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Biomedical subjects

Yu Zhu

Publications and source records attributed to Yu Zhu.

At least 37 records · Page 2Linked to original sources

RSIR: regularized sliced inverse regression for motif discovery.

MOTIVATION: Identification of transcription factor binding motifs (TFBMs) is a crucial first step towards the understanding of regulatory circuitries controlling the expression of genes. In this paper, we propose a novel procedure called regularized sliced inverse regression (RSIR) for identifying TFBMs. RSIR follows a recent trend to combine information contained in both gene expression measurements and genes' promoter sequences. Compared with existing methods, RSIR is efficient in computation, very stable for data with high dimensionality and high collinearity, and improves motif detection sensitivities and specificities by avoiding inappropriate model specification. RESULTS: We compare RSIR with SIR and stepwise regression based on simulated data and find that RSIR has a lower false positive rate. We also demonstrate an excellent performance of RSIR by applying it to the yeast amino acid starvation data and cell cycle data. AVAILABILITY: Matlab programs are available upon request from the authors.

Algorithms↗

Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root ganglia: pathogenic effects of STAT-1 and inducible nitric oxide synthase.

Distal sensory polyneuropathy (DSP) is currently the most common neurological complication of HIV infection in the developed world and is characterized by sensory neuronal injury accompanied by inflammation, which is clinically manifested as disabling pain and gait instability. We previously showed that feline immunodeficiency virus (FIV) infection of cats caused DSP together with immunosuppression in cats, similar to that observed in HIV-infected humans. In this study, we investigated the pathogenic mechanisms underlying the development of FIV-induced DSP using feline dorsal root ganglia (DRG) cultures, consisting of neurons, Schwann cells, and macrophages. FIV-infected cultures exhibited viral Ags (p24 and envelope) in macrophages accompanied by neuronal injury, indicated by neurite retraction, neuronal loss and decreased soma size, compared with mock-infected (control) cultures. FIV infection up-regulated inducible NO synthase (iNOS), STAT-1, and TNF-alpha mRNA levels in DRG cultures. Increased STAT-1 and iNOS mRNA levels were also observed in DRGs from FIV-infected animals relative to mock-infected controls. Similarly, immunolabeling studies of DRGs from FIV-infected animals showed that macrophages were the principal sources of STAT-1 and iNOS protein production. The iNOS inhibitor aminoguanidine reduced nitrotyrosine and protein carbonyl levels, together with preventing neuronal injury in FIV-infected DRG cultures. The present studies indicate that FIV infection of DRGs directly contributes to axonal and neuronal injury through a mechanism involving macrophage immune activation, which is mediated by STAT-1 and iNOS activation.

Animals↗

[Primary pigmented nodular adrenocortical disease report of 5 cases].

OBJECTIVE: To study the pathology, diagnostic and therapeutic method of primary pigmented nodular adrenocortical disease (PPNAD). METHODS: The data of 5 cases of PPNAD were analyzed retrospectively. Among the 5 cases, 2 were male and 3 were female. The range of age was from 12 to 53 years. All the 5 cases had symptoms of Cushing syndrome. The diagnose depended on the results of endocrine exams, ultrasound, CT, MR and pathological reports. All patients received operation of unilateral adrenalectomy. The therapeutic effects were determined by post-operative results, which concluded clinical symptoms and endocrine exams. RESULTS: The follow-up time was from 4 months to 3 years. All patients' symptoms of Cushing syndrome were relieved in 6 months after operation. The endocrine exam was normal in one case and obvious improved in the other four cases. Up to now, one patient drop out of the follow-up, the other 4 cases had no evidence of recurrence. CONCLUSION: PPNAD is a rare type of Cushing syndrome. Diagnose depends on endocrine exams and pathological results. Operation is the effective method for the disease.

Adolescent↗

Decreased IgG production but increased MIP-1beta expression in collagen-induced arthritis in C-C chemokine receptor 5-deficient mice.

Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid arthritis (RA) characterized by chronic inflammation of the synovial joints. The pathogenesis of RA and CIA has not been completely defined, but both involve the recruitment of leukocytes and lymphocytes to the joints and Th1-type cell mediated autoimmune responses. The C-C chemokine receptor 5 (CCR5) is preferentially expressed on Th1 cells and has been strongly implicated in inflammatory process through trafficking of leukocytes and lymphocytes into the sites of inflammation. We investigated the role of the CCR5 in CIA using CCR5 knockout mice (CCR5-/-) in which we analyzed the consequences of CCR5 deficiency for the immune response and inflammation. We found that CCR5-/- mice showed a significant reduction in the incidence of CIA after collagen II (CII)-immunization as compared to wild-type (CCR5+/+) mice. The reduced incidence seen in CCR5-/- mice was associated with these animals having significantly lower IgG levels, especially IgG2a and IgG2b antibodies against CII, as well as an obviously augmented IL-10 production in splenocytes. Overproduction of MIP-1beta in CCR5-deficient mice after CII-immunization may contribute partially to the occurrence of arthritis.

Animals↗

Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice.

BACKGROUND: Normal chow (low fat)-fed mice deficient in both the HDL receptor SR-BI and apolipoprotein E (SR-BI/apoE dKO) provide a distinctive model of coronary heart disease (CHD). They exhibit early-onset hypercholesterolemia characterized by unesterified cholesterol-rich abnormal lipoproteins (lamellar/vesicular and stacked discoidal particles), occlusive coronary atherosclerosis, spontaneous myocardial infarction, cardiac dysfunction, and premature death ( approximately 6 weeks of age). Mice in which similar features of CHD could be induced with a lipid-rich diet would represent a powerful tool to study CHD. METHODS AND RESULTS: To generate a diet-inducible model of CHD, we bred SR-BI-deficient (SR-BI KO) mice with hypomorphic apolipoprotein E mice (ApoeR61(h/h)) that express reduced levels of an apoE4-like murine apoE isoform and exhibit diet-induced hypercholesterolemia. When fed a normal chow diet, SR-BI KO/ApoeR61(h/h) mice did not exhibit early-onset atherosclerosis or CHD; the low expression level of the apoE4-like murine apoE was atheroprotective and cardioprotective. However, when fed an atherogenic diet rich in fat, cholesterol, and cholate, they rapidly developed hypercholesterolemia, atherosclerosis, and CHD, a response strikingly similar to that of SR-BI/apoE dKO mice fed a chow diet, and they died 32+/-6 days (50% mortality) after initiation of the high-fat feeding. CONCLUSIONS: The SR-BI KO/ApoeR61(h/h) mouse is a new model of diet-induced occlusive coronary atherosclerosis and CHD (myocardial infarction, cardiac dysfunction and premature death), allowing control of the age of onset, duration, severity, and possibly regression of disease. Thus, SR-BI KO/ApoeR61(h/h) mice have the potential to contribute to our understanding of CHD and its prevention and treatment.

Animals↗

Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis.

Human Kruppel-like factor 2 (KLF2) is a Cys(2)/His(2) zinc-finger-containing transcriptional factor, which is involved in multiple cellular pathways. Utilizing gene expression profiling to identify aberrantly expressed genes in ovarian cancer, we found that KLF2 was significantly and specifically downregulated in ovarian tumors. After reintroducing KLF2 into ovarian cancer cell lines, we observed decreased cell growth and increased sensitivity to DNA damage-induced apoptosis. Analysis of genes that could be potential targets of KLF2 revealed that KLF2 negatively regulated WEE1 expression. WEE1 encodes a tyrosine kinase that regulates the G2/M cell cycle transition. Expression of KLF2 markedly repressed the transcription of WEE1 by directly binding to an SP1/CPBP motif located between -252 bp and the start codon of the WEE1 promoter. Both activation and zinc-finger domains of KLF2 were required for this suppression of Wee1 expression. In addition, we demonstrated that Wee1 expression prevents cancer cells from undergoing apoptosis in response to DNA damage; however, this resistance was abolished by coexpression of KLF2, which inhibits WEE1 transcription. Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis.

