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Arabidopsis thaliana has a number of response regulators (ARRs) implicated in the histidine (His)-->aspartate (Asp) phosphorelay signal transduction. According to the current consistent model, both the type-A and type-B ARR family members play crucial roles in the cytokinin signaling circuitry. However, this higher plant has a few extra ARRs, on which no attention has been paid so far. Characterization of these extra ARRs might provide us with new insight into the His-->Asp phosphorelay signal transduction in plants. For this reason, in this study we extensively examined the natures of such a representative (named ARR22). Transcripts of ARR22 were expressed predominantly in reproductive organs, and a GFP::ARR22 fusion protein was localized in the cytoplasmic space in onion epidermal cells. The purified ARR22 protein had the ability to undergo phosphorylation in vitro, when incubated with phospho-AHP5, indicating that ARR22 has the fundamental ability to participate into a His-Asp phosphorelay pathway in its own right. In plants, transgenic lines overexpressing ARR22 were characterized (referred to as ARR22-ox), which showed the characteristic dwarf phenotypes with poorly developed root systems. The results of Northern blot hybridization with selected sets of hormone-responsive genes suggested that cytokinin responses are selectively attenuated in ARR22-ox, while other hormone responses (auxin, ABA and ethylene) occur normally. The results of microarray analyses with cytokinin-treated wild-type and ARR22-ox plants further supported the view that cytokinin responses are globally attenuated in ARR22-ox, at least, at the level of gene regulation. Finally, we demonstrated that the dwarf phenotypes of ARR22-ox are very similar to those of the wooden leg (wol) mutant, which has a severe lesion in the AHK4/CRE1 cytokinin-receptor of histidine protein kinase. These results suggested that ARR22 might also be implicated, directly or indirectly, in the cytokinin-responsive His-->Asp phophorelay signal transduction.

In Arabidopsis thaliana, a Histidine-to-Aspartate (His-->Asp) phosphorelay is involved in the signal transduction for propagation of certain stimuli, such as plant hormones. Through the phosphorelay, the type-B phospho-accepting response regulator (ARR) family members serve as DNA-binding transcriptional regulators, whose activities are most likely regulated by phosphorylation/dephosphorylation. Based on the fact that this higher plant has 11 type-B ARR family genes, we clarified the expression profiles for all of their transcripts in plants. We constructed and characterized a series of transgenic lines, each carrying a given ARR-promoter::GUS transgene. Transcripts of some type-B ARR family genes were detected more or less ubiquitously in many organs tested, while others were expressed predominantly in reproductive organs. These ARR family members were phylogenetically classified into three sub-families, the largest of which includes the well-characterized ARR1, ARR2, and ARR11. Comparative studies were conducted focusing on ARR20 and ARR21, each of which is a representative member of an uncharacterized minor sub-family. A set of transgenic lines was constructed, in each of which a C-terminal DNA-binding domain lacking the N-terminal phospho-accepting receiver of a given ARR was aberrantly overexpressed. These resulting transgenic lines, including ARR14-C-ox, ARR20-C-ox, and ARR21-C-ox, showed characteristic anomalies during development. These results are discussed with special reference to the His-->Asp phosphorelay signal transduction in A. thaliana.

Purpose: To assess the accuracy of pattern-based classification of contrast material-enhanced wideband harmonic gray-scale ultrasonographic (US) images in the differential diagnosis of hepatic tumors., Materials and Methods: A total of 183 hepatic lesions in 183 patients were studied; lesions included 116 hepatocellular carcinomas, 42 liver metastases, and 25 liver hemangiomas. After injection of a galactose-palmitic acid contrast agent, lesions were scanned with contrast-enhanced wideband harmonic gray-scale US in the arterial, portal venous, and late venous phases. The enhancement patterns were classified, and multiple logistic regression analysis was used to identify diagnostic patterns that enabled differentiation between hepatic tumors., Results: Five enhancement patterns were found to be significant in predicting different hepatic tumors. In hepatocellular carcinomas, the presence of intratumoral vessels in the arterial phase and homogeneous or heterogeneous enhancement in the portal phase were the most typical patterns. In metastases, the absence of intratumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase were the most typical patterns. In hemangiomas, the absence of intratumoral vessels in the arterial phase and peripheral nodular enhancement in the portal phase were the most typical patterns. The sensitivity, specificity, and accuracy of diagnosis based on combinations of enhancement patterns were, respectively, 94.8%, 94.0%, and 94.5% for hepatocellular carcinoma; 90.5%, 94.3%, and 93.4% for metastasis; and 88.0%, 99.4%, and 97.8% for hemangioma., Conclusion: Contrast-enhanced wideband harmonic gray-scale US is a useful tool for differentiating among the hepatic tumors studied.

