Mediastinoscopic extended thymectomy for pediatric patients with myasthenia gravis.

BACKGROUND: Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. METHOD: A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. RESULTS: The operation time and the amount of blood loss were 182±44 minutes and 34±43 ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5 days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. CONCLUSIONS: This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.

Activation of OASIS family, ER stress transducers, is dependent on its stabilization.

Endoplasmic reticulum (ER) stress transducers transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins accumulate in the ER. BBF2 human homolog on chromosome 7 (BBF2H7) and old astrocyte specifically induced substance (OASIS), ER-resident transmembrane proteins, have recently been identified as novel ER stress transducers that have roles in chondrogenesis and osteogenesis, respectively. However, the molecular mechanisms that regulate the activation of BBF2H7 and OASIS under ER stress conditions remain unresolved. Here, we showed that BBF2H7 and OASIS are notably unstable proteins that are easily degraded via the ubiquitin-proteasome pathway under normal conditions. ER stress conditions enhanced the stability of BBF2H7 and OASIS, and promoted transcription of their target genes. HMG-CoA reductase degradation 1 (HRD1), an ER-resident E3 ubiquitin ligase, ubiquitinated BBF2H7 and OASIS under normal conditions, whereas ER stress conditions dissociated the interaction between HRD1 and BBF2H7 or OASIS. The stabilization of OASIS in Hrd1(-/-) cells enhanced the expression of collagen fibers during osteoblast differentiation, whereas a knockdown of OASIS in Hrd1(-/-) cells suppressed the production of collagen fibers. These findings suggest that ER stress stabilizes OASIS family members and this is a novel molecular mechanism for the activation of ER stress transducers.

Irreducible indirect inguinal hernia containing uterus, ovaries, and Fallopian tubes.

An indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes is extremely rare in pediatrics. The present report describes the very rare case of a 1-month-old girl with an irreducible indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes, and the successful surgical treatment of simple herniorraphy. We review the literature on this type of relationship between indirect inguinal hernia and hernial visceras of the uterus, ovaries, and Fallopian tubes and discuss the clinical features of this complication. Furthermore, the possible cause of indirect inguinal hernia containing the uterus, ovaries, and Fallopian tubes was explored.

Congenital anomalies induced by triamcinolone acetonide in murine embryos.

INTRODUCTION: We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration. MATERIAL AND METHODS: TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR). RESULTS: The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens. CONCLUSION: The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.

[Three-channeled aortic dissection; report of a case].

The formation of 2 adjacent lumens is rarely observed in aortic dissection. We report herein a case of ruptured 3-channeled aortic dissection in a short time of hospitalization. A 58-year-old man who had been followed up for aortic dissection (Stanford type B) was admitted to Kumamoto National Hospital with an abdominal pain and a lumbago. A computed tomography (CT) revealed that a 3-channeled aortic dissection from the aortic arch to the right common iliac artery. An intramural hematoma was generated in the abdominal aorta and the left kidney was not enhanced. We initially adopted conservative therapies. But on the next day, he suddenly complained a severe back pain and died. At autopsy, the thoracic aorta was found to have ruptured into the mediastinum, and massive hematoma was formed.

Therapeutic value of selective salpingography for infertile women with patent fallopian tubes: the impact on pregnancy rate.

OBJECTIVE: To determine the therapeutic value of selective salpingography (SSG) for infertile women with patent fallopian tubes. DESIGN: Retrospective, case-control analysis. SETTING: University Hospital, infertility clinic. PATIENTS: Infertile cases with patent tubes documented by hysterosalpingography (HSG) or by HSG followed by laparoscopic examination (n = 80). INTERVENTION(S): Hysteroscopic SSG. MAIN OUTCOME MEASURE(S): Patency rate of tubes by SSG. Pregnancy rate following SSG. RESULT(S): Eighty cases were divided into the study group (SSG performed, 37 cases) and the case-control group (SSG not performed, 43 cases). Successful SSG of at least one tube was obtained in all of 37 cases (100%) in whom SSG was attempted. A patency rate of 95.9% was documented in the 73 cannulated tubes of these cases. The total subsequent pregnancy rate (48.6%) within 12 months of follow-up after SSG was significantly higher than that (11.6%) obtained in the control group (p < 0.001). The cumulative pregnancy rate in the study group was also significantly higher than that in the control group (p < 0.001). CONCLUSION(S): The findings of the present study encourage the application of SSG to infertile women, either as a sole therapeutic approach or in association with other methods of assisted reproductive technology, even if their fallopian tubes are shown to be patent by HSG.

