Selective growth inhibition by suppression of F1Fo ATPase in canine malignant melanoma cell lines.

Canine malignant melanoma (CMM) is a highly aggressive and fatal neoplasm. To identify potential therapeutic compounds and/or targets, 320 compounds were screened for their growth inhibitory activity in a CMM line (CMM-1) using a chemical library known to target specific signaling pathways/cell growth-related molecules. Among the compounds screened, the F1Fo ATPase inhibitor oligomycin showed potent growth inhibitory effects in CMM-1 cells, while exhibiting less toxic effects in a non-neoplastic control cell line (MDCK cells). The growth inhibitory effect of oligomycin A was then examined using six CMM lines and MDCK cells. Three CMM lines were highly sensitive to oligomycin A, with around 3000-20 000 times lower IC50 compared with oligomycin A-resistant CMM lines and MDCK cells. Oligomycin A-sensitive CMM-1 cells exhibited much greater oligomycin A-induced decreases in cellular ATP compared to oligomycin A-resistant cell lines. Although the oligomycins are clinically unsuitable because of its in vivo toxicity, these findings implicate the potential of F1Fo ATPase as a therapeutic target in a subset of CMM.

A rare case of Lemierre`s syndrome caused by Porphyromonas asaccharolytica.

Lemierre's syndrome is only very rarely caused by Porphyromonas asaccharolytica. Here, we report the case of a 35-year-old man who developed a left peritonsillar abscess, thrombophlebitis of the left internal jugular vein, and septic embolization of both lungs. Anaerobic P. asaccharolytica was isolated in the blood cultures, and we subsequently confirmed the diagnosis as Lemierre's syndrome. Our case indicates that although P. asaccharolytica is not commonly found in oral cavities, this organism may still cause Lemierre's syndrome. Consequently, when it is detected in blood cultures, the treating physician should perform the medical examination while keeping in mind the possibility that the patient could have Lemierre's syndrome.

Oxygen reduction activity of carbon nitride supported on carbon nanotubes.

Fuel cells offer an alternative to burning fossil fuels, but use platinum as a catalyst which is expensive and scarce. Cheap, alternative catalysts could enable fuel cells to become serious contenders in the green energy sector. One promising class of catalyst for electrochemical oxygen reduction is iron-containing, nanostructured, nitrogen-doped carbon. The catalytic activity of such N-doped carbons has improved vastly over the years bringing industrial applications ever closer. Stoichiometric carbon nitride powder has only been observed in recent years. It has nitrogen content up to 57% and as such is an extremely interesting material to work with. The electrochemical activity of carbon nitride has already been explored, confirming that iron is not a necessary ingredient for 4-electron oxygen reduction. Here, we synthesize carbon nitride on a carbon nanotube support and subject it to high temperature treatment in an effort to increase the surface area and conductivity. The results lend insight into the mechanism of oxygen reduction and show the potential for carbon nanotube-supported carbon nitride to be used as a catalyst to replace platinum in fuel cells.

Persistent hyperparathyroidism in renal allograft recipients: vitamin D receptor, calcium-sensing receptor, and apoptosis.

The phenotypic changes in parathyroid cells after successful renal transplantation remain to be elucidated. We compared 10 diffuse and 11 nodular hyperplastic parathyroid glands from five renal allograft recipients with persistent hyperparathyroidism, with five diffuse and 13 nodular hyperplasia from seven uremic patients on hemodialysis, and 13 normal glands. Comparisons included expressions of both vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), proliferative activity (Ki67), and apoptosis (TUNEL). Immunoreactivity was assessed semiquantitatively and expressed as labeling index. The area/cell was also measured to assess cellular hypertrophy. The labeling indexes of VDR (587+/-71; mean+/-s.e.m.) and CaSR (45.0+/-2.8) in recipients' diffuse hyperplasia were significantly higher than those in uremic diffuse hyperplasia (224+/-44, 29.3+/-2.3, respectively) (P<0.01, each). However, these expressions remained low in recipients' nodular hyperplasia (42+/-8, 11.8+/-1.4, respectively). Ki67 labeling index in recipients' nodular hyperplasia (7+/-1) was significantly smaller than in uremic patients (24+/-6, P<0.01). TUNEL labeling index in recipients' diffuse hyperplasia (30+/-5) was the highest among the groups. The cell volume tended to be smaller in both patterns of hyperplasia in allograft recipients compared with uremic patients. Our results suggest that the phenotypic change in parathyroid cells after renal transplantation depends on the pattern of hyperplasia, where it is normalized only in diffuse hyperplastic glands in which the number of cells also regresses with significant induction of apoptosis.

Infrasternal mediastinoscopic surgery for anterior mediastinal masses.

