Histochemical Demonstration of Interleukin-2 in Decidua Cells of Patients With Preeclampsia

PROBLEM : The objective of this study was to gain insight into the immunological aspects of preeclampsia. METHOD : The presence of interleukin-2 (IL-2) protein in the decidua was examined in five preeclamptic patients and seven normal pregnant women employing the immunohistochemistry. RESULTS : The decidua cells were strongly stained for IL-2 in four out of five preeclamptic patients, while only very weak, if any, staining was observed in all the uncomplicated pregnant women. CONCLUSIONS : IL-2 was clearly present in decidua cells in the preeclamptic setting, suggesting the possible involvement of immune-activation in the phathophysiology of preeclampsia.     

Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. METHODS AND RESULTS: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in approximately 11% of the Japanese population. This 1727G>A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in approximately 30% reduction in the slow delayed rectifier K+ current I(Ks) without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. CONCLUSION: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I(Ks) dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population.     

Novel Form of Atrial Tachycardia Originating at the Atrioventricular Annulus

We report two patients with reentrant atrial tachycardia that originated at the AV annulus. Atrial tachycardia originated in the posterior portion of mitral annulus in one patient (case 1) and the posterolateral portion of tricuspid annulus in one patient (case 2). Tachycardia was successfully eliminated by RF catheter ablation in both patients, with the catheter placed underneath the mitral valve in case 1 and on the tricuspid annulus in case 2. Spiky potentials were recorded in the diastolic phase of the atrium during tachycardia at the sites of successful ablation. Spiky potentials were also recorded after atrial electrogram during sinus rhythm, and showed decremental properties during atrial pacing. An accelerated atrial rhythm was observed during RF application, and tachycardia could not be induced after ablation in either patient. Tachycardia in these patients seemed to be due to reentrant tachycardia originating in the accessory AV node (Mahaim fiber) without ventricular connection.     

Constitutive activation of the 41- and 43-kDa mitogen-activated protein (MAP) kinases in the progression of prostate cancer to an androgen-independent state

AIM: The 41- and 43-kDa mitogen-activated protein kinases (MAPK; ERK2 and ERK1, respectively) play pivotal roles in the mitogenic signal transduction pathway. We previously demonstrated that constitutive activation of the MAPK cascade was related to the carcinogenesis of human tumors. In this study, we examined whether constitutive activation of MAPK was related to the progression to androgen independence of prostate cancer. METHODS: MAPK activation was examined by the appearance of phosphorylated forms and an in vitro kinase assay in four human (androgen-dependent and independent) prostate cancer cell lines and rat prostate cancer cell line Dunning (androgen-sensitive G line, and androgen-independent AT-3, AT-6 sublines). In addition, when androgen-dependent mouse Shionogi Carcinoma 115 (SC115) cells were serially cultured without androgen to obtain androgen-independent cells, the time and degree of MAPK activation were examined. RESULTS: One of three human androgen-independent cell lines (DU145) showed constitutive activation of MAPK, while an androgen-dependent cell line (LNCaP) did not show MAPK activation. While MAPK were not activated in an androgen-sensitive Dunning G cell line, MAPK were activated in androgen-independent sublines (AT-3 and AT-6) derived from a G cell line. In addition, when SC115 cells were serially cultured without androgen, the cells 16-24 weeks after androgen removal showed MAPK activation. Furthermore, in subcloned cells, MAPK activation was observed even in the cells maintained for 9 weeks in medium without testosterone. CONCLUSIONS: The present fi ndings suggest that constitutive activation of MAPK may be associated with the acquisition of hormone independence in prostate cancer and that clonal selection after androgen removal and hormone-independent growth through the MAPK signal transduction pathway could begin at a relatively early period in the individual cells.     

