Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope.

Chromosome movement is prominent during meiosis. Here, using a combination of in vitro and in vivo approaches, we elucidate the basis for dynamic mid-prophase telomere-led chromosome motion in budding yeast. Diverse findings reveal a process in which, at the pachytene stage, individual telomere/nuclear envelope (NE) ensembles attach passively to, and then move in concert with, nucleus-hugging actin cables that are continuous with the global cytoskeletal actin network. Other chromosomes move in concert with lead chromosome(s). The same process, in modulated form, explains the zygotene "bouquet" configuration in which, immediately preceding pachytene, chromosome ends colocalize dynamically in a restricted region of the NE. Mechanical properties of the system and biological roles of mid-prophase movement for meiosis, including recombination, are discussed.

Intermetallic: A Pseudoelement for Catalysis.

A clear correlation between electronic structure and CO2 selectivity for steam reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd intermetallics on the basis of experiments and calculations. In order to rule out the effects of oxide supports, the intermetallic powders were simply prepared by alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd exhibit valence electronic densities of states similar to that of Cu and significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy (HXPS) measurements and density functional theory (DFT) calculations. Consequently, they show the similar high selectivity of CO2 for the SRM reaction. However, this is not the case for PtZn and NiZn because of the slight differences in their valence electronic structures from that of PdZn. The interval between the Fermi level and the top of the d band is closely related to the selectivity of CO2 for the SRM: the larger the interval is, the higher is the selectivity of CO2. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys. Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in an equimolar ratio are more stable than the (001) or (110) surfaces terminated by alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn, and NiZn show that bond breaking on the surface leads to a reduction in the d bandwidth but that the d band for stable (111) or (100) surfaces remains essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd do not contain Cu but show similar valence electronic structure and catalytic selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as pseudoelements of Cu. The basis of this concept is like electronic structure, like catalysis, which has been demonstrated by experiments and calculations. This is a logical way to enable us to look for new catalysts in which precious metals are partially or completely replaced by base metals. We do not expect that this concept can be applied to all catalytic reactions, but this approach is one of most promising ways to derive a better understanding of the origin of catalytic mechanisms and eventually allow us to design useful catalysts intentionally in the future. This Account reviews the authors' published works on this topic.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.

Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC50 in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 µM concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 µM. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity.

Three-body nonmesonic weak decay of the (Lambda)12C hypernucleus.

We have measured the branching ratio of the three-body process in the nonmesonic weak decay of Lambda12C to be 0.29+/-0.13. This result was obtained by reproducing the nucleon and the nucleon pair yields introducing a measured final state interaction. At the same time, we have determined the absolute decay widths, Gamma(n) and Gamma(p), along with Gamma2N, whose relative ratio has been a long-standing puzzle. Including the three-body process, we have successfully reproduced the nucleon energy distribution, the coincidence two-nucleon angular correlation, and the momentum sum distribution simultaneously.

School-based psychoeducation and storytelling: Associations with long-term mental health in adolescent survivors of the Wenchuan earthquake.

