Enteral metallic stenting by balloon enteroscopy for obstruction of surgically reconstructed intestine

We present three cases of self-expandable metallic stent (SEMS) placement using a balloon enteroscope (BE) and its overtube (OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine.     

Colonic Lymphoid Follicle Hyperplasia after Gastrectomy in Rats

Nodular lymphoid hyperplasia (NLH) of the human colon has been associated with multiple diseases and symptoms. Causes include food allergies, infections, inflammatory bowel disease, and immunodeficiency, and gastrectomy is not usually considered to be the etiology. Nine rats two weeks after total gastrectomy and 12 control rats were sacrificed and submitted for histological examination. In the gastrectomy group, we found lymphoid hyperplasia throughout the entire colon mucosa. The cross-sectional area of lymphoid follicles was increased to be five-fold larger than that in the rats in the control group (sham surgery). Lymphoid follicles were classified into primary and secondary follicles according to the presence/absence of germinal centers; the gastrectomy group had a significantly larger number of secondary follicles. When T cell and B cell classification of lymphocytes was performed, there was no difference between gastrectomy and control groups at T:B = 40:60. When the lymphoid follicles were classified, the proportion of T lymphocytes increased in the secondary follicle (T:B = 40:60) compared with in the primary follicle (T:B = 20:80). Gastrectomy significantly activated lymphocytic intestinal immunity by altering the intestinal environment, causing colonic NLH. Gastrectomy in rats is a good animal model for the study of NLH in colorectal diseases.     

Effects of transforming growth factor-β1 on formation and activation of osteoclasts

Transforming growth factor-₁ (TGF-₁) has biological functions in various types of cells. However, its roles in the regulation of osteoclast formation and function are unclear. To examine them, we employed a culture system in which unfractionated cells obtained from long bones of 13-day-old mice were cultured on a dentine slice. We found that TGF-₁ has a potent inhibitory effect on osteoclastic bone resorption at a dose of 0.2–5 ng/ml. By electron microscopy the osteoclasts appeared to have fewer mitochondria and ruffled borders than those in control cultures. But in the presence of 1,25-dihydroxyvitamin D₃, [1,25-(OH)₂D₃], TGF-₁ at a dose of 0.2–1 ng/ml stimulated the formation of osteoclasts from unfractionated bone cell cultures in which preexistent osteoclasts had degenerated. Thus, using stromal cell-free he-mopoietic blast cells, we examined the direct action of TGF-₁ on osteoclast precursors. Although TGF-₁ inhibited tartrate-resistant acid phosphatase-positive (TRAP) multinucleate cell (MNC) formation induced by 1,25-(OH)₂D₃, the conditioned medium (CM) of TGF-₁-treated MC3T3-E1 cells stimulated such formation. These results suggest that TGF-₁ inhibits osteoclastic bone resorption but stimulates osteoclast formation via the action of factor(s) produced by TGF-₁-treated osteoblasts in the presence of 1,25-(OH)₂D₃.     

Solid-pseudopapillary pancreatic tumor, mimicking submucosal tumor of the stomach: A case report

Solid-pseudopapillary tumors of the pancreas(SPTs) are comparatively rare and have low malignancy,with a predilection for young women.Diagnosis is difficult when a SPT develops in a boundary region with other organs.Here,we report a 42-year old woman with a SPT of the pancreas mimicking a submucosal tumor of the stomach on imaging.She was admitted to our hospital complaining of abdominal pain.We suspected a submucosal tumor of the stomach from the f indings of endoscopy,endoscopic ultrasonography and abdominal computed tomography.However,angiography showed that some of the tumor vessels arose from the pancreas.Intraoperative f indings revealed the tumor originated from the pancreas.Therefore,distal pancreatectomy was performed.The pathological diagnosis was SPT of the pancreas.     

Dilatation of the temporal horn in subarachnoid haemorrhage

Summary CT studies of 50 patients with spontaneous subarachnoid haemorrhage (SAH) and 100 randomly selected patients were reviewed with regard to the size of the frontal and temporal horns of the lateral ventricles. The temporal horn was classified into four grades, based on the size of its posterior portion at the level of the midbrain. The horn was clearly visible in 66% of patients with SAH, but in only 2% of controls. In the SAH group, the temporal horn tended to dilate sooner than the frontal horn after haemorrhage and could be seen clearly in a larger proportion of patients. Thus, assessment of the size of the temporal horn appears to be a simple and sensitive method for assessing ventricular dilatation. In addition, dilatation of the temporal horn may prove to be an important indirect sign suggesting SAH in patients in whom no high density clot is seen on CT.     

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Purpose Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). Methods The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. Results We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. Conclusions The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.     

Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport (RCT), a protective system against atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with marked hyperalphalipoproteinemia (HALP). Genetic CETP deficiency is the most important and common cause of HALP in the Japanese. Ten mutations of the CETP gene have been demonstrated as causes of HALP, including two common mutations: an intron 14 splicing defect (Int14 + 1 G --> A) and an exon 15 missense mutation (D442G). The subjects with CETP deficiency show a variety of abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). CETP deficiency is considered a physiological state of impaired RCT, which may possibly lead to the development of atherosclerosis despite high HDL cholesterol levels. However, the pathophysiological significance of CETP in terms of atherosclerosis has been controversial. Epidemiological studies in Japanese-Americans living in Hawaii and Japanese in the Omagari area, where HALP subjects with an intron 14 splicing defect of the CETP gene are markedly frequent, have shown a relatively increased incidence of coronary atherosclerosis in CETP deficiency. On the other hand, the TaqIB polymorphism-B2 allele with low CETP mass and increased HDL cholesterol has been related to a decreased risk for coronary heart disease (CHD) in many studies, including the Framingham Offspring Study. The current review focused on the characterization of the Japanese subjects with CETP deficiency, including our recent findings.     

Relation between strain dyssynchrony index determined by comprehensive assessment using speckle-tracking imaging and long-term outcome after cardiac resynchronization therapy for patients with heart failure

Strain dyssynchrony index (SDI), which was a marker of dyssynchrony and residual myocardial contractility, can predict left ventricular reverse remodeling short-term after cardiac resynchronization therapy (CRT). We investigated SDI-predicted long-term outcome after CRT in patients with heart failure (HF). We studied 74 patients with HF who underwent CRT. SDI was calculated as the average difference between peak and end-systolic strain from 6 segments for radial and circumferential SDIs and 18 segments for longitudinal SDI using 2-dimensional speckle-tracking strain. Based on our previous findings, the predefined cutoff for significant dyssynchrony and residual myocardial contractility was a radial SDI ≥6.5%, a circumferential SDI ≥3.2%, and a longitudinal SDI ≥3.6%. The predefined principal outcome variable was the combined end point of death or hospitalization owing to deteriorating HF. Long-term follow-up after CRT was tracked over 4 years. The primary end point of prespecified events occurred in 14 patients (19%). An association with a favorable long-term outcome after CRT was observed in patients with significant radial, circumferential, and longitudinal SDIs (p <0.001, <0.005, and 0.010 vs patients without significant SDIs, respectively). Furthermore, cardiovascular event-free rate after CRT in patients with positivity of 3 for the 3 SDIs was 100% better than that in patients with positivity of 1 (52%, p <0.005) or 0 (31%, p <0.001) for the 3 SDIs. In conclusion, SDIs can successfully predict long-term outcome after CRT in patients with HF. Moreover, the approach combining the 3 types of SDI leads to a more accurate prediction than the use of individual parameters. These findings may have clinical implications in patients with CRT.     

Podogigants A and B,two new potentiators of amphotericin B activity,from Sordariomycete Podostroma giganteum

Journal of Natural Medicines - Two new compounds, podogigants A (1) and B (2), were isolated from the culture broth of Podostroma giganteum. This is the first report on the identification of...     

Helices F-G are important for the substrate specificities of CYP3A7.

CYP3A7 is a member of the human CYP3A family and a major form of P450 expressed in human fetal livers. Although CYP3A7 shares nearly 90% base sequence with CYP3A4, CYP3A7 shows striking functional differences in the catalytic preference for several substrates, such as dehydroepiandrosterone (DHEA) or dehydroepiandrosterone 3-sulfate (DHEA-3S). First, to clarify the reason for the differences between CYP3A7 and CYP3A4, a homology model of CYP3A7 was constructed using the CYP3A4 crystal structure. Because these two structures were similar, four kinds of chimeric enzymes were constructed to determine which sequences are important for exhibiting the characteristics of CYP3A7. The results of kinetic analysis of DHEA and DHEA-3S 16alpha-hydroxylations by CYP3A7, CYP3A4, and CYP3A chimeras suggested that the amino acid residues from Leu(210) to Glu(279) were important to express the specificity for substrates as CYP3A7. This region was on the F and G helices of the modeled CYP3A7. Furthermore, to assess which amino acid in this sequence is important for the substrate specificity of CYP3A7, a one-point mutation of CYP3A7 to CYP3A4 was made by site-directed mutagenesis. The mutants of K224T and K244E had lost DHEA and DHEA-3S 16alpha-hydroxylation activities. The mutants also greatly decreased the metabolism of testosterone, erythromycin, nevirapine, and triazolam relative to those activities of CYP3A7 wild-type enzyme. From these results, it is expected that CYP3A7 can recognize specific substrates using the lysines in F-G loops.