Fatigue occurs when the interval of intermittent tetanic contraction of skeletal muscle is shortened to a certain degree and the contractile tension declines. After fatigue, prolongation of the contraction interval can make the contractile tension recover. In atrophic soleus, the recovery rate is slower. It has been shown that a decrease in the contractile tension is caused by the inhibition of the myofibrils and sarcoplasmic reticulum Ca(2+) release channels during fatigue. So the mechanism of the recovery of contractile tension is the recovery of the inhibited myofibrils and sarcoplasmic reticulum Ca(2+) release channels. But how the inhibition affects the recovery course is still unclear. To specify the factors modulating the recovery rate after intermittent tetanic fatigue in soleus, and to seek the reasons for the decrease in recovery rate in atrophic soleus, we observed the recovery time course of different types of fatigue in isolated soleus muscle strips. The 10% or 50% decrease in the maximal tetanic contractile tention (P(0)) was defined respectively as slight or moderate fatigue. After short-term (S10P, 10 s) and long-term (L10P, 300 s) slight fatigue, the tetanic contractile tension recovered to nearly 100% P(0) at the 20th minute. In both slight fatigue groups, perfusion with 10 mumol/L of ruthenium red (an inhibitor of Ca(2+) release channels in sarcoplasmic reticulum) slowed down the recovery rate. It was suggested that slight fatigue only induced inhibition of myofibrils. After short-term (S50P, 60 s) or long-term (L50P, 300 s) moderate fatigue, the tetanic contractile tension at the 20th minute recovered to about 95% P(0) in S50P group and 90% P(0) in L50P group, respectively. The recovery rate in L50P group was significantly lower than that in S50P group. So the recovery rate after moderate fatigue was related to the tetanic contraction duration. In both moderate fatigue groups, perfusion with 5 mmol/L of caffeine (an opener of Ca(2+) release channels in sarcoplasmic reticulum) resulted in nearly 100% recovery at the 5th minute. It was suggested that moderate fatigue induced inhibition of myofibrils and sarcoplasmic reticulum Ca(2+) release channels. In 1-week tail-suspended rats, soleus muscles showed a 40% of atrophy. After slight fatigue, the tetanic contractile tension in unloaded soleus recovered to 94% P(0) in S10P group and 95% P(0) in L10P. After moderate fatigue, the tetanic contractile tension in unloaded soleus recovered to 92% P(0) in S50P and 84% P(0) in L50P at the 20th minute. There were significant decreases in all of the fatigue groups as compared with the control groups. These results suggest that both slight and moderate fatigue inhibit the myofibrils and sarcoplasmic reticulum Ca(2+) release channels in 1-week unloaded soleus, so the recovery rate after tetanic fatigue is slower than that in the control group.
Animals ; Caffeine ; pharmacology ; Calcium ; metabolism ; Hindlimb Suspension ; Male ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; pathology ; physiopathology ; Muscular Atrophy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Ruthenium Red ; pharmacology ; Ryanodine Receptor Calcium Release Channel ; physiology

BACKGROUNDThe induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.

METHODSThe model of rat orthotopic liver transplantation was established by modified Kamada's technique. Recipients were divided into group A (control group): SD-->SD; group B (group of rejection): SD-->Wistar without any treatment; group C: SD-->Wistar with CsA monotherapy from day 1 to day 5; and group D: SD-->Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.

RESULTSThe survival period of recipients in groups A (> 60 days) and D (> 60 days) was significantly longer than that in group B (13.8 +/- 2.4 days). The serum levels of interleukin 2 (IL-2) and interferon gamma in group B were significantly higher than those in other groups; the level of tumor necrosis factor alpha was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P < 0.05).

CONCLUSIONSCombined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.