Essential components of the Ti plasmid trb system, a type IV macromolecular transporter.

The trb operon from pTiC58 is one of three loci that are required for conjugal transfer of this Ti plasmid. The operon, which probably codes for the mating bridge responsible for pair formation and DNA transfer, contains 12 genes, 11 of which are related to genes from other members of the type IV secretion system family. The 12th gene, traI, codes for production of Agrobacterium autoinducer (AAI). Insertion mutations were constructed in each of the 12 genes, contained on a full-length clone of the trb region, using antibiotic resistance cassettes or a newly constructed transposon. This transposon, called mini-Tn5Ptrb, was designed to express genes downstream of the insertion site from a promoter regulated by TraR and AAI. Each mutation could trans complement downstream Tn3HoHo1 insertions in the trb operon of full-sized Ti plasmids. When marker-exchanged into the transfer-constitutive Ti plasmid pTiC58DeltaaccR mutations in trbB, -C, -D, -E, -L, -F, -G, and -H abolished conjugal transfer from strain UIA5, which lacks the 450-kb catabolic plasmid pAtC58. However, these mutants retained residual conjugal transfer activity when tested in strain NT1, which contains this large plasmid. The trbJ mutant failed to transfer at a detectable frequency from either strain, while the trbI mutant transferred at very low but detectable levels from both donors. Only the trbK mutant was unaffected in conjugal transfer from either donor. Transfer of each of the marker-exchange mutants was restored by a clone expressing only the wild-type allele of the corresponding mutant trb gene. An insertion mutation in traI abolished the production of AAI and also conjugal transfer. This defect was restored by culturing the mutant donor in the presence of AAI. We conclude that all of the trb genes except trbI and trbK are essential for conjugal transfer of pTiC58. We also conclude that mutations in any one of the trb genes except traI and trbJ can be complemented by functions coded for by pAtC58.

Purification of haemorrhagic proteinase from the venom of Agkistrodon caliginosus (Kankoku-Mamushi).

A haemorrhagic proteinase was purified from A. caliginosus venom by ion-exchange chromatography on CM-Sephadex C-50, DEAE-Sephadex A-50, S-Sepharose Fast Flow and Q-Sepharose Fast Flow, and gel-filtration on a Sephadex G-100 column. By this procedure, about 17.6 mg of the enzyme were obtained from 4 g of the venom. The enzyme showed a single band on polyacrylamide gel electrophoresis at pH 8.3 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme had weak caseinolytic and potent haemorrhagic activities, and the minimum haemorrhagic dose of the enzyme was about 0.04 microg. The haemorrhagic activity of the enzyme was only suppressed by treatment with ethylenediamine tetraacetic acid-disodium or o-phenanthroline. The enzyme is composed of a single polypeptide chain with a molecular weight of about 70 kDa and is a glycoprotein. These results indicate that the enzyme is a metalloproteinase as are haemorrhagic proteinases from other snake venoms.

Long-lasting abnormalities in cardiac sympathetic nervous system in patients with coronary spastic angina: quantitative analysis with iodine 123 metaiodobenzylguanidine myocardial scintigraphy.

Quantitative analysis of iodine 123 metaiodobenzylguanidine (MIBG) myocardial tomographic imaging showed that the regional uptake reduction and abnormally high washout of MIBG in the myocardial territories of the coronary artery with spasm were observed in 33 (75%) and in 30 (68%) of 44 patients with coronary spastic angina, whereas it was observed in two (7%) and in four (15%) of 27 control subjects, respectively. The patients with higher disease activity of the anginal attack and those with life-threatening ventricular arrhythmias were frequently associated with either the uptake reduction or the abnormally high washout of MIBG (91% in patients with high disease activity, 100% in patients with ventricular arrhythmias). The repeated studies of MIBG myocardial tomographic imaging at 2 and 6 months after suppression of anginal attacks by medical treatments showed that the scintigraphic abnormalities still remained in 85% of the patients at 2 months and 32% at 6 months. Thus the abnormalities in sympathetic nervous system assessed with MIBG scintigraphy has been shown to be highly associated with patients with coronary arteries with spasm, particularly high-risk patients, and lasted for several months despite suppression of anginal attack.

[A case of tubercular liver and splenic abscesses].

