Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION: Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.

[Phenotypic detection and structure analysis of a PC missense mutation (Met406Ile) resulted in venous thromboembolism].

OBJECTIVE: To identify the phenotypic detection and structure analysis of a protein C (PC) missense mutation (Met406Ile) resulting in venous thromboembolism. METHODS: Pedigree research was performed for a hereditary PC deficiency pedigree. Chromogenic assay was used for phenotypic diagnosis to detect the AT activity. All 9 exons were amplified by polymerase chain reaction (PCR) and direct sequencing analysis was performed for PCR products. The corresponding mutation sites of family members were detected.Homology modeling was used for reconstructing mutant PC construction. The effects of construction change were analyzed. RESULTS: The PC activities of proband and 4 family members decreased to different extents by 29.7%, 42.2%, 42.4%, 67.3% and 70.7% respectively. Among them, the proband and other three family members carried the same mutation (c.1218G > A, Met406Ile) while another family member had a PC polymorphism (rs1799810). Homology modeling showed that VDW's interaction radius of amino acids decreased after mutation (Met406Ile).In particular, the radius of Gly418:C and Ile406CG2, Gly418:C and Ile406HG23, Leu419:N and Ile406:HG23 decreased to 2.0733å, 1.620 45å and 1.446 52å respectively. Compared with normal PC, the interaction energy of mutant PC rose from -8.504 54 to 1210.04 kal/mol. And the change of VDW interaction energy was significant. CONCLUSION: The mechanism of this pedigree is caused by PROC gene missense mutation on exon 9 (c.1218G > A, Met406Ile). The regional amino acids of mutant PC collide with each other and lead to an instability of PC reconstruction.

[Molecular mechanisms of antithrombin deficiency caused by novel double heterozygous mutations].

OBJECTIVE: To explore the molecular mechanisms of antithrombin (AT) deficiency caused by novel double heterozygous mutations. METHODS: Wild-type and mutant AT cDNA expression plasmids (ATwt, AT-c.134G > A, AT-c.342T > G, AT-c.134G > A and AT-c.342T > G) were transfected into HEK293T cells. Western blot was used to detect the AT:Ag in cell lysates. Homology was used to reestablish 3-D spatial structure of AT. Laser confocal assay was utilized to analyze the distribution of AT in endoplasmic reticulum (ER). RESULTS: Compared to the wild-types, the AT expression of HEK293T cells sharply increased when they were transfected by AT-c.342T > G or AT-c.134G > A and c.342T > G. Homology modeling showed that the mutation (AT-c.342T > G) caused a decreased distance between Arg and surrounding bases as Arg's side chain was significantly longer than Ser's. The mutation of 13th base pair decreases the distance between AT and heparin. Laser confocal assay showed that the AT protein concreted in HEK293T cells when they were transfected by mutant plasmids (AT-c.134G > A and c.342T > G) and aggregated in ER. CONCLUSIONS: The main molecular mechanism of AT deficiency in this pedigree is the disturbed AT secretion as a result of the mutation of AT-c.342T > G.

Endovenous laser ablation of great saphenous vein with ultrasound-guided perivenous tumescence: early and midterm results.

BACKGROUND: Endovenous laser ablation (EVLA) is an improved method to treat varicose great saphenous veins (GSV) with a high satisfactory rate. This study aimed to evaluate the efficiency and safety of treatment by EVLA procedures with ultrasound-guided perivenous tumescence. METHODS: Thirty-one patients (31 limbs) with symptomatic varicose vein primary to chronic venous insufficiency (CVI) treated with EVLA were prospectively studied. The entire procedure was performed under ultrasound-guided tumescent local anesthesia. The patients were evaluated with a 18 month follow-up postoperation using clinical examination and venous duplex ultrasonography. Pain scores and quality of life (QOL) were recorded using visual analog scale (VAS) and the chronic venous insufficiency questionnaire (CIVIQ) at 1 week, 1 month, and 12 months after operation. RESULTS: All patients tolerated EVLA procedure well. The overall success occlusion rates of GSV were 92%, 94%, and 94% at 1, 12, and 18 months follow-up, respectively. The score of CIVIQ one week preoperation was 69.14 ± 11.44 while that of CIVIQ one month postoperation was 85.32 ± 4.89. The life quality has significantly improved after the operation of EVLA (t = 12.71, P < 0.05). The VAS one month after treatment was lower than 1 week before therapy (t = 8.048, P < 0.05). Major complications such as deep vein thrombosis and skin burns were not found. Most of the complications were minor and improved quickly. CONCLUSIONS: This refinement type of EVLA procedure is a safe and effective treatment with a high satisfaction rate; it displayed noteworthy features including shortening hospitalization, early ambulant activity, and preferable occlusion rates.

[Effect of radiotherapy on the thyroid of patients with nasopharyngeal cancer].

OBJECTIVE: To determine the effect of radiotherapy on the thyroid of patients with nasopharyngeal cancer. METHODS: Thyroid dynamic imaging was performed on 51 patients with nasopharyngeal cancer who had the metastasis of the jugular lymph node before and after the radiotherapy. The peak time of the thyroid artery perfusion and the constant K were obtained. The levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in the blood serum were measured at the same time. RESULTS: The peak time of the left and right thyroid artery perfusion before the radiotherapy was (14.5+/-2.1)s and (15.1+/-1.9)s, respectively, while that after the radiotherapy was (19.3+/-3.2)s and (20.2+/-3.5)s, respectively. There was significant difference between the pre- and post-radiotherapy (P<0.001). The constant K of the left and right thyroid before the radiotherapy was significantly higher than that after the radiotherapy (0.0265+/-0.0074 vs. 0.0173+/-0.0062; 0.0249+/-0.0065 vs. 0.0167+/-0.0053, P<0.001, respectively). The level of FT3 and FT4 was significantly higher than that after the radiotherapy, but the TSH level had no obvious change[(4.76+/-0.95) pmol/L vs. (3.85+/-0.71) pmol/L,P<0.001; (18.63+/-3.84) pmol/L vs. (15.69+/-3.27) pmol/L,P<0.001; (1.17+/-0.52) mU/L vs. (1.22+/-0.76)mU/L ,P>0.05, respectively]. CONCLUSION: The peak time of the thyroid artery perfusion and the constant K which reflect blood stream status after the radiotherapy are all damaged in patients with nasopharyngeal cancer. The level of FT3 and FT4 in the blood serum is dropped but the TSH level has no obvious change.

