Short-term outcomes of delta-shaped anastomosis versus functional end-to-end anastomosis using linear staplers for colon cancer.

BACKGROUND: Several methods are used for reconstruction in colon cancer surgery, including hand-sewn or stapled anastomosis. However, few reports have compared short-term outcomes among reconstruction methods. This study compared short-term outcomes between delta-shaped anastomosis (Delta) and functional end-to-end anastomosis (FEEA). METHODS: We retrospectively reviewed 1314 consecutive patients who underwent colorectal surgery with FEEA or Delta reconstruction between January 2016 and December 2023. Patients were divided into two groups according to reconstruction by FEEA (F group; n = 1242) or Delta (D group; n = 72). Propensity score matching was applied to minimize the possibility of selection bias and to balance covariates that could affect postoperative complications. Short-term outcomes were compared between groups. RESULTS: Postoperative complications occurred in 215 patients (17.3%) in F group and 8 patients (11.1%) in D group. Before matching, transverse colon cancer was more frequent (p = 0.002), clinical N-positive status was less frequent (44.1% versus 16.7%, p < 0.001), distant metastasis was less frequent (11.7% versus 1.4%, p = 0.003), and laparoscopic approach was more frequent (87.8% versus 100%, p < 0.001) in D group. After matching, no differences in any clinical factor were evident between groups. Blood loss was significantly lower (28 mL versus 10 mL, p = 0.002) in D group, but operation time and postoperative complication rates were similar between groups. CONCLUSIONS: Delta and FEEA were both considered safe as reconstruction methods. Further studies are needed to clarify appropriate case selection for Delta and FEEA.

Efficiency of genomic selection for breeding population design and phenotype prediction in tomato.

Genomic selection (GS), which uses estimated genetic potential based on genome-wide genotype data for a breeding selection, is now widely accepted as an efficient method to improve genetically complex traits. We assessed the potential of GS for increasing soluble solids content and total fruit weight of tomato. A collection of big-fruited F1 varieties was used to construct the GS models, and the progeny from crosses was used to validate the models. The present study includes two experiments: a prediction of a parental combination that generates superior progeny and the prediction of progeny phenotypes. The GS models successfully predicted a better parent even if the phenotypic value did not vary substantially between candidates. The GS models also predicted phenotypes of progeny, although their efficiency varied depending on the parental cross combinations and the selected traits. Although further analyses are required to apply GS in an actual breeding situation, our results indicated that GS is a promising strategy for future tomato breeding design.

A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model.

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.

Insulin secretion and sensitivity before and after surgical treatment for aldosterone-producing adenoma.

AIM: Primary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed. METHODS: To assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic-euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27-559 (194±132) days, and 14-142 (51±38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp analyses were evaluated. RESULTS: Surgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic-euglycaemic clamp was reduced after surgery. CONCLUSION: Primary aldosteronism impairs insulin secretion.

Magnetic resonance imaging of pilocytic astrocytomas: usefulness of the minimum apparent diffusion coefficient (ADC) value for differentiation from high-grade gliomas.

BACKGROUND: On contrast-enhanced magnetic resonance (MR) images, pilocytic astrocytomas (PAs) are usually well-enhanced tumors that may mimic high-grade gliomas (HGGs). On the other hand, it has been suggested that areas exhibiting minimum apparent diffusion coefficient (ADC) values reflect the sites of highest cellularity within heterogeneous tumors. PURPOSE: To test the hypothesis that the cellularity of PAs is significantly different to the cellularity of HGGs, which should result in significant differences in minimum ADC values. MATERIAL AND METHODS: Between 1999 and 2005, 15 patients (nine males, six females) with histopathologically confirmed PAs underwent pretreatment MR examination including diffusion-weighted (DW) imaging. We reviewed their MR findings with respect to the size, location, morphology, contrast enhancement, and minimum ADC value of the tumors. The minimum ADC values of the 15 PAs were compared with those of 104 HGGs diagnosed during the same period. RESULTS: The diameter of the 15 PAs ranged from 11 to 60 mm (mean 36 mm); all were located around the ventricles, and all contained enhancing components. All except two small (11 and 14 mm) PAs contained cystic components. The minimum ADC values were significantly higher in PAs (median 1.688, range 1.375-1.897 x 10(-3) mm(2)/s) than HGGs (0.997, 0.543-2.024 x 10(-3) mm(2)/s) (P < 0.0001), although there was substantial overlap. Among the tumors with enhancing components, all but one PA were differentiated from the 76 HGGs with enhancing components (0.922, 0.543-1.462 x 10(-3) mm(2)/s) when the minimum ADC cutoff value was set at 1.5 x 10(-3) mm(2)/s. CONCLUSION: The minimum ADC value may be helpful for the differentiation between PAs and HGGs. A tumor with enhancing components should be PA instead of HGG when the minimum ADC value is higher than 1.5 x 10(-3) mm(2)/s.