Apoptosis↗

Peripheral nerve-derived HIV-1 is predominantly CCR5-dependent and causes neuronal degeneration and neuroinflammation.

HIV-related peripheral neuropathy is a major neurological complication of HIV infection, although little is known about its pathogenesis. We amplified HIV-1 C2V3 envelope sequences from peroneal nerves obtained from HIV/AIDS patients. Sequence analysis and infectious recombinant viruses containing peripheral nerve-derived C2V3 sequences indicated a predominance of CCR5-dependent and macrophage-tropic HIV-1, although dual tropic viruses using both CCR5 and CXCR4 were identified. The neuropathogenic effects of recombinant HIV-1 clones were investigated using a novel dorsal root ganglion culture system that was comprised of sensory neurons, macrophages and Schwann cells from transgenic rats expressing human CD4 and CCR5 on monocytoid cells. Despite restricted viral replication, HIV-1 infection caused a reduction in the percentage of neurons with neuritic processes together with significant neurite retraction, which was accompanied by induction of IL-1beta and TNF-alpha expression, depending on the individual virus. Our results suggest that HIV-1 infection of the peripheral nervous system causes axonal degeneration, possibly through the induction of pro-inflammatory cytokines.

Adult↗

Synthesis, structure, and large optical limiting effect of the first coordination polymeric cluster based on an {I@[AgI(inh)]6} hexagram block.

In this paper, treatment of N-(isonicotinoyl)-N'-nicotinoylhydrazine (inh) and AgI with excess KI afforded a unique coordination polymeric cluster {[AgI(inh)]6(KI)}n (1) with the hexagram cluster units centered by mu6-I. In the polymer these hexagram units are parallel to the ab plane and are linked by separated K+ centers through inh. Polymer 1 represents the first example of coinstantaneous cation-anion-induced supramolecular self-assembly with nanoscale inner cavities. The polymer's third-order nonlinear optical (NLO) properties were determined by the Z-scan technique in DMF solution. The results show that the polymer has strong third-order optical nonlinearities. The nonlinear absorptive index a2 and refractive index n2 are calculated to be 1.044 x 10(-9) mW(-1) and 2.827 x 10(-11) esu, respectively. The values are comparable to those of the reported cluster polymers. The optical limiting experiments show that the present cluster exhibits a large optical limiting capacity. The value of the limiting threshold was measured as 0.53 J cm(-2) from the optical limiting experimental data. This value is three times better than 1.6 J cm(-2) of C60. This paper also gives a summary and comparison on the optical limiting properties of oligomeric and polymeric clusters.

Journal Article↗

[Evaluation and selection of different procedures in the treatment of pancreatic pseudocyst].

OBJECTIVE: To evaluate the effect of different procedures in the treatment of pancreatic pseudocyst. METHOD: This retrospective review analyzed the outcome of 114 patients with pancreatic pseudocysts managed in PUMC Hospital from January 1990 to March 2002. RESULT: There were 25 patients without intervention, the spontaneous resolution of pseudocysts occurred in 23 of these patients during follow up. Twenty-nine cases underwent CT-guided percutaneous catheter drainage; the effective rate of therapy was 67.85%. Surgical procedures performed in 60 cases and the overall mortality was 5% (3/60). The procedures included external drainage (8 cases) with 1 death (12.5%), excision (13 cases), cyst-duodenostomy (1 cases), cyst-gastrostomy (19 cases) with 7 postoperative gastrointestinal bleeding (36.8%) and 1 death (5.26%), Roux-en-Y cyst-jejunostomy (19 cases) with 3 postoperative gastrointestinal bleeding (15.8%) and 1 death (5.26%). CONCLUSIONS: CT-guided percutaneous catheter drainage has the advantage of minimal invasive and simple technique; it can be as an effective substitute method of traditional open external drainage. Although minimally invasive techniques offer a variety of treatment options, surgical procedures are still indicated for significant number of patients. The incidence of postoperative gastrointestinal bleeding in cyst-gastrostomy was higher than those patients with Roux-en-Y cyst-jejunostomy, but most of them were not difficult to treatment, so cyst-gastrostomy is still a simple and reasonable procedure for selected patients. Excision is a correct choice for cases in which pseudocysts cannot be differentiated from neoplastic cysts.

