The impact of human herpesvirus 6B reactivation on early complications following allogeneic hematopoietic stem cell transplantation.

Although human herpesvirus 6 (HHV-6) has been considered an important opportunistic and potentially fatal pathogen for allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of HHV-6 reactivation remains controversial. In this study, we monitored HHV-6 DNAemia in 72 consecutive allogeneic HSCT recipients by real-time quantitative polymerase chain reaction. A total of 680 peripheral blood specimens were collected from the recipients before HSCT or at weekly intervals after HSCT. As the predominant variant, HHV-6B was detectable at least once in 47.2% (34/72) of HSCT recipients on the median day 21 (range, 7-84 days); HHV-6A reactivation occurred in only 1 recipient (1.4%). Detectable HHV-6B reactivation was associated with increased probability of skin rash by day 30 after HSCT (hazard ratio [HR], 3.68; 95% confidence interval [CI], 1.24-10.92; P = .019), cytomegalovirus (CMV) antigenemia (HR, 2.35; 95%CI, 1.32-4.19; P = .004), and hemorrhagic cystitis (HC) (HR, 2.59; 95%CI, 0.96-6.98; P = .061) by day 100 after HSCT. Neutrophil and platelet engraftment, mortality for 100 days after HSCT were not affected by HHV-6B reactivation. In conclusion, HHV-6 reactivation is a common event, and this study demonstrates a correlation between HHV-6B infection and CMV reactivation, early rash, and possibly increased incidence of HC after transplantation.     

阿狄森病患者外周血白细胞性激素受体的改变及意义

应用放射配体结合法检测１６例阿狄森病患者外周血白细胞雌激素受体（ＥＲ）和雄激素受体（ＡＲ），同时用放射免疫分析检测血浆雌二醇（Ｅ２）和睾酮（Ｔ）水平，结果如下：１）阿狄森病患者血浆Ｅ２高于对照组，但无统计学意义，血浆Ｔ无明显改变，Ｅ２／Ｔ比值明显高于对照组（Ｐ〈０．０５）；２）阿狄森病患者白细胞ＥＲ明显高于对照组（Ｐ〈０．０１），ＡＲ轻度降低（Ｐ〉０．０５），ＥＲ／ＡＲ比值明显高于对照组（Ｐ〈０．     

Design and Simulation of Active Biochip System

To solve the problems existing in passive biochip systems, we designed a novel active biochip system. This system introduces negative pressure and controlling devices to adjust the antigen-antibody reaction on the nitrocellulose membrane. Computational simulation demonstrated that this system is a rapid, stable, robust and practical system that may enhance the efficiency of antigen-antibody reactions and improve the repeatability and accuracy of biochip analysis.     

胫骨上端外部形状及内部结构的模拟

目的，进行胫骨上端内部结构和外部形状的模拟。方法，采用高阶非线性骨再造速率方程和有限元方法相结合，引入拓扑优化的思想，选取大于模拟的胫骨上端外形的模拟域，从不固定外形出发，对正常力学环境下的胫骨上端内部结构及外部形状进行模拟。结果，模拟的胫骨上端的外部形状和内部结构与真实结构十分接近。     

Morphine modulates glutamate release in the hippocampal CA1 area in mice

Opiate abuse is associated with long-lasting neural adaptative changes in the brain. Increasing evidence demonstrates that opiates significantly alter the function of the glutamatergic system, while how the system is regulated still remains elusive. In the present study, we studied the effect of morphine on extracellular glutamate concentration in the hippocampus, a nucleus rich of the glutamatergic neurons. The results showed that glutamate concentration in the extracellular fluid of the hippocampus was decreased following either acute or chronic treatment of morphine. However, naloxone-induced withdrawal increased glutamate concentration significantly. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine treatment.     

Peripheral blood mononuclear-cell interleukin-2 production,receptor generation and lymphokine-activated cytotoxicity in inflammatory bowel disease

The interleukin-2 pathway is essential for the normal immune response to antigen stimulation; we have examined the possibility that this may underlie abnormal peripheral blood lymphocyte immunoregulatory function that has been observed in patients with inflammatory bowel disease. We studied 11 patients with Crohn's disease and 5 with ulcerative colitis, all with quiescent disease activity. Peripheral blood mononuclear cells were isolated from these patients and from healthy age- and sex-matched controls. Interleukin-2 production after mitogen and phorbol-myristate acetate stimulation was similar in both groups: 381±71 (mean ± SE) U/ml by control cells and 451±70 by patient cells. Interleukin-2 receptor generation was also measured pre- and poststimulation by labeling with anti-Tac antibody. This was 10.45±1 and 69.95±3.85% for control cells and 11.41±1.38 and 60.9±4.25% for patients cells. Finally, we examined the response of these cells to interleukin-2 stimulation by generating cells with direct cytotoxicity to⁵¹Cr-labeled Daudi-cell targets. Control cells caused 59.5±46%⁵¹Cr release, whereas patient cells caused 50.8±5.18% release. None of the above results achieved statistical significance. We conclude that the peripheral blood interleukin-2 pathway is normal in inactive inflammatory bowel disease.     

