Role of a mutation at position 167 of CTX-M-19 in ceftazidime hydrolysis

CTX-M-19 is a recently identified ceftazidime-hydrolyzing extended-spectrum beta-lactamase, which differs from the majority of CTX-M-type beta-lactamases that preferentially hydrolyze cefotaxime but not ceftazidime. To elucidate the mechanism of ceftazidime hydrolysis by CTX-M-19, the beta-lactam MICs of a CTX-M-19 producer, and the kinetic parameters of the enzyme were confirmed. We reconfirmed here that CTX-M-19 is also stable at a high enzyme concentration in the presence of bovine serum albumin (20 micro g/ml). Under this condition, we obtained more accurate kinetic parameters and determined that cefotaxime (k(cat)/K(m), 1.47 x 10(6) s(-1) M(-1)), cefoxitin (k(cat)/K(m), 62.2 s(-1) M(-1)), and aztreonam (k(cat)/K(m), 1.34 x 10(3) s(-1) M(-1)) are good substrates and that imipenem (k(+2)/K, 1.20 x 10(2) s(-1) M(-1)) is a poor substrate. However, CTX-M-18 and CTX-M-19 exhibited too high a K(m) value (2.7 to 5.6 mM) against ceftazidime to obtain their catalytic activity (k(cat)). Comparison of the MICs with the catalytic efficiency (k(cat)/K(m)) of these enzymes showed that some beta-lactams, including cefotaxime, ceftazidime, and aztreonam showed a similar correlation. Using the previously reported crystal structure of the Toho-1 beta-lactamase, which belongs to the CTX-M-type beta-lactamase group, we have suggested characteristic interactions between the enzymes and the beta-lactams ceftazidime, cefotaxime, and aztreonam by molecular modeling. Aminothiazole-bearing beta-lactams require a displacement of the aminothiazole moiety due to a severe steric interaction with the hydroxyl group of Ser167 in CTX-M-19, and the displacement affects the interaction between Ser130 and the acidic group such as carboxylate and sulfonate of beta-lactams.     

Dietary instructions focusing on meal-sequence and nutritional balance for prediabetes subjects: An exploratory,cluster-randomized,prospective, open-label,clinical trial

BackgroundAlthough lifestyle modifications are known to be effective in type 2 diabetes (T2D) as well as in prediabetes, adherence to a healthy diet is difficult for some, and interventions of lifestyle modifications need to be revised occasionally. Meal sequence has been gaining attention as a part of a healthy diet among T2D individuals to improve glycemia and body weight. In addition, a dietary instruction program, SMART Washoku®, which can help individuals to consume a more nutritionally balanced diet, has been developed.MethodsThe current exploratory trial was designed to examine the effects of dietary instructions focusing on meal sequence and nutritional balance in individuals with prediabetes in the Japanese national health check-up and guidance program. Participants were cluster-randomized into three groups: Group A, receiving a conventional health guidance program (n = 11); Group B, receiving health guidance with dietary instructions focusing on meal sequence (n = 18); and Group C, receiving health guidance with dietary instructions focusing on nutritional balance (n = 13). Participants received health guidance education and various measurements before and 6 months after the instructions.ResultsBody weight in Group B was significantly reduced compared to that in Group A, with similar adherence, while the effects on glycemia were similar between the two Groups. Body weight reduction was greater in Group C compared to that in Group A, although adherence in Group C was significantly lower than that in Group A.ConclusionThe group receiving health guidance with dietary instructions focusing on meal sequence exhibited similar adherence and greater reduction in body weight than the group receiving conventional health guidance.     

Importance of abdominal X-ray to confirm the position of levonorgestrel-releasing intrauterine system: A case report

BACKGROUNDLevonorgestrel-releasing intrauterine systems (LNG-IUSs) gradually release levonorgestrel into the uterus and is effective against hypermenorrhoea and dysmenorrhea. Complications associated with the insertion include expulsion, displacement, and uterine perforation. Ultrasonic identification of copper intrauterine devices (IUDs) is possible due to echogenicity from the copper coils. However, the barium sulfate coatings of LNG-IUSs do not always provide hyperechoic images. Both barium sulfate and copper are radiopaque and clearly identifiable on X-ray. Thus, X-ray imaging is required to locate LNG-IUSs.CASE SUMMARYA 46-year-old woman with hypermenorrhoea due to submucosal myomas was treated with LNG-IUS at another hospital. Three LNG-IUS insertions had apparently been followed by spontaneous expulsion, although objective confirmation using imaging was not performed. The patient was referred to our institution for surgery. At the first visit, there appeared to be no device in the uterus, and none was observed on transvaginal ultrasound. However, two LNG-IUSs were observed in the pelvis on abdominal plain X-rays prior to surgery. Hysteroscopic myomectomy was performed, and the two LNG-IUSs were found to have perforated the myometrium. The devices were safely removed during surgery, and the submucosal myomas were also removed. The perforated section of the myometrium was minimal+ADs- therefore, a repair operation was not required.CONCLUSIONPlain abdominal X-rays facilitate the determination of whether an LNG-IUS is in the uterine cavity. Therefore, it is important to confirm a device’s location, regardless of whether spontaneous expulsion is suspected, prior to inserting another device.     

