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Structural variation, vitrification, and crystallization processes in liquid nickel are simulated on continuous cooling and isothermal holding using a classical molecular-dynamics computer simulation procedure with an embedded-atom method potential at constant pressure. Structural changes are monitored with direct structure observation in the simulation cells, as well as by pair distribution and radial distribution functions created using the atomic coordinates. A cluster analysis is also performed. The crystallization kinetics is analyzed under isothermal conditions by monitoring density and energy variation as a function of time. As a result, a time-temperature-transformation diagram can be constructed over a wide temperature range.

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Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I-II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 microg) was given on days 3-12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m(-2)). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m(-2), respectively, and the recommended doses were 50 and 80 mg m(-2). Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 non-haematologic toxicities except for nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39-78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61-711 days) and 415 days (range: 74-801 days). This new regimen is promising for cervical cancer.

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On a farm raising approximately 75,000 Japanese quail (Coturnix coturnix japonica) for egg production, the diseased quail showed clinical signs of swelling of the head, nasal discharge, increased lacrimation, and decreased egg production. The flock experienced a mortality rate of 5.7% per day. Macroscopic observation revealed large, gelatinous masses of caseous exudate in the sinuses, egg peritonitis, and airsacculitis. Microscopically, non-purulent or purulent inflammation accompanied by lymphoid hyperplastic tissue with germinal centers was observed in the oculofacial respiratory mucosa. The developing stage of the lesions was abscess formation. In the investigation of pathogens, antigens to Mycoplasma gallisepticum and Pasteurella multocida serotype D were immunolabeled on and demonstrated in the mucosal membranes. In addition, P. multocida, Escherichia coli, Staphylococcus sp., and Streptococcus sp. were isolated from the infraorbital sinuses, and Mycoplasma isolated from a diseased bird was confirmed as M. gallisepticum by polymerase chain reaction (PCR). Furthermore, Cryptosporidium sp. was frequently found in the brush border. Serological, bacteriological and PCR examinations, some with negative outcomes, were carried out concerning microbes that are known to cause swollen heads in birds (Haemophilus paragallinarum, Newcastle disease virus and turkey rhinotracheitis virus). The average concentration of ammonia fumes in the cages was 30.6 parts/106, which suggests that the high levels of ammonia fumes promoted infection and multiplication of M. gallisepticum in the quail, and that the clinical disease then worsened due to mixed infection with M. gallisepticum and Cryptosporidium sp. or other bacteria.

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When calcified lesions in the liver or spleen are found during follow-up of patients who have undergone debulking surgery and chemotherapy for advanced ovarian carcinoma, it is very difficult to differentiate recurrent cancer from secondary change after chemotherapy. We present here a patient in whom calcified lesions in the liver and spleen were diagnosed as malignancy on the basis of a preoperative PET study. Malignancy was confirmed by histologic examination after surgery.

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The preoperative diagnosis of uterine leiomyosarcoma (LMS) is very difficult. Magnetic resonance (MR) imaging is usually used for it; however, precise diagnosis by MR imaging is limited to typical LMS with coagulative tumor cell necrosis. We presented a case of LMS that was diagnosed preoperatively by positron emission tomography (PET) using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG).

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High expression of interleukin-11 (IL-11) and the IL-11 receptor alpha chain in developing decidual cells in mice has been reported, and mice lacking IL-11 receptor expression have been reported to show impaired implantation owing to defective decidualization. However, the direct effect of IL-11 on endometrial stromal cells has not been studied. In this study, we examined the direct effects of IL-11 on normal human endometrial stromal cells using an in vitro decidualization assay system. IL-11 enhanced cell viability and prolactin secretion of 8-Br-cAMP-induced decidualized cells but not of non-stimulated stromal cells. IL-11 dose-dependently enhanced the viability of stromal cells co-stimulated with 8-Br-cAMP and IL-11 without any significant effect on prolactin secretion from the cells. The extracellular matrix did not affect the effect of IL-11 on the viability of 8-Br-cAMP-stimulated stromal cells. These results indicate that IL-11 enhances the viability of 8-Br-cAMP-stimulated stromal cells and of decidualized stromal cells, and that the cell survival signals generated by IL-11 are independent of those generated by the extracellular matrix. IL-11 produced locally in decidual tissues may enhance the viability of decidualized stromal cells and possibly protect against cell damage during embryo implantation and trophoblastic invasion.

