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This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents.Cross-sectional study.Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11-19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms.The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%).Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms.

Time-series and case-crossover are two main study designs in environmental epidemiology. However, due to the differences in design principles and model construction between the two analyses, the results of the two analyses may not be consistent. Herein, we examined the short-term effect of cold spells on cardiovascular mortality in Nanjing using both time series and case-crossover analyses, aiming to provide a basis for the selection of appropriate research design in environmental epidemiology.时间序列和病例交叉是环境流行病学研究常用的两种方法，由于两种方法在设计原理和模型构建等方面存在差异，所得出的结论可能并不完全一致。本文以南京市气象和人群心血管病死亡数据为基础资料，分别应用时间序列和病例交叉方法分析寒潮对心血管病死亡的短期效应，为今后在环境与健康研究中选择合适的研究方法提供参考。.

原发性醛固酮增多症（primary aldosteronism，PA）根据肾上腺病变部位不同分为单侧和双侧PA，前者可手术治疗，后者应药物控制。单侧PA影像学上常表现为肾上腺低密度结节或增粗。肾上腺CT显像“无异常”的单侧PA既往国内未见报道。本文通过对1例肾上腺CT显像“无异常”的单侧PA患者的临床特点及诊治过程进行分析，总结诊治要点并结合文献复习进行讨论，以期为影像学阴性的单侧PA的临床诊治提供一些借鉴和思路。.

A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.患者男，57岁，因腹泻10个月，头晕4个月入院。患者每天1~2 L水样便，不含脓血，禁食试验阳性，胃肠镜检查无异常发现，血红蛋白及白蛋白大致正常；同时伴有双下肢感觉异常以及显著的直立性低血压症状。既往有多年的血糖异常及长期大量饮酒史。入院后经多科讨论，通过腓肠神经活检找到了淀粉样变的证据，并结合尿免疫固定电泳、血清游离轻链及心肌核磁检查，确诊为轻链型淀粉样变。予马法兰联合地塞米松化疗后病情缓解。.

Background The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD. Methods We analyzed Scientific Registry of Transplant Recipients data for all KT candidates with prior LT from 1998 to 2014; the benefits of KT relative to remaining on dialysis were compared by means of multivariate Cox proportional hazards regression analysis. Results The number of these KT candidates with prior LT has tripled from 98 in 1998 to 323 in 2015; LT recipients with ESRD remaining on dialysis have a 2.5-times increase in the risk of liver graft failure and a 3.6-times increase in the risk of patient death compared with these patients receiving KT. The adjusted liver graft and patient survival rates after donors from donation after cardiac death or expanded-criteria donor kidney transplantation were significantly higher than in patients remaining on dialysis in LT recipients with ESRD. Conclusions The number of referrals to KT with prior LT is increasing at a rapid rate. Remaining on dialysis in LT recipients with ESRD has profound increased risks of liver graft failure and patient death in comparison to receiving a KT. LT recipients with ESRD can benefit from expanded-criteria donor and donation after cardiac death kidney transplantation.

功能性便秘的治疗中推荐增加膳食纤维摄入，有助于改善粪便性状、增加排便次数。膳食纤维在促进肠道动力、保护肠黏膜屏障、调节肠道菌群等方面均有积极作用，这主要与膳食纤维的理化特性及其分解产物短链脂肪酸的相关生理作用有关。但膳食纤维可能也存在一些副作用，如腹胀、胃肠胀气，这主要由膳食纤维在代谢过程中产生气体导致。伴明显腹胀的功能性便秘患者和有结肠扭转风险或病史的患者应慎重增加膳食纤维摄入。.

The low survival rate of patients with ovarian cancer largely results from the advanced ovarian tumors as well as tumor resistance to chemotherapy, leading to metastasis and recurrence. However, it is missing as to an effective therapeutic approach that focuses on these aspects to prolong progression-free survival and to decrease mortality in ovarian cancer patients. Here, based on our cancer drug discovery studies, we provide prospective insights into the development of a future line of drugs to effectively reduce ovarian cancer deaths. Pathways that increase the probability of cancer, such as the defective Fanconi anemia (FA) pathway, may render cancer cells more sensitive to new drug targeting.

