Aiolos collaborates with Blimp-1 to regulate the survival of multiple myeloma cells.

The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) has crucial roles in the control of plasma cell differentiation and in maintaining survival of plasma cells. However, how Blimp-1 ensures the survival of plasma cell malignancy, multiple myeloma (MM), has remained elusive. Here we identified Aiolos, an anti-apoptotic transcription factor of MM cells, as a Blimp-1-interacting protein by mass spectrometry. ChIP coupled with DNA microarray was used to profile the global binding of Aiolos and Blimp-1 to endogenous targets in MM cells, which revealed their co-binding to a large number of genes, including apoptosis-related genes. Accordingly, Blimp-1 and Aiolos regulate similar transcriptomes in MM cells. Analysis of the binding motifs for Blimp-1 and Aiolos uncovered a partial motif that was similar across sites for both proteins. Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1-dependent transcriptional repression. Furthermore, treatment with an anti-MM agent, lenalidomide, caused ubiquitination and proteasomal degradation of Blimp-1, leading to the de-repression of a new Blimp-1 direct target, CULLIN 4A (CUL4A), and reduced Aiolos levels. Accordingly, lenalidomide-induced cell death was partially rescued by reintroduction of Blimp-1 or knockdown of CUL4A. Thus, we demonstrated the functional impacts and underlying mechanisms of the interaction between Aiolos and Blimp-1 in maintaining MM cell survival. We also showed that interruption of Blimp-1/Aiolos regulatory pathways contributes to lenalidomide-mediated anti-MM activity.

Evaluation of discrepancies between oxacillin and cefoxitin disk susceptibility for detecting methicillin-resistant Staphylococcus aureus.

The Clinical Laboratory Standards Institute recommends that if both cefoxitin and oxacillin are tested against Staphylococcus aureus and either result is measured as resistant, the organism should be reported as oxacillin resistant. This indicates that discrepancies may be present between oxacillin and cefoxitin sensitivities in S. aureus. In this study, we aimed to investigate the discrepancy between oxacillin and cefoxitin susceptibility in S. aureus clinical isolates. Of 10,980 S. aureus isolates recovered from 2005 to 2010, 27 (0.3%) isolates with discordant results between oxacillin and cefoxitin were collected. Fourteen (oxacillin diameters 10-12 mm) of the 27 strains were susceptible (MICs = 0.5-2 µg/ml) and 13 (6-13 mm) were resistant (4->256 µg/ml) to oxacillin. The cefoxitin MICs of 14 oxacillin-susceptible and 13 oxacillin-resistant strains ranged between 4 and 8 and 8 to 32 µg/ml, respectively. Discrepancies were present between oxacillin and cefoxitin in S. aureus, and these strains should be further tested for oxacillin MICs and for the mecA gene or ß-lactamase activity.

Evaluation of discrepancies between oxacillin and cefoxitin susceptibility in coagulase-negative staphylococci.

The Clinical and Laboratory Standards Institute (CLSI) recommends testing coagulase-negative staphylococci (CoNS) strains to determine resistance against oxacillin by testing for mecA, PBP2a, or with cefoxitin disk. However, discrepant results of resistance to oxacillin and susceptibility to cefoxitin were found. In this study, we aimed to investigate the oxacillin resistance and cefoxitin susceptibility of CoNS in Taiwan. Of 9,017 strains collected from 2005 to 2010, 131 (1.5%) of the isolates were oxacillin-resistant and cefoxitin-susceptible. Species identification was carried out using the Vitek 2 system or 16S ribosomal RNA sequencing. Oxacillin minimum inhibitory concentrations (MICs) were examined by the agar dilution method. The presence of mecA and the activity of ß-lactamase were performed by polymerase chain reaction (PCR) and Cefinase disks, respectively. Overall, 33% (43/129) of the strains carried mecA and 43% (37/86) of mecA-negative isolates tested positive for ß-lactamase. The remaining 49 isolates were negative for both mecA and ß-lactamase, and were mainly Staphylococcus cohnii ssp. urealyticus and S. saprophyticus (oxacillin MICs 0.5-2 µg/ml) obtained from bloodstream and urinary tract infections. Our study suggests that incorrect reporting can be found in CoNS using cefoxitin disk alone to determine the susceptibility to oxacillin, and the strains should be further tested for oxacillin MICs and detection of the mecA gene or ß-lactamase activity.

Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication.

