Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases.

Serine hydroxymethyltransferase (SHMT) provides activated one-carbon units required for the biosynthesis of nucleotides, protein, and methyl group by converting serine and tetrahydrofolate to glycine and N(5),N(10)-methylenetetrahydrofolate. It is postulated that SHMT activity is associated with the development of methotrexate resistance and the in vivo activity of SHMT is regulated by the binding of N(5)-CHO-THF, the rescue agent in high-dose methotrexate chemotherapy. The aim of this study is to advance our understanding of the folate-mediated one-carbon metabolism in zebrafish by characterizing zebrafish mitochondrial SHMT. The cDNA encoding zebrafish mitochondrial SHMT was cloned, overexpressed in Escherichia coli, and purified with a three-step purification protocol. Similarities in structural, physical, and kinetic properties were revealed between the recombinant zebrafish mitochondrial SHMT and its mammalian orthologs. Surprisingly, leucovorin significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. This is, to our knowledge, the first report on zebrafish mitochondrial folate enzyme as well as the differential inhibition of leucovorin on these two SHMT isoforms. Western blot analysis revealed tissue-specific distribution with the highest enrichment present in liver for both cytosolic and mitochondrial SHMTs. Intracellular localization was confirmed by confocal microscopy for both mitochondrial and cytosolic SHMTs. Unexpectedly, the cytosolic isoform was observed in both nucleus and cytosol. Together with the previous report on zebrafish cytosolic SHMT, we suggest that zSHMTs can be used in in vitro assays for folate-related investigation and antifolate drug discovery.     

Lipid extract from completely sporoderm‐broken germinating Ganoderma sinensis spores elicits potent antitumor immune responses in human macrophages

Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.     

复杂主动脉病变的腔内血管外科治疗

目的 探讨复杂主动脉病变的腔内血管外科治疗方法。方法 对21例合并有内脏动脉缺血等复杂的主动脉病变,双球管定位下经锁骨上动脉到股动脉交换导丝以确保真腔内植入带膜支架,对真腔完全被假腔压闭的患者采取真腔内加压推进以通过导丝,用超长带膜支架来封堵大破口治疗夹层合并巨大假性动脉瘤形成,对夹层合并腹主动脉瘤患者采取血管腔内技术联合开腹手术等方法。结果 术后内漏3例,其中2例7 d后停止,1例漏血持续存在。3例主动脉创伤术后完全康复,余18例复杂主动脉夹层术后即时造影示瘘口已被完整覆盖,假腔无血漏入,内脏动脉等恢复真腔供血。18例中6例合并肠管缺血,3例合并肾动脉缺血,3例肠管缺血、肾动脉缺血,2例腹主动脉真腔完全被假腔压迫,以及2例合并下肢缺血术后均逐渐恢复,无脏器及肢体缺血坏死发生。2例合并腹主动脉瘤夹层行支架型人工血管封闭夹层破口后行开腹手术切除腹主动脉瘤、人工血管置换。16例随访5～36个月,平均22.3月,1例内漏持续存在,但假腔未继续加大,其余患者存活良好。结论 对复杂的主动脉病变的治疗,通过对腔内血管外科技术进行改进,并适当结合传统手术方法,使某些过去被认为不能够治疗的复杂主动脉病变可得以成功治疗。     

Arterial and venous effects of serotonin in the forearm of healthy subjects are not age-related

The influence of age on the regional arterial and venous effects of serotonin (5-HT) was investigated in 13 young (aged 22-31 years) and seven older (aged 50-69 years) healthy volunteers. Single-dose infusions of 5-HT (1, 10, and 80 ng/kg/min) and of the 5-HT2 receptor antagonist ritanserin (50, 150, and 500 ng/kg/min) were administered into the brachial artery. Subsequently, the relative arterial and venous effects of the highest dose of 5-HT were investigated. Forearm blood flow (FBF) and maximum venous outflow (MVO) were measured by venous occlusion plethysmography. Heart rate (HR) and intraarterial (i.a.) blood pressure were recorded semicontinuously. In both age groups, 5-HT induced an initial transient arterial dilation, followed by a persistent increase in FBF for the doses of 1 and 10 ng/kg/min and a relative small decrease in FBF for the highest dose. In both age groups, the highest dose of 5-HT induced a similar large reduction in MVO (p less than 0.05 for both). The reduction in MVO was attenuated by ritanserin (500 ng/kg/min, p less than 0.05 for both groups). In the younger subjects, this dose of ritanserin also unmasked an arterial dilator effect of the highest dose of 5-HT (p less than 0.05). The single infusions of ritanserin did not influence FBF significantly in either study group. No significant differences were observed between the age groups. These results show that in the forearm of healthy subjects arterial and venous vascular responses to 5-HT were not age-related. In the arterial vascular bed, 5-HT acted predominantly as a vasodilator; at high doses, mainly venous vasoconstriction was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

原位杂交法检测BP1基因在乳腺癌组织中表达

目的探讨BP1同源盒基因在乳腺癌中的表达及其与临床病理指标的关系。方法收集165例乳腺癌临床和病理资料,采用原位杂交法检测BP1的表达,同时用二步法进行ER、p53、PCNA、bcl2、cerbB2免疫组化染色。结果BP1基因表达率为67.88%,免疫组化:ER70.30%、p5349.09%、PCNA74.55%、bcl253.33%、cerbB275.52%。BP1与bcl2具有相关性(P<0.01),且均与ER相关(P<0.05),与p53呈负相关(P<0.05)。BP1与PCNA、cerbB2、患者年龄、组织学类型、淋巴结转移等无相关性。结论BP1可能通过某种非依赖p53基因调控机制,与bcl2、ER协同抑制肿瘤细胞的凋亡而参与乳腺癌的发生。     

Intussusception in Taiwanese children: analysis of incidence, length of hospitalization and hospital costs in different age groups.

