Arginine vasopressin produces inhibition upon respiration without pressor effect in the rat

The purpose of the current study was to examine where arginine vasopressin (AVP) inhibits respiration by direct action on the areas of the ventrolateral medulla (VLM) in the rat. The animal was anesthetized by urethane (1.2 g/kg, i.p.), paralyzed with gallamine triethiodide, and artificially ventilated. Catheterization of the femoral artery and vein, and bilateral vagotomy were performed. The rat was then placed upon a stereotaxic instrument in a prone position. The phrenic nerve was separated and cut peripherally. Phrenic nerve activity (PNA) was monitored at normocapnia and hypercapnia in hyperoxia. Microinjection of AVP into various subregions of the VLM was then performed. In response to AVP microinjection, a transient period of apnea and then a significant decrease in PNA amplitude were observed. Arterial blood pressure was unchanged. This inhibition of PNA with AVP treatment was site-specific, attenuated by raising CO2 concentration, and totally abolished by pretreatment with AVP V1A receptor antagonist. Data of the present study indicate that endogenous resource of AVP may produce an inhibitory effect upon respiration via AVP receptors presented on neurons within the VLM.     

两种陀螺藻囊壳的微细结构和元素组成分析

利用从自然界水体中采集到的标本为材料,对2种陀螺藻的囊壳的微细结构和元素组成进行分析比较,结果表明：组成陀螺藻囊壳的主要矿质元素是硅(Si)、铁(Fe)和铝(A1),并含有少量的镁(Mg)、锌(Zn)、钙(Ca)等元素。囊壳的表面形态是不规则的,不宜作为分类依据。     

Determinants of the substrate specificity of multidrug resistance protein 1: role of amino acid residues with hydrogen bonding potential in predicted transmembrane helix 17

Human multidrug resistance protein 1 (MRP1) confers resistance to many natural product chemotherapeutic agents and actively transports structurally diverse organic anion conjugates. We previously demonstrated that two hydrogen-bonding amino acid residues in the predicted transmembrane 17 (TM17) of MRP1, Thr(1242) and Trp(1246), were important for drug resistance and 17beta-estradiol 17-(beta-d-glucuronide) (E(2)17betaG) transport. To determine whether other residues with hydrogen bonding potential within TM17 influence substrate specificity, we replaced Ser(1233), Ser(1235), Ser(1237), Gln(1239), Thr(1241), and Asn(1245) with Ala and Tyr(1236) and Tyr(1243) with Phe. Mutations S1233A, S1235A, S1237A, and Q1239A had no effect on any substrate tested. In contrast, mutations Y1236F and T1241A decreased resistance to vincristine but not to VP-16, doxorubicin, and epirubicin. Mutation Y1243F reduced resistance to all drugs tested by 2-3-fold. Replacement of Asn(1245) with Ala also decreased resistance to VP-16, doxorubicin, and epirubicin but increased resistance to vincristine. This mutation also decreased E(2)17betaG transport approximately 5-fold. Only mutation Y1243F altered the ability of MRP1 to transport both leukotriene 4 and E(2)17betaG. Together with our previous results, these findings suggest that residues with side chain hydrogen bonding potential, clustered in the cytoplasmic half of TM17, participate in the formation of a substrate binding site.     

ILPIP,a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis

We have previously described a new aspect of the Inhibitor of Apoptosis (IAP) family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal transduction pathway (1,2). Our findings suggest the existence of a novel mechanism that regulates the anti-apoptotic activity of IAPs that is separate from caspase inhibition but instead involves TAK1-mediated activation of JNK1. In a search for proteins involved in the XIAP/TAK1/JNK1 signaling pathway we isolated by yeast two-hybrid screening a novel X chromosome-linked IAP (XIAP)-interacting protein that we called ILPIP (hILP-Interacting Protein). Whereas ILPIP moderately activates JNK family members when expressed alone, it strongly enhances XIAP-mediated activation of JNK1, JNK2, and JNK3. The expression of a catalytically inactive mutant of TAK1 blocked XIAP/ILPIP synergistic activation of JNK1 thereby implicating TAK1 in this signaling pathway. ILPIP moderately protects against interleukin-1beta converting enzyme- or Fas-induced apoptosis and significantly potentiates the anti-apoptotic activity of XIAP. In vivo co-precipitation experiments show that both ILPIP and XIAP interact with TAK1 and tumor necrosis factor receptor-associated factor 6. Finally, expression of ILPIP did not affect the ability of XIAP to inhibit caspase activation, further supporting the idea that XIAP protection against apoptosis is achieved by two separate mechanisms: one requiring JNK1 activation and a second involving caspase inhibition.     