BACKGROUND AND AIM: To test whether the chronic users of celecoxib, a selective cyclo-oxygenase-2 inhibitor, had less Helicobacter pylori-related intestinal metaplasia or if such users' intestinal metaplasia could be prone to disappear after H. pylori eradication. METHODS: The study enrolled 150 chronic celecoxib users and 216 non-users who underwent pan-endoscopy to detect H. pylori infection and its related intestinal metaplasia. One hundred and three H. pylori-infected patients with intestinal metaplasia (43 chronic celecoxib users and 60 non-users) received anti-H. pylori therapy and completed the 12-month follow-up to survey the regression of intestinal metaplasia by mean intestinal metaplasia score. RESULTS: There were no differences in the prevalence of H. pylori-related intestinal metaplasia between the chronic celecoxib users and controls (P > 0.05). On the 12th month of follow-up, chronic celecoxib users had a lower mean intestinal metaplasia score (1.2 vs. 1.8, P < 0.005) and a higher regression rate of intestinal metaplasia (42% vs. 20%, P = 0.027) than non-users. CONCLUSIONS: With H. pylori infection, chronic celecoxib users still showed limited effects to decrease intestinal metaplasia. Nevertheless, celecoxib should be promising to assist H. pylori eradication for the control of gastric intestinal metaplasia and cancer risk.

Contrasting phylogeographical patterns between mainland and island taxa of the Pinus luchuensis complex.

Species whose geographical distribution encompasses both mainland and island populations provide an ideal system for examining isolation and genetic divergence. In this study, paternally transmitted chloroplast DNA (cpDNA) and maternally transmitted mitochondrial DNA (mtDNA) were used to estimate population structure and phylogeography of Pinus luchuensis, a species found in eastern China (ssp. hwangshanensis), Taiwan (ssp. taiwanensis), and the Ryukyu Archipelago (ssp. luchuensis). Gene genealogies of both mtDNA and cpDNA reveal two major lineages. Molecular dating indicates that these lineages diverged before the colonization of P. luchuensis subspecies in Taiwan and the Ryukyu Archipelago. Both mtDNA and cpDNA show a lack of correspondence between molecular phylogeny and subspecies designation. Phylogeographical analysis suggests that paraphyly of the subspecies is the result of recent divergence rather than secondary contacts. In spite of the short divergence history of P. luchuensis on islands, the island populations show the same degree of genetic divergence as mainland populations. Low levels of genetic diversity in the mainland ssp. hwangshanensis suggest demographic bottlenecks. In contrast, the high heterogeneity of genetic composition for island populations is likely to be associated with a history of multiple colonization from the mainland. The spatial apportionment of organelle DNA polymorphisms is consistent with a pattern of stepwise colonization on island populations.

Incidental primary hyperparathyroidism in a hypercalcaemic woman with tuberculous peritonitis.

We report on a 51-year-old woman with initial hypercalcaemia and unknown ascites. In spite of unyielding laparoscopy, laparotomy showed findings compatible with tuberculous peritonitis (TBP). Unexpectedly, a series of examinations eventually revealed the concurrence of hyperparathyroidism due to a parathyroid adenoma. Anti-tuberculous regimen was given and was uneventful. However, hypercalcaemia was not decreased but sustained at a high level even after anti-tuberculous therapy for 3 months. Parathyroidectomy was performed with subsequent normalisation of hypercalcaemia. The aetiology of hypercalcaemia in a patient with an explored disease able to cause this electrolyte abnormality such as TBP may be a coexistent occult parathyroid adenoma.

Hypercalcaemia and haemophagocytic syndrome: rare concurrent presentations of disseminated tuberculosis in a dialysis patient.

Tuberculosis remains an important cause of infection in chronic haemodialysis patients. Frequent extrapulmonary involvement, non-specific presentation and limited diagnostic tools usually make early diagnosis difficult. Herein, we report on an 83-year-old female patient who had been on regular heamodialysis therapy for 15 years, who presented with asymptomatic hypercalcaemia and pancytopenia. Haemophagocytic syndrome was documented during the admission period. Mycobacterium tuberculosis was cultured from bone marrow 1 month after her demise. This case report highlights the non-specific manifestations of extrapulmonary tuberculosis in dialysis patients and the limited value of conventional diagnostic methods. We would like to recommend aggressive intervention and early tissue aspiration from possible infectious sites when tuberculosis cannot be completely ruled out. Disseminated tuberculosis should be considered as an indication of hypercalcaemia where haemophagocytic syndrome occurs simultaneously.

Tuberculous peritonitis in uremic patients.