BACKGROUND AND PURPOSE: This study investigated the characteristics of intussusception in Taiwanese children of different age groups, including the incidence, length of hospitalization and hospital costs. METHODS: Children with a diagnosis of intussusception who were hospitalized from 1999 through 2001 were identified from a nationwide health insurance claims database. The incidence of intussusception was calculated by age, gender, and season. Length of hospitalization and hospital costs were also analyzed. RESULTS: A total of 6988 cases of intussusception were identified in Taiwan from 1999 to 2001. Among them, 4859 cases occurred in children below 15 years of age. The average incidence among children below age 15 years was 34.5 per 100,000, with a peak incidence of 118.8 per 100,000 observed among children younger than 24 months old. The highest incidence of intussusception in Taiwanese children occurred between 12 and 24 months of age. According to the data for patients below 15 years of age hospitalized for intussusception in year 2000, males were more likely to be affected than females (61.3% vs 38.7%). Intussusception-related hospitalizations were rare in infants in the first few months of life, increased in those 6 to 12 months old, and peaked among children 1 to 3 years old. Among the 952 patients with intussusception admitted to hospitals in 2000, 297 (31.2%) received surgery, incurring higher median medical costs (New Taiwan Dollars [NT dollars] 42,265 or US dollars 1234) and longer median hospital stay (6.2 days) than the 655 patients who did not require surgery (NT dollars 6290 or US dollars 185 for hospitalization of 2.4 days). CONCLUSIONS: The study found that the incidence of intussusception peaked in the second year of life in Taiwanese children. There was also a male predominance and lack of seasonal variation in incidence.     

Acute pancreatitis combined with acute Budd-Chiari syndrome as the initial manifestation of small cell lung cancer.

Tumor metastasis to the pancreas is a rare but recognized cause of acute pancreatitis. Autopsy series have reported a 24-40% of pancreatic involvement in small cell lung cancer. However, only a very few cases of tumor-induced acute pancreatitis have been described. Budd-Chiari syndrome complicating lung cancer is a rarely reported condition. We report a 68-year-old woman with extensive small cell lung cancer with the unusual initial presentation of both acute pancreatitis and acute Budd-Chiari syndrome. This patient suffered from progressive epigastralgia for 3 weeks. Severe epigastralgia with radiation to back and progressive jaundice developed 2 days prior to admission. After admission, the liver enlarged rapidly and the ascites increased markedly. Chest roentgenogram showed a mass lesion over the left lower lung field. Poorly differentiated carcinoma cells were found in ascites and bone marrow. The patient died on the ninth day of hospitalization before chemotherapy was initiated. Prompt diagnosis of extensive-stage small cell lung cancer may allow early chemotherapy treatment which favorably influences recovery when the pancreatitis is mild. Although prolonged survival might have been expected had this patient recovered from pancreatitis and received chemotherapy, diagnosis was delayed due to difficulty in immunohistochemical diagnosis of the tumor and the unusual clinical presentation. The use of stains employing antibodies against neurofilament and neuron-specific enolase cell antigens is important for early diagnosis of poorly differentiated metastatic tumor cells.     

Unusual case of Klüver-Bucy syndrome in a Chinese boy.

Following an encephalopathic illness, a 13-year-old Chinese boy had a partial form of Klüver-Bucy syndrome with emotional disturbance, recent memory loss, hypersexuality, and polyphagia. Other unusual features included narcolepsy, polydipsia, and polyuria. Virologic studies failed to incriminate the etiologic agent, including herpes simplex virus. Brain biopsy of the frontal lobe demonstrated Alzheimer type II astrocytosis.     

Premercapturic acid metabolites of bromobenzene derived via its 2,3- and 3,4-oxide metabolites

1. A new premercapturic acid metabolite of bromobenzene was isolated from the urine of beta-naphthoflavone-induced rats; using 1H-n.m.r., FAB mass spectrometry and chemical degradation it was identified as S-(2-hydroxy-3-bromocyclohexa-3,5-dienyl)-N-acetylcysteine. 2. Two regioisomeric premercapturic acids apparently derived from bromobenzene-3,4-oxide were isolated as an inseparable 1:1 mixture from the urine of phenobarbital-induced rats and characterized by similar means. 3. Acid dehydration of bromobenzene 3,4- and 4,3-premercapturic acids (mixture) afforded only p-bromophenylmercapturic acid, whereas acid dehydration of 3,2-premercapturic acid gave both o- and m-bromophenylmercapturic acids. This implies a shift of sulphur in acid dehydration of the 3,4- and 3,2- but not the 4,3-premercapturic acids. 4. Base dehydration of the 3,4- and 4,3-premercapturic acid mixture gave a mixture of p- and m-bromophenylmercapturic acids, whereas base dehydration of the 3,2-premercapturic acid gave only m-bromophenylmercapturic acid. This indicates these premercapturic acids dehydrate by direct elimination without rearrangment. 5. The 3,2-premercapturic acid was detected only in the urine of BNF-induced animals, whereas the 3,4- and 4,3-premercapturic acids were detected in the urines of untreated as well as PB- and BNF-induced animals. 6. Together with earlier reports of the isolation of the 2,3-dihydrodiol, the isolation of the 3,2-premercapturic acid as a urinary metabolite of bromobenzene implies that bromobenzene-2,3-oxide is a discrete metabolite of bromobenzene and not merely a hypothetical intermediate.