Animals ; Antibodies, Monoclonal ; therapeutic use ; CD40 Ligand ; antagonists & inhibitors ; Cyclosporine ; therapeutic use ; Cytokines ; blood ; Enzyme-Linked Immunosorbent Assay ; Graft Survival ; Immunosuppressive Agents ; therapeutic use ; Liver Transplantation ; Male ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVEMuscle contraction may prompt glucose uptake through non-insulin-dependent ways, and it may be due to the enhanced activation of key proteins known to regulate glucose metabolism, like p38 and Akt. Our experiment focused on the impact of different contraction modes on the phosphorylation of the molecules, thus to explore effective ways to lower blood glucose.

METHODSIsolated muscle strips perfusion technique and Western blot analysis were employed to investigate the influence of different modes of contraction on the activation of the molecules.

RESULTSMuscle contraction led to an increase in p38 phosphorylation, with the greatest effect observed after 5 minutes of 10% DC (duty cycle) contraction and 5 minutes of 1% DC contraction. However, phosphorylation of Akt were not altered by the two contraction modes.

CONCLUSIONThe level of phosphorylation of p38 was higher at the optimal contraction modes, but these modes could not increase the level of phosphorlation of Akt.

Animals ; Glucose ; metabolism ; In Vitro Techniques ; Male ; Muscle Contraction ; physiology ; Muscle, Skeletal ; physiology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Physical Conditioning, Animal ; physiology ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors.

METHODSA search of studies in PubMed and MedLine (from 1999 to 2008) was performed to assess the effect of c-kit mutation on the prognosis of gastrointestinal stromal tumors. The articles were retrieved with the entries of "gastrointestinal stromal tumors", "imatinib", "c-kit" and "mutation". A meta-analysis was performed to assess the data included.

RESULTSA total of 15 articles were collected in this analysis. No significant differences was found in incidence of mitoses (> 5/50 HPF) between the patients with wild type c-kit (wild type group) and the ones with mutated c-kit (mutation group) (P = 0.710); tumor recurrence and metastasis rate after surgery was significant higher in the mutation group than that in wild type group (P = 0.010); as for imatinib response with different c-kit mutation types, the results showed the incidence of clinical response (complete response + partial response) was significantly higher in mutation group than that in wild type group (P = 0.009), but the imatinib resistance rate was lower in mutation group (P = 0.000); three studies provided data for imatinib resistance with c-kit second mutations, the results showed the second mutations mainly focus on exon 13, 14, 17.

CONCLUSIONSC-kit mutation is related closely with the incidence of recurrence and metastasis in GIST after surgery. The mutations of c-kit influences the therapeutic effects of imatinib.

Antineoplastic Agents ; therapeutic use ; Benzamides ; Case-Control Studies ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; Mutation ; Piperazines ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; therapeutic use

OBJECTIVETo study the clinical feature of a Chinese family with muscle-eye-brain disease (MEB) and the mutation of protein O-linked-mannose beta-1, 2-N-acetylglucosaminyltransferase 1 gene (POMGNT1).

METHODSClinical data of the proband and his family members were collected. Genomic DNA from the patient and his parents was extracted using standard procedures from the peripheral blood leukocytes. Polymerase chain reaction and DNA direct sequencing were employed to analyze all of the exons to determine the mutation, and the relationship between genotype and phenotype was analyzed.

RESULTSThe proband was diagnosed as floppy baby, presented with delayed psychomotor development and myopathic face. His serum creatine kinase (CK) level elevated moderately and brain MRI showed cerebral and cerebellar gyrus abnormalities with white matter signal intensity changes, cerebellar cysts and cerebellar and brain stem hypoplasia, consistent with congenital muscular dystrophy with eye brain disorder. Further test with DNA detected a compound heterozygous mutation of c.1896 1 G to C before exon 22 which may induce splicing error, and missense mutation c.1319T to G, p.L440R in exon 16. Both parents had a heterozygous mutation at the mutation sites.

CONCLUSIONAccording to our study, the family is diagnosed as MEB. The proband carried compound heterozygous mutations in the POMGNT1 gene, and his parents are heterozygous carriers, which is consistent with autosomal recessive inheritance. The child is definitely diagnosed as having muscle eye brain disease.

Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; Base Sequence ; Brain ; pathology ; Child, Preschool ; Exons ; genetics ; Female ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Male ; Molecular Sequence Data ; Mutation ; genetics ; N-Acetylglucosaminyltransferases ; genetics ; Phenotype ; Sequence Alignment ; Walker-Warburg Syndrome ; diagnosis ; genetics

OBJECTIVETo investigate the clinical pathological characteristics and prognosis of gastrointestinal stromal tumors (GISTs).

METHODSOne hundred and seven cases, admitted to our hospital from Apr. 1996 to Oct. 2005, were detected by Envision immunohistochemical method and diagnosed as GISTs. Their pathological features, immunohistochemical phenotypes, clinical manifestations and imaging findings were analyzed.

RESULTSOf the 107 GISTs, 107 cases were positive for vimentin (107/107, 100%), 107 cases were positive for CD117 (107/107, 100%), 89 cases were positive for CD34 (89/107, 83.2%), 14 cases were positive for SMA (14/107, 13.1%), 10 cases were positive for desmin (10/107, 9.3%), 22 cases were positive for S-100 (22/87, 20.6%) and 15 cases were positive for NSE (15/107, 14.0%). Among all the GISTs, 73 cases occurred in stomach (68.2%), 28 in small intestine (26.2%), 1 in colon (0.9%) and 5 occurred in other position including mesentery, omentum, and retroperitoneum (4.7%). Fifteen cases were diagnosed as very low grade (14.0%), 25 cases as low grade (23.4%), 33 cases as low malignancy (30.8%) and 34 cases as high malignancy (31.8%). The follow-up was obtained successfully in 89 cases (83.2%). Fourteen cases (13.1%) were confirmed to have recurrences or metastases by review and medical records.

CONCLUSIONSThe diagnosis of GIST depends on pathological observation and immunohistochemical study. CD117 is a sensitive marker for the diagnosis of GIST. Surgical resection is the choice for treating GIST. Extended resection, even combined resection of involved organs, is required for malignant GIST.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; surgery ; Humans ; Immunohistochemistry ; Male ; Middle Aged

Objective To realize the high-efficient capture of circulating tumor cells (CTCs) in the blood of tumor patients by analytic modeling and optimization on the herringbone micro-fluidic chip. Methods By simulating the fluid flow within the herringbone chip with Fluent 15.0 and calculating the capture efficiency with MATLAB to understand how geometric parameters (the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height), flow rates and flow directions (forward flow, reverse flow) affected the cell-surface contact for capture of the CTCs, the capture efficiency was predicted and then validated by experiments. Results The herringbone micro-fluidic chip could achieve the optimal capture rate when the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height were 75, 125, 70 and 30 μm, respectively, at a flow rate of 1 mL/h with forward direction. Conclusions In this study, cell capture in different micro-fluidic chips was simulated by the method of computational fluid dynamics. The statistic model of capture efficiency is established by MATLAB and optimized to quickly screen a group of physical parameters for high-efficient cell capture. These optimized micro-fluid chip parameters are validated by experiment, which can realize the high-efficient capture of CTCs.

OBJECTIVETo study the clinical and pathologic features of tumors and tumor-like lesions in the bones of hands and feet.

METHODSClinical, X-ray and pathologic features of 154 cases of tumors and tumor-like lesions in the bones of hands and feet between 1991 and 2002 were investigated.

RESULTSIn the bones of hands and feet the frequency and distribution of many lesions were distinctive when compared to those of other skeletal sites. Cartilaginous lesions were most common (60%), and 72% of them were enchondromas. Enchondromas were most often situated in the second to fifth phalanges and metacarpal bones. Chondroblastomas most frequently involved the irregular bones (such as calcaneus, talus and osnaviculare) of the feet. Whereas the occurance of osteochondromas in the bones of the hands and feet was lower than in the long bones. Most "osteochondromas" of the phalanges were subungual exostoses. A group of reactive or reparative lesions, which are related to trauma, such as subungual exostosis, giant cell reparative granuloma, florid reactive periostitis and bizarre parosteal osteochondromatous proliferations typically occurred in the bones of the hands and feet, but these tumor-like lesions were often misdiagnosted. Another feature of lesions in the bones of the hands and feet was that there were much more benign than malignant lesions (21:1), and that chondrosarcomas were common in malignancies. The diagnostic criteria for benign and malignant cartilaginous tumors in the bones of hands and feet were different from those in long bones and flat bones.