AIMS: We explored the factors promoting long-term mental health among adolescent survivors of the 2008 Wenchuan earthquake in China. We examined the associations of their long-term mental health with disaster-related storytelling and school-based psychoeducation, and of school-based psychoeducation with disaster-related storytelling. METHODS: A secondary school-based cross-sectional survey was conducted 6 years after the disaster. Participants with traumatic experiences such as injury, loss, witnessing someone's death/injury and home destruction (N = 1028, mean age 15, standard deviation 1.38, male 51%) were eligible. Mental health/disaster education (MHE/DE) was defined as taking one or more lessons in MHE and/or DE at school since the earthquake. Experiences of storytelling about the disaster involved expressing distressing memories and feelings regarding the earthquake since the disaster happened, according to four groups: never expressed distressing memories and feelings, expressed them through writing/drawing, expressed them through talking to lay supporters and expressed them through talking to health professionals. Analysis of covariance was used to compare mean scores on five selected subscales of the Symptom Checklist-90 (SCL-90), the Athens Insomnia Scale (AIS) and the Psychotic-Like Experiences (PLEs) scale among the four storytelling groups. Linear regression analysis was used to identify the relationships between MHE/DE and current mental health as measured by the SCL-90, AIS and PLEs. The relationship between education and storytelling was probed by χ2 test. RESULTS: The talked-to-lay-supporters group showed better mental health on the SCL-90 (p ⩽ 0.001), AIS (p < 0.001) and PLEs (p = 0.004), while the consulted-health-professionals group showed worse mental health on the three dimensions of the SCL-90: depression (p = 0.05), anxiety (p = 0.02) and fear (p = 0.04), and on PLEs (p = 0.02) compared with the never-expressed group. MHE and DE were inversely associated with SCL-90, AIS and PLE scores. Participants who received these forms of education talked about their disaster experiences to lay supporters more than those who did not. CONCLUSIONS: MHE and DE at school may promote adolescents' mental health after a disaster. Experience of storytelling about the disaster to lay supporters may be helpful for long-term psychological recovery, and may be a potential mediating factor for school-based education and better mental health. Because of the cross-sectional nature of this study, causality cannot be inferred; therefore, further prospective intervention studies are needed to elucidate the effect of these factors on adolescent survivors' mental health.

Protective effect of diltiazem on hepatic ischemia-reperfusion injury in rats by improving liver tissue blood flow.

BACKGROUND: Cytosolic calcium ions are known to play an important role in ischemia-reperfusion (IR) injury. However, the protective effect of calcium channel blockers remains controversial in liver IR injury. Moreover, calcium channel blockers improve hepatic IR injury not due to blocking an increase in hepatic calcium concentration. Therefore, we hypothesized that calcium antagonists protected a liver from IR injury by a vasodilatory action rather than by the inhibition of an increase in Ca2+ within parenchymal cells. This study evaluated the effects of diltiazem, a calcium channel blocker, on liver energy metabolism and blood flow after IR injury. METHODS: Twenty-seven rats underwent hepatic ischemia for 30 minutes followed by 60 minutes of reperfusion. The animals were allocated into group C (without drug); group D5 (diltiazem, 5 microg/kg per min); or group D10 (diltiazem, 10 microg/kg per min). Diltiazem was infused before laparotomy and then throughout the experiment. RESULTS: After 60 minutes of reperfusion, liver tissue blood flow and ATP concentrations were significantly higher in group D10 than the other animals (both, P < .05). Changes in ATP values strongly correlated those observed in blood flow (R = 0.80, P < .001). CONCLUSION: Diltiazem improved ATP-generating capacity during reperfusion by improving liver tissue blood flow. An improvement in hepatic tissue perfusion may be a therapeutic strategy for liver IR injury.

Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids.

Dietary flavonoids are known to scavenge free radicals but little information is available on their roles in antioxidant protein gene expression. The goal of this paper is to investigate the effect of flavonoid treatment on the antioxidant protein expression in human intestinal Caco-2 cells. The antioxidant proteins of interest were metallothionein (MT), catalase (CAT), and superoxide dismutase (SOD). Treatment of Caco-2 cells with 100 microM genistein, biochanin A, daidzein or kaempferol significantly increased MT mRNA up to 15 fold. On the contrary, CAT mRNA level was not affected by various flavonoids. We also developed gel activity assays to determine the specific activities of CAT and Cu/Zn SOD in flavonoid-treated Caco-2 cells. Compared to the conventional spectrophotometric assays, the gel assays allow a separation of antioxidant activities of the enzymes from that of the flavonoids. CAT and Cu/Zn SOD were found not to be affected by 48-h treatment of 100 microM dietary flavonoids (genistein, biochanin A, daidzein, flavone, quercetin, or kaempferol). In conclusion, the effects of flavonoids on antioxidant protein expression are structure- and gene-specific. When evaluating antioxidant capacity of flavonoids, their ability to modulate antioxidant protein expression should also be taken into consideration.