Comparison of survival between anatomic and non-anatomic liver resection in patients with hepatocellular carcinoma: significance of surgical margin in non-anatomic resection.

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.

OBJECTIVE: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods. METHODS: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group. CONCLUSION: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Maternal weight gain ranges for optimal fetal growth in Japanese women.

OBJECTIVE: To identify adequate weight gain ranges during pregnancy in Japanese women. METHOD: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: "very low" (under the 25th), "low" (25th to 49th), "moderate" (50th to 74th), "high" (75th to 89th), and "very high" (90th and over). RESULTS: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. CONCLUSION: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women.

Human standing posture control system depending on adopted strategies.

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20-140%) (ANOVA, p < 0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Cyclic AMP specific phosphodiesterase activity and colon cancer cell motility.

To investigate mechanisms for regulation of intracellular cAMP involved in cancer cell invasion, phosphodiesterase (PDE) activity in a colon cancer cell line, DLD-1, was studied. Activities of PDE 2, 4, and 5 were detected in DLD-1 cells by pharmacological approach. Specific and cell permeable inhibitors for those PDEs were used to determine which PDE is responsible for cAMP turnover involved in cancer cell motility. Treatment of DLD-1 cells with rolipram and Ro-20-1724 inhibitors for PDE 4, elevated intracellular cAMP contents three to five times of control. EHNA, an inhibitor for PDE 2, and zaprinast. an inhibitor for PDE 5, did not affect cAMP levels. To assess cellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, suppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 plays a critical role in regulating intracellular cAMP levels of colon cancer cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.

Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy.

During pregnancy, the uterus shows marked morphological and physiological changes under the regulation of ovarian steroid. To elucidate the molecular cues of these changes, we tried to identify the transcripts differentially expressed in the pregnant rat uterus by using the suppression subtractive hybridization method. Seven independent clones were isolated and one of the up-regulated genes was secreted frizzled-related protein 4 (sFRP4). sFRP4 contains a Wnt-binding domain and belongs to the secreted frizzled protein family whose members are assumed to function as modulators of the Wnt signal. The expression level of sFRP4 mRNA reached a peak in the pregnant uterus on day 12, when uterine decidualization was almost complete in the rat. In situ hybridization histochemistry revealed that sFRP4 transcripts were observed in the decidual cells. In addition, proliferating cell nuclear antigen (PCNA)-positive cells were shown to be overlapped in decidua, suggesting that sFRP4 mRNA expression was accompanied by the late phase of decidual cell proliferation. Moreover, sFRP4 and estrogen receptor-alpha transcripts were co-localized. Furthermore, we analyzed the regulation of sFRP4 by estrogen using 17 beta-estradiol-treated ovariectomized rats. sFRP4 mRNA was detected in the uterus at 48 h after estrogen treatment, especially in endometrial stroma where PCNA-positive cells were also observed. The results in this study led us to the notion that sFRP4 mRNA may be up-regulated after estrogen treatment in the late phase of uterine cell proliferation.

Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation.