BACKGROUND: Infrasternal mediastinoscopic surgery is a new alternative to the thoracoscopic approach for patients with anterior mediastinal masses. METHODS: We applied this technique to 18 thymectomies, one thymomectomy, and one cystectomy in a total of 20 patients with anterior mediastinal masses and then assessed the surgical results. RESULTS: Infrasternal mediastinoscopic surgery was accomplished in 18 of the 20 patients (90%). The pathological diagnoses included 13 Masaoka stage I thymomas, one stage II thymoma, two stage III thymomas, one thymic cyst, one pericardial cyst, one thymic granuloma, and one mature teratoma. Two patients with stage III thymoma required conversion to sternotomy, one for invasion into the innominate vein and the other for invasion into the pericardium. There was no surgically related mortality or complications in any patients. CONCLUSION: Infrasternal mediastinoscopic surgery is safe and feasible for stage I thymoma and other benign tumors in the anterior mediastinum.

Serum 7alpha-hydroxycholesterol levels during liver regeneration after hepatectomy in humans.

BACKGROUND/AIMS: Changes in bile acid synthesis during liver regeneration after hepatectomy is little known in humans. Since it has been reported that the serum 7 alpha-hydroxycholesterol levels reflect the hepatic bile acid synthesis and that the determination of bile acid synthesis is useful to assess the liver regeneration rate, we determined the serum 7 alpha-hydroxycholesterol level during liver regeneration after hepatectomy in clinical patients. METHODOLOGY: The serum 7 alpha-hydroxycholesterol levels were determined by gas-liquid chromatography-mass spectrometry-selected ion monitoring method before and on days 1, 3, 5, 7, 14 and 21 after hepatectomy in twenty consecutive patients. RESULTS: The 7 alpha-hydroxycholesterol levels became lower between days 1 and 7, were increased on day 14, and then decreased on day 21 after hepatectomy. The patients with preoperative external biliary drainage showed a higher serum 7 alpha-hydroxycholesterol level than those without biliary drainage before hepatectomy. The former showed lower serum 7 alpha-hydroxycholesterol levels than the latter throughout the 21 days after hepatectomy. In patients whose liver resection rate was more than 50%, the serum 7 alpha-hydroxycholesterol levels were kept lower until 21 days after hepatectomy compared with those whose liver was excised less than 50%. CONCLUSIONS: It is concluded that the patients who had preoperative biliary drainage or major hepatic resection seem to have less hepatic reserve capacity for bile acid synthesis after hepatectomy.

Thoracic cage extent of melorheostosis depicted by multislice CT.

The ribs and vertebrae are rarely affected by melorheostosis. We present a case of melorheostosis of the ribs and thoracic vertebrae, in which multislice computed tomography (CT) was useful in depicting its extent and defining its sclerotome distribution.

Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage.

Necessity of preoperative biliary drainage for patients with obstructive jaundice is still controversial. We recently reported that liver regeneration after major hepatectomy was better restored in a rat model of obstructive jaundice with preoperative internal biliary drainage than that without biliary drainage or with external biliary drainage. The aim of this study was to investigate the differences in biliary lipid excretion after hepatectomy in obstructive jaundiced rats with or without preoperative internal or external biliary drainage. After bile duct ligation for 7 days, rats were randomly divided into the three groups; obstructive jaundice-hepatectomy (OJ-Hx), internal biliary drainage-hepatectomy (ID-Hx), and external biliary drainage-hepatectomy (ED-Hx) groups. 70% hepatectomy and internal biliary drainage were carried out 7 days after biliary decompression in the latter two groups and without biliary decompression in the OJ-Hx group. On the day of and on days 1, 2, 3 and 7 after hepatectomy, the liver weight, DNA synthesis rate, biliary lipids excretion rates, and bile acid composition were determined. In the ID-Hx group, the DNA synthesis rate and relative liver weight were significantly higher than those of the OJ-Hx and ED-Hx groups. The excretion rates of biliary lipids were disturbed in the ED-Hx group compared with those in the ID-Hx group and the values in the OJ-Hx group were in-between the ID-Hx and ED-Hx group. The liver regeneration rate was significantly correlated with bile flow and excretion rates of biliary lipids. The maintenance of enterohepatic circulation of biliary lipids before hepatectomy may be important for the liver regeneration.

Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and limitations for evaluating esophagopharyngeal invasion.