A 34-years male was admitted to our hospital with a hypochondria pain and low grade fever. Abdominal CT revealed an encapsulated 8 x 3 cm low density lesion on the surface of the liver (S5, S8) and multiple low density lesions of the spleen. The patient had already been treated with anti-tuberculous drugs for the past 7 months after being diagnosed as tuberculous pleuritis. Although echo-guided percutaneous needle biopsy was tried for the hepatic lesion, no special finding was obtained. Therefore a diagnostic laparotomy was performed and the hepatic lesion was resected. Abscess formation of the resected lesion was noted. Histopathology of the lesion revealed epithelioid granuloma, but microscopy, culture and PCR for tuberculosis revealed negative results. Abdominal CT, 3 weeks after surgery, revealed enlargement of the splenic lesion. Splenectomy was carried out to avoid splenic rupture. Multiple abscess of the resected spleen was noted. Pathological finding, Ziehl-Neelsen stain and PCR for tuberculosis confirmed the diagnosis of tubercular splenic and liver abscess. Although tubercular liver and splenic abscess are very rare recently, it should be included in the differential diagnosis of unknown hepatic and splenic lesions.

Mixed gonadal dysgenesis with gonadoblastoma in a female with Y chromosome: case report.

A young female with primary amenorrhea and male karyotype (46/XY) is reported. Physical examination and clinical investigation of the patient suggested mixed gonadal dysgenesis (MGD). After gonadectomy, a tumor was found on the left side and histologically diagnosed gonadoblastoma. Postoperative decreased level of testosterone and estradiol reflected the activities of the tumor.

Anion-selective electrodes based on long-chain methyltrialkylammonium salts.

A new series of methyltrialkylammonium salts with an alkyl chain length (n) longer than the conventional methyltridodecylammonium (MTDDA, n = 12) has been developed, and these materials were examined for use as the ion-sensing component (ligand) in anion-selective electrodes (ISEs). Syntheses of the higher ammoniums with n = 16, 18, and 20 were carried out. In combination with an alcoholic plasticizer, the ammoniums with n = 12, 16, and 18 led to ISEs with fundamental characteristics, such as slope sensitivity, impedance, and time response, that were sufficient for practical applications. Compared with the conventional MTDDA, the ISEs based on the ligands of n = 16 and 18 showed marked improvement in chloride selectivity over both lipophilic and hydrophilic anions, deviating from the Hofmeister regime in some cases. Taking perchlorate as an example, the magnitude of the improvement was a factor of 20 for n = 16 and 15 for n = 18. When the new ISEs were applied to chloride analysis in blood serum, they improved the accuracy by a factor of 2-6. Therefore, the methyltrialkylammonium salts with alkyl chain lengths of 16 and 18 offer definite advantages over the conventional alternative and are strong candidates to become the standard compounds for use in future chloride ISEs.

Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.

We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.

[A case report of miliary tuberculosis with acute respiratory failure diagnosed by polymerase chain reaction method].

A 51-year-old male was admitted because of cough and high fever. His chest X-ray and CT revealed miliary shadows, he was administered some antibiotics. But on the 8th day, his chest X-ray revealed ground glass shadows and he was under severe hypoxemia. We suspected miliary tuberculosis with acute respiratory failure due to his clinical course. The intensive therapy with antituberculosis drugs, hydrocortisone (1 g/day) was started and intubation was performed. The smear of the clinical samples did not show acid-fast bacilli on admission. However, by the polymerase chain reaction amplification method specific DNA fragments of Mycobacterium tuberculosis complex were detected from BALF and bone marrow. He was extubated after the 13th day and he recovered. It is difficult to separate and identify tubercle bacilli rapidly, but PCR is available for early diagnosis.

Effects of ouabain on contractile response to norepinephrine in isolated rat aorta.

1. Inhibition of sodium(Na+), potassium(K+)-ATPase activity was dependent on the concentration of ouabain and inverse to the concentration of potassium ([K+]) in the reaction mixture. 2. Contractility of isolated rat aorta preparation in response to norepinephrine was augmented by ouabain and low [K+]. 3. Results suggest that inhibition of Na+,K(+)-ATPase activity will be correlated with augmentation of vascular contractility maybe through activation of Na(+)-calcium exchange system.

Enhancement of vascular contractility by plasma substances obtained from pregnancy-induced hypertension.

