Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.     

NPHS1两种新突变蛋白分子的细胞内分布

目的：研究NPHS1两种新突变编码蛋白在细胞内的分布与先天性肾病综合征发病机制的关系。方法：构建野生型和两种突变型NPHS1克隆，并转染至COS7细胞内，应用免疫荧光双标记的方法，分别进行细胞内及细胞表面的荧光标记，通过共聚焦显微镜对裂隙膜分子Nephrin在细胞内的分布进行研究。结果：野生型Nephrin表现为细胞内和细胞膜染色模式；V822M和C265R则主要为细胞内内质网染色模式，细胞膜着色几乎缺失。结论：突变的Nephrin蛋白由于错误折叠，不能由内质网被输送至细胞表面，这可能是先天性肾病综合征发病的机制之一。     

Successful surgical repair of delayed chronic type a dissection after previous coronary artery bypass grafting.

This reports a case of a 68-year-old woman who had undergone coronary artery bypass 5 years previously. Magnetic resonance angiography (MRA) revealed that the ascending aorta was dilated to about 8 cm in diameter, with type A dissection, and with a patent left internal thoracic artery (LITA) graft to the left anterior descending artery (LAD). Angiography at the ascending aorta did not reveal a coronary artery, nor did it show the sequential saphenous vein graft (SVG) to the obtuse marginal and posterolateral branches. Although the risk of surgical treatment via repeat median sternotomy was very high, we successfully performed the reoperation using profound hypothermic circulatory arrest. The dissection in the mediastinum was facilitated by a sternum retractor for ITA-graft dissection, intraoperative surface echocardiography, and ultrasonic scalpel, with a widely opened bilateral pleural cavity. Furthermore, assuming that most of the myocardium was maintained by perfusion from the in-situ, patent, ITA graft, it was thought that cardioplegia was not necessary during profound hypothermic circulation.     

MANAGEMENT TO PREVENT BLEEDING DURING ENDOSCOPIC SUBMUCOSAL DISSECTION USING THE FLUSH KNIFE FOR GASTRIC TUMORS

The gastric vasculature responsible for intraoperative bleeding in endosocpic submucosal dissection (ESD) is the ramified vascular network occupying the middle of the submucosal layer and large vessels penetrating the muscle layer. Appropriate management for these vessels must be addressed. The trimming of the ramified vascular network can be safely performed with coagulation mode following shallow mucosal cutting. A large penetrating vessel usually requires precoagulation prior to dissection. These procedures are effectively performed with the water jet short needle knife (Flush knife).     

Eosinophilic gastroenteritis in the esophagus, stomach, and small intestine in a patient with a choking feeling in the esophagus]

A 75-year-old man was admitted to our hospital with the chief complaint of a choking feeling around the esophagus. Laboratory examinations revealed eosinophilia, and high levels of serum immunoglobulin (Ig) E. A computed tomography scan (CT) showed wall thickening of the esophagus and terminal ileum, and ascites around the liver. An endoscopic examination revealed mild mucosal edema in the esophagus, stomach, and small intestine. Biopsy specimens showed diffuse eosinophilic infiltration in the mucosa. We therefore diagnosed eosinophilic gastroenteritis. Oral prednisolone relieved clinical conditions and the CT image improved. This case was considered valuable, because there have been few reports of eosinophilic esophagitis in Japan.     

Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels

The differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) single sodium channel currents in rat dorsal root ganglion (DRG) neurons were investigated using the outside-out configuration of patch-clamp technique. Channel conductances were 10.7 and 6.3 pS for TTX-S and TTX-R sodium channels, respectively, at a room temperature of 24–26°C. The single-channel current of TTX-S sodium channels at the test potential of −30 mV was −1.27 ± 0.25 pA, and was not changed after exposure to 10 μM tetramethrin (−1.28 ± 0.23 pA). The open time histogram of TTX-S single-channel currents could be fitted by a single exponential function with a time constant of 1.27 ms. After exposure to 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 1.36 ms (τ_fast) and 5.73 ms (τ_low). The percentage of contribution of each component to the population was 62% for the fast component representing the normal channels and 38% for the slow component representing the tetramethrin modified channels. The amplitudc of TTX-R single-channel currents was slightly changed from −0.72 ± 0.14 to −0.83 ± 0.07 pA by 10 μM tetramethrin. The open time histogram of TTX-R single-channel currents could be fitted by a single exponential function with a time constant of 1.92 ms. In the presence of 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 2.07 ms (τ_fast) and 9.75 ms (τ_slow). The percentage of contribution of each component was 15% for the fast, unmodified component and 85% for the slow, modified component. Differential effects of tetramethrin on the open time distribution of single sodium channel currents explains the differential sensitivity of TTX-S and TTX-R sodium channels.     

HTLV-I, HIV-I, and Hepatitis B and C Viruses in Western Province, Papua New Guinea: A Serological Survey

Seven hundred and twenty-three serum samples from individuals in 13 Gidra-speaking villages in Western Province, Papua New Guinea were tested for evidence of infection with human T- lymphotropic virus type I (HTLV-I), human immunodeficiency virus type I (HIV-I), hepatitis B virus (HBV) and hepatitis C virus (HCV). No samples were positive for antibodies to HIV-I. Antibodies to HTLV-I were found in 13 samples (1.8%), HBV surface antigens (HBsAg) were found in 86 samples (11.9%), and antibodies to HCV were found in 30 samples (4.1%). Six (46.2%) of 13 HTLV-I positive samples were positive for HCV or HBsAg. The seropositive rate varied in different villages and the incidence of HTLV-I and HCV was higher in coastal and riverine areas than inland.