High acid secretion may protect the gastric mucosa from injury caused by ammonia produced by Helicobacter pylori in duodenal ulcer patients

The aim of the present study was to investigate the mechanism by which gastric atrophy does not tend to occur in patients with duodenal ulcer despite frequent Helicobacter pylori infection. This investigation was performed in 60 patients with duodenal ulcer and 63 age-matched gastritis patients. Endoscopic findings in the antrum and corpus were classified as normal, atrophic and superficial changes. Biopsy specimens were taken from the antrum and corpus. Ninety per cent of patients with duodenal ulcer and 63.5% of patients with gastritis had H. pylori infection (P<0.01). The incidence of normal findings in duodenal patients was 30% in antral regions and 50% in the corpus (P<0.05). Atrophic change was observed in 21.7% of patients in the antrum and 3.3% of patients in the corpus (P<0.01). The grade of inflammation in duodenal ulcer specimens was significantly higher in the antrum than in the corpus (P<0.01). >H. pylori density was significantly higher in the antrum than in the corpus in ulcer patients (P<0.01). No significant difference in endoscopic findings, >H. pylori density or the grade of inflammation was found between the antrum and corpus in patients with gastritis. The mean intragastric ammonia concentration was 10.3 mg/dL in duodenal ulcer patients and 6.2 mg/dL in gastritis patients (P<0.01). The mean pH was 3.5 and 4.6 in ulcer and gastritis specimens, respectively (P<0.01). Our data suggest that gastric mucosa injury is less frequently associated with duodenal ulcers than with gastritis due to the low >H. pylori density in the corpus and to the higher acid output that neutralizes the ammonia produced by H. pylori.     

A case of Arnold-Chiari Type I malformation presenting with dysrhythmic breathing during sleep

Abstract A 43-year-old woman presented with dull headache, left tinnitus and dizziness. Neurological examination revealed down-beat gaze nystagmus, left tinnitus, positive Romberg sign, poor standing on the left foot, poor tandem gait, left spastic gait and positive pathological reflexes in the bilateral upper and lower extremities. Plain X-ray of the skull and cervical vertebrae demonstrated basilar impression and atlantoaxial fusion. Magnetic resonance imaging of the brain and cervical spine showed cerebellar tonsil descent and syringomyelia located in the left side of the spine at the II-III vertebral level which communicated with the fourth ventricle. The patient was diagnosed as having cervical syringomyelia, Arnold-Chiari type I malformation and basilar impression. Preoperative polysomnography showed dysrhythmic breathing and bradypnea during sleep. Abnormal breathing improved after suboccipital decompression craniotomy and upper cervical laminectomy. It was suggested that dysrhythmic breathing was caused by a disorder of the medullary respiratory center. Herniation of the cerebellar tonsil and syringomyelia might have compressed the medulla.     

Follow-up of clinical stage I testicular cancer patients: Cost and risk benefit considerations

BACKGROUND: Regardless of the way it is managed, a high cure rate has been achieved for recurrent low-stage testicular cancer. Achieving a balance between survival and the patient's inconvenience and expense during follow-up, has therefore become an important issue. METHODS: Prognoses and recurrence patterns were investigated in 39 patients with stage I non-seminomatous germ cell tumor of the testis (NSGCT), and 82 patients with stage I seminomatous germ cell tumor of the testis (SGCT), who underwent high orchiectomy between 1970 and 1997 at our institution. We considered the cost benefits and the risks by reviewing our results together with other reported results. RESULTS: Patients with clinical stage I NSGCT under surveillance showed no progression later than 4 years after orchiectomy. The ability to detect progression using chest X-ray alone appeared very low. There was no infradiaphragmatic recurrence after adjuvant radiotherapy for patients with stage I SGCT. Only two of 204 patients showed progression, which included eight of our patients who underwent two cycles of adjuvant carboplatin therapy. CONCLUSIONS: Four years of intensive follow-up is probably sufficient for patients with stage I NSGCT under surveillance, and routine chest X-rays may be required only during the first year of surveillance. The benefit of using adjuvant radiotherapy for patients with stage I SGCT is that we could remove abdominal and pelvic CT scans from the routine follow-up protocol. Randomized trials will clarify whether the adjuvant carboplatin therapy is less toxic, provides better prognosis and is more cost-effective than adjuvant radiotherapy.