Sequence-dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) Monohydrate

We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.     

Excessive rapid palatal expansion with Latham appliance for distal repositioning of protruded premaxilla in bilateral cleft lip and alveolus.

OBJECTIVE: This article reports a case of bilateral cleft lip and alveolus (BCLA) for which excessive rapid palatal expansion with a Latham appliance was performed for preoperative alignment of the protruded premaxilla. Postoperative changes of maxillary width were investigated with serial plaster casts. PATIENT AND RESULTS: A 3-month-old girl presented with complete BCLA in which the premaxilla was markedly protruded. Preoperative alignment of the protruded premaxilla with a Latham appliance was planned to facilitate primary lip repair. The appliance was placed when the patient was 4.5 months old. The necessary palatal expansion was estimated to be 7.0 mm in order to move the premaxilla backward into the ideal position. After palatal expansion and posterior repositioning of the protruded premaxilla, the primary operation, including cheiloplasty and gingivoperiosteoplasty, was performed when the patient was 7 months old. Excessive maxillary expansion might be a cause of transverse maxillomandibular discrepancy. Measurement with serial plaster casts demonstrated that maxillary widths increased from 42.3 mm pretreatment to 49.0 mm after orthopedic treatment but relapsed markedly to 43.5 mm at 3 months after the primary operation. Therefore, the net change of maxillary widths was only 1.2 mm. After alignment of the protruded premaxilla, tension-free soft tissue repairs were performed, and a harmonious alveolar arch was obtained without change in maxillary width. CONCLUSION: These results indicate that this method is useful for preoperative management of BCLA with protruded premaxilla.     

Comparative study of functional outcomes of three laparoscopic intestinal surgical procedures

ObjectivesLaparoscopic abdominal surgery (LS) has been prevailing over open surgery (OS). However, its functional outcomes in the aging generation have not been sufficiently examined. We compared changes in physical status and earlier resumption of oral intake between LS and OS.MethodsUsing the Japanese administrative database, we matched variables affecting LS and compared them between LS and OS patients. During the 6-month period from July to December of 2006–2010, we examined the data from data from surviving patients of ≥15 year old who underwent isolated gastrectomy, colectomy, or anterior resection. Functional status was estimated by the Barthel index (BI) at admission and discharge. Outcomes were postoperative complications, BI deterioration, change in BI, and day of recommencing postoperative oral intake.ResultsWe identified 30,763 gastrectomies (laparoscopic: 7297), 31,958 colectomies (laparoscopic: 9364), and 12,545 anterior resections (laparoscopic: 4351). Variation in LS indications was observed in patient and hospital mixes. Among the paired-matched gastrectomy, colectomy, and anterior resection groups, LS was associated with fewer complications and earlier recovery of postoperative oral intake. Laparoscopic anterior resection (LAR) and colectomy were associated with less frequent BI deterioration. Longer operative time was associated with more complications, which then influenced BI deterioration in patients who underwent anterior resection.ConclusionsShorter operative time for LAR was associated with less functional deterioration than for laparoscopic gastrectomy and colectomy. Physicians should consider the appropriate indications for LS by concurrently avoiding unnecessary longer operations and their associated complications. More investment in teaching the skills necessary for LAR is recommended.     

Elucidating the Function of Non catalytic Domains of Collagenases and Aggrecanases

Metalloproteinases that degrade extracellular matrix molecules play important roles in development and progression of various diseases. Among them, collagenases are unique as they have an ability to degrade triple helical interstitial collagens into 3/4 and 1/4 fragments, a crucial step for collagenolysis in the tissue. Collagenases, consisting of a catalytic domain and a hemopexin domain, requires both domains for collagenolysis. The enzymes unwind triple helical collagen before they hydrolyze the peptide bonds. Aggrecanases are also multidomain metalloproteinases belonging to the ADAMTS family, and the noncatalytic ancillary domains also play an important role in recognition of aggrecan and their activities. Attenuation of collagenase and aggrecanase activities will be achieved by inhibitors or antibodies that interact directly with those noncatalytic ancillary domains (exosite inhibitors). Such molecules will be attractive for therapy as they will be highly selective because they are based on the unique mechanism of each proteinase.     