A nonsurgical technique to create an esophagostomy for difficult cases of percutaneous endoscopic gastrostomy.

BACKGROUND: We developed a minimally invasive technique of esophagostomy called percutaneous transesophageal gastrotubing (PTEG) using a rupture-free balloon (RFB) for enteral nutrition and drainage as well as percutaneous endoscopic gastrostomy (PEG). PTEG using RFB allows surgeons to create a nonsurgical esophagostomy even in difficult cases of PEG (i.e., total gastrectomized patients and massive ascites). METHODS: To create the PTEG, a RFB is inserted into the esophagus through the nose and inflated. The RFB is punctured with a needle at the left neck under ultrasonographic vision. A guidewire is inserted through the needle, followed by dilatation of the punctured site using a dilator with sheath. Finally, the tube is inserted into the gastrointestinal tract and the sheath is peeled off. RESULTS: From January 1998 to June 2002, we treated 115 patients using PTEG with a RFB and there were no major complications. Therapeutic results are as good as those for PEG and it took approximately 15 min to perform. CONCLUSIONS: PTEG with RFB is as safe as PEG and is simple and less invasive. It can be used in some cases for which PEG is contraindicated.

Bu ji (hozai) for treatment of postoperative gastric cancer patients.

We proposed that postgastrectomy cancer patients with organ deficit were xu zheng, or of deficient constitution, and administered bu ji or supplementary regimen to them. With alleviation of the symptoms, our diagnosis seemed correct from the traditional medicine perspective. Interleukin 2 reactivity, natural killer activity, nutritional index and bone mineral indices also improved. Such results suggest that our diagnosis was also correct according to Western medical theory. In addition, nutrition seemed to have positive relationship with NK activity and bone mineral content. Therefore, administration of bu ji seemed useful to improve the quality of life of postoperative cancer patients.

[A Case of central venous catheter-related infection with Malassezia sympodialis].

We report a 63-year-old male with central venous catheter-related infection caused by Malassezia sympodialis after total gastrectomy for a gastric cancer. He had fever and his leukocyte counts and C-reactive protein were elevated 14 days after his operation. After his central venous hyperalimentation catheter was removed, the inflammatory signs immediately disappeared, suggesting an intravenous catheter-related infection. A yeast-like fungus was cultured in brain-heart infection semi-solid agar ten days later, and was diagnosed morphologically as Malassezia sp. This strain was identified as M. sympodialis by Tween assimilation test and was confirmed by whole-sequence of internal transcribed spacer 1 regions (ITS1). This is the first report of catheter-related infection caused by M. sympodialis. This strain grew and was subcultured on CHROMagar Candida, potato dextrose agar and Sabouraud agar. There have been no reports of such a lipid-independent Malassezia sp. except for M. pachydermatis. The mechanism of lipid independence of this strain is undetermined and future work is needed. Malassezia sp. is receiving increased attention as an etiologic pathogen of catheter-related fungemia in clinical microbiology laboratories and infectious disease sections.

[Home therapy approach in cancer patients-nutrition therapy (case 1-1)--a case of recurrent gastric cancer with home parenteral nutrition].

This paper describes a case of recurrent gastric cancer with home parenteral nutrition (HPN). A 48-year-old man underwent nutrition support with HPN for the last 6 months. We treated the patient with adjuvant chemotherapy and provided pain management along with HPN treatment. The patient was able to achieve a meaningful and satisfactory quality of life. We concluded that HPN for recurrent cancer patients is a relatively safe and effective means of improving and maintaining the nutritional status. We think the following is important in order to establish home infusion therapy. 1) Organization of a home care team (physician, nurse, pharmacist, dietitian, and caseworker) and a practice-team approach. 2) Establishment of a home infusion system in home care. 3) Preparation of patient manuals by the medical staff. 4) Establishment of sterility preparation and delivery system in home infusion therapy. 5) Establishment of a patient-information-communication system by connection with other hospitals, clinics, and home care companies.