The Arabidopsis thaliana AHK4 histidine kinase (also known as CRE1 or WOL) acts as a cytokinin signal transducer, presumably, in concert with downstream components, such as histidine-containing phosphotransfer factors (AHPs) and response regulators (ARRs), through the histidine-to-aspartate (His-->Asp) phosphorelay. Among 10 members of the type-A ARR family, the cytokinin-induced expression of ARR15 in roots is selectively impaired in the cre1-1 mutant, which carries a mutation in the AHK4 gene, suggesting a link between this type-A response regulator and the AHK4-mediated cytokinin signal transduction in roots. To address this issue further, we characterized a T-DNA insertion mutant of ARR15, and also constructed transgenic lines (referred to as ARR15-ox) that overexpress the ARR15 gene in a manner independent of cytokinin. While the T-DNA insertion mutant (arr15-1) showed no apparent phenotype, the cytokinin-independent overexpression of ARR15 in ARR15-ox plants resulted in a reduced sensitivity toward exogenously applied cytokinin, not only in elongation of roots in plants, but also in green callus formation (or shoot formation) in explants. Cytokinin-induced expressions of certain type-A ARRs were also down-regulated in ARR15-ox plants. These results support the view that ARR15 acts as a repressor that mediates a negative feedback loop in the cytokinin and AHK4-mediated His-->Asp phosphorelay.

We treated a 75-year-old man who had non-B and non-C, and Child's class C liver cirrhosis and acute hepatic encephalopathy with neostigmine and polyethylene glycol electrolyte solution. He received repeated transcatheter artrial embolization and percutaneous ethanol injection combination therapy for multiple hepatocellular carcinomas, which controlled his disease for 25 months from the first treatment. He was admitted in a state of hepatic coma after being found unresponsive at his home. With the consent of the patient's family, we gave him 1.0 mg of neostigmine intramuscularly to improve his peristaltic movement, and 2 L of polyethylene glycol electrolyte solution through a nasogastric tube for 4 hours to reduce the production and absorption of gut-derived toxins of nitrogenous compounds. Using these treatments, the blood ammonia level decreased to the normal range within 8 hours, and the coma disappeared after 2 days. We suggest that a combination approach of neostigmime and polyethylene glycol electrolyte solution may be one of the most effective treatments for acute hepatic encephalopathy associated with liver cirrhosis and ascites.

In Arabidopsis thaliana, Histidine-to-Aspartate (His--> Asp) phosphorelay is a paradigm of a signaling system that is considered to be involved in response to plant hormones, including ethylene and cytokinin. In the current framework of His-->Asp phosphorelay in this higher plant, the type-B ARR (response regulator) family members appear to act as DNA-binding transcriptional regulators. Although Arabidopsis thaliana has 11 type-B ARR family members, except for ARR1 and ARR2, no biological information is available with regard to others. As the main objective of this study, we characterized another example, ARR11, in terms of not only its in vitro biochemical properties, but also its biological activity in plants. In plants, the ARR11 gene was expressed predominantly in roots. In vitro, ARR11 showed the ability to acquire a phosphoryl group from a histidine-containing phosphotransfer intermediate (AHP), and also it showed the ability to recognize a specific nucleotide sequence, GGATT. These in vitro results supported the view that ARR11 is indeed a DNA-binding transcription factor, the ability of which is most likely modulated by phosphorylation in its receiver domain. In vivo, when a C-terminal DNA-binding domain lacking the N-terminal phospho-accepting (or receiver) domain was aberrantly expressed, the resulting transgenic plants showed characteristic anomalies during development of apical parts. The observed anomalies included "unusual proliferation of tissues in cotyledons" and "outgrowth of adventitious shoots near cotyledons". These results with regard to the functions of ARR11 are mainly discussed in comparison with those of the previously characterized type-B response regulators.

Objective: The newly developed contrast-enhanced harmonic gray-scale sonography technique enables us to improve the real-time detectability of viable tumor tissue in hepatocellular carcinoma lesions. We evaluated the usefulness of real-time percutaneous ablation therapy under guidance with this method for patients with hepatocellular carcinoma that is not depicted on conventional sonography., Subjects and Methods: We examined 30 patients with 56 hepatocellular carcinomas using real-time contrast-enhanced harmonic gray-scale sonography after injection of a galactose-palmitic acid contrast agent and compared the results with the findings of contrast-enhanced helical CT. We performed percutaneous ablation therapy guided by this modality for treatment of viable hepatocellular carcinoma lesions that could not be detected using conventional sonography., Results: High detection rates of viable hepatocellular carcinoma lesions were obtained using real-time contrast-enhanced harmonic gray-scale sonography (52/56 lesions, 93%); these rates were comparable to those of helical CT (54/56 lesions, 96%). Nine (90%) of the 10 lesions that were not detected on conventional sonography but were depicted on real-time contrast-enhanced harmonic gray-scale sonography (incomplete local treatment, n = 4; small new lesion, n = 6) were successfully treated with percutaneous ablation therapy guided by this method., Conclusion: Real-time contrast-enhanced harmonic gray-scale sonography improved the sensitivity for the detection of viable hepatocellular carcinoma lesions. Percutaneous ablation therapy guided by this modality may be useful in patients with hypervascular hepatocellular carcinoma lesions that cannot be detected using conventional sonography.

