changes in the localization of vinculin, Type IV collagen, laminin, and fibronectin during the damage-repair process in the skeletal muscle over several days following acute blunt trauma. A single blunt trauma to the gastrocnemius muscle of the rat was induced by applying 1.57 J of kinetic energy to one leg. By day 2 after trauma, vinculin had disappeared rapidly from the intracellular submembraneous region corresponding to the costamere, whereas Type IV collagen and laminin persisted around the degenerating myofibers (corresponding to the basement membrane). Fibronectin could be observed filling the widened endomysium and in the ruptured myofibers. In the early phase of muscle regeneration (day 5 after trauma), newly synthesized vinculin, Type IV collagen, and laminin formed ring-like structures around the regenerating myotubes. Fibronectin could also be observed filling the widened endomysium around the regenerating myotubes. Further, when small newly formed or splitted myofibers were observed in the areas of regenerating myofibers (day 10 after trauma), vinculin, Type IV collagen, laminin, and fibronectin were localized in specialized regions corresponding to the costamere, basement membrane, and endomysium. These results demonstrated that restoration of the costamere, basement membrane, and endomysium are essential to the maturation of regenerating myofibers after injury.

Theoretical studies on capillary microviscometry of skeletal muscle actin.

For improving Ostwald's viscometry, which is time-consuming and requires a relatively large volume of specimen to determine viscosity, we developed a capillary microviscometric method with an appropriate mathematical model, and have compared this method with Ostwald's method.

Purification and partial amino acid sequences of the binding protein from Bombyx mori for CryIAa delta-endotoxin of Bacillus thuringiensis.

The binding protein for Bacillus thuringiensis delta-endotoxin, CryIAa, from the brush border membrane of the midgut of Bombyx mori was purified by the dot blot method and delta-endotoxin affinity chromatography. The binding protein was purified to 235-fold enrichment from cholic acid extracts of brush border membranes from B. mori midgut by activated CryIAa-affinity chromatography and DEAE ion-exchange chromatography. The purified binding protein showed a single band of 180 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and this band specifically reacted to 125I-labeled CryIAa on Immobilon membrane. The affinity of the binding protein for CryIAa was equivalent to that of the brush border membrane vesicles and solubilized membrane proteins. Partial amino acid sequences of the binding protein showed sequence similarity to the cadherin-like binding protein for CryIAb from Manduca sexta, but not for CryIAc binding protein from M. sexta and Heliothis virescens.

[Effects of a warning signal on heart rate and 17-hydroxycorticosteroid in urine (author's transl)].

The purpose of this study was to test whether a warning signal given prior to an unpleasant stimulus would influence heart rate (HR) and 17-Hydroxycorticosteroid in urine (17-OHCS). The results for HR were as follows: (a) In the anticipation period, subjects given no warning signal (NS group) showed higher degree in their HR than that of those given a warning signal (S group), (b) On at impact, a warning signal tended to decrease subjects' HR when an unpleasant stimulus was given, (c) In the recovery period, subject group indicated lower degree in their HR than that of NS group, and (d) Subject group showed more adaptation by repeated trials to an unpleasant stimulus in their HR. However, as for urinary 17-OHC, nosignificant difference was observed.

Effects of muscle contraction timing during resistance training on vascular function.