The fatty acid composition of the serum phospholipids of children with sickle cell disease in Nigeria

The purpose of this study was to determine the fatty acid composition of the serum phospholipids of children with sickle cell disease (SCD) in Nigeria and to compare the relative fluidity of the acyl chains of the serum phospholipids of controls versus the subjects with SCD. It is widely accepted that the fatty acid composition of an individual's serum phospholipids reflects that of their tissue phospholipids. An alteration in the fatty acid composition of membrane phospholipids could affect critical membrane-dependent enzymes and processes (e.g., ion and solute transport, hormone-receptor interactions, signal transduction pathways). We found a significant reduction in the content of polyunsaturated n-3 fatty acids in the phospholipids of subjects with SCD which could result in a reduction of the fluidity of their tissue membranes. Specifically, there was a 40-50% reduction in the proportion of total n-3 fatty acids in subjects with SCD. On the basis of calculated melting points and double bond indices of the acyl chains of the serum phospholipids, the phospholipids of the children with SCD are less fluid relative to those of their healthy counterparts. In addition, we determined that linoleic acid, arachidonic acid, and stearic acid were the major determinants of the fluidity of the acyl chains of the serum phospholipids of the healthy controls and children with SCD.     

Stool antigen assay to screen H. pylori infection and to assess the success of 3-Day and 7-Day eradication therapy in the patients with partial gastrectomy

Background. Even after partial gastrectomy, Helicobacter pylori may persist in the residual stomach but be less abundant in the bacterial load. H. pylori stool antigen is a reliable noninvasive tool to detect H. pylori infection in patients without gastrectomy. We thus test whether [ 1 ] the course of H. pylori eradication therapy could be diminished [ 2 ]; stool antigen can effectively detect H. pylori infection for the patients with gastrectomy. Methods. One hundred and eight patients who had undergone partial gastrectomy were enrolled to receive panendoscopy and provided stool samples for H. pylori stool antigen within 3 days after endoscopy. The H. pylori‐infected patients were then randomized to receive either a 3‐ or 7‐day triple therapy for H. pylori eradication. Six weeks later, to evaluate the success of H. pylori eradication, patients received a follow‐up endoscopy and again provided stool samples for H. pylori stool antigen. Results. Seventy out of 108 patients, proven to have H. pylori infection, were evenly randomized into 3‐day and 7‐day therapy groups. The H. pylori eradication rates were similar between the 3‐day and 7‐day triple therapy (90.9 vs. 93.8%, p > .05). Before therapy, the H. pylori stool antigen was 93% sensitive and 100% specific to detect H. pylori. After therapy, H. pylori stool antigen remain 100% sensitive and 88.3% specific to detect the failure of eradication therapy. Conclusion. H. pylori stool antigen is a highly reliable tool to screen H. pylori infection before therapy and to assess the success of eradication therapy in partial gastrectomy patients. To eradicate H. pylori infection for patients with partial gastrectomy, the duration of triple therapy can be shortened.     

Solution structure of the DNA-binding domain of interleukin enhancer binding factor 1 (FOXK1a)

Interleukin enhancer binding factor (ILF) binds to the interleukin-2 (IL-2) promoter and regulates IL-2 gene expression. In this study, the 3D structure of the DNA-binding domain of ILF was determined by multidimensional NMR spectroscopy. NMR structure analysis revealed that the DNA-binding domain of ILF is a new member of the winged helix/forkhead family, and that its wing 2 contains an extra alpha-helix. This is the first study to report the presence of a C-terminal alpha-helix in place of a typical wing 2 in a member of this family. This structural difference may be responsible for the different DNA-binding specificity of ILF compared to other winged helix/forkhead proteins. Our deletion studies of the fragments of ILF also suggest that the C-terminal region plays a regulatory role in DNA binding.     

Penoscrotal extramammary Paget's disease: a review of 33 cases in a 20-year experience

Extramammary Paget's disease in men most frequently involves the penoscrotal area. The uncertainty of the outcome and of the relationship to the underlying adnexal carcinoma and associated internal malignancy still exists. From 1982 to 2001, 33 patients with penoscrotal extramammary Paget's disease were treated and followed up. Therapeutic modalities included carbon dioxide laser ablation (two patients) and local wide excision (31 patients). Split-thickness skin graft (22 patients), local scrotal flap (six patients), and primary closure (three patients) were utilized to reconstruct the penoscrotal defects after local wide excision. An underlying adnexal carcinoma occurred in seven of 33 patients (21.2 percent). The incidence of associated internal malignancy was 9.1 percent (three of 33 patients), including one concurrently and two nonconcurrently associated malignancies. Eight of 33 patients had local recurrence, representing an incidence of 24.2 percent. Three patients (9.1 percent) had distant metastasis and ultimately died of metastatic carcinoma. Of these patients, 31 were grouped according to the degrees of involvement: limited to the epidermis (group 1, n = 14), involvement of the adnexal gland and/or hair follicle (group 2, n = 10), and the presence of an underlying adnexal carcinoma (group 3, n = 7). Local wide excision with subsequent reconstruction by split-thickness skin graft was favored in this series. Patients with an underlying adnexal carcinoma or pathological invasion of the dermis (group 2 or 3) had a worse prognosis than patients without. From this study, it is difficult to address the particular relationship between the outcome and the associated internal malignancy.     

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma

The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node-positive versus node-negative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and disease-free and overall survival probabilities were compared between positive and negative groups using the log-rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty-five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow-up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false-negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow-up. Disease-free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor-positive lymph nodes (two-sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node-negative patients but not in sentinel node-positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node-negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result.