Objective: To evaluate the usefulness of contrast-enhanced wideband harmonic gray scale sonography in assessing the vascularity of small pancreatic mass lesions., Methods: Twenty-five patients with 25 pancreatic mass lesions (20 pancreatic carcinomas, 1 islet cell tumor, 1 malignant lymphoma, and 3 focal inflammatory pancreatic masses due to chronic pancreatitis) were examined. All patients held their breath for 20 to 50 seconds after injection of a contrast agent while the vascularity of the tumor was observed on contrast-enhanced wideband harmonic gray scale sonography (early phase). We then monitored the tumor enhancement 60 to 120 seconds after the injection while the patients held their breath for a few seconds (delayed phase)., Results: All 20 (100%) of the pancreatic carcinomas showed no contrast enhancement in the early phase. Fifteen (75%) of the 20 pancreatic carcinomas also showed no contrast enhancement in the delayed phase. The remaining 5 (25%) pancreatic carcinomas showed mild enhancement in the peripheral regions of the tumor in the delayed phase. The other pancreatic masses showed mild or pronounced enhancement throughout the entire lesions in both the early and delayed phases., Conclusions: Contrast-enhanced wideband harmonic gray scale sonography is a useful tool for differentiating pancreatic carcinomas from focal inflammatory pancreatic masses or hypervascular pancreatic tumors.

The cytokinin receptor AHK4 histidine kinase, identified in Arabidopsis thaliana, presumably acts in concert with downstream components, such as histidine-containing phosphotransfer (HPt) factors (AHPs) and response regulators (ARRs). In this respect, we characterized a loss-of-function mutant of the AHK4 gene, named cre1-1, which showed a reduced cell number within the vascular tissues in roots. Among the 10 type-A ARR members, the expression of ARR15 and ARR16 in roots was specifically and markedly reduced in cre1-1, suggesting a link between these response regulators and the AHK4-mediated signal transduction in roots. The results for transgenic plants expressing promoter::GUS or promoter::LUC fusion genes showed that both the ARR15 and the ARR16 gene products are accumulated upon cytokinin treatment in roots. The results of GFP-fusion experiments with onion epidermal cells further showed that ARR15 was found in the nucleus, and ARR16 mainly in the cytoplasm. Together, it was suggested that ARR15 and ARR16 are distinctly implicated in the presumed AHK4-mediated signaling pathway in roots.

We report a case of advanced gastric cancer complicated by disseminated intravascular coagulation successfully treated with chemotherapy consisting of 5-fluorouracil and cisplatin. The patient was a 53-year-old woman who complained of loss of appetite, weight loss, and low back pain. Based on the laboratory data, a diagnosis of disseminated intravascular coagulation was made. Gastroscopy revealed gastric carcinoma (Borrmann type 3) that was continuously bleeding, and chest computed tomography showed a solitary lung metastasis and bilateral pleural effusion. Bone scintigraphy revealed multiple bone metastases. Accordingly, we made a diagnosis of stage IV gastric cancer complicated by disseminated intravascular coagulation. We selected the 5-fluorouracil and cisplatin combination chemotherapy for treatment and obtained the patient's consent. After two cycles of the 5-fluorouracil and cisplatin therapy, the bleeding symptoms improved and the disseminated intravascular coagulation process was successfully controlled. We concluded that disseminated intravascular coagulation caused by gastric cancer may be improved when the primary cancer and its metastases are brought under control by treatment with FP combination chemotherapy.