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This study investigated the differences in Salmonella isolation rates in environmental samples taken from several types of hen houses in Chiba, Japan. In addition, for the detailed epidemiologic survey, environmental samples, hens, and rodents were collected from Salmonella-contaminated windowless houses on three farms. As a result, Salmonella was isolated from four (80%) of five farms with windowless hen houses; Salmonella enteritidis was isolated from a single windowless house. In contrast, only one serotype of Salmonella was isolated from 1 (6.7%) of 15 farms with open hen houses. In the S. enteritidis-contaminated windowless hen house, the isolation rates of S. enteritidis as compared with the other serotypes were 90.9% of environments, 94.1% of hens, and 86.4% of roof rats (Rattus rattus) that resided in the environments. In reference to the phage type (PT) of these isolates, PT1 was detected in environments and roof rats, and PT9 was detected in both these samples and in hens. Thus, the Salmonella isolation rate in hen houses seems to be associated with whether the premises are windowless or open. Moreover, roof rats appear to be the most important vectors in the spread of S. enteritidis in the windowless hen house because the S. enteritidis PTs coincide with each other.

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Tumor necrosis factor-alpha (TNF-alpha) release has been implicated in a sepsis-like syndrome following cardiopulmonary bypass (CPB). This also may be important in patients who have had a left ventricular assist device (LVAD) implanted. This report investigates the effect of reducing systemic blood flow on hemodynamic response, mixed venous oxygen saturation (SvO(2)), and the release of TNF-alpha. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha in the femoral artery (FA) and superior mesenteric vein (SMV) was measured at baseline and following systemic blood flow changes. Simultaneously, hemodynamic parameters and oxygen saturation in the pulmonary artery (SvO(2)) were measured. Following reductions in systemic blood flow, plasma TNF-alpha increased gradually to a maximum level at a systemic blood flow of 20%. There was no significant difference between TNF-alpha levels in the SMV and the FA. There was a significant (p < 0.05) correlation between cardiac index, stroke volume index, and TNF-alpha. The SvO(2) decreased significantly (p < 0.05) at a systemic blood flow of 30 and 20%. A rise in TNF-alpha occurred when the SvO(2) was less than 75%. The data demonstrate that a reduction in systemic blood flow causes an increase in plasma TNF-alpha. This can lead to the development of a sepsis-like syndrome in a group of patients who already are hemodynamically compromised. While weaning short-term LVAD support, rapid diminution of the cardiac output and the pump flow must be avoided.

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OBJECTIVE: The effectiveness of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) for diagnosis of uterine sarcoma was evaluated in comparison to the effectiveness of magnetic resonance (MR) imaging and power Doppler imaging. METHOD: The cases of five Osaka City University Hospital patients diagnosed with uterine sarcoma based on histopathological examination, in whom FDG-PET, MR imaging, and power Doppler imaging studies had been performed preoperatively, were reviewed. A comparative study of the usefulness of these three imaging modalities for diagnosis of sarcoma was conducted. Tumors comprised three leiomyosarcomas, one endometrial stromal sarcoma, and one carcinosarcoma. RESULTS: FDG-PET examinations were 100% positive for the five sarcomas; MR imagings were 80% positive (four of five cases), and US was 40% positive (two of five cases). The mean standardized uptake value of the sarcomas was 4.5 +/- 1.3. CONCLUSION: The sarcoma lesions were clearly imaged by FDG-PET. FDG-PET may be a most useful diagnostic method for uterine sarcoma.

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We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) increased following a reduction in systemic blood flow to 60% or less of the original cardiac output using a left ventricular assist device (LVAD). The aim of this study was to investigate the effect of reducing systemic blood flow on tissue oxygenation in the gastrointestinal tract (GIT) and the consequences of this on TNF-alpha release. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF-alpha of the superior mesenteric vein was measured at baseline and during systemic blood flow changes. Simultaneously, pH, lactate, oxygen delivery index (DO(2)I), oxygen consumption index (VO(2)I), and oxygen extraction (O(2)ER) in the GIT were measured. The pH decreased and the lactate level increased significantly (p < 0.05) at a systemic blood flow of 50% or less. The VO(2)I was positively correlated with DO(2)I. The O(2)ER increased significantly (p < 0.05) with reductions in systemic blood flow to 30% or less. There was a significant (p < 0.01) correlation between TNF-alpha and O(2)ER at levels higher than 55%. These data demonstrate that the GIT oxygenation is inadequate with a reduction in systemic blood flow to 50% and that GIT oxygenation becomes critical at a reduction of 30%. During LVAD weaning, careful attention must be given to the GIT. The pH and lactate may be good markers of the adequacy of tissue oxygenation in the GIT.