To investigate the bowel symptoms and psychological status of patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D), and to verify whether sigmoid colon mucosal mast cells (MCs) and their activation have effect on the symptoms and psychological status of IBS-D patients.Patients meeting Rome Ⅲ diagnostic and subtyping criteria of IBS-D who visited the outpatient clinic of gastroenterology of Peking Union Medical College Hospital were consecutively enrolled between July 2009 and June 2012. IBS symptoms questionnaire was completed using face-to-face interview, and Hamilton Anxiety Scale (HAMA)/ Hamilton Depression Scale (HAMD) were administrated to evaluate psychological status, both by well-trained investigators. Mast cell tryptase monoclonal antibody was used for immunohistochemical staining to detect MCs and degranulated MCs in mucosal biopsy of sigmoid colon. MCs and degranulated MCs were blindly counted by a senior pathologist, and presented as number of cells in high power field (HPF) and percentage of activated MCs. Correlation analysis was performed using Spearman rank correlation analysis.Ninety-seven patients with IBS-D were enrolled in this study, with mean age of (44±11) years. 70.10%(68 cases) of the IBS-D patients had comorbid anxiety and/or depression. The median total numbers of MCs, activated MCs, and percentage of activated MCs in sigmoid mucosa were 11.60 (7.09)/HPF, 2.00 (1.40) /HPF, and 17.50% (10.90%), respectively. Patients having abdominal pain/discomfort before bowel movement "every day with intermediate to high severity" had significantly larger numbers of total MCs in sigmoid colon compared with those with pain or discomfort "not every day and mild" [13.80(4.85)vs 7.60(5.90)/HPF, P=0.019]; the patient having "frequent" urge to have a bowel movement and mushy stools showed significantly higher percentage of activated MCs in sigmoid colon mucosa compared to those having the symptoms "some of the time" [18.75%(9.12%) vs 14.50%(13.14%), P=0.031; 21.33%(7.43%)vs 11.51%(10.65%)vs 18.42%(8.61%), P=0.030]. There was a positive correlation between the bowel movement during IBS-D onset and the percentage of activated MCs (r=0.221, P=0.030). There were no statistically significant differences in the total number of MCs and percentage of activated MCs between the patients with anxiety/depression and those without anxiety/depression (P=0.255, P=0.315). Scores of HAMA and HAMD were found not correlated with either total MCs number or percentage of activated MCs in sigmoid colon mucosa(all P0.05).The majority of IBS-D patients had comorbid anxiety and/or depression. The total number and activation status of MCs in sigmoid colon mucosa might be related with some intestinal symptoms in IBS-D patients. Psychological disorders might influence the pathogenesis and regression of IBS-D through brain-gut axis other than MCs in sigmoid colon mucosa.

To compare the different expressions of CD27, CD28, IL-17A, IFN-γ and TNF-α in the peripheral blood sampled from patients with colorectal carcinoma and healthy volunteers.Vδ2 T cells were isolated from the peripheral blood mononuclear cells (PBMCs) of patients with the colorectal carcinoma (CRC, n = 30) and healthy controls (HC, n = 21). The proportion of CD27, CD28, IL-17A, IFN-γ and TNF-α of Vδ2 T cells was detected by the flow cytometry.We found that the proportion of IL-17A of Vδ2 T cells in PBMCs was higher in the CRC vs. the HC group (p0.05). A significant positive correlation was observed between the expression of IFN-γ and TNF-α of Vδ2 T cells. In the CRC patients, the proportions of IL-17A of CD27- Vδ2 T cells and CD28+ Vδ2 T cells were higher than those of CD27+ Vδ2 T cells and CD28- Vδ2 T cells, whereas the expression of IFN-γ and TNF-α of CD27-Vδ2 T cells was lower than that of CD27+ Vδ2 T cells.Vδ2 T cells from PBMCs had higher expression of IL-17A in CRC patients than that in the HC group. The expression of IFN-γ and TNF-α of Vδ2 T cells from PBMCs was positively correlated. The cytokine profiles of peripheral Vδ2 T cells were likely determined by a CD27 and CD28 involving mechanism.

To analyze the metabolic profiles of the female papillary thyroid carcinoma (PTC) and the relationship between the metabolic profiles and primary tumor size and cervical lymph node metastasis using a metabolomics approach.Forty-three cases of female PTC were enrolled in this study. Gas chromatography-time-of-flight mass spectrometry and ultra performance liquid chromatography-time of flight-mass spectrometry were employed for analyzing metabolic profiles of tumor tissues and adjacent normal tissues in the female PTC. Cases were divided into Group T1 (tumor size≤2.0 cm) and Group T2 (tumor size2.0 cm) according to the tumor size, and divided into Group N- (with negative cervical lymph node) and Group N+ (with positive cervical lymph node) according to the cervical lymph node conditions. We compared the metabolomic profiles between these groups.A panel of 46 differentially expressed metabolites was identified in the PTC specimens, compared with normal tissues. Increased metabolism of amino acid, purine and pyrimidine, tryptophan acid, one carbon, glycolysis, taurine and hypotaurine, and fatty acid were found in PTC tumors tissues. Amino acids, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the tumor tissues of Group T2 compared with Group T1, while glycolysis, amino acid, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the specimens of Group N+ .Distinct metabolic profiles were identified in the female PTC tissues, which were related to the primary tumor size and cervical lymph node metastases.

