Inorganic polyphosphate differentiates human mesenchymal stem cells into osteoblastic cells

The existence of inorganic polyphosphates [poly(P)] in human cells has been demonstrated. In osteoblasts, it is suggested that the concentration of cellular poly(P) is relatively high. In this study, we examined whether poly(P) accelerates the differentiation of human mesenchymal stem cells (hMSCs) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) into osteoblastic cells. Alkaline phosphatase (ALP) activity was induced by poly(P) in hMSCs from both OA and RA. In Alizarin Red S and osteocalcin EIA, there was a significant difference between the control and poly(P) group. In real-time PCR, there was a significant difference in ALP, collagen type 1A, osteocalcin, and bone sialoprotein between the control and poly(P) group. Our findings suggest that poly(P) have the potent role of differentiating hMSCs into osteoblastic cells at the early and later stages of osteoblastic differentiation.     

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for large superficial colorectal neoplasias including ileocecal lesions

Background

Large superficial neoplasias of the ileocecal region pose an increased degree of complexity for endoscopic resection. This study aimed to evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) for large superficial colorectal neoplasias including ileocecal lesions.

Methods

A total of 33 superficial colorectal neoplasias, including eight neoplasias in the ileocecal region, were treated with ESD from December 2005 to April 2009. Therapeutic efficacy, complications, and follow-up results were retrospectively evaluated among three groups: ileocecal region, colon, and rectum.

Results

The mean size of all resected neoplasias was 35 ± 15 mm (range, 20–80 mm) and that of all resected specimens was 41 ± 15 mm (range, 23–82 mm). The mean procedural time was 121 ± 90 min (range, 22–420 min). The difference in mean values among the three groups was not significant. The overall rate of en bloc resection was 91% (30/33). Histopathologically, both the lateral and vertical margins in the specimens resected en bloc tested negative (30/30). The rate for en bloc resection in the ileocecal region did not differ significantly from that for the other two groups (p = 0.20 compared with the rate for the colon and p = 0.12 compared with the rate for the rectum). Complications such as perforation and postoperative bleeding did not occur in the ileocecal group. No recurrence was observed in any cases during the mean follow-up period of 20 ± 12 months (range, 4–44 months).

Conclusions

The ESD approach is safe and effective for treating large superficial neoplasias of the ileocecal region such as other colorectal neoplasias.     

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for superficial esophageal neoplasia. Is it safe for elderly patients?

Background

Safety and efficacy of endoscopic submucosal dissection (ESD) for esophageal neoplasias have not been adequately investigated in elderly patients. This study was designed to evaluate the safety and efficacy of ESD for esophageal neoplasias in elderly patients.

Methods

Fifty-three superficial esophageal neoplasias treated with ESD using a combination of small-caliber-tip transparent hood and flex knife from May 2006 to June 2009 were divided into elderly group (aged 70 years or older: 25 lesions in 23 patients) and nonelderly group (younger than aged 70 years: 28 lesions in 25 patients). Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively.

Results

The history of cerebral infarction or cardiopulmonary disease and the usage of antiplatelet agents or anticoagulants were significantly higher in elderly group (p 0.0050 and p 0.0013, respectively). Median procedural times in the elderly group and the nonelderly group were 93 ± 53 (range, 42–235) min and 95 ± 55 (range, 40–230) min (p 0.73), respectively. Median sizes of the neoplasias and the resected specimens were 14 ± 11 (range, 5–45) mm and 15 ± 17 (range, 5–83) mm (p 0.56), and 35 ± 12 (range, 18–60) mm and 38 ± 17 (range, 18–90) mm (p 0.38), respectively. En bloc resection rate was 100% in each group. Body temperature and white blood cell counts of the next day after ESD were significantly higher in the nonelderly group than in the elderly group (p 0.0087 and p 0.0043, respectively). There were no complications, such as postoperative bleeding or perforation, in each group. The median follow-up period of 23 ± 10 (range, 4–35) months in the elderly group revealed no local or distant metastasis.

Conclusions

ESD with a combination of small-caliber-tip transparent hood and flex knife is a safe and effective treatment for superficial esophageal neoplasia in elderly and nonelderly patients.     