Hepatocytes have a great replicative capacity and are capable of repopulating the liver. Previous studies have suggested that the autonomic nervous system regulates liver regeneration and apoptosis. Moreover, the central nervous system modulates them through the autonomic nervous system. The lateral hypothalamus (LH) area and the ventromedial hypothalamus (VMH) nucleus have been studied for their role in the integration of neurohumoral information. The LH is part of the parasympathetic system, while the VMH belongs to the sympathetic system. Lesions of the LH reportedly induced an increase in sympathetic nerve activity, while those in the VMH produced facilitation of vagus nerve activity. Moreover, VMH or LH lesions facilitate hepatic regeneration after partial hepatectomy. Furthermore, the hypothalamus mediates hepatic apoptosis through the autonomic nervous system. Although further studies are needed to define the role clearly, the autonomic nervous system is one of the important factors that regulate liver regeneration and apoptosis., (Copyright 2002 S. Karger AG, Basel)

Objective: The purpose of our study was to evaluate the usefulness of percutaneous ethanol installation using CO(2)-enhanced sonography for patients with nonresectable hepatocellular carcinoma (HCC)., Subjects and Methods: Forty-six patients with 65 HCC lesions were examined with contrast-enhanced sonography with direct injection of CO(2) into the proper hepatic artery during arteriography. We performed percutaneous ethanol injection guided by CO(2)-enhanced sonography for the treatment of hypervascular HCC lesions that could not be treated with conventional percutaneous ethanol injection or with transcatheter arterial embolization., Results: CO(2)-enhanced sonography detected five additional small HCC lesions before treatment (p<0.05) and 14 new lesions during follow-up (p<0.01), than conventional sonography detected. CO(2)-enhanced sonography showed positive enhancement of residual lesions after initial treatment (n = 3) and incomplete local treatment (n = 5) that were not detected on conventional sonography. These 27 lesions were successfully treated with percutaneous ethanol injection using a mixture of iodized oil and ethanol and guided by CO(2)-enhanced sonography., Conclusion: CO(2)-enhanced sonography is a sensitive method for detecting residual viable lesions and small new HCC lesions that cannot be detected with conventional sonography. Percutaneous ethanol injection guided by CO(2)-enhanced sonography can treat hypervascular HCC lesions that cannot be treated with conventional percutaneous ethanol injection or transcatheter arterial embolization.

A 66-year-old woman complained of supraclavicular lymph node swelling during her initial visit to an outpatient clinic. Computed tomography revealed a hypervascular tumor in the uncus of the pancreas (2.0 x 2.0 cm), therefore a needle biopsy of the pancreas was performed. A poorly differentiated adenocarcinoma was identified. Transcatheter arterial embolization using adriamycin and gelatin sheet was performed. To alleviate her symptoms (movement disorder of neck, etc.), initial chemotherapy; FP (5-fluorouracil and cisplatin intravenously) was continued for 6 cycles with her consent, and subsequently MF (methotrexate and 5-fluorouracil intravenously) for 14 cycles. This patient survived with transcatheter arterial embolization, FP and MF combination chemotherapies for 24 months after presenting with the symptoms. To our knowledge, this is the longest surviving case of pancreatic poorly differentiated adenocarcinoma (Stage IV). In conclusion, this present case suggests that transcatheter arterial embolization, FP and MF combination therapy may have an effect at prolonging survival in poorly differentiated pancreatic adenocarcinoma.

We examined whether the Fas (APO-1/CD95)/Fas ligand system mediates apoptosis in rats with ventromedial hypothalamus (VMH) lesions. Northern and Western blotting indicated that VMH lesions lead to a significant increase in Fas mRNA and protein expression from day 1 to day 7 and in Fas ligand mRNA and protein expression from day 2 to day 7. Immunohistochemistry indicated that the region of strongest Fas expression shifted from acinar zone 1 to zones 2 and 3 by day 7 after VMH lesioning and that at days 2-7 Fas-ligand-positive hepatocyte cell membranes and cytoplasm were randomly distributed in acinar zones 1-3. We also analyzed activation of caspase 3-like proteases in hepatocytes, Kupffer cells, and sinusoidal endothelial cells. Spectrofluorometric assay demonstrated that caspase 3-like activity significantly increased only in hepatocytes after VMH lesioning. Moreover, electron microscopy and TUNEL assay showed that VMH lesions induced apoptosis. All of these effects were completely inhibited by hepatic vagotomy and administration of atropine. Vagal firing after VMH lesioning may stimulate Fas/Fas ligand system-mediated apoptosis through the cholinergic system in the rat liver.