[Application of percutaneous trans esophageal gastro-tubing (PTEG) in to home care for a patient with terminal stage of gastric cancer].

PURPOSE: Since 1994, we devised and have continued to develop a percutaneous trans esophageal gastro-tubing (PTEG) as an effective technique to drain gastrointestinal contents of critical patients suffering from gastric carcinoma. Here we report our satisfactory experience with a critical gastric cancer patient for whom we improved QOL by the application of the PTEG technique. The patient suffered from severe stenosis or obstruction of the digestive tract. This method was found to be effective enough to enable the patient to receive further medical care at home. CASE: The patient was a 36-year-old female who had far-advanced, inoperable gastric carcinoma. It was therefore decided to use the PTEG method. METHOD: The PTEG method was performed using a rupture-free balloon (RFB) catheter to drain the gastrointestinal contents. A reservoir-port for IVH use was embedded to control the patient's nutrition. A morphine hydrochloride suppository was then given for the pain. REMARK: PTEG was found to be effective, safe and simple; moreover, it is a less-invasive, intestine-maintaining method, which enabled the patient to continue receiving further medical treatment at home.

[Percutaneous trans-esophageal gastro-tubing (PTEG): experience of home care with a long-term PTEG].

PURPOSE: Percutaneous trans-esophageal gastro-tubing (PTEG) was developed as a new method of esophagostomy for drainage and feeding. It is especially easy to create a PTEG for patients in whom it is difficult to perform a percutaneous endoscopic gastrostomy (PEG). Here we report a satisfactory experience with a patient with dysphagia for whom we improved the patient's QOL with PTEG. The patient suffered from terrible dysphagia due to Parkinson's disease and was in the postoperative recovery status after undergoing a gastrectomy for gastric cancer. PTEG allowed the patient to receive further long-term medical care at home. CASE: The patient was a 74-year-old man with severe dysphagia due to Parkinson's disease and had a residual stomach as a consequence of a gastrectomy. He had to continue receiving long-term enteral nutrition at home, however it was difficult to create a PEG. We therefore decided to use a PTEG. MATERIALS/METHOD: For the PTEG, a rupture-free balloon (RFB) catheter for enteral nutrition was used. First, an RFB was inserted through the nose into the esophagus and inflated. The RFB was punctured percutaneously aided by ultrasonography and conventional fluoroscopy. Then, a guide wire followed by a dilator with a sheath were inserted. Finally, an indwelling catheter was inserted into the digestive tract through the sheath. REMARK: PTEG using an RFB catheter was a safe, simple and less invasive method; it enabled the patient to continue receiving further medical treatment at home without major complications for a long term.

[Attempt to create a HPN database].

We experienced fifty cases of HPN (home parenteral nutrition) from January 1987 to May 1994. Using effectively these important data, we attempted to make a database for these fifty cases of HPN. We constructed a database based on Windows 3.1-J and Access 2.0-J produced by Microsoft company. At this time, we introduce a part of the database, which must be completed in terms of input items and simplicity.

[Intraarterial infusion combination therapy with LV and 5-FU in hepatic metastases from colorectal cancer].

Intraarterial infusion combination therapy with LV and 5-FU was performed on 8 patients with hepatic metastases from colorectal cancer. Briefly, immediately after administration of LV 30 mg/body, 5-FU was administrated in doses of 750 to 1,250 mg/body over about 2 hours. The therapy was repeated at every weekly visit to the clinic. The number of courses per patient averaged 22. The response rate was 50% (4 PR). Clinical responses were obtained 6 months on average. The 50% survival period was 300 days. Five patients died, 3 due to metastases to other sites. This therapy on an out-patient basis could be continued in all but one patient who was withdrawn from the treatment because of leucopenia. The results of this study suggest that this combination therapy is effective for hepatic metastasis from colorectal cancer.

[Home parenteral nutrition (HPN) for cancer patients].