Endoscopic submucosal dissection and preoperative assessment with endoscopic ultrasonography for the treatment of rectal carcinoid tumors

Background

Rectal carcinoid tumors 10 mm in diameter or smaller located within the submucosal layer can be cured by local excision including endoscopic treatment. But complete resection of these tumors with endoscopic polypectomy is difficult. This study aimed to evaluate the usefulness of endoscopic submucosal dissection (ESD) and endoscopic ultrasonography (EUS) for the treatment of rectal carcinoid tumors.

Methods

In this study, 22 rectal carcinoid tumors in 21 patients were evaluated with EUS and treated using ESD from January 2004 to December 2008.

Results

The mean size of the resected tumors was 6.1 mm (range, 2.0–10 mm) on histopathologic evaluations. When the sizes of the tumors shown by EUS and histopathologic evaluation were compared, the mean values were not significantly different. All the tumors were located within the submucosal layer, and the accuracy of the preoperative depth determination with EUS was 100% (22/22). The mean duration of the ESD procedure was 37 min (range, 20–71 min). The overall rate of en bloc resection with ESD was 100% (22/22). Although postoperative bleeding occurred in two cases (9%), both cases were successfully managed by endoscopic hemostasis. No perforation or recurrence was observed during the mean follow-up period of 30 months (range, 7–66 months).

Conclusions

Endoscopic submucosal dissection and preoperative assessment with EUS are effective for treating rectal carcinoid tumors and enabling en bloc resection.     

A case of afebrile miliary tuberculosis that progressed from tuberculous spondylitis with iliopsoas abscess

We present a case of a 78-year-old woman who visited our hospital for chronic atrial fibrillation. She consulted an orthopedic surgeon for lumbar pain in August 2009 and has been followed up for osteoporosis. However, her lumbar pain became exacerbated. In December 2009, clinical examination revealed that the pain was caused by tuberculous spondylitis and iliopsoas abscess. Diffuse miliary shadow, which was undetected earlier, was noted on chest roentgenogram; she was diagnosed with miliary tuberculosis. Lumbar pain is common in elderly individuals and should be regarded as one of the tuberculosis symptoms, considering its atypical course in elderly patients.     

Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na+�CHCO 3 ? cotransporter NBCe1A

The electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1 encoded by SLC4A4 plays essential roles in the regulation of intracellular/extracellular pH. Homozygous mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. In the present study, we tried to perform functional characterization of the four nonsynonymous single nucleotide polymorphisms (SNPs), E122G, S356Y, K558R, and N640I in NBCe1A. Functional analysis in Xenopus oocytes revealed that while the K558R variant had a significantly reduced transport activity corresponding to 47% of the wild-type activity, the remaining variants E122G, S356Y, and N640I did not change the NBCe1A activity. Apparent Na(+) affinity of K558R was not different from that of wild-type NBCe1A. Immunohistological analyses in HEK293 cells and MDCK cells indicated that none of these SNPs changed the trafficking behaviors of NBCe1A. Functional analysis in HEK293 cells also revealed that only the K558R variant had a reduced transport activity, corresponding to 41-47% of the wild-type activity. From these results, we conclude that among four SNPs, only the K558R variant, which is predicted to lie in transmembrane segment 5, significantly reduces the NBCe1A activity without changing the trafficking behavior or the apparent extracellular Na(+) affinity.     

When do infants differentiate profile face from frontal face? A near‐infrared spectroscopic study

The objective of the present study was to determine whether a developmental difference occurs in brain activity when infants look at frontal and profile views using near-infrared spectroscopy (NIRS), which is an optical imaging technique used to measure changes in the concentrations of oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total-Hb). For this objective, we compared NIRS results in two age groups, 5- and 8-month-old infants, while they were looking at frontal views, profile views, and objects. We found that the concentration of oxy-Hb and total-Hb in the 5-month-old group increased for only frontal views in the right temporal regions. In contrast, the concentration of oxy-Hb and total-Hb in the 8-month-old group increased for both frontal and profile views in the right temporal regions. Therefore, the present study indicated that the right hemisphere was dominant for the perception of profile views as well as frontal views. In addition, the most important and interesting finding was that the infants' brain activity of the face area would become view-invariant at the age of 8 months but not at 5 months. The developmental period for view-invariant face recognition has been discussed in previous psychological studies, but this is the first objective study to confirm that the period is between 5- and 8-months by measuring the blood flow in the brain using NIRS.     

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.