Adolescent↗

[The diagnosis and treatment of solid-pseudopapillary tumor of pancreas].

OBJECTIVE: To summarize the experience of diagnosis and treatment in solid-pseudopapillary tumor of pancreas (SPT). METHOD: Retrospectively analyzed 12 cases of SPT diagnosed between 2000 August and 2004 February in Peking Union Medical College Hospital. RESULTS: The average age of these 12 cases was 29.1, including 11 women and 1 men. The tumors of 6 cases were located in the pancreatic head, one tumor was in the neck of pancreas and 5 tumors were in the body and tail of pancreas. There were no characteristic clinical manifestations. Solid and solid-cystic masses of low echo were found in pancreas in ultrasonic examinations. CT scan found masses of low density in pancreas, while irregular enhancement appeared in the circumference of all tumors in enhanced CT scan sequences. Tumor markers in patients' serum were all negative. Pancreaticoduodenectomy were performed in 2 cases. Resection of tumors and pancreaticojejunostomy were performed in 3 cases. Simple resection of tumor was performed in 1 case. Segmental pancreatectomy and pancreaticojejunostomy was performed in one patient. Five patients underwent distal pancreatectomy and spleen resection. Ten patients were followed up with the average time of 14.3 months. No evidence of relapses and metastasis in these cases was found. CONCLUSION: Solid-pseudopapillary tumor of pancreas was one of rare pancreatic neoplasm with low malignant potential, affecting primarily young women. Complete resection resulted in long-term survival.

Adolescent↗

Increased cyclin E expression may obviate the role of cyclin D1 during brain development in cyclin D1 knockout mice.

Cyclins D and E play critical roles during the G1 phase of mammalian cell division. Cyclin D1 expression is high and expected to play an important role during mouse brain development. However, in the present study, we found no difference in CNS morphology between cyclin D1 knockout (KO) and control wild-type mice at the ages of 1, 4 and 12 months. Analysis of protein expression in embryonic brains revealed that cyclin E is obviously increased in cyclin D1 KO mice at 13.5 days post coitum. At the same age a high level of cyclin D1 expression is detected in the embryonic brain of wild-type mice. The data indicate that enhanced cyclin E protein expression in cyclin D1 KO mice may obviate the role of cyclin D1 and contribute to the normal brain development of cyclin D1 KO mice.

Animals↗

[Surgical management of pancreatic cancer: current practice and future prospect].

Pancreatic cancer still represents a serious medical concern for which no adequate solution has thus far been found. Surgical resection, when possible, remains the primary treatment modality and can result in long-term cure. The value of more radical resection remains open to debate, despite the negative results of some recent randomized trials with standard vs. extended lymphadenectomy. More effective patient selection, more rational resection, and more compositive treatment should be emphasized in management strategies. In the future, appropriately designed randomized trials of standard vs. extended resections may confirm the benefit of extended surgical resections. In addition, well powered trials of adjuvant therapies strategies together with surgical resections may identify more effective combinations, which may improve the survival of patients with pancreatic cancer.

Humans↗

[Perioperative nutrition support of the patients with pancreatic head cancer].