AIMS: To identify clinical features and treatment response of tuberculous peritonitis (TBP) in a uremic population, a retrospective case-control study was performed. MATERIALS AND METHODS: Thirteen uremic patients with TBP (Group I: 62.7 +/- 6.8 years, male 54%) collected between January 1986 and January 2002 were compared with another two age- and sex-matched controls: 19 non-azotemic patients with TBP (Group II: 62.9 +/- 7.3 years, male 47%) and 30 uremic patients without TBP (Group III: 61.1 +/- 8.7 years, male 47%). Clinical information and data of ascites and blood examinations were evaluated. RESULTS: Significant differences between Groups I and II were found in comorbidity, hypertension, anorexia, percentages of neutrophil and lymphocyte from blood and ascites, and serum calcium (sCa), phosphorus and albumin-adjusted calcium (sAACa). However, no significant differences in duration of symptoms, coexistent pulmonary tuberculosis (p = 0.061), duration or complications of therapy and mortality (p = 0.13) were detected. Significant differences between Groups I and III were found in peripheral white cell counts and percentages of neutrophil and lymphocyte as well as in serum creatinine (sCr), albumin, sCa, sAACa and intact parathyroid hormone (iPTH). CONCLUSIONS: Non-specific symptoms make the diagnosis of TBP in a uremic population difficult. However, neutrophil predominance in blood and ascites, hypoalbuminemia, relatively lower sCr and hypercalcemia with suppressed serum iPTH were found to be characteristic. In TBP uremic patients, therapy complications were not common and there was a tendency for higher mortality, largely due to septic shock.

Successful pregnancy by transmyometrial and transtubal embryo transfer after IVF in a patient with congenital cervical atresia who underwent uterovaginal canalization during Caesarean section: case report.

Successful pregnancy in a patient with congenital cervical atresia is a great challenge for assisted reproductive techniques and reproductive medicine. We report a case of successful pregnancy by transmyometrial and transtubal embryo transfer simultaneously after in-vitro fertilization (IVF) in a 33 year-old patient with congenital cervical atresia diagnosed at the age of 18 years. The patient had experienced cyclic abdominal pain and amenorrhoea since she was 13 years old. She had had two unsuccessful attempts to create a new uterovaginal canal in another hospital. At the age of 32 years, she was referred to our unit and had a successful pregnancy after transmyometrial and transtubal embryo transfer. Caesarean section was performed at 36 weeks gestation due to progressive pre-eclampsia and gestational diabetes. A healthy male baby weighing 2812 g was safely delivered. Uterovaginal canalization with amniotic membrane for the covering of the neo-endocervical wall was performed during Caesarean section. Normal menstrual outflow and symptomatic relief have continued for 5 months after the operation. To the best of our knowledge, this is the first reported case of successful pregnancy by transmyometrial and transtubal embryo transfer as well as uterovaginal canalization performed during Caesarean section in a patient with congenital cervical atresia.

Neglected bilateral femoral neck fractures in a patient with end-stage renal disease before chronic dialysis.

Bilateral femoral neck fractures are rarely reported in patients with end-stage renal disease before chronic dialysis. We report on a 39-year-old woman with neglected bilateral femoral neck fractures, who presented with severe uremic complications prior to chronic dialysis. Three years before admission, she had injured herself in a trivial slip with subsequent bilateral hip pain. She had progressively waddled since then. Pelvic X-ray taken after admission revealed bilateral femoral neck fractures. Bilateral hip hemiarthroplasties were subsequently performed. Displaced femoral neck fractures were found intraoperatively. Pathologic findings and results of examinations supported the coexistence of osteoporosis and high turnover renal osteodystrophy, rendering this woman at high risk of bilateral femoral neck fractures. Therefore, preventing a simple fall or trivial accident and treating renal osteodystrophy and osteoporosis are paramount in patients with chronic renal failure even before the start of dialysis therapy. We also emphasize the need to seek any possible underlying metabolic bone disease once a patient presents with unusual fractures.

Implications of sonographic identification of duplex kidney in adults.