[Relevant factors of nm23 protein expression and dangerous factors of bone metastasis in breast cancer].

OBJECTIVE: To investigate the relevant factors of the expression of nm23 protein and the dangerous factors of bone metastasis in breast cancer. METHODS: Seventy-six breast cancer patients confirmed by histological examination after surgeries were enrolled in this study. nm23 protein expressions in original breast cancer tissues were detected by immunohistochemical procedures. The relevant factors of nm23 protein expression and the dangerous factors of bone metastasis were conducted logistic regression analysis. RESULTS: Among the 58 breast cancer patients who did not have bone metastasis in the observation period, 55 did not have bone metastasis;while the other 18 breast cancer patients having bone metastasis were confirmed in only 14 patients. The correction was 94.83% and 77.78% respectively. The general correction was 90.79%. CONCLUSION: The detection of nm23 protein is helpful to evaluate prognosis and improve the therapy. It is one of the important methods to instruct the breast cancer patients to perform radio-nuclide imaging in the follow-up.

[99mTc-MIBI myocardial perfusion tomography for monitoring the anthracycline cardiotoxicity].

OBJECTIVE: To investigate the value of 99mTc-MIBI myocardial perfusion tomography monitoring the cardiotoxicity induced by anthracycline. METHODS: Twenty-three patients with anthracycline chemotherapy were examined by electrocardiogram (ECG), myocardial enzyme (CK-MB), nuclear angiography for detecting left ventricular ejection fraction (LVEF) and 99mTc-MIBI myocardial perfusion tomography for detecting myocardial relative quantity (MRQ). These examinations were repeated after every chemotherapy. RESULTS: The MRQ after one period of anthracycline chemotherapy was significantly lower than the pretherapy in 23 patients (P < 0.01). The MRQ significantly decreased after one period of chemotherapy in 11 patients treated by pirarubicin, in 6 by epirubicin, and 6 by mitoxantrone (P < 0.05). There was not significant change in the mean value of ECG and CK-MB after one period of chemotherapy (P > 0.05). After multiple-period anthracycline chemotherapy in 10 patients, a decrease was observed in MRQ (P < 0.01). There was not significant difference in MRQ between multiple periods and one period therapy (P > 0.05) and in LVEF in the period before and after multiple-period chemotherapy (P > 0.05). CONCLUSION: 99mTc-MIBI myocardial perfusion tomography can monitor the anthracycline cardiotoxicity and its changes are earlier than LVEF's. 99mTC-MIBI myocardial perfusion tomography may be helpful to the clinical treatment for anthracycline.

[Application of rCBF imaging in PD, AD and OPCA].

OBJECTIVE: To evaluate the diagnosis and differential diagnosis of rCBF imaging in Parkison's disease (PD), Alzheimer's disease (AD) and olivopontocerebellar atrophy (OPCA). METHODS: The characteristics of the radioactive distribution of rCBF imaging in PD, AD and OPCA were analyzed, and the laws of the radioactive distribution were identified. RESULTS: The sensitivity of rCBF imaging in PD, AD and OPCA was 88.4% (38/43), 95.8% (23/24), and 85.7% (30/35) respectively. The characteristics of the radioactive distribution were that the radioactivity decreased in the cerebral cortex (25/43), basal nuclei (21/43) and thalamus (18/43) in PD, that the radioactivity decreased in the bilateral cerebral cortex (17/24) in AD, that the radioactivity decreased in the cerebral cortex (17/35), cerebellum (14/35), basal nuclei (14/35) and thalamus (10/35) in OPCA. CONCLUSION: rCBF imaging could sensitively diagnose PD, AD and OPCA, and also could differentially diagnose them according to their different characteristics of the radioactive distribution.

[Application of SPECT bone scan for multiple myeloma].

OBJECTIVE: To study the diagnostic value of SPECT for multiple myeloma (MM). METHODS: Single photon emission computed tomography (SPECT) bone scan, marrow puncturing, x-ray and other related examinations were performed in 46 patients with MM. We analysed the diagnostic value of SPECT bone scan combined with marrow puncturing and other examinations for MM. Some patients were examined with SPECT bone scan in order to estimate the efficacy of MM. RESULTS: SPECT bone scan images of 44 patients were abnormal in the 46 patients with MM. The masculine rate was 95.6%. In most of the patients, there was multiple abnormal osseous metabolism in the whole body, especially in the spine, double ribs, and pelvis. We observed the efficacy of 2 patients with SPECT bone scan. After the therapy, SPECT bone scan was performed again in 1 patient, and the image showed that the range of abnormal osseous metabolism was reduced; SPECT bone scan was performed again in the other patient, and the abnormal range was found to have increased obviously. CONCLUSION: SPECT bone scan is one of the important assistant examination methods for MM. Its sensitivity is high. The nuclear medical diagnoses should be combined with clinical documents. SPECT bone scan might be available for monitoring the efficacy of MM.