BACKGROUND AND STUDY AIMS: Although computed tomography (CT) and magnetic resonance imaging (MRI) are useful for detecting esophagopharyngeal invasion by thyroid cancer, they cannot assess the depth of invasion, which is important for the surgical planning. In the present study, endoscopic ultrasonography (EUS) of the esophagus was used to assess esophagopharyngeal invasion by thyroid cancer, and the value of this technique was assessed prospectively. PATIENTS AND METHODS: Between 1 December 1998 and 31 December 2000, EUS examinations were carried out in 59 patients in whom esophagopharyngeal invasion by thyroid cancer was suspected due to large tumors or tumors with poor mobility. The EUS findings were evaluated in 52 patients (10 men, 42 women; mean age 62.4 years; mean tumor size 39.5mm) with complete resections, and compared with the pathological results. RESULTS: The diagnostic specificity and accuracy of EUS in assessing invasion into the muscularis propria (82.9 %, 82.7 %) were greater than those of MRI (60 %; P = 0.034, 65.4 %; P = 0.044) and esophagography (58.8 %; P = 0.034, 60 %; P = 0.028). The accuracy for detecting cancer invasion located in the upper part of the lobe was less than for invasion in the middle and/or lower parts of the lobe ( P = 0.020). Conclusions. EUS is useful for assessing esophagopharyngeal invasion by thyroid cancer, although its effectiveness may be limited in thyroid lesions located in the upper part of the lobe.

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Video-assisted parathyroidectomy for primary hyperparathyroidism: a new approach involving a skin-lifting method.

BACKGROUND: Recent advances have allowed the performance of parathyroidectomy as an endoscopic procedure. Carbon dioxide (CO2) insufflation can be used to create a working space in the anterior neck, but it has been associated with a number of complications. We have devised a skin-lifting method to overcome these problems. METHODS: Eleven consecutive patients underwent video-assisted parathyroidectomy. Preoperative imaging revealed a solitary adenoma in all 11 cases. A 3-cm oblique incision was made below the clavicle, and a 5-mm incision was made on the lateral neck. After the skin was lifted, video-assisted parathyroidectomy was performed. RESULTS: Surgery required 186 +/- 50 min. No conversions to conventional cervicotomy were needed. Levels of serum calcium and intact parathormone decreased significantly in all patients on postoperative day 1. Laryngeal recurrent nerve paresis and seroma were noted in one patient each. CONCLUSIONS: Our procedure eliminates any potential CO2 problems and offers the advantages of direct manipulation and improved cosmesis. Endoscopic parathyroidectomy should be considered a viable option for the surgical treatment of a solitary adenoma.

[Adjuvant GM-CSF cytokine gene therapy for breast cancer].

UNLABELLED: The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells. METHODS: BALBMC mouse were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells, BALBMC (1 x 10(6)/mouse), infected or not infected with recombinant adenovirus harboring GM-CSF gene on day-7. Mice were injected with parental cells (1 x 10(5)/mouse) on day 0. RESULTS: No mice vaccinated with irradiated GM-CSF producing BALBMC cells developed a tumor during the observation period of up to 16 weeks, whereas 100% of mice injected with saline developed a tumor. CONCLUSION: Our study demonstrates the feasibility of this immunotherapeutic approach as a novel adjuvant cancer therapy after surgery for breast cancer.

[Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF in 2 cases of advanced breast cancer].

Docetaxel was effective as a second line neoadjuvant chemotherapy after failure of cyclophosphamide, epirubicin and 5-FU (CEF) in 2 cases of breast cancer. In Case 1, 4 cycles of trans-arterial neoadjuvant chemotherapy of docetaxel showed a PR effect after failure of 2 cycles of trans-arterial neoadjuvant chemotherapy with CEF. This patient died of pleuritis carcinomatosa 18 months after surgery for breast cancer (latissimus dorsi muscle myocutaneous flap after radical mastectomy). In Case 2, 6 cycles of neoadjuvant venous drip infusion of docetaxel resulted in a CR effect after failure of 2 cycles of transarterial neoadjuvant chemotherapy with CEF. This patient is alive and disease-free 27 months after the operation for breast cancer (same operation as for Case 1). Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF.

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

New phenylpropanoid esters of sucrose from Polygonum lapathifolium.

Four new phenylpropanoid esters of sucrose, lapathosides A (1), B (2), C (3), and D (4), were isolated from the aerial parts of Polygonum lapathifolium together with known esters, vanicoside B (5) and hydropiperoside (6). The structures of 1-4 were determined by spectral (1D and 2D NMR and MS) analysis. Lapathoside A (1) and vanicoside B (2) showed significant inhibitory effects on the Epstein-Barr virus early antigen activation by tumor-promoters.

Pericaval fat collection mimicking an intracaval lesion on CT in patients with chronic liver disease.