Chinese hamster ovary cells stably expressing a rat dopamine transporter (designated D8 cells) and neuroblastoma SK-N-SH cells were used as two model systems to study dopamine neurotoxicity. Within 24 h, 1-10 mM dopamine induced D8 cells into apoptosis while 20-200 muM dopamine induced SK-N-SH cells into cell death. The viability of both cell types decreased in a dose-dependent manner. However, the dopamine uptake activity of D8 cells at 10 mM was not significantly higher than the uptake at 100 muM, suggesting that it was not the high concentration of intracellular dopamine that induced D8 cells into apoptosis, but rather dopamine found in the extracellular space. Furthermore, cocaine, an inhibitor of dopamine uptake, could not block cell death induced by dopamine. Forskolin, an agonist of protein kinase A (PKA), stimulated dopamine uptake in D8 cells and blocked apoptosis induced by the drug. These results suggest that the dopamine transporter mediates a dopamine-dependant apoptotic signal transduction pathway that is independent of dopamine uptake into the cell. NeuroReport 12:3293-3297 (C) 2001 Lippincott Williams & Wilkins.

Background We analyzed outcomes of kidney transplantation (KTx) from donation after brain death (DBD) or cardiac death (DCD) in China under the current level of the health care system. Methods Among 94 KTx performed from February 2007 to March 2012 in two organ transplant centers in the south of China, 50 KTx were used DBD and 44 DCD donors. We retrospectively analyzed the clinical outcomes. Results At a mean follow-up of 25.5 months, the 1-year and 2-year graft survival rates were 96.8% and 95.2% respectively. Delayed graft function (DGF) occurred in 27.7% recipients, three of whom lost graft function. Among six observed acute rejection episodes, five were reversed. When compared to the DCD group in DBD patients were apt to recover from DGF. Serum creatinine decreased more promptly in the DBD than in DCD group. Serum creatinine in the DCD group increased after months 12, when it was significantly higher than that in the DBD group ( P Conclusions Kidney transplantation from DBD donors showed good outcomes with few complications. Although KTx from DCD donors showed a higher DGF rate and longer duration of graft recovery, we achieved favorable short-term clinical outcome using this source.

We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.

We have identified three types of alpha-thalassemia in 28 members of an Indian family from Durban, South Africa. The rare South African (SA) type of alpha-thalassemia-1, which is characterized by an approximately 23-kb deletion involving the psi zeta, psi alpha 2, psi alpha 1, alpha 2, alpha 1, and theta 1 genes, was present in 13 members [6 simple heterozygotes, 5 with Hb H disease of the --(SA)/-alpha(-3.7 kb) type, and 2 with Hb H disease of the --(SA)/-alpha(-4.2 kb) type]. Seven others were heterozygotes for alpha-thalassemia-2 (-3.7 kb), 1 was homozygous for this deletion, and 1 was a compound heterozygote [-alpha(-3.7 kb/-alpha(-4.2 kb)]. Hematological and hemoglobin composition data indicated a moderate anemia in all 7 patients with Hb H disease with severe microcytosis and hypochromia, no elevation of gamma-chain synthesis, low levels of Hb A2 (0.3-0.7%), and low levels of Hb H. The most severe disease was present in 2 teenagers with the --(SA)/-alpha(-4.2 kb) combination.

The present study investigated the influence of the pretransplant dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), on renal transplant complications and outcomes.402 cadaveric renal transplant patients maintained on HD (N = 303) or PD (N = 99) for more than 3 months prior to transplantation were studied retrospectively, and a total of 345 patients were followed up for 30.2 +/- 15.2 months. The impact of HD or PD on acute rejection, delayed graft function (DGF), infection, chronic rejection, and the survival rate of graft and patients were analyzed.There was no significant difference between the HD and PD groups with regard to the causes of end-stage renal disease, age, gender, blood pressure, hemoglobin, HLA match, hot and cold ischemia time, and hepatitis C virus infection. The incidence rates of DGF, acute rejection, chronic rejection and cytomegalovirus and other infections were also not significantly different between the HD and PD groups. However, compared to HD, patients with PD had longer dialysis duration (p0.05), but less hepatitis B infection (p0.05) and post-transplant infection (p0.05). In contrast, in those PD patients with hepatitis B infection, graft loss was significantly increased (19.23% vs. 8.86% , p = 0.021). The incidence of acute rejection episodes was higher in HD patients who had pretransplant dialysis for more than 12 months (p0.05). The overall patient and graft survival rates within 5 years between the HD and PD groups were not significantly different (p0.05).The influence of PD and HD on complications after renal transplant at 1 year and 5 years and graft survival rates was similar, and therefore, either HD or PD can be chosen as the pretransplant dialysis modality. However, patients in the PD group had a reduced incidence of hepatitis virus infection, suggesting that PD may have certain advantages over HD as a preoperative substitution therapy for renal transplantation.