OBJECTIVE: To explore the effect of perioperative nutrition support on nutritional condition and complications of the patients with postoperative pancreatic head cancer. METHODS: Thirty four patients received perioperative nutrition support, including enteral nutrition and parenteral nutrition (treatment group). Forty eight patients received routine postoperative parenteral nutrition (control group). According to the operative method, these two groups were further divided into two sub-groups: (1) pancreaticoduodenectomy (PD) subgroup, including 13 cases from treatment group, and 24 cases from control group; (2) palliative operation subgroup, including 21 cases from treatment group, and 24 cases from control group. Body weight, total protein (TP), serum albumin (ALB), and the complications after operation were compared. RESULTS: The concentrations of ALB and TP in the treatment group were significantly higher than those in the control group (P< 0.05). Body weight and TP of the patients received PD in the treatment group were significantly better than those of the control group (P < 0.05). CONCLUSION: Perioperative nutrition support can improve postoperative nutritional condition and reduce the postoperative complications in patients with pancreatic head cancer.

Adult↗

[Diagnosis and treatment of pancreatic serous cystadenoma].

OBJECTIVE: To summarize our experience on the diagnosis and treatment of pancreatic serous cystadenoma. METHOD: Data from 20 patients with pancreatic serous cystadenoma in Peking Union Medical College Hospital from 1994 to 2004 were analyzed retrospectively. RESULTS: Ultrasound test was a good choice for primary diagnosis, while computed tomography scan and endoscopic retrograde cholangiopancreatography (ERCP) were better choice for the suspected cases. Most tumors (60%) were located in the body and tail of pancreas. The distal pancreatectomy was the commonest operation procedure. The main complications were pancreatic leakage (35%). The symptoms were resolved after surgical treatment. CONCLUSIONS: The treatment of pancreatic serous cystadenoma depends on the accurate diagnosis. Ultrasound and computed tomography are useful diagnostic methods. Surgical operation is the treatment of choice. Long-term follow-up has shown satisfactory outcomes if the tumors are resected completely.

Adult↗

New types of the flexible self-assembled metal-organic coordination polymers constructed by aliphatic dicarboxylates and rigid bidentate nitrogen ligands.

The reaction of metal ions, flexible aliphatic dicarboxylates and rigid bidentate linear ligands under mild conditions in water afford four novel metal-organic coordination polymers, [Cd(mu-mal)(mu-pyz)(0.5)(H(2)O)](n) 1 (mal = malonate dianion, pyz = pyrazine), [Cd(2)(mu-suc)(2)(mu-pyz)(H(2)O)(2)](n) 2 (suc = succinate dianion), and ([M(mu-bipy)(H(2)O)4][suc].4H(2)O)(n)(M = Co, 3, M = Zn, 4, bipy = 4,4'-bipyridine). The molecular structures of 1-4 have been established by single-crystal X-ray crystallography. 1 is a 3D network being composed of layers of octahedrally coordinated Cd atoms bridged by malonate anions in syn-anti configurations within the layers and pyz molecules between layers. Unlike that in 1, each Cd atom in 2 displays uncommon pentagonal-bipyramidal geometry to form 2D infinite grid sheets with square grid dimensions of ca. 7.936 x 7.936 [Angstrom]. Both 3 and 4 exhibit 1D linear -M-bipy-M-bipy- chain polymers, and these chains were packed as ...ABCABC... layered structures. The bridging succinate ligands in 2 adopt the syn-anti mode with a torsion angle of 60.8(7) degrees, while the solvated succinate ligands in 3 and 4 adopt the anti-anti mode with a torsion angle of 180.0 degrees. To our knowledge, compound 2 represents the first example of flexible self-assembled succinate-pyrazine mixed bridging ligand coordination network. 3 and 4 are the first two cases of succinate-bipy polymers with non-coordinated succinate. The magnetic behavior for 3 was studied in the temperature range of 5-300 K. The result indicates the occurrence of a weak antiferromagnetic coupling between the cobalt(II) ions.

Journal Article↗

Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional promoter element.