1. Augmentation of norepinephrine (NE)-induced contraction of isolated dog mesenteric arteries by ouabain was significantly enhanced under 4 mM potassium ([K+]) medium condition compared with usual medium condition at 6 mM [K+]. 2. Vascular contractility to NE was significantly enhanced by plasma substances obtained from pregnancy-induced hypertension (PIH) patients compared with that from normotensive pregnant women under 4 mM [K+] medium condition despite of no difference between them under 6 mM [K+] medium condition. 3. These results suggest the possible involvement of the ouabain-like substance in development of hypertension in PIH patients.

Ouabain-like Na+,K(+)-ATPase inhibitory activity of a plasma extract in normal pregnancy and pregnancy induced hypertension.

To estimate the participation of a Na+,K(+)-ATPase-inhibiting plasma factor in pregnancy induced hypertension (PIH), the inhibitory activity and the characteristics of plasma extract eluted with ethanol through a C8 column were examined in normotensive non-pregnant women (N) and women with normal pregnancy (NP) and PIH. There were no differences among the 3 groups in the Na+,K(+)-ATPase activity of erythrocyte ghosts. The heat- and acid-stable plasma extract dose-dependently inhibited Na+,K(+)-ATPase activity with a pattern similar to that of ouabain, but different from that of vanadate. The inhibitory activity of plasma extract was not influenced by polyclonal digoxin antibody which almost completely prevented digoxin-induced inhibition and slightly but significantly reduced the ouabain-induced one. The results indicate that the plasma extract has ouabain-like inhibitory activity on Na+,K(+)-ATPase and that it is not endogenously synthesized digoxin itself, but a substance differing in structure from digoxin. Furthermore, the ouabain-like Na+,K(+)-ATPase inhibitory activity in NP plasma was significantly lower than that in PIH plasma, which was similar to that in N plasma. There were significant relationships between the ouabain-like Na+,K(+)-ATPase inhibitory activities in plasma and the diastolic and systolic blood pressures in NP and PIH groups. The results suggest that the lower ouabain-like Na+,K(+)-ATPase inhibitory activity in plasma probably participates in maintaining the blood pressure within the normal range during pregnancy and its failure may be involved in the genesis of PIH.

[Adoptive immunotherapy for pulmonary tuberculosis caused by multi-resistant bacteria using autologous peripheral blood leucocytes sensitized with killed Mycobacterium tuberculosis bacteria].

A patient with pulmonary tuberculosis caused by bacteria resistant to various anti-microbial agents was treated with adoptively transferred autologous peripheral blood leucocytes (PBL) sensitized with killed Mycobacterium tuberculosis organisms in vitro. The 32-year-old man was admitted to our hospital from National Sanitarium Okinawa Hospital with weight loss, high fever, and rapid aggravation on chest X-ray. Patient's PBL obtained by leukapheresis and separated with Ficoll-Hypaque solution were cultured with killed Mycobacterium tuberculosis bacteria of 0.4 microgram per ml at 1 x 10(6) cells per ml for 7 days in media containing 0.5 U recombinant 1L-2 per ml. After incubation, PBL were layered and centrifuged on Ficoll-Hypaque solution and washed three times with saline. PBL (1-3 x 10(8)) were combined and concentrated for infusion in 20 to 30 ml saline. After injection, patient displayed fever and transitory drop of PaO2. Although the patient did not have an improved on chest X-ray, his fever was alleviated, weight was increased, accelerated ESR was slightly improved, and the number of organisms in sputum (Number of Gaffky) temporarily decreased. Adoptive immunotherapy using the autologous PBL which were sensitized with killed bacteria may be an effective anti-tuberculous immunotherapy.

Magnesium deficiency detected by intravenous loading test in variant angina pectoris.

To study whether magnesium (Mg) deficiency is present in patients with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body weight) administered intravenously over 4 hours in 20 patients with variant angina was examined. No patient had received calcium antagonists before or during the study. All had attacks of chest pain associated with ST elevation on electrocardiograms. Twenty-one subjects without ischemic heart disease were studied as control subjects. Ten patients with variant angina were restudied 10 to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists (diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete suppression of anginal attacks. The mean serum Mg concentrations in the patients with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03 mg/dl, respectively (difference not significant). However, 24-hour Mg retention in the patients with variant angina was 60 +/- 5%, while that in the control subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is present in at least some patients with variant angina. The mean serum Mg concentrations before and after calcium antagonist treatment in 10 patients with variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively (difference not significant). However, 24-hour Mg retention decreased significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment. There is Mg deficiency in many patients with variant angina and it is corrected after treatment with calcium antagonists.