Objective: We evaluated the usefulness of contrast-enhanced wideband harmonic gray-scale sonography in assessing the therapeutic effects of transcatheter arterial embolization for patients with hepatocellular carcinoma and compared the findings of this imaging modality with those of helical CT., Subjects and Methods: Twenty-nine patients with 39 hepatocellular carcinoma lesions were examined. We scanned lesions before and after therapy using contrast-enhanced wideband harmonic gray-scale sonography after injection of a galactose-palmitic acid contrast agent. All patients held their breath for 20--50 sec after injection while the vascularity of the tumor was observed. We then monitored tumor enhancement between 60 and 180 sec after injection with patients breath-holding for a few seconds. Lesions were considered to exhibit viable tumor residue if hypervascular enhancement was observed in the tumor. We compared this enhancement with helical CT findings., Results: After therapy, 36 of the 39 lesions showed viable tumor residue on contrast-enhanced wideband harmonic gray-scale sonography, with no artifacts from iodized oil. Helical CT revealed a high-attenuation area in 12 of the 36 lesions, whereas 24 of the 36 lesions could not be evaluated for tumor residue as a result of artifacts from iodized oil accumulation in the tumor. The remaining three lesions showed complete deposition of iodized oil and complete necrosis on contrast-enhanced wideband harmonic gray-scale sonography., Conclusion: Contrast-enhanced wideband harmonic gray-scale sonography is useful in evaluating the therapeutic effects of transcatheter arterial embolization for hepatocellular carcinoma.

We treated a 63-year-old man who had recurrent large hepatocellular carcinomas (> 5 cm in diameter) and left adrenal metastasis with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization. He received repeated transcatheter arterial embolization and percutaneous ethanol injection combination therapy for intrahepatic hepatocellular carcinomas, which controlled his disease for 6 months from the first treatment. After that, left adrenal metastasis was detected by biopsy specimen. Therefore, we repeated more transcatheter arterial embolization and percutaneous ethanol injection to the liver and left adrenal gland, but this combination therapy could not control the hepatocellular carcinomas in these organs. With the patient's consent, he was treated with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization for hepatocellular carcinomas of the liver and left adrenal gland. After this combination therapy, we followed-up the viable lesions by color Doppler ultrasonography and computed tomography examination. However, we could not detect these viable lesions of hepatocellular carcinomas in his body until one month before he died. When the degree of hepatic failure worsened due to the natural course of cirrhosis, this combination therapy was stopped 7 months before he died. He died of pulmonary tumor emboli from metastasis of inferior vena cava 24 months after the combination therapy started. However, on autopsy there was almost no remaining hepatocellular carcinoma found in the main lesions of liver and left adrenal gland. We suggest that a combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization may be indicated in elderly cases of intrahepatic large hepatocellular carcinoma and adrenal metastasis, which are not under control only by transcatheter arterial embolization and percutaneous ethanol injection.

Background: Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). Preliminary data on this combination therapy in humans demonstrated no drug interactions between CPT-11 (or its metabolite, SN-38) and 5-FU however, because there is so little information on the combination, the possibility for an interaction still exists., Material and Methods: CPT-11 and 5-FU were injected intravenously into rats and the pharmacokinetics of CPT-11 and SN-38 and alternations in blood cell count were investigated., Results: In the group of rats administered 5-FU prior to CPT-11, the area under the concentration-time curve (AUC) of CPT-11 was approximately eight-fold larger compared with the group administered CPT-11 prior to 5-FU. On the other hand, the grade of leukocytopenia or thrombocytopenia was not significantly different among the two groups., Conclusion: In rats, the conversion of CPT-11 into SN-38 is possibly delayed by prior administration of 5-FU.

Background: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours., Methods: Using nested reverse-transcription-polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and fit-1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens., Results: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non-tumour portion of the specimens in eight patients (57%; P= 0.08). No differences were found between the tumour portion and the corresponding non-tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and fit-1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non-tumour portions, respectively (chi2 test: KDR, P< 0.01; fit-1, P= 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non-tumour portions (Mann-Whitney U-test: P<0.001) but no differences were detected for fit-1., Conclusions: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF.

Interferon (IFN) receptor mRNA expression patterns in the liver have been shown to correlate with the effectiveness of IFN therapy in patients with hepatitis C virus (HCV) infection. However, it is not clear to what extent this factor contributes to the short (primary)- and long (sustained)-term results of IFN treatment with respect to biochemical and virological remission. Eighty-two patients who subsequently received lymphoblastoid IFN-alpha therapy underwent liver biopsies before IFN therapy. Possible factors that might correlate with IFN response were chosen and analyzed. The primary biochemical and virological responses at the end to treatment (24 weeks) were 63% and 43% vs. 46% and 32% for sustained biochemical and virological remission at the end of follow-up (48 weeks), respectively. In univariate analysis, the absence of HCV genotype 1b, a low titer of HCV RNA, and the expression of IFN receptor mRNA were significantly correlated with sustained biochemical and virological responses to IFN therapy. Multiple logistic regression analysis showed that IFN receptor mRNA expression and the absence of genotype 1b were significant predictors of the sustained biochemical and virological effectiveness of IFN therapy. IFN receptor mRNA expression predicted a sustained virological response to IFN therapy with a positive predictive value of 100% with genotype non-1b and had a negative predictive value of 97% with genotype 1b. It is concluded that expression of IFN receptor genes in the liver is a useful index for predicting the short- and long-term efficacy of IFN therapy in patients with chronic HCV infection.