To explore whether human umbilical cord blood hematopoietic progenitor cells transduced with human O6-methylguanine-DNA-methyltransferase (MGMT) and multidrug resistance gene (MDR1) increase resistance to 1,3-Bis(2-Chloroethy1)-1-Nitrosourea (BCNU) and P-glycoprotein effluxed drugs, the present authors obtained a full length cDNA fragment encoding MGMT from liver tissue of a patient with cholelithiasis by RT-PCR. A bicistronic retroviral vector G1Na-MGMT-IRES-MDR1 cDNA was constructed and transfected the packaging cell lines GP + E86 and PA317 by electric performation method, using the medium containing VCR and BCNU for cloning selection and ping-ponging supernatant infection between ecotropic producer clone and amphotropic producer clone, cord blood CD34+ cells were enriched with a high-gradient magnetic cell sorting system (MACS), and then transfected repeatedly with supernatant of retrovirus containing human MGMT and MDR1cDNA under stimulation of hemapoietic growth factors. PCR, RT-PCR, Southern blot, Northern blot, Western blot, FACS and MTT assay were used to evaluate the transfer and expression of the double genes in cord blood CD34+ cells. The cDNA encoding MGMT was verified by DNA sequencing and the bicistronic retroviral vector was confirmed by restriction endonuclease analysis. The purity of cord blood CD34+ cells was approximately 92% and recover rate was 75%, the highest titer of recombinant amphotropic retrovirus in the supernatant was up to 5.8 x 10(5) cfu/ml. The efficiency of gene transduction was 18% and 20% tested by colony formation and PCR, respectively. No helper virus was found by both nested PCR and rescue assay. The results showed that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The MTT analysis showed a 4.5 to 7.8-fold increase of resistance of transducted cells to BCNU and P-glycoprotein effluxed drug as compared with the nontransduced cells. This study provided a foundation for ameliorating combination chemotherapy toxicity in tumor clinical trial.

Bilateral primary talon cusps are uncommon. This case report documents two new cases of bilateral talon cusps in the primary dentition. The clinical features, radiographic characteristics, and differential diagnosis of this developmental anomaly are described. The terminology, epidemiological data, potential complications, and various modes of treatment are reviewed and discussed. A new classification system was proposed. The dental anomalies of these two cases were not associated with any other somatic or dental abnormality. The general prognosis of this abnormality is satisfactorily good. However, the dentist needs to have early recognition of this anomaly in order to provide timely treatment in order to prevent potential complications.

To construct transgenic mice bearing human Fas ligand (FasL/CD95L) cDNA, and further explore the physiological effects of ubiquitous expression of FasL on such animals.Transgenic mice were produced by pronuclei microinjection method. Integration and transmission of transgene were identified by nest-PCR and Southern-blot analysis. Level of FasL mRNA was evaluated by semi-quantitative RT-PCR analysis. FasL protein was detected by immunofluorescence analysis. Morphological alterations in tissues were analyzed by histological examination. The percentage of alphabetaT cells in the spleen was determined by flow cytometry analysis.Two independent founder mice bearing human FasL cDNA under the control of CMV promoter were generated healthily. Human FasL was moderately expressed in the majority of tissues examined in F1 heterozygotic mice. Although developing normally, adult transgenic mice exhibited a slight form of graft-versus-host (GVH)-like disease characterized by many morphological abnormalities occurring locally in the spleen, testis, lung and liver. In addition, the percentage of alphabetaT cells in the spleen was respectively decreased approximately by 32 % and 24 % in two independent transgenic lines, relative to wild-type mice.Ubiquitous expression of Fas ligand can lead to slight GVH-like disease

To explore the effect of antisense alpha(1,3) galactosyltransferase alpha(1,3) GT cDNA on production of Gal alpha(1,3) Gal (Gal epitope) xenoantigen in vivo.Transgenic mice bearing the porcine antisense alpha(1,3) GT cDNA (nt 1alpha-640) were generated by pronuclei microinjection method. The integration of transgene was identified by PCR and Southern-blot analysis. The expression of murine alpha(1,3) GT was characterized by RT-PCR. Morphology of the spleen was examined by histological technique. Gal epitope was detected by immunofluorescent analysis. Binding of human natural xenoantibodies (IgM and IgG) and complement (C3c) to cells from mice was determined by flow cytometric assay.Transgenic mice bearing the porcine antisense alpha(1,3) GT cDNA were born healthy and developed normally. However, necrosis occurred in the spleen of some mice heterozygous for transgene. Cell surface Gal epitope in transgenic heterozygotes was evidently reduced. Substantially less (30 % - 60 %) xenoantibodies in human serum bound to cells from a variety of tissues of transgenic heterozygotes compared with wild-type controls. Consequentially, human complement activation on cells from these mice was reduced by 40 % - 50 %.Human xenoreactivity could be effectively reduced by inhibiting the expression of alpha(1,3) galactosyltransferase with an antisense gene.