It has been proposed that immune responses in mammalian normal pregnancy are Th2-like, thereby protecting the fetus and placenta from being rejected. Administration of exogenous Th1 cytokines into pregnant mice is reported to induce feto-placental resorption. However, the effects of exogenous Th2 cytokines and Th2 directed responses in pregnant animals have not been well studied. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1 responses, respectively, in the induction of fetal resorption and development of experimental pre-eclampsia. Transfer of either IL-4 and/or IL-12 stimulated splenocytes from BALB/C virgin female mice into BALB/C pregnant mice mated with either C57BL/6 or BALB/C male mice resulted in fetal resorption and glomerular nephritis associated with hypertension and proteinuria. In mice treated with IL-12 stimulated splenocytes, fatty liver degeneration associated with bile retention was observed. These results indicate that both excessive Th1 and Th2 activation contribute to the development of fetal resorption and pre-eclampsia, but that Th1 is critical to the development of liver degeneration.

Identification of new low-molecular-weight glutenin subunit genes in wheat.

To clarify the composition of low-molecular-weight glutenin subunits (LMW-GSs) in a soft wheat cultivar, we cloned and characterized LMW-GS genes from a cDNA library and genomic DNA in Norin 61. Based on alignment of the conserved N- and C- terminal domains of the deduced amino-acid sequences, these genes are classified into 12 groups. One of these groups (group 5), the corresponding gene of which has not been reported previously, contains two additional hydrophobic amino-acid clusters interrupting the N-terminal repetitive domain. Other groups (groups 11 and 12), which were not identified in other cultivars as a protein product, showed all eight cysteines in the C-terminal conserved domain. With specific primer sets for these groups it was revealed that Glu-D3 and Glu-A3 encoded the former and the latter, respectively. Both groups of genes were expressed in immature seeds. The presence of these groups of LMW-GSs may affect the dough strength of soft wheat.

Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 beta in the rat.

The contribution of the activity of afferent fiber filaments to pain and hyperalgesia after administration of a plantar injection of interleukin-1 beta (IL-1 beta) to the hind-paw skin was investigated by recording action potentials of the rat dorsal root in response to mechanical and thermal stimuli. Touch stimuli were delivered by stroking with a cotton-tipped applicator and thermal stimulation was applied by cooling or heating of the skin. After the administration of IL-1 beta (100 pg-1 microgram), responses to touch, cold, and heat stimulation increased to 143%, 200%, and 392%, respectively, of control values on average. IL-1 beta induced transient spontaneous discharge in 50% of experiments. The effects of IL-1 beta were apparent within 1 min. To examine responses to pressure stimulation, an area of 1 mm2 of the hind-paw skin was pressed by a mechanical stimulator. IL-1 beta (0.1 pg-200 ng) decreased the threshold value to 58% of the control pressure required for firing. IL-1 beta also increased responses to various levels of pressure (range: 1-20 g/mm2). These data suggest that IL-1 beta may play an important role in cutaneous hyperalgesia by activating polymodal receptors to mechanical and thermal stimulation.

A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress.

Acute stress increases circulating ACTH and glucocorticoid levels. The hippocampus (HIP) is a target of such stress hormones as glucocorticoid and it also expresses receptors for growth hormone (GH), particularly in the dentate gyms (DG). In order to understand the interactions between glucocorticoids and functions of GH in HIP during acute stress, the mRNA levels for GH receptor (GHR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were investigated in DG in rats exposed to restraint stress in the water (RSW). Using in situ hybridization histochemistry (ISHH), high level expressions of GHR mRNA were detected in DG. These were down-regulated by 14% after 0.5 h of RSW and then up-regulated by 38% over the initial level after 4 h of RSW. This biphasic enhancement of GHR mRNA expression in DG followed the elevation of plasma glucocorticoid levels and paralleled with biphasic expressions of mRNAs for GR and MR in DG. Although circulating GH levels did not show any correlation with the hippocampal GHR mRNA expression, adrenalectomy (ADX) decreased GHR mRNA expression in DG, and the dexamethasone treatment (DEX; 20 microg/100 microl, i.p.) of ADX rats rapidly increased the GHR mRNA expression in DG. These results have suggested that the GHR mRNA expression in the DG is regulated, at least in part, by glucocorticoids and that GH may be involved in responses of the DG to acute stress.