We assessed a possible correlation between the hepatic tumor index (as the ratio of the tumoral peak systolic velocity to the peak systolic velocity of the right or left hepatic artery) and grade of tumor vessel in large hepatocellular carcinomas (HCCs). Color Doppler sonographic findings were evaluated and compared with selective hepatic arteriographic findings in 78 patients with 93 hepatocellular carcinomas larger than 2.0 cm in diameter. Pulsatile color flow images were obtained in 78 of 93 lesions. The hepatic tumor index was equal to or greater than 1.0 in 57 of 78 lesions. These lesions were revealed arteriographically to have distinct tumor vessels and/or arteriovenous shunting. When this index was 1.0 or greater, we calculated 90% accuracy in distinguishing HCCs with distinct tumor vessels from those without distinct tumor vessels. The hepatic tumor index correlated with the grade of tumor vessels and the presence of arteriovenous shunting.

A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma.

From January 1996 to August 1997, 24 patients with advanced hepatocellular carcinoma (HCC) equal to or more than 2 cm (mean +/- SD; 4.1 +/- 3.0 cm) in main tumor diameter were treated by SMANCS-TAE (20 cases) or SMANCS-TAI (4 cases) combined with PEI. Six cases had solitary lesion, 16 cases had multiple lesions, and 2 cases had massive lesions. After this combination therapy, 21 of 24 cases had complete tumor necrosis. During 3 to 19 months follow up period, 12 cases had cancer-free survival (SMANCS-TAI; 3 cases), and 9 cases had tumor recurrences (3 cases were local recurrences and 6 cases involved new lesions). Two cases died of hepatic infarction and cancer death, however, the remaining 22 cases were surviving. SMANCS-TAE combined with PEI is useful treatment for advanced large or multiple HCC lesions in patients who are poor surgical risks.

Hepatitis G virus (HGV), which was recently identified, is a single, plus-stranded RNA virus that is thought to replicate via minus-stranded RNA, but no information is available about the distribution of either plus- (genomic) or minus- (replicative) stranded HGV RNAs in HGV infected patients. We, therefore, tested the serum, liver tissue, and peripheral blood mononuclear cells (PBMCs) of six hepatitis patients with HGV infection for the presence of plus- and minus-stranded HGV RNA. The RT-nested PCR was used with primers derived from 5'-noncoding region of the genome. Before RT-PCR analysis, the 3'-termini of RNA specimens were chemically modified to discriminate between plus- and minus-stranded HGV RNA. Plus-stranded HGV RNA was detected in the serum and liver tissue of all six patients and in the PBMCs of five patients. Minus-stranded RNA was detected in the liver tissue of all six patients, in the serum of two patients, and in the PBMCs of one patient. In summary, the detection of minus-stranded HGV RNA in liver tissue may indicate that HGV replicates in the liver.

Objective: Color flow patterns on Doppler sonography are nonspecific for differentiating various hepatic tumors. We previously reported that a tumoral peak systolic flow velocity of 0.40 m/sec or greater suggested a malignant hepatic tumor rather than a hemangioma. However, tumoral peak systolic flow velocity failed to differentiate hepatocellular carcinomas and metastatic tumors. In this study, we attempted to assess the value of the hepatic tumor index for differentiating hepatocellular carcinomas and other hepatic tumors., Materials and Methods: Color Doppler sonography was performed in 80 patients with 108 hepatic lesions larger than 2.0 cm in diameter. The hepatic tumor index was calculated as the ratio of the tumoral peak systolic velocity to the peak systolic velocity of the right or left hepatic artery., Results: Pulsatile color flow images were obtained in 42 of 48 hepatocellular carcinomas, 25 of 32 hepatic metastases, and 13 of 28 hemangiomas. The mean hepatic tumor indexes obtained from hepatocellular carcinomas, metastases, and hemangiomas were 1.14 +/- 0.37 (+/-SD), 0.63 +/- 0.22, and 0.60 +/- 0.17, respectively. The hepatic tumor indexes of hepatocellular carcinomas significantly exceeded those of metastases and hemangiomas (p < .01 in both cases). A hepatic tumor index equal to or greater than 1.0 was associated with 76% sensitivity, 92% specificity, and 82% accuracy in distinguishing hepatocellular carcinomas from hepatic metastases. In lesions with a tumoral peak systolic velocity of 0.40 m/sec or greater, a hepatic tumor index equal to or greater than 1.0 was associated with 91% sensitivity, 83% specificity, and 89% accuracy in distinguishing hepatocellular carcinomas from hepatic metastases., Conclusion: The hepatic tumor index on color Doppler sonography was useful in differentiating large hepatocellular carcinomas from hepatic metastases.