To examine the effects of the expression of antisense RNA transcripts complementary to the pig alpha(1,3) galactosyltransferase [alpha(1,3)GT]mRNA on the expression of Gal alpha(1,3) Gal structure (gal epitope) in cultured cell lines.Human adenoviral vectors were used to mediate the expression of antisense RNA. The expression levels of H blood group antigens and gal epitopes were analyzed by flow cytometry using FITC-UEA-I and FITC-GS-IB4 lectins, respectively.Recombinant adenoviruses, Ad5anti-sGT600 and Ad5-anti-sGT1100, which express antisense RNA complementary to different regions of the pig alpha(1,3) GT mRNA, were constructed and used to infect cell line of NIH3T3. The results showed about 30% reduction in the expression level of gal epitopes on the surface of NIH3T3 cells. In addition, co-expression of human secretor type alpha(1,2) fucosyltransferase [alpha(1,2)FT]cDNA and antisense RNA complementary to the pig alpha(1,3) GT mRNA led to a further reduction in the gal epitope level.Recombinant adenoviruses, Ad5anti-sGT600 and Ad5anti-sGT1100, are effective to down-regulate the gal epitope expression.

To test the potential of human secretor type alpha(1, 2) fucosyltransferase [Se alpha(1,2)FT] to downregulate the expression of Gal alpha(1,3)Gal epitope (gal epitope) in cultured cell lines.Expression of Se alpha(1,2) FT was mediated by human adenoviral vector. Flow cytometric analysis was used to compare the expression level of H blood group antigen or gal epitope. MTT was employed to assess the susceptibility of mouse NIH3T3 cells to human natural antibody and complement mediated lysis.A recombinant replication-deficient adenovirus (rAdv) containing human Se alpha(1,2)FT cDNA (Ad5hSeFT) was designed and successfully constructed. Flow cytometric analysis showed that after mock infection, Ad5null infection, and Ad5hSeFT infection, the mean fluorescence intensity (MFI) values for the binding of Ulex europaeus I (UEA-I) lectin to NIH3T3 cells were 2.3 +/- 0.6, 2.1 +/- 1.0, and 36.5 +/- 5.9, respectively; MFI values for the binding of Griffonia simplicifolia isolectin B4 (GS-IB4) lectin to NIH3T3 cells were 167 +/- 23, 170 +/- 19, and 100 +/- 14, respectively; MFI values for the binding of human natural IgG and IgM antibodies to NIH3T3 cells were 31 +/- 3, 32 +/- 4, and 22 +/- 4, respectively.H blood group antigen was detected on NIH3T3 cells after Ad5hSeFT infection and resulted in more than 40% reduction in the level of gal epitope on the cell surface. This reduction increased the resistance of NIH3T3 cells to lysis by normal human serum.

N-Acetylaspartate is a highly specific marker for neurons and is present at high concentrations in the central nervous system. It is not present at detectable levels anywhere else in the body other than brain. Glial cells express a high-affinity transporter for N-acetylaspartate, but the molecular identity of the transporter has not been established. The transport of N-acetylaspartate into glial cells is obligatory for its intracellular hydrolysis, a process intimately involved in myelination. N-Acetylaspartate is a dicarboxylate structurally related to succinate. We investigated in the present study the ability of NaDC3, a Na(+)-coupled high-affinity dicarboxylate transporter, to transport N-acetylaspartate. The cloned rat and human NaDC3s were found to transport N-acetylaspartate in a Na(+)-coupled manner in two different heterologous expression systems. The Michaelis-Menten constant for N-acetylaspartate was approximately 60 microM for rat NaDC3 and approximately 250 microM for human NaDC3. The transport process was electrogenic and the Na(+):N-acetylaspartate stoichiometry was 3:1. The functional expression of NaDC3 in the brain was demonstrated by in situ hybridization and reverse transcription-polymerase chain reaction as well as by isolation of a full-length functional NaDC3 from a rat brain cDNA library. In addition, the expression of a Na(+)-coupled high-affinity dicarboxylate transporter and the interaction of the transporter with N-acetylaspartate were demonstrable in rat primary astrocyte cultures. These studies establish NaDC3 as the transporter responsible for the Na(+)-coupled transport of N-acetylaspartate in the brain. This transporter is likely to be an essential component in the metabolic role of N-acetylaspartate in the process of myelination.