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The usefulness of positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-PET) in diagnosing recurrence and lymph node metastasis of uterine cervical cancer was evaluated as a preliminary study. The FDG uptake of 13 cervical cancer patients, including 4 patients with recurrence, was evaluated. The FDG uptake of the cervices of 5 patients who underwent PET studies for non-cervical tumors were used as control. In 2 patients who had undergone radical hysterectomy, we compared the diagnosis of lymph node metastasis based on FDG-PET and magnetic resonance imaging. The FDG uptake in the 9 primary cervical cancers was greater than that in normal cervices (p=0.025). Examination of the 4 recurrent tumors revealed a higher FDG uptake than that in normal cervices (p=0.0022). Metastatic lesions in lymph nodes showed an accumulation of FDG on the PET scan. In conclusion, FDG-PET may be an effective diagnostic tool for detecting recurrence and lymph node metastasis of uterine cervical cancers.

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Prognosis of patients with stage IVB endometrial adenocarcinoma is quite poor. Combination therapy of radiation with surgery or chemotherapy is a common therapy for advanced endometrial cancers. However, radiation therapy is effective only for localized cancer, and the chemotherapeutic effect on stage IVB endometrial cancers is very low. We present a patient with stage IVB endometrial adenocarcinoma, whose tumor was not resected completely at the first surgery. She showed a remarkable response to a PEP (pirarubicin, etoposide, cisplatin) regimen and has survived without disease over 8 years. This case suggests that reduction surgery following PEP therapy is a new therapeutic modality for stage IVB endometrial carcinoma.

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We evaluated the effects of a combined chemotherapy regimen on endometrial carcinoma in 14 patients with lymph node metastasis. After surgery, the patients were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day 1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant chemotherapy was evaluated based on progression-free survival (PFS), overall survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The major toxicity was myelosuppression. One hundred percent of patients had neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy may be an effective adjuvant therapy for endometrial carcinoma patients with lymph node metastasis used as an alternative to radiation therapy.

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Massive ovarian edema (MOE) is a rare disease. Therefore, preoperative diagnostic method of massive ovarian edema (MOE) has not been established. We have succeeded in making a preoperative diagnosis of MOE aided by ultrasonogram and magnetic resonance imaging (MRI) and the patient's ovaries were preserved. Characteristics and proposed diagnostic imaging criteria for MOE are discussed.

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The diagnostic imaging characteristics of uterine carcinosarcoma have not been established because the tumor is very rare. We studied magnetic resonance (MR) imaging, power Doppler ultrasonography, and positron emission tomography (PET) in one such carcinosarcoma to define its imaging characteristics. On T1-weighted MR images, the tumor mass in the uterus was low-signal intensity and had a slight inhomogeneous appearance. On T2-weighted images, it had a heterogeneous appearance and was of medium- or high-signal intensity; marked flow void was apparent from the myometrium to the tumor mass. The MR flow void was also detected by power Doppler ultrasonography. Increased glucose metabolism was detected on PET images, suggesting a malignant tumor in the endometrial cavity. Combined diagnostic images with MR, power Doppler ultrasonography, and PET is recommended as the diagnostic method for uterine carcinosarcoma.

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Effects of granulocyte colony-stimulating factor (G-CSF) on proliferation and differentiation of normal human endometrial stromal cells were investigated in an in vitro decidualization culture of stromal cells. Unstimulated stromal cells secreted little prolactin and G-CSF, whereas 8-Br-cAMP-stimulated stromal cells secreted higher levels. There was no relationship, however, between the levels of prolactin and G-CSF secreted from the stimulated cells. Detectable levels of prolactin secretion were not found in two of six stromal cell cultures stimulated with 8-Br-cAMP; however, these two culture supernatants contained high concentrations of G-CSF. Co-stimulation of the stromal cells with 8-Br-cAMP and G-CSF enhanced prolactin secretion from the stimulated cells in a G-CSF concentration-dependent manner without any change in viable cell numbers. However, G-CSF did not affect prolactin secretion or viable cell numbers of 8-Br-cAMP-stimulated decidualized cells. These results indicate that G-CSF enhances cAMP-mediated decidualization of human endometrial stromal cells in an autocrine or paracrine fashion.