We have treated thirty-five cancer patients with HPN since 1987. This paper describes its efficacy and problems. Their average age was 62 years old. The duration of HPN varied from 31 to 573 days (mean: 167 days). The catheter was removed in three cases because of catheter fever or obstruction. Metabolic complications arose in three cases, but they were easily treated. Twenty-three cases underwent pain control. Twelve cases were given cancer chemotherapy. We concluded that HPN for recurrent cancer patients is a relatively safe and effective means to improve the quality of life. We consider the following important in order to carry out HPN more smoothly. 1) Improvement of drug delivery system. 2) Establishment of home care system with other hospitals, clinics, and home care companies. 3) The easing of health-insurance restrictions on making out prescriptions to outpatients.

[Development of quality of life questionnaire for patients with colorectal cancer in surgical area--a study of reliability and validity of Tokyo Yamabuki Forum Version].

We developed a new questionnaire in the surgical area based on a core quality of life (QOL) questionnaire for patients with gastrointestinal cancer. In this study, we investigated the validity and reliability of a QOL questionnaire (Tokyo Yamabuki Forum Version) for patients with colorectal cancer. The questionnaire was composed of 17 items including 5 scales (basic sensory scale, psychological scale, physiological scale, defection-related scale and active scale) and a face scale as an global scale. The time needed to answer questionnaires was expected to be around 7 minutes and the questionnaires should basically be answered by the patients themselves everyday in the hospital. The study was performed in 10 hospitals in the Tokyo area, and 394 samples collected from 21 patients with rectal and colonic cancers were analyzed. A number of respondents failed to answer the question "Do you feel your foods tasty?", so we judged this item inappropriate and deleted it from the analysis. Fifteen items, including 5 scales showed satisfactory internal consistency and construct validity in correlation and factor analyses. Performance status showed a low correlation between each item, each scale and the global scale, while SDS and STAI showed an inordinately negative correlation with the fundamental and physical scales. Especially, SDS revealed an extremely close correlation with the active scale, and STAI showed an excessive correlation with the psychological scale. In the time course of QOL under chemotherapy, reductions (aggravations) were observed in both the total score of 15 items and global scale within one week postoperatively, but after that recovered to preoperative levels at 2 weeks postoperatively. A tendency to QOL improvement was observed 2 weeks after starting chemotherapy or chemoimmunotherapy. QOL of 13 patients was measured over 3 months, and the longest term was 8 months. The results suggested that this QOL questionnaire has sufficient reliability and validity to be usable for patients with colorectal cancer in the surgical area and that this model is applicable for long-term QOL surveys and frequent measurement.

[Ultrasonographic diagnosis of breast cancer with intraductal spreading of cancer cells].

The estimation of intraductal lesions of the breast has become possible due to the careful examination of ultrasonic ductal images. The diagnostic accuracy ratio of the lesions was 94.4% by using our classification of dilated ducts by ultrasonography. The characteristics of the findings of intraductal spreading of breast cancer are that the wall of the duct is thick and uneven because of the proliferation of cancer cells, the tumor usually has a broad base all along the walls, and, when the duct is filed with cancer cells, the circumference becomes so varied that it appears outwardly irregular in size and shape. Microcalcifications and irregular nodules along the ductal network are also sometimes apparent. The diagnosis of the area of intraductal spreading of cancer cells could come about from examining the continuous spreading throughout the network by ultrasonography. We have succeedingly obtained successful results from using this method for the past eight years. The diagnostic accuracy ratio to determine the indication for breast conservative surgery and the extent of the breast excision was 94.2% in cases in which the tumor size was less than 3.0cm and the distance from the nipple was over 3.1cm, and in nonpalpable cases. In breast conservative surgery, the firm establishment of a proper diagnostic method is needed to prevent any cancerous tissue from being left. At this point in the evolution of the diagnostic method for intraductal spreading, ultrasonography is one of the key elements to achieve this goal. From now on, ultrasonography will be in the spotlight and take a more leading role in the continuing development of this diagnostic procedure.