In clinical trials, valganciclovir, the valyl ester of ganciclovir, has been shown to enhance the bioavailability of ganciclovir when taken orally by patients with cytomegalovirus infection. We investigated the role of the intestinal peptide transporter PEPT1 in this process by comparing the interaction of ganciclovir and valganciclovir with the transporter in different experimental systems. We also studied the interaction of these two compounds with the renal peptide transporter PEPT2. In cell culture model systems using Caco-2 cells for PEPT1 and SKPT cells for PEPT2, valganciclovir inhibited glycylsarcosine transport mediated by PEPT1 and PEPT2 with K(i) values (inhibition constant) of 1.68+/-0.30 and 0.043+/- 0.005 mM, respectively. The inhibition by valganciclovir was competitive in both cases. Ganciclovir did not interact with either transporter. Similar studies done with cloned PEPT1 and PEPT2 in heterologous expression systems yielded comparable results. The transport of valganciclovir via PEPT1 was investigated directly in PEPT1-expressing Xenopus laevis oocytes with an electrophysiological approach. Valganciclovir, but not ganciclovir, induced inward currents in PEPT1-expressing oocytes. These results demonstrate that the increased bioavailability of valganciclovir is related to its recognition as a substrate by the intestinal peptide transporter PEPT1. This prodrug is also recognized by the renal peptide transporter PEPT2 with high affinity.

We have cloned the human Na+-dependent multivitamin transporter (SMVT), which transports the water-soluble vitamins pantothenate, biotin, and lipoate, from a placental choriocarcinoma cell line (JAR). The cDNA codes for a protein of 635 amino acids with 12 transmembrane domains and 4 putative sites for N-linked glycosylation. The human SMVT exhibits a high degree of homology (84% identity and 89% similarity) to the rat counterpart. When expressed in HRPE cells, the cDNA-induced transport process is obligatorily dependent on Na+ and accepts pantothenate, biotin, and lipoate as substrates. The relationship between the cDNA-specific uptake rate of pantothenate or biotin and Na+ concentration is sigmoidal with a Na+:vitamin stoichiometry of 2:1. The human SMVT, when expressed in Xenopus laevis oocytes, induces inward currents in the presence of pantothenate, biotin, and lipoate in a Na+-, concentration-, and potential-dependent manner. We also report here on the structural organization and chromosomal localization of the human SMVT gene. The SMVT gene is approximately 14 kilobase pairs in length and consists of 17 exons. The SMVT gene is located on chromosome 2p23 as evidenced by somatic cell hybrid analysis and fluorescence in situ hybridization.

Work in the area of molecular biology of transport proteins has unveiled the presence of a distinct peptide transporter superfamily whose members extend from the prokaryotic to the eukaryotic kingdom. There are two subgroups within this superfamily, one subgroup harnessing the energy necessary for active transport from a transmembrane H+ gradient and the other subgroup relying directly on ATP hydrolysis. In addition to the use of different driving forces, the two subgroups are also distinguishable with regard to molecular structure and operational mechanism. This review is intended to analyze critically the molecular nature of the members of the H+ gradient-dependent peptide transporter subgroup, with emphasis on the cloning strategies utilized in the isolation of the individual transporter cDNAs or genes; on the structural patterns, motifs, and conserved amino acid residues common to constituent members of the subgroup; and on the characteristic topological features of the individual members.

From September, 1985 to April, 1994, 33 patients underwent surgical repair of corrected transposition of the great arteries associated with other congenital heart anomalies. Of them, 31 patients were SLL type, the other 2 patients were attributed to IDD type. Operations were performed on ventricular septal defect in 28 patients, atrial septal defect in 15, pulmonary stenosis in 29 and two had valvuloplasty for left atrioventricular valve regurgitation, patent ductus arteriosus closure was performed on one and modified Fonton procedure on one. There were five peri-operative deaths being 15.7% of operative morbility; late death was only one patient. The following-up of the survival 27 patients for 2 months to 9 years showed a satisfactory results.

In mammalian small intestine, a H(+)-coupled peptide transporter is responsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotransporter has been isolated from a rabbit intestinal cDNA library (Fei, Y.J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F.H., Romero, M.F., Singh, S.K., Boron, W. F., and Hediger, M. A. (1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a probe derived from the rabbit H+/peptide cotransporter cDNA resulted in the identification of a cDNA which when expressed in HeLa cells or in Xenopus laevis oocytes induced H(+)-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-spanning domains and two putative sites for protein kinase C-dependent phosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino beta-lactam antibiotics but not free amino acids as substrates. The human H+/peptide cotransporter exhibits a high degree of homology (81% identity and 92% similarity) to the rabbit H+/peptide cotransporter. But surprisingly these transporters show only a weak homology to the H(+)-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell hybrid analysis and in situ hybridization have located the gene encoding the cloned human H+/peptide cotransporter to chromosome 13 q33--q34.