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct

To learn the reasons for the high incidence of biliary carcinomain patients with anomalous arrangement of the pancreaticobiliaryduct (APBD) mutagenicity of the bile of APBD-modeled dogs thathad received a dorsal pancreatico-cholecystostomy was assayedby the Ames Salmonella mutation test. The bile from two outof 18 APBD dogs was mutagenic for Salmonella typhimurium strainTA98 under the condition of metabolic activation by rat liverS9 fraction, while the bile from 17 normal dogs was not mutagenic.Furthermore, the bile from five APBD dogs i.p. administered1-nitropyrene (1-NP), which is a typical environmental mutagen,was more mutagenic for strain TA98 than that from 1-NP-treatednormal dogs. The bile from the APBD dogs had very high amylaseactivity, indicating that the bile contained pancreatic juiceas a result of the pancreatico-cholecystostomy. When pancreaticjuice from a normal dog was added to the bile from 1-NP-treatednormal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold.Furthermore, sulfatase increased the mutagenic activity of thebile in the presence of the pancreatic juice. HPLC revealedthat the bile from a 1-NP-treated APBD dog contained mutagenic1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, whilebile from a 1-NP-treated normal dog did not contain these deconjugatedproducts. The pancreatic juice from a normal dog had very high-glutamyltransferase (GGT) and aminopeptidase activities andlow sulfatase activity, but it had no ß-glucuronidaseactivity. In addition, the bacteria that easily infect the biliaryduct of APBD dogs, Escherichia coli, Klebsiella, Enterobacterand Proteus, had high ß-glucuronidase activity. Inparticular, Klebsiella showed a very high sulfatase activity.These results suggest that pancreatic juice enzymes and bacteriainfecting the biliary duct deconjugate the detoxified mutagensin the bile and induce mutagenicity of the bile from APBD dogsor APBD patients.     

β-Cyclodextrin tetradecasulfate/tetrahydrocortisol±minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic lewis lung carcinoma

Tetrahydrocortisol, -cyclodextrin tetradecasulfate, and minocycline used alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor cells growing in monolayer. Tetrahydrocortisol (100 M, 24 h) and -cyclodextrin tetradecasulfate (100 M, 24 h) protected EMT-6 cells from the cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays under various conditions of oxygenation and pH. Minocycline (100 M, 24 h) either had no effect upon or was additive with the antitumor alkylating agents or X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination of the three modulators either had no effect upon or was to a small degree protective against the cytotoxicity of the antitumor alkylating agents or X-rays. The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and tumor lung-metastases studies. Tetrahydrocortisol and -cyclodextrin tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14 days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post tumor implantation. The combination of tetrahydrocortisol/-cyclodextrin tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan and produced modest increases in the tumor growth delay produced by cyclophosphamide and radiation. Minocycline co-treatment increased the tumor growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially cyclophosphamide, where 4 of 12 animals receiving minocycline (14×5mg/kg, days 4–18) and cyclophosphamide (3×150 mg/kg, days, 7, 9, 11) were long-term survivors. The 3 modulators given in combination produced further increases in tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the animals treated with the 3-modulator combination and cyclophosphamide were long-term survivors. Although neither tetrahydrocortisol/-cyclodextrin tetradecasulfate, minocycline, nor the three modulator combination impacted the number of lung metastases, there was a decrease in the number of large lung metastases. Treatment with the cytotoxic therapies alone reduced the number of lung metastases. Addition of the modulators to treatment with the cytotoxic therapies resulted in a further reduction in the number of lung metastases. These results indicate that agents that inhibit the breakdown of the extracellular matrix can be useful additions to the treatment of solid tumors.Abbreviations 14(SO₄)ßCD -cyclodextrin tetradecasulfate - THC tetrahydrocortisol - CDDP cis-diamminedichloroplatinum(II) - 4-HC 4-hydroperoxycyclophosphamide - BCNU N,N-bis(2-chloroethyl)-N-nitrosourea - CAM chick embryo chorioallantoic membrane; IC₅₀, concentration of a drug required to kill 50% of the cells This work was supported by NIH grant P01-CA38493 and a grant from Bristol-Myers-Squibb, Inc., Wallingford, Connecticut