BACKGROUND: Duplication of the renal pelvis and ureter constitutes the most common anomalies of the upper urinary tract. Most patients are asymptomatic and don't need treatment. However, the associated anomaly and acquired renal disease may cause morbidity and mortality. The aim of this study was to investigate the prevalence of duplex kidney in sonographic examinations and the predictive capability of this method. An analysis of patients with urography-confirmed duplication anomaly was also performed. METHODS: During a period of 9 year (from 1988 to 1996), sonographic examination records of 19,287 patients were reviewed. Patients with a diagnosis of duplex kidney were enrolled. Their clinical characteristics and radiological images were recorded and evaluated. RESULTS: One hundred and sixty-three patients were found by sonography to have duplex kidney, for an prevalence of 0.85%. Urography studies were done on 64 (39.2%) patients, and 42 patients were proven to have duplex kidney. The positive predictive rate of sonography was 65.6%. Eighty percent of patients with duplex kidney had associated ureteral duplication. No associated anomalies were found. Four patients had urolithiasis, and 3 patients had recurrent urinary tract infection. One patient had coexisting uroepithelial malignancy, and 1 patient had refractory gross hematuria. CONCLUSIONS: Duplex kidney is an uncommon finding during adult sonographic examinations. The sensitivity and specificity of sonography in identifying this anomaly are controversial. An experienced hand with good knowledge of the anomaly and its sonographic signs is helpful in more accurately diagnosing this anomaly.

Ischemic bowel disease in chronic dialysis patients.

BACKGROUND: Ischemic bowel disease, especially acute mesenteric ischemia, carries high morbidity and mortality rates. Any delay in diagnosis or treatment aggravates the patient's outcome. Owing to the scarcity of reports concerning ischemic bowel disease in chronic dialysis patients, we investigated the ischemic bowel disease in chronic dialysis patients. METHODS: From January 1986 through April 1997, medical records of 2416 chronic dialysis patients at our hospital were reviewed. Among them, 5 patients with surgically documented ischemic bowel disease were enrolled. The clinical manifestations, laboratory findings, operative findings, pathologic test results and prognoses of these patients are reported. RESULTS: Abdominal pain, abdominal distension and bloody stool were major initial presentations. The mean age of the patients was 62.4 years at the time of diagnosis of ischemia. All patients had hypertension, 3 patients had hyperlipidemia, three patients had diabetes mellitus and three patients had history of shunt occlusion. Four patients had leukocytosis. Image studies revealed dilatation of bowel loops in four patients. Peritonitis made exploratory laparotomy necessary. The findings during operation showed turbid ascites and variable degrees of bowel ischemia or gangrene. The methods of surgical intervention depended on the severity of the disease. Only one patient died due to extensive ischemic bowel involvement and subsequent sepsis. CONCLUSION: It is mandatory to have an index suggestive of ischemic bowel disease in chronic dialysis patients with unexplained abdominal pain or discomfort. Early diagnosis and aggressive surgical intervention is the cure modality for patients with acute ischemic bowel disease.

Intracranial acute arterial ischemia of the anterior circulation: evaluation with three-dimensional time-of-flight magnetic resonance angiography.

BACKGROUND: Stroke has been the second most common cause of death, after cancer, in Taiwan since 1983. The cost of stroke to society in terms of morbidity, mortality and economics is profound. Heightened interest in the early diagnosis and treatment of acute stroke challenges neuroimagers to optimize available modalities and to develop new techniques for the evaluation of cerebrovascular disease. The aim of this study was to investigate the effectiveness of magnetic resonance angiography (MRA) in conjunction with spin-echo imaging in patients with acute brain infarction of the anterior circulation. METHODS: Magnetic resonance imaging and three-dimensional Fourier transformed time-of-flight MRA studies, performed on 50 patients within one week after the onset of cerebral ischemia, were retrospectively reviewed and correlated with clinical records. Five of the 50 MRAs were considered nondiagnostic and excluded because of poor patient cooperation. RESULTS: In 41 of the 45 cases, the area of infarct corresponding to the clinical deficit at the time of study was identified on T2-weighted spin-echo images. Arterial occlusions or severe stenoses that corresponded to ischemic manifestations were identified with MRA in 37 of the 45 patients. A focal discontinuity with decreased arterial caliber corresponded to stenosis and nonvisualization of distal branches represented arterial occlusion. MRA provided information for 23 cases not obtained from the MR images. CONCLUSIONS: Vascular lesions demonstrated on intracranial MRA show a high correlation with infarct distribution. MRA, which provides information adjunctive to conventional MR imaging in a majority of cases, is concluded to be an important component of the complete evaluation of brain infarction.

Traumatic dissection of the vertebral artery: a case report.

This report concerns a patient suffering from a severe neck pain on the third day after a traffic accident. This condition was followed by a lateral medullary infarction on the next day. One week later, he was transferred to this hospital and dissection of the vertebral artery was disclosed. It should be emphasized that in case of acute cervical spine injury or severe neck pain after a major trauma, vertebral artery dissection should be considered, as its early diagnosis may have crucial therapeutic implications. In addition, the advantages of the combination of magnetic resonance imaging and magnetic resonance angiography as diagnostic tools-of-choice are emphasized.