Platelet-derived endothelial cell growth factor expression is an independent prognostic factor in colorectal cancer patients after curative surgery.

AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas. METHODS: PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had received curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68. RESULTS: PD-ECGF expression in the normal mucosa was 34.4+/-15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group (P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. CONCLUSIONS: The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.

Runx2-deficient mice lack mandibular condylar cartilage and have deformed Meckel's cartilage.

Runx2 (runt-related transcription factor 2) deficient mice lacked the mandibular condylar cartilage and the mandibular bone. The anlage of the condylar process consisted of mesenchymal condensation, which expressed Type I collagen mRNA and alkaline phosphatase activity, but not Type II collagen and aggrecan mRNAs. Therefore, the differentiation of the mandibular condylar cartilage stopped at the preosteoblast (skeletoblast) stage. The lateral pterygoid muscle was attached to this anlage, and relatively abundant mesenchymal condensations were also formed at the muscle-attaching sites, e.g. the anlage of the mandibular body, the angular and coronoid processes. Three-dimensional reconstruction models showed that each mesenchymal condensation was connected to one another, and roughly outlined the shape of the mandible. Meckel's cartilage in the Runx2-deficient mice had two ectopic cartilaginous processes to which the digastric and myohyoid muscles were attached. These findings indicate that Runx2 is essential for the formation of the mandibular condylar cartilage, as well as for normal development of Meckel's cartilage and that muscle tissues influence mandible morphology.

Direct gene delivery into isolated microspores of rapeseed (Brassica napus L.) and the production of fertile transgenic plants.

A procedure for direct gene transfer into isolated microspores of rapeseed (Brassica napus L.) and the production of fertile transgenic plants is presented. By modifying the microspore culture method and adopting the firefly luciferase (Luc) gene as a non-destructive marker, we could obtain stably transformed androgenetic embryos from bombarded microspores. Luc-positive embryos were easily isolated from the large non-transformed population using a high-sensitivity bioluminescent image analyzer. PCR and Southern blot analyses confirmed that the introduced transgene was integrated stably into the genome of the selected embryos. Diploidized plants obtained from the haploid embryos were self-pollinated, and all of the offspring tested were Luc-positive, indicating rapid fixation of the transgene which is characteristic of doubled haploids.

Agrobacterium-mediated transformation of monocot and dicot plants using the NCR promoter derived from soybean chlorotic mottle virus.

The NCR promoter (PNCR) from soybean chlorotic mottle virus (SoyCMV) was used to express the selectable marker, neomycin phosphotransferase (nptII) gene, in Agrobacterium-mediated transformation of both monocot (rice) and dicot (tobacco) plants. A multi-cloning site for insertion of a gene of interest into the binary vector pTN is located proximal to the right border region of T-DNA. When chimeric genes under the control of other strong promoters were located in a head-to-head orientation to the PNCR-nptII gene, kanamycin-resistant tobacco shoots were generated more efficiently than when using the original pTN vectors. This suggests that the enhancer-like sequences in the promoters adjacent to PNCR may promote expression of the PNCR-nptII gene.

ANP decreases arterial oxygen partial pressure by increasing shunt flow in pulmonary circulation.

This study was designed to clarify the decreased arterial oxygen partial pressure (PaO2) mechanism induced by atrial natriuretic peptide (ANP) infusion. In order to examine the effects of ANP on gas exchange across the normal lungs, ANP was infused to eight anesthetized dogs, ventilated with mixed gases of oxygen and nitrogen. PaO2 and venous oxygen partial pressure (PvO2), ventilation-perfusion ratio (VA/Q), shunt-total blood flow ratio (QS/QT) were measured before and during ANP infusion under ventilation with 10, 20, 30% oxygen. In this study ANP decreased PaO2 from 89.0 +/- 4.2 to 85.4 +/- 5.4 mmHg during 20% oxygen ventilation, and from 138.1 +/- 3.6 to 132.5 +/- 4.1 mmHg during 30% oxygen ventilation. ANP increased VA/Q and QS/QT. We conclude that the decrease in PaO2 caused by ANP infusion was mainly due to the increased venous admixture.