BACKGROUND: Localized fat collections, which mimic fat-containing lesions of the inferior vena cava (IVC) on computed tomographic (CT) images, have been reported as rare incidental findings. Our goal was to evaluate the association of this CT finding with chronic liver disease. METHODS: Sixty-one patients with chronic liver disease were prospectively studied with contrast-enhanced abdominal CT. The prevalence, attenuation, location, shape, and size of the pericaval fat collections were assessed. Multidirectional reformatted CT images were obtained from helical CT data to identify origins of the pericaval fat collections. Sixty-one patients without chronic liver disease were studied as control subjects. RESULTS: Pericaval fat collections were seen on abdominal CT in 16 (26.2%) of the 61 patients. On the reformatted images, the fat collections were contiguous to the fat tissue around the subdiaphragmatic esophagus in all 16 patients. The fat collections were located at the posterior aspect of the IVC in 12 patients. In the control group, pericaval fat collection mimicking an intracaval lesion was not seen. CONCLUSION: In patients with chronic liver disease, pericaval fat collections are not rare CT findings and their characteristic location is considered to be posterior to the IVC. It is important not to misinterpret such CT findings as abnormalities of the IVC, such as thrombus or tumors.

Three patients with ophthalmoplegia associated with Campylobacter jejuni.

Cranial polyneuropathy is idiopathic in most patients. Idiopathic cranial polyneuropathy is an acute postinfectious syndrome, along with Guillain-Barré syndrome and Miller Fisher syndrome, in which the common preceding pathogen is Campylobacter jejuni. Serum anti-GQ1b antibodies are elevated in Miller Fisher syndrome and Guillain-Barré syndrome with ophthalmoplegia. Three patients with idiopathic cranial polyneuropathy with predominant ocular involvement are presented. C. jejuni isolated from stool specimens belonged to Penner serotypes O:4, O:23, and O:33. Serum anti-GQ1b antibodies were elevated in all patients but demonstrated rapid reduction concomitant with clinical recovery. All patients recovered completely. Because both preceding C. jejuni infection and elevated anti-GQ1b antibodies decreasing with time were seen in all patients, the pathogenesis of idiopathic cranial polyneuropathy with ophthalmoplegia may be similar to that of Miller Fisher syndrome.

Effects of internal biliary bypass on the regulation of hepatic cholesterol 7alpha-hydroxylase activity in rats.

In order to re-evaluate the importance of the enterohepatic circulation of bile acid in the regulation of the activities of hepatic cholesterol 7alpha-hydroxylase, bile acid metabolism was examined in internal biliary bypass models of rats. A polyethylene tube was inserted into the common bile duct and another side of the tube was placed in the duodenum (DD), lower jejunum (JD), cecum (CeD), or transverse colon (CoD) as internal biliary bypass models and in the urinary bladder as an external biliary drainage (ED). After bile diversion for 7 days in each group, hepatic cholesterol 7alpha-hydroxylase activities, bile acid concentrations in bile, serum, and portal vein, biliary bile acid compositions, and intestinal absorption rates of infused labeled taurocholic acid were analyzed. Hepatic cholesterol 7alpha-hydroxylase activity was similar in the JD group compared with the DD group, however, it was significantly up-regulated in the CeD (227% of the DD group), CoD (312%), and ED groups (316%). Biliary, serum, and portal bile acid concentrations were not significantly changed in the DD, JD, and CeD groups but those were significantly lower in the CoD and ED groups compared with the DD group. The proportion of the secondary bile acids was significantly increased in the CeD group and was decreased in the CoD and ED groups. The absorption rate of taurocholic acid was almost 100%, 56%, and 23% in the JD, CeD, and the CoD group, respectively. As the cholesterol 7alpha-hydroxylase activity was not significantly changed in the JD group and the predominance of secondary bile acids did not suppress the enzyme activity in the CeD group, the luminal factor, which is absorbed in the presence of bile acids, and the bile acid metabolites are not likely the regulatory factor. The cholesterol 7alpha-hydroxylase activity seems to be primarily regulated by the intestinal absorption of bile acids and partly by the intestinal mucosal factor which is linked to the intestinal bile acid absorption.

Video-assisted parathyroidectomy by a skin-lifting method for primary hyperparathyroidism.

OBJECTIVE: The use of endoscopic surgical procedures has rapidly spread to abdominal and thoracic surgeries and subsequently to surgeries of the neck region. Several surgeons initiated endoscopic parathyroidectomy using CO2 insufflation to create the working space; however, they reported various complications. We describe here a skin-lifting method that may have few complications. METHODS: A 65-year-old man was diagnosed with primary hyperparathyroidism due to a solitary adenoma of the left inferior parathyroid gland. A 3-cm oblique incision was made below the left clavicle, and a 5-mm incision was made on the lateral neck. After the skin was lifted up, we performed video-assisted parathyroidectomy. RESULTS: Parathyroid extirpation took 2 hours and blood loss was minimal. The patient had minimal pain and no complications postoperatively. Serum concentrations of calcium and intact parathyroid hormone were normalized on the next day. CONCLUSION: Using the skin-lifting method, we obtained a sufficient operative view and encountered no complications. This procedure is cosmetically desirable, and we consider it a feasible alternative for the treatment of parathyroid adenoma.