Cortical Distribution of Fragile Periventricular Anastomotic Collateral Vessels in Moyamoya Disease: An Exploratory Cross-Sectional Study of Japanese Patients with Moyamoya Disease

BACKGROUND AND PURPOSE:Collateral vessels in Moyamoya disease represent potential sources of bleeding. To test whether these cortical distributions vary among subtypes, we investigated cortical terminations using both standardized MR imaging and MRA.MATERIALS AND METHODS:Patients with Moyamoya disease who underwent MR imaging with MRA in our institution were enrolled in this study. MRA was spatially normalized to the Montreal Neurological Institute space; then, collateral vessels were measured on MRA and classified into 3 types of anastomosis according to the parent artery: lenticulostriate, thalamic, and choroidal. We also obtained the coordinates of collateral vessel outflow to the cortex. Differences in cortical terminations were compared among the 3 types of anastomosis.RESULTS:We investigated 219 patients with Moyamoya disease, and a total of 190 collateral vessels (lenticulostriate anastomosis, n = 72; thalamic anastomosis, n = 21; choroidal anastomosis, n = 97) in 46 patients met the inclusion criteria. We classified the distribution patterns of collateral anastomosis as follows: lenticulostriate collaterals outflowing anteriorly (P < .001; 95% CI, 67.0–87.0) and medially (P < .001; 95% CI, 11.0–24.0) more frequently than choroidal collaterals; lenticulostriate collaterals outflowing anteriorly more frequently than thalamic collaterals (P < .001; 95% CI, 34.0–68.0); and choroidal collaterals outflowing posteriorly more frequently than thalamic collaterals (P < .001; 95% CI, 14.0–34.0). Lenticulostriate anastomoses outflowed to the superior or inferior frontal sulcus and interhemispheric fissure. Thalamic anastomoses outflowed to the insular cortex and cortex around the central sulcus. Choroidal anastomoses outflowed to the cortex posterior to the central sulcus and the insular cortex.CONCLUSIONS:Cortical distribution patterns appear to differ markedly among the 3 types of collaterals.

Collateral vessels in Moyamoya disease develop as the disease progresses.¹ Lenticulostriate arteries (LSAs), perforators from the posterior communicating artery (PcomA), and anterior and posterior choroidal arteries (choAs) are representative collateral vessels that supply the cortex.^2-4 Development of such collateral vessels represents a risk factor for intracerebral hemorrhage,^3,5-7 and these vessels have frequently been considered as the vessels responsible for bleeding in recent reports.^8-10 These collateral vessels connect with medullary arteries near the lateral ventricle and thus supply the cortex via the medullary arteries.^3,4 However, no reports have addressed the cortical distributions of these collateral vessels.Bypass surgery reduces the risk of rebleeding in patients with hemorrhagic onset of Moyamoya disease^7,11-13 and also shrinks collateral vessels in Moyamoya disease.^7,12,14,15 Augmentation of cerebral blood flow via bypass seems to decrease the necessity for development of collateral flow and shrinks existing collaterals.¹⁵ To shrink risky collateral vessels effectively and prevent hemorrhage, well-designed and planned bypass surgeries may be required.¹⁶ Comprehension of the nature and cortical distribution of collateral vessels may thus be clinically useful.MRA performed using a 3T scanner has proved useful for detecting the abnormally extended collateral vessels in Moyamoya disease.² We investigated the cortical distribution of collateral vessels using 3T MR imaging and MRA to clarify whether cortical distributions vary among anastomotic subtypes and to better understand collateral networks.     

Prevalence of Depressive Symptoms and Related Factors in Japanese Employees as Measured by the Center for Epidemiologic Studies Depression Scale (CES-D)

This study aimed to examine the prevalence of depressive symptoms and related factors in Japan. For this purpose, a questionnaire including the Center for Epidemiologic Studies Depression Scale (CES-D) was administered to employees from Akita prefecture, Japan. The cutoff point for CES-D scores was 16 or above (high scorers). We analyzed the results of this survey in order to identify relationships between the prevalence of high scores on the CES-D, sociodemographic status, and employment-related variables. In total, 2,220 employees—of whom 1,069 were men and 1,151, women—satisfactorily responded, and their responses indicated that 45.0 % (41.4 % for men, 48.2 % for women) had high scores on the CES-D. The identified sociodemographic and occupation-related factors from the binomial multivariate logistic regression for high scorers were as follows: a high risk of depression was associated with being women, short and/or long sleep durations, the occasional consumption of alcohol in men, and professional work and over 8 h of work per day in women. Older age groups and non-smoking women were associated with a lower risk. These results can be used in the future as CES-D benchmark values, and might be useful in predicting the occurrence of depressive disorders.     