CONCLUSIONSBone tumors of the hands and feet are different from that of long bones, flat bones and axial bones. Because the hands and feet are frequently exposed to trauma, reactive and reparative lesions often occur in these sites. These tumor-like lesions may simulate benign and malignant neoplasia. Knowledge of different types of lesions which commonly affect these sites is of benefit in assessing lesions of the bones of hands and feet.

Bone Neoplasms ; pathology ; Cartilage ; pathology ; Chondroblastoma ; pathology ; Chondroma ; pathology ; Chondrosarcoma ; pathology ; Foot ; Hand ; Humans ; Osteochondroma ; pathology

Using two-kidney one-clip renal hypertensive (2K1C group), stress-induced hypertensive (neural group), DOCA-salt treated hypertensive (DOCA group) and spontaneously hypertensive rats (SHR group), to investigate the change in AT(1A)-receptor autoantibodies (AT(1A)-AAs) during the development of the four types of hypertension. The biological activities of AT(1A)-AAs were examined. It was shown that the frequency of occurrence and titres of AT(1A)-AAs increased significantly during the development of hypertension. In the four hypertensive groups studied, the occurrence of AT(1A)-AAs was most prominent in SHR, 2K1C and neural groups. The biological effects of AT(1A)-AAs were shown to increase the beating frequency of cultured neonatal myocardial and vascular contractile tension. It is suggested that autoimmune mechanisms are involved the pathogenesis of different types of hypertension and the AT(1A)-AAs may be one of the mechanisms leading to cardiac hypertrophy.
Animals ; Autoantibodies ; blood ; Desoxycorticosterone ; administration & dosage ; Hypertension ; classification ; etiology ; immunology ; physiopathology ; Hypertension, Renovascular ; immunology ; physiopathology ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; immunology ; Stress, Physiological ; physiology

The troponin I subunit (TnI) was used as a molecular marker to explore the relationship between the resting intracellular Ca(2+) concentration and myofibril degradation in muscle fibers. The isolated soleus muscle strips of rats were treated by caffeine and H2O2. Caffeine is an opener to increase the calcium release channel open probability of sarcoplasmic reticulum (SR) in contraction phase. H2O2 induces a calcium leak of SR calcium release channel in relaxation phase. The expression and degradation of TnI were detected by Western blot. The resting tension of tetanic contraction and expression of TnI were not changed, but the developed tension was lowered in isolated soleus muscle strips during 40 min of calcium-free Krebs perfusion. Low concentrations of caffeine (1 and 5 mmol/L) perfusion induced a transient increase in resting tension during fatigue period, but did not alter the extent of fatigue, recovery rate after fatigue and expression of TnI in muscle strips. High concentration of caffeine (10 mmol/L) perfusion induced a progressive increase in resting tension, a higher rate of fatigue and a decrease in recovery rate after fatigue in muscle strips. There was a detectable degradation of TnI in soleus after 10 mmol/L caffeine treatment. H2O2 perfusion facilitated a progressive increase in resting tension in a dose-dependent manner, but did not influence the fatigue rate of tetanic contraction. The recovery rate after fatigue showed a quick resumption before decline during H2O2 perfusion. Degradation of TnI occurred in 5 and 10 mmol/L H2O2-treated soleus muscles. Since resting tension is dependent on intracellular Ca(2+) concentration, the above-mentioned results suggest that SR Ca(2+) leakage in relaxation phase may induce a degradation of TnI in skeletal muscle fibers.
Animals ; Caffeine ; pharmacology ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Hydrogen Peroxide ; pharmacology ; In Vitro Techniques ; Muscle Fibers, Skeletal ; metabolism ; Rats ; Sarcoplasmic Reticulum ; pathology ; Troponin I ; metabolism