Muscle contractions in normal resistance training are performed by eccentric (ECC, lowering phase) and concentric (CON, lifting phase) muscle contractions. However, the difference in effects of timing of muscle contraction during resistance training on arterial stiffness is unknown. This study investigated the effect of muscle contraction timing during resistance training on vascular function in healthy young adults. Thirty healthy men were randomly assigned to group of resistance training with quick lifting and slow lowering (ERT, n=10), group of resistance training with slow lifting and quick lowering (CRT, n=10) and sedentary groups (SED, n=10). The ERT and CRT groups underwent two supervised resistance-training sessions per week for 10 weeks. The ERT group performed the on set of 8-10 repetitions with 3 s ECC and 1 s CON muscle contractions. In contrast, the CRT group performed the on set of 8-10 repetitions with 1 s ECC and 3 s CON muscle contractions. Brachial-ankle pulse wave velocity (baPWV) after ERT did not change from baseline. In contrast, baPWV after CRT increased from baseline (from 1049+/-37 to 1153+/-30 cm s(-1), P<0.05). No significant changes in flow-mediated dilation were observed in the ERT and CRT groups. These values did not change in the SED group. These findings suggest that although both training does not deteriorate a vascular endothelial function, resistance training with quick lifting and slow lowering (that is, ERT) prevent the stiffening of arterial stiffness.

The expression patterns of Pax7 in satellite cells during overload-induced rat adult skeletal muscle hypertrophy.

AIM: Activated satellite cells (SCs) have the ability to reacquire a quiescent, undifferentiated state. Pax7 plays a crucial role in allowing activated SCs to undergo self-renewal. Because the increase in the SC population is induced during overload-induced skeletal muscle hypertrophy, it is possible that Pax7-regulated SC self-renewal is involved in the modulation of the SC population during the functional overload of skeletal muscles. However, the characteristics of the expression patterns of Pax7 in SCs during the functional overload of adult skeletal muscles are poorly understood. METHODS: Using immunohistochemical approaches, we examined the temporal and spatial expression patterns of Pax7 expressed in SCs during the functional overloading of rat skeletal muscles. RESULTS: The time course of Pax7 expression in SCs was similar to that of the expression of the differentiation regulatory factor myogenin during the early stage of functional overload. However, the percentage of SCs that expressed Pax7 was markedly higher than that of the SCs that expressed myogenin. Coexpression of Pax7 and myogenin was not detected in SCs. In addition, the expression of cyclin-dependent kinase inhibitor p21, which regulates cell cycle arrest and differentiation, was not detected in Pax7-positive SCs. CONCLUSION: These results suggest that Pax7-regulated self-renewal of SCs may be induced during the early stage of functional overload and may contribute to modulating the SC population in hypertrophied muscles. Furthermore, it was suggested that the numbers of SCs which underwent self-renewal may be higher than that of SCs which were provided as the additional myonuclei for hypertrophying myofibres.

Localization of MyoD, myogenin and cell cycle regulatory factors in hypertrophying rat skeletal muscles.

AIM: MyoD, myogenin, proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase inhibitor p21 (p21) proteins are key molecules in inducing the growth of myogenic cells in vitro. However, it has not been determined which cell types express these factors in hypertrophying skeletal muscles in vivo. METHODS: Using immunohistochemical techniques, we examined the spatial and temporal expression patterns of MyoD, myogenin, PCNA and p21 proteins in functionally overloaded rat plantaris muscles induced by ablation of the soleus and gastrocnemius muscles. RESULTS: MyoD and myogenin were detected in myonuclei located inside the dystrophin-positive plasma membrane of myofibres, m-cadherin-positive satellite cell nuclei and nuclei located in the interstitial spaces between myofibres on days 1, 3, 5 and 7 post-surgery. Entry of satellite cells into the cell cycle was indicated by the expression of PCNA on day 3 post-surgery, and withdrawal from the cell cycle was observed by the expression of p21 in satellite cell nuclei on day 5 post-surgery. However, the expression of both PCNA and p21 in satellite cell nuclei disappeared on day 7 post-surgery. CONCLUSION: These results indicate that proliferated satellite cell-derived myoblasts and undefined myogenic cells located in the interstitial spaces may contribute to an increase in myonuclear number and/or hyperplasia. Furthermore, we provide evidence that all of myonuclei, satellite cells and undefined myogenic cells express both MyoD and myogenin proteins. These results suggest that continual expression of MyoD and myogenin proteins in these cells is an essential molecular event which induces the successful hypertrophy of skeletal muscles.