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Massive ovarian edema (MOE) is a very rare disease characterized by a tumor-like enlargement of the ovary. The ultrasound findings have been reported as a solid tumor-like mass or as a solid mass containing a cystic component. Recent reports using magnetic resonance imaging of MOE have demonstrated that multiple ovarian follicles situated around the periphery of the cortex of the enlarged ovary is the most important diagnostic indicator of MOE. This finding was first demonstrated by ultrasound in the case we present here. Thus we suggest that the ultrasound detection of multiple peripheral ovarian follicles in a solid ovarian tumor-like mass may make the preoperative diagnosis of MOE possible by ultrasound alone.

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Positron emission tomography (PET) using 2-[18F]fluoro-2 deoxy-D-glucose (FDG) was performed on two uterine cervical cancer patients in whom recurrent tumors, one pelvic and the other at the vaginal wall had not been precisely diagnosed using the usual imaging examinations. One recurrence was confirmed by the acccumulation of FDG to the pelvic mass as detected by magnetic resonance imaging (MRI). During chemotherapy, changes in FDG-PET findings were detected earlier than those in MRI. In the other, PET detected a recurrent tumor that could not be found by MRI, and was also useful for evaluating chemotherapeutic effects. These cases suggest that PET with FDG can be a useful examination not only for diagnosing recurrent cervical cancer after radical hysterectomy, especially pelvic recurrence, but also for evaluating chemotherapeutic effects on recurrent cancers.

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Epidermal growth factor (EGF) has been reported to regulate apoptosis in various cell lineages. Throughout the menstrual cycle overexpression of the EGF receptor in the secretory epithelium and constitutive expression of EGF in all types of endometrial cells were identified by immunohistochemical study of normal human endometrial tissues. However, it is not known whether EGF also regulates endometrial apoptosis. This study examined the regulatory functions of EGF in endometrial apoptosis by using a human endometrial epithelial cell line HHUA which is susceptible to Fas-mediated apoptosis. Although EGF alone did not affect the cell growth of HHUA, EGF pretreatment of HHUA enhanced Fas-mediated growth suppression and Fas-mediated DNA fragmentation in the cells. Flowcytometric analyses demonstrated that EGF did not induce Fas expression on the cell surface while expressions of the EGF receptor were down-regulated. These results suggest that EGF may enhance apoptotic susceptibility of the endometrial epithelium, especially in the secretory epithelium.

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We investigated renal, intestinal, and whole body metabolic changes in response to variations in Left Ventricle Assist Device (LVAD) flow and inspired oxygen concentration (FiO2). Left ventricular assist devices were implanted in 10 adult pigs (weight, 55 +/- 1.76 kg). Renal vein (RV), superior mesenteric vein (SMV), and pulmonary artery (PA) blood oxygen saturation and lactate concentration were measured and used as tissue perfusion markers. These measurements were made before and after changes in LVAD flow or FiO2. Oxygen saturation in PA, SMV, and RV decreased significantly after a reduction in LVAD flow (p = 0.05), with a greater reduction in SMV than in the PA and RV (p < 0.05 at LVAD flow 3.5 l/min; p < 0.01 at LVAD flow 2.0 and 1.0 l/min). The lactate concentration in the PA and SMV increased significantly (p < 0.01) with decreased flow, with a greater increase in the SMV than in the PA (p < 0.05). whereas it remained unchanged in the RV. Oxygen saturation in the PA, SMV, and RV decreased significantly after a reduction in FiO2 (p < 0.05). Lactate concentration in the PA, SMV, and RV increased significantly at FiO2 of 0.10 (p < 0.05). Lactate concentration in the PA and SMV was significantly higher than that in the RV at FiO2 of 0.10 (p < 0.01). The results show that the gastrointestinal tract is at high risk during low perfusion or low FiO2, whereas in the kidneys metabolic function appears to be less disturbed. In clinical practice, this emphasizes the need to ensure adequate blood flow and respiratory function, especially after extubation, in patients with implanted LVAD. This might avoid intestinal ischemia and subsequent endotoxemia.

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