Predicting initial recurrence pattern of esophageal cancer after neoadjuvant chemotherapy

BACKGROUND/AIMS: No report has reviewed which clinicopathological factors including 3-field dissection and the response to neoadjuvant chemotherapy can predict the recurrence pattern of an esophageal carcinoma. The aim of this study was to reveal clinicopathological predictors for the initial recurrence pattern of a thoracic esophageal carcinoma. METHODOLOGY: Sixteen parameters derived from 98 patients who underwent a curative esophagectomy with neoadjuvant chemotherapy for a squamous cell carcinoma of the thoracic esophagus were examined using univariate and multivariate logistic regression analyses. RESULTS: Thirty-seven (37.8%) of the 98 patients had recurrences (hematogenous; 16, lymphatic; 13, others; 8). Univariate analyses revealed that the completion of 3-field dissection was the only factor for suppressing the lymphatic recurrence (P = 0.009; odds ratio: 0.2). Multivariate analyses showed that the number of positive nodes was a significant predictor for recurrence including all modalities (P = 0.02; odds ratio: 1.2) and both the number of positive nodes (P = 0.04; odds ratio: 1.1) and the poor response to neoadjuvant chemotherapy (P = 0.02; odds ratio: 6.9) were significant predictors for the hematogenous recurrence. CONCLUSIONS: The number of positive nodes and the response to neoadjuvant chemotherapy could predict the hematogenous recurrence of esophageal carcinoma.     

Specialists Play a Vital Role in General Practitioners' Prescription Behavior: A Qualitative Study of Asthma Care in Japan

Background. The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. Objectives. We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. Methods. The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. Results. Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. Conclusions. Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.     

Acid precipitation of Clostridium botulinum type C and D toxins from whole culture by addition of ribonucleic acid as a precipitation aid.

The ratios of ribonucleic acid to protein contents of Clostridium botulinum type C, D, and E cultures were lower than those of type A, B, and F cultures. Addition of ribonucleic acid at 0.4 mg/ml to culture satisfactorily aided acid precipitation of type C and D toxins, but not that of type E toxin.     

Initial experience in Japan with HeartWare ventricular assist system

We describe the first clinical experiences in Japan with the HeartWare ventricular assist device (HVAD: HeartWare Inc., Miami Lakes, FL, USA) in patients awaiting heart transplantation. Nine patients (6 males, 3 females; mean 33.5 ± 7.8 years; New York Heart Association class III or IV) received the HVAD as a bridge to transplantation between 2011 and 2012. Six had dilated cardiomyopathy, 2 secondary cardiomyopathy, and 1 dilated phase hypertrophic cardiomyopathy. All operations were uneventful, with a mean operation time of 269 ± 77 min and cardiopulmonary bypass time of 121 ± 40 min. One required a temporary right ventricular assist device and was weaned on postoperative day 20, while another required pump exchange due to foreign tissue in the inflow. Mean support duration was 245 ± 162 days (range: 50–535 days) and mean pump blood flow at 1 month postoperatively was 4.8 ± 0.8 l/min. There was no mortality after 30 days, though 1 patient died during support due to cerebral hemorrhage. Presently, the others are waiting for heart transplantation without problems, except 1 who suffered from an active infection. There was no pump mechanical failure in any case. The HeartWare pump enables quick implantation with acceptable morbidity and mortality. Our preliminary results indicate that this left ventricular assist device is safe for circulatory assistance for heart transplant candidates in Japan.     

Doppel induces degeneration of cerebellar Purkinje cells independently of Bax

Doppel (Dpl) is a prion protein paralog that causes neurodegeneration when expressed ectopically in the brain. To investigate the cellular mechanism underlying this effect, we analyzed Dpl-expressing transgenic mice in which the gene for the proapoptotic protein Bax had been deleted. We found that Bax deletion does not alter either clinical symptoms or Purkinje cell degeneration in Dpl transgenic mice. In addition, we observed that degenerating Purkinje cells in these animals do not display DNA fragmentation or caspase-3 activation. Our results suggest that non-Bax-dependent pathways mediate the toxic effects of Dpl in Purkinje cells, highlighting a possible role for nonapoptotic mechanisms in the death of these neurons.