Isolated cortical tuber in an infant with genetically confirmed tuberous sclerosis complex 1 presenting with symptomatic West syndrome

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disorder caused by mutations in either TSC1 on chromosome 16 or TSC2 on chromosome 9, clinically characterized mainly by facial angiofibroma, epilepsy, and intellectual disability. Cortical dysplasias, subependymal nodules, and subependymal giant cell astrocytoma are characteristic central nervous system lesions among 11 major features in the current clinical diagnostic criteria for TSC. We encountered an unusual case of genetically confirmed TSC1 presenting with symptomatic West syndrome due to an isolated cortical dysplasia in the left occipital lobe of a six‐month‐old male infant who did not meet the clinical diagnostic criteria for TSC. The patient underwent left occipital lesionectomy at age 11 months and has been seizure‐free for nearly six years since then. Histological examination of the resection specimen revealed cortical neuronal dyslamination with abundant dysmorphic neurons and ballooned cells, consistent with focal cortical dysplasia (FCD) type IIb. However, the lesion was also accompanied by unusual features, including marked calcifications, dense fibrillary gliosis containing abundant Rosenthal fibers, CD34‐positive glial cells with abundant long processes confined to the dysplastic cortex, and multiple nodular lesions occupying the underlying white matter, consisting exclusively of ballooned cell and/or balloon‐like astrocytes with focal calcifications. Genetic testing for TSC1 and TSC2 using the patient's peripheral blood revealed a germline heterozygous mutation in exon 7 (NM_000368.5: c.526dupT, p.Tyr176fs) in TSC1. Isolated FCD with unusual features such as calcification, dense fibrillary gliosis, Rosenthal fibers and/or subependymal nodule‐like lesions in the white matter may indicate the possibility of a cortical tuber even without a clinical diagnosis of TSC. Identification of such histopathological findings has significant implications for early and accurate diagnosis and treatment of TSC, and is likely to serve as an important supplementary feature for the current clinical diagnostic criteria for TSC.     

Schwannoma mimicking pancreatic carcinoma: A case report

BACKGROUNDSchwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery.CASE SUMMARYA 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement.CONCLUSIONSchwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.     

Comparing outcomes of nonoperative treatment for adhesive small bowel obstruction with and without antibiotics

IntroductionSome clinicians administer antibiotics in adhesive SBO treatment to prevent bacterial translocation without evidence confirming reduced sepsis and mortality. We aimed to evaluate the effectiveness of preventive antibiotic administration in nonoperative treatment of adhesive small bowel obstruction (SBO) in a retrospective study.MethodsUsing a Japanese national inpatient database, we identified 114,786 eligible patients with adhesive SBO and divided patients into a group who did not receive intravenous antibiotics in the initial 2 consecutive days after admission (control group, n = 71,666) and a group who received intravenous antibiotics ≥2 days after admission (antibiotic group, n = 43,120). To compare the in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, length of stay, and total costs between the two groups, we performed instrumental variable analyses to adjust for measured and unmeasured confounding factors.ResultsOverall, in-hospital mortality was 2.2%, and the occurrence of sepsis was 0.8%. In the instrumental variable analyses, no significant differences were found for in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, or total hospitalization costs. The antibiotic group showed a longer length of stay than the control group (coefficient, 1.9 days; 95% confidence interval, 0.6–3.2).ConclusionsIn this large nationwide cohort of patients with adhesive SBO, we found no benefit regarding preventive antibiotic administration in nonoperative treatment; however, antibiotic administration was associated with a longer hospital stay. These results did not support routine administration of antibiotics at admission to prevent bacterial translocation.