Regulation of the retina-specific expression of the interphotoreceptor retinoid-binding protein (IRBP) gene in transgenic mice requires sequences between nucleotide (nt) −156 and +19. DNAse I footprinting and electrophoretic mobility shift assays identified a region between nt −69 and −40 that interacts with some nuclear proteins from bovine and mouse retinas but not from a variety of other neural and non-neural tissues. The selectivity of this sequence to elicit IRBP promoter activity is indicated by their failure to bind some nuclear proteins following mutagenesis. Therefore, IRBP promoter activity is linked to nuclear protein binding at a regulatory motif between nt −69 and −40.

This paper reported surgical treatment on 154 patients with CMVI. Of them, pure CMVI only existed in 23 cases, the associated anomalies in 131 cases. Surgical repair of mitral valve were performed in 144 cases, replacement of valve were done in 10 cases. Surgical repair included plication of the commissure in 125 cases, closure of the fenestration of the large leaflet in 1 case, partial resection of the small leaflet with approximation and valve ring annuloplasty in 3 cases, shortening of elongated chordae taeniae in large leaflet in 4 cases, respectively. The smallest age within all patients undergoing mitral replacement was 3 years. There were 1 early and late death, respectively, in this group. However, reoperation were performed in 2 cases for unsatisfactory repair and 1 case for failure of prosthetic valve. The results showed that echocardiography is a simple and effective tool in preoperative diagnosis and making selection of operative indication, finally, leading to proper repair of associated anomalies. Surgical repair on cases of CMVI should be the first choice, and proper procedure should be selected according to the type of mitral valve deformity. The results were satisfactory even without artificial valve ring. Valve replacement was considered to be essential on severe patients and unsatisfactory repair. On children, slight large valve with double leaflets was preferable.

A large novel alpha-thalassemia-1 deletion which includes the zeta-, alpha 2-, alpha 1-, and theta 1-globin genes is described in a Black family living in Georgia and Florida. The deletion which was characterized by restriction enzyme analysis, extends 15 to 35 kb 5' and at least 35 kb 3' to the Cap site of the zeta-globin gene. Mental retardation was not observed. The deletion was present in a 35-year-old male with Hb H disease and his mother; the major hemoglobin type in the propositus was Hb G-Philadelphia or alpha (2)68(E12)Asn--Lys beta 2 because his second chromosome carried the -alpha G(-3.7 kb) alpha-thalassemia-2 deletion.

Since Fei et al reported a tentative linkage between ADRP and the Rhesus(Rh) blood group in the unrelated Chinese families in 1987, additional individuals of these ADRP families have been typed for Rh. Further linkage analysis with the LIPED Program on the Rh data of the ten ADRP families showed a maximum summed LOD score of 2.01 at theta = 0.12, which is a further suggestion of linkage between ADRP and Rh. However, genetic heterogeneity certainly exists in these families. It is our presumption that ADRP in those families, which do not exhibit linkage to 3q markers, may map to the short arm of chromosome 1.

A large pedigree of congenital stationary night blindness (CSNB) was investigated by both the family method and the family history method, and the diagnosis was confirmed by dark adaptation and full-field electroretinogram tests. There were 57 affected members of 7 successive generations in the pedigree which showed typical autosomal dominant inheritance with a complete gene penetrance. Based on this study and other sources, the genetic aspect and the clinical manifestations of CSNB, especially the characteristics of dark adaptation and electroretinogram, were discussed.

A new deletion of approximately 8.5 kb that includes the alpha 2-, alpha 1-, and theta 1-globin genes was detected in a father and newborn son of a black family from Georgia. In the newborn baby the chromosome with the deletion occurred together with a rightward (-alpha 3.7) deletion chromosome. The resulting Hb H disease was detected at birth by the high level of Hb Bart's; a moderate anemia with severe microcytosis and hypochromia was present at the age of 5 months. A review of cord blood testing results for a period of over 20 years, involving at least 200,000 black newborns, indicated that this baby was the first with a level of Hb Bart's in excess of 10-15%; this underscores the rarity of alpha-thalassemia-1 in this population.

We have analysed the alpha-globin gene defects present in several members of a large family from Southern Turkey. One deletional alpha-thalassaemia-1 (type MED-II) was found in 10 subjects: this deletion is in excess of 26.5 kb and includes all zeta- and alpha-globin genes. Besides the common types of deletional alpha-thalassaemia-2 (-3.7 kb and -4.2 kb) we observed a nondeletional alpha-thalassaemia-2 that results from an A----G mutation (AATAAA----AATGAA) in the polyadenylation signal of the alpha 2-globin gene: the same A----G replacement is present in the psi alpha l gene. The mutation must cause a considerable alpha-chain deficiency as is evidenced by the haematological data for five members with Hb H disease due to a compound heterozygosity for alpha-thalassaemia-1 (MED-II) and the newly discovered poly A mutation. Several members had additional beta-chain abnormalities (Hb S, Hb D-Los Angeles, beta-thalassaemia); the 11 persons with a Hb S heterozygosity and various alpha-globin gene defects (-alpha/alpha alpha; alpha T alpha/alpha alpha, - -/alpha alpha, -alpha/-alpha and - -/alpha T alpha) showed a decrease in the level of Hb S that was directly related to the severity of the alpha-chain deficiency.