It has been reported that ventromedial hypothalamic lesions facilitate hepatic regeneration through the hepatic vagal nerve after partial hepatectomy. However, whether the lateral area of the hypothalamus is involved in liver regeneration after partial hepatectomy is unknown. To determine the role of the lateral hypothalamic area in this phenomenon, we studied hepatic DNA synthesis during liver regeneration after partial hepatectomy with bilateral lesions of the area. Lesioning of the lateral hypothalamus accelerated the increase in hepatic DNA synthesis and raised the peak level of [methyl-3H]thymidine incorporation after partial hepatectomy. These effects of hypothalamic lesioning were inhibited by combined hepatic vagotomy and sympathectomy. Our results demonstrate that lesioning of the lateral hypothalamus promotes hepatic regeneration through the autonomic nervous system after partial hepatectomy and suggest that the lateral hypothalamic area is involved in liver regeneration through neural mediation.

Whether or not the hypothalamus is involved in initiating hepatic DNA synthesis after partial hepatectomy is unclear. To determine the role of the ventromedial hypothalamic nuclei in liver regeneration after partial hepatectomy, we studied hepatic DNA synthesis during liver regeneration in rats with bilateral lesions of these nuclei. Lesions of the ventromedial hypothalamus accelerated the increase in hepatic DNA synthesis and raised the peak level of thymidine incorporation after partial hepatectomy. These effects of hypothalamic lesions were completely inhibited by hepatic vagotomy. Thus, lesions of the ventromedial hypothalamus appear to promote hepatic regeneration by increasing vagal stimulation of the liver.

Ventromedial hypothalamic (VMH) lesions cause excessive fat accumulation in white adipose tissue (WAT), and brown adipose tissue (BAT); however, little information is available on whether or not cell proliferation occurs in WAT and BAT after VMH lesioning. In this study, we determined the DNA content and thymidine incorporation in unilateral parametrial WAT and interscapular BAT 0, 1, 3, and 7 days after VMH lesioning, and examined the mechanism of increased DNA content in WAT. In rats with VMH lesions, the weight of WAT and BAT had increased significantly at 7 days, and the DNA content and thymidine incorporation of WAT had increased significantly at 3 days and continued to increase for up to 7 days, while those of BAT did not increase for as long as 7 days after VMH lesioning. Restricted food intake according to the pair-feeding method partially inhibited the increased DNA content in WAT. The increased DNA content in WAT was mostly restored but not completely by the administration of anti-insulin antibody, and by administration of propranolol, a beta-adrenergic blocker. The results demonstrated that VMH lesions induced DNA synthesis in WAT early after VMH lesioning, but did not induce DNA synthesis in BAT, and suggested that either hyperinsulinemia or a beta-adrenergic receptor mechanism or both may be responsible for the increased DNA content in WAT.

Background: It was recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in gastrointestinal DNA content in rats. In the present study, the mechanism of this alteration was examined., Methods: The DNA content and synthesis after VMH lesioning in rat gastrointestinal tracts were determined., Results: Total content of DNA in stomach and small intestine began to increase at 3 days and continued to increase for 7 days, whereas DNA content in the large intestine began to increase at 3 days and maintained the same level until 7 days after VMH lesioning. DNA synthesis of these organs increased and reached maximum at 3 days and then decreased to the initial level 7 days following the lesions. This increase in DNA content and synthesis in these organs was largely inhibited by bilateral subdiaphragmatic vagotomy or the administration of atropine, a cholinergic blocker, but not by the administration of anti-insulin antibody., Conclusions: VMH lesions induce cell proliferation in the rat gastrointestinal tract by the firing of vagus nerve activity mainly through the cholinergic receptor mechanism.

The incidence and pattern of mutations of the ras oncogenes and the p53 tumor suppressor gene have been shown to differ among different cancer types and even among the same cancer types with different etiological backgrounds. For example, in a previous study we showed that not only the etiology but also the incidence of point mutation of the c-Ki-ras oncogene in cholangiocellular carcinomas (CCCs) differ between Japanese and Thai patients. In the study presented here, we examined the incidence of mutations in the ras gene family and the p53 gene in CCCs of both Japanese and Thai patients by single-strand conformation polymorphism and direct sequencing analyses and compared the pattern of p53 mutation between these two CCC groups. Although the incidence of ras mutation differed markedly between Japanese (seven of 12, 58%) and Thai (two of 26, 8%) cases, the incidence of p53 mutation was similar: four of 12 (33%) and nine of 26 (35%), respectively. Except for one case in which deletion-insertion was detected in the second exon of the N-ras gene, all ras mutations occurred at codon 12 or 13 of the c-Ki-ras gene. All p53 mutations but one were detected in a highly conserved region, and the predominant form of the mutations was G:C-->A:T transition at CpG sites in both Japanese and Thai cases, similar to that reported for colorectal cancers. Therefore, in contrast to the ras oncogenes, mutation of the p53 gene was frequently involved in the development of CCCs in both Japanese and Thai patients, irrespective of any difference in etiology.