In order to understand how gene regulation is achieved in eukaryotes in response to DNA damage, we used budding yeast as a model lower eukaryotic organism and investigated the molecular events leading to the expression of two closely clustered damage-inducible genes, MAG1 and DDI1. MAG1 and DDI1 are co-activated by a shared 8 bp repeat sequence, UAS(DM). In this study, we screened a yeast genomic library, identified Pdr3 as the transcriptional activator and demonstrated in vivo and in vitro that Pdr3 binds UAS(DM). Pdr3 is required for the activation of a number of genes encoding membrane efflux pumps and deletion of PDR3 results in reduced basal-level expression and loss of DNA damage induction of MAG1 and DDI1. Interestingly, Pdr1, another transcriptional activator homologous to Pdr3 that is also required for the activation of multidrug-resistance genes, is not involved in the regulation of MAG1 and DDI1 expression, although it may also bind to UAS(DM). Deletion of PDR3 does not affect the expression of other well-documented DNA damage-inducible genes; hence, yeast DNA damage-inducible genes appear to have distinct effectors although to a certain extent they share a common regulatory pathway mediated by DNA damage checkpoints.

Binding Sites↗

[The clinical characteristics and therapy of multiple endocrine neoplasia type 2].

OBJECTIVE: To study the clinical characteristics and treatment of multiple endocrine neoplasia (MEN) type 2. METHODS: The clinical features, diagnosis and treatment of from 1980 to 2002 8 cases of multiple endocrine neoplasia type 2 from Peking Union Medical College Hospital were reviewed and analyzed in clinical features, diagnosis and treatment retrospectively. RESULTS: Seven cases were with paroxysmal hypertension, the highest blood pressure was over 200 mm Hg (1 mm Hg = 0.133 kPa). Tumor was found in 3 cases. The diagnosis was confirmed by B-ultrasonography, CT and urine catecholamine test: six cases with MEN 2a 2 with MEN 2b. Six cases were medullary carcinoma of thyroid with or without parathyroidoma or hyperplasia, 1 with multiple mucosal neuromata. One case was pheochromocytoma with marfan's syndrome; 7 cases were with bilateral adrenal tumor. Total resection or resection ectomy was performed on different stages on adrenal gland, parathyroid tubercle. Average follow-up was 9 years. And the feedback was good. CONCLUSION: The diagnosis of multiple endocrine neoplasia type 2 depends on endocrine biochemical tests, B-ultrasonography and CT. When the pheochromocytoma and the other tumor exists at the same time, operation is the primary treatment, and it is better to remove the pheochromocytoma at the first.

Adolescent↗

Novel one-dimensional polymers generated from p-Ferrocenylbenzoate: syntheses, structures, and magnetic properties.

Treatment of p-ferrocenylbenzoate [p-HOOCH4C6Fc, Fc = (eta5-C5H5)Fe(eta5-C5H5)] with Mn(OAc)2 x 2H2O or Cd(OAc)2 x 2H2O afforded one-dimensional linear chain polymer [[Mn(OOCH4C6Fc)2(mu2-OH2)(H2O)2](H2O)]n (1), double-bridge polymer [Mn(mu2-OOCH4C6Fc)2(phen)]n (phen = phenanthroline) (2), and ladderlike framework [[Cd(mu2-OOCH4C6Fc)(eta2-OOCH4C6Fc)(bbp)](CH3OH)]n (bbp = 4,4'-trimethylene-dipyridine) (3). The solution-state cyclic voltammograms indicate that the half-wave potentials of the ferrocenyl moieties in these polymers are all shifted to positive potential compared to that of sodium p-ferrocenylbenzoate. Both 1 and 2 behave as 1D Heisenberg Mn(II) chains with weak intrachain antiferromagnetic interactions between the local high-spin Mn(II) ions, and the exchange coupling parameters J (-5.20 and -3.25 cm(-1) for 1 and 2, respectively) are larger than those of most of the reported di-Mn(II) complexes that contain mu2-aqua and mu2-carboxylato units and one-dimensional Mn(II) carboxylic polymers.

Journal Article↗