Comprehensive genetic segregation analysis performed in 150 pedigree of retinitis pigmentosa (RP) showed that the disease manifested genetic heterogeneity. Families of the mating type Affected x Normal were autosomal dominant (AD), with 80% of penetrance and no sporadic cases. Families of the mating type Normal x Normal were 80% autosomal recessive (AR), with 20% of sporadic cases. In the present series, the RP pedigrees were AD in 13.3%, X-linked in 2.7%, AR in 67.3% and sporadic in 16.7%, and most sporadic cases were nongenetic. It was also demonstrated that, with the conventional mode of pedigree analysis, the proportions of AR and AD cases were underestimated, and the proportion of sporadic RP was overestimated.

We have identified 7 patients with Hb H disease as homozygotes for a mutation in the polyadenylation site (AATAAA--AATAAG) and have compared their hematological data with those of Hb H patients having other types of alpha-thalassemia determinants. All 7 patients exhibited moderate anemia with microcytosis and hypochromia being similar to that observed in the other patients. Relatives with a heterozygosity for this mutation are borderline microcytic and hypochromic without a significant anemia but with a low in vitro alpha/beta chain synthesis ratio. Analyses of the hemoglobin components identified low levels of Hb A2 and Hb H that were comparable to those found in other patients with Hb H disease; the level of the zeta-chain was low (average 0.14%).

We have examined the molecular basis of three inherited hemoglobin (Hb) disorders present in a Czechoslovakian girl with a severe, transfusion-dependent, hemolytic anemia. She is heterozygous for Hb E (on a genetic background specific for Czechoslovakian families), heterozygous for the beta zero-thalassemia (thal) allele IVS-I-1 (G----A), and heterozygous for an alpha-globin gene triplication. The combination of these three undesirable traits results in a severe chain imbalance that is the basis of the serious hemolytic disorder observed in this teenager.

Peripheral fibroma/fibrous epulis accounts for the great majority of localised gingival swellings as was substantiated by various reports in the literature. A study was undertaken to investigate the clinical features of a series of 204 localised fibrous gingival swellings received by the Histopathology Laboratory, Department of Oral Surgery, National University of Singapore. The female patients were more affected than the male patients and the lesions occurred predominantly among the Chinese. The lesions were mainly pedunculated and most commonly occurred in anterior maxilla. The recurrence rate was about 10.3%. In conclusion the results obtained in this study were overall in agreement with those of other authors.

Structural analyses of an abnormal gamma chain, present in a relative amount of approximately 10% in a cord blood sample of a Black newborn baby, identified two substitutions (gamma 75 Ile----Thr and gamma 136 Ala----Gly) in an apparent variant of the A gamma chain. Gene mapping analysis of genomic DNA and hybridization with specific probes confirmed the presence of these two mutations and provided the evidence to indicate that the abnormal gamma chain was indeed a variant of A gamma with the two listed mutations.

We describe a newly detected alpha-thalassemia-2 (alpha-thal-2) deletion characterized by a small -2.7-kb deletion involving the alpha 1 globin gene. This deletion has thus far been observed in only one Chinese subject with Hb H disease.

Two different theta 1 globin gene deletions have been detected in the Black population of the southeastern U.S.A. Restriction mapping of the alpha globin gene cluster indicated that one deletion removes approximately 1.8 kb of DNA including most of the theta 1 globin gene, while the second removes approximately 6 kb of DNA including the entire theta 1 globin gene. These defects do not cause haematological alterations in the newborn or in the adult (established for the smaller deletion only), nor were changes observed in polypeptide chain patterns at birth.

DNA amplification combined with hybridization with 32P-labeled synthetic oligonucleotide probes has been used to identify base substitutions in the 5′ promoter region of the A gamma globin gene in members of eleven families from China, Sardinia, Canada, and the United States who had a heterozygosity for the A gamma-beta+-hereditary persistence of fetal hemoglobin (HPFH), and in members of six black families with a possible G gamma-beta+-HPFH heterozygosity. All three known A gamma types were observed, ie, the British type (-198, T----C), the Chinese type (-196, C----T), and the Green type (-117, G----A); the latter has been found in a black family. Of the six families with G gamma-beta+-HPFH, three had C----G at -202 and none T----C -175. Conditions for hybridization of amplified DNA with the specific probes are provided and the usefulness of the technique is discussed. The increase in numbers of A gamma(G gamma)-beta+-HPFH heterozygotes with specific base substitutions greatly enhances the probability of a direct correlation between these substitutions and the increase in the production of a specific gamma chain.