Bilateral lesions of ventromedial hypothalamus are followed by a number of changes including vagal hyperactivity and hyperinsulinemia. To investigate if cell proliferation occurs in visceral organs in rats with ventromedial hypothalamic (VMH) lesions and fed a high fat diet, we determined DNA contents of visceral organs (liver, pancreas, small and large intestines, spleen, kidney and heart) 1 and 4 week after VMH lesions or start of high fat diet. In rats with VMH lesions, DNA contents increased significantly in liver, pancreas, and small and large intestines at 1 week, and maintained the same levels until the 4th week. DNA contents increased most in the pancreas, followed by small and large intestines, and liver. DNA content did not change in spleen, kidney, or heart. In rats fed a high fat diet, there was no increase in the DNA content of these organs, except in the small intestine at 4 weeks. The results suggest that VMH lesions produce excessive DNA synthesis in visceral organs, whereas a high fat diet does not. VMH lesions may induce cell proliferation in visceral organs through vagal hyperactivity and/or changes of humoral growth factors.

A new method is presented for the quantitative separation and determination of selenium by direct evolution with the bromide-condensed phosphoric acid reagent (Br(-)-CPA) from rocks, marine sediments and plankton. In the reaction with the Br(-1)-CPA, selenium(IV) and (VI) in the solid samples are evolved as selenium tetrabromide, and can be collected in an absorbing solution of 0.3M hydrochloric acid and 06M perchloric add (1:1), and then determined spectrophotometrically with 4-substituted o-phenylenediamines followed by the extraction of the resulting 5-substituted piazselenol into toluene. Elemental selenium and selenide do not react with the Br(-)-CPA, but can be determined after oxidation to selenite with potassium iodate. Therefore, successive distillations, the first with Br(-)-CPA and the second with IO(3)(-)-Br(-)-CPA, give a satisfactory means of diflerential determination of selenium(IV) and (VI), and elemental selenium and selenide. This method can be successfully applied for the separation of selenium in the neutron-activation analysis of standard rock samples, marine sediments and plankton, giving good and reliable results.

The extraction of the ion-association complexes formed by Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)-4,7-diphenyl-1, 10-phenanthroline (BP) chelates and perchlorate ions into 1,2-dichloroethane has been investigated. Extraction equilibrium for Mn(II), Cu(II), Zn(II) and Cd(II) is reached within 1 hr, but equilibration for Fe(II), Co(II) and Ni(II) is very slow; the equilibration rate depends on the structure of the chelating agent, the nature of the organic solvent, and pH. In the extraction equilibrium of Co(II) the rate-determining step seems to be the complexation of hydrated Co(II) by BP in the aqueous phase.

The preparation and characteristics of ammonium molybdophosphate and potassium or ammonium hexacyanocobalt ferrate supported in silica gel, and their application to the determination of (137)Cs in natural waters are described. Use of columns of these materials gives better recovery of (137)Cs from natural waters (in comparison with co-precipitation with ammonium molybdophosphate), requires less exchanger, so raising the gamma-counting efficiency of (137)Cs, and permits elimination of other radionuclides by washing with hydrofluoric acid.

End-point detection in some precipitation titrations is achieved by measurement of the surface tension between mercury and the solution ("stalagmometric" titration). The drop-time of a polarographic dropping mercury electrode in open circuit is plotted against volume of surface-active titrant added, and shows a break or a peak at the end-point. The stalagmometric titration of sodium tetraphenylborate with Zephiramine (tetradecyldimethylbenzylammonium chloride) was satisfactory and made possible the determination of potassium by back-titration. Potassium was also titrated directly with tetraphenylborate and with calcium dipicrylaminate. Sodium dodecylbenzenesulphonate was titrated directly with Zephiramine and the results were compared with those obtained by the p-toluidine method and Epton's method.

A neutron-activation method is described for the determination of rhenium in molybdenite. Radiochemical separation by a carrier technique was carried out very rapidly by means of successive liquid-liquid extraction processes. The recovery of rhenium, which was determined by a spectrophotometric method, was about 93%. About 10 samples could be analysed within 6 hr in parallel runs.