Biomedical subjects
Publications and source records attributed to K Zhu.
The applications and advances of nerve guidance channel used as peripheral nerve repair and regeneration have been reviewed. There are two main aspects: the design of nerve guidance channel itself, and the creation of regeneration microenvironment in the nerve guidance channel.
OBJECTIVE: To observe engraftment kinetics, incidence and severity of graft-versus-host disease (GVHD) and clinical outcome in 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: 40 leukemia patients with a median age of 35 years underwent allo-PBSCT from June 1997 to May 1999. PBSC were mobilized with G-CSF at a dose of 5 microg/kg S. C. every 12 hours for 5 days. A median of 7.7 (range 2.0 to 16.8) x 10(6) CD(34)(+) cells/kg was infused into the recipients. Busulfan (BU) and cyclophosphamide (CY) were used as conditioning regimen. All patients received cyclosporine A and either methotrexate (n = 34) or methylprednisolone (n = 6) for GVHD prophylaxis. RESULTS: Engraftment of neutrophils and platelets was achieved at a median of day + 13 (9 - 28) and day +12 (7 - 60) respectively. Patients receiving >or=4 x 10(6) CD(34)(+) cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of the 40 patients (42.5%), with grade II-IV acute GVHD in 10 patients (25.0%); chronic GVHD developed in 21 out of the 30 evaluable patients (70.0%) with a median follow up of 480 days (range 300 - 1,000). The transplant related mortality is 20.0% and the relapse rate is 10.0%. The probability of leukemia free survival at 3 years is 70.0%. CONCLUSIONS: These results indicate that allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with high risk of chronic GVHD.
OBJECTIVE: To evaluate the efficacy of continuous hepatic arterial infusion of 5-fluorouracil (5-Fu)/calcium folinate (CF) through an implanted percutaneous arterial infusion system for nonresectable liver metastasis. METHODS: Sixty-eight patients with nonresectable liver metastasis received continuous hepatic arterial infusion of 5-Fu 500 mg/m2.d, CF 100 mg/m2.d and dexamethasone 10 mg/d1-5 via a drug delivery system (DDS) implanted percutaneously with the catheter introduced via the femoral artery or left subclavian artery for 5 days, once every month in combination with cisplatin and/or mitomycin-C, epirubicin and cytoxan as a multi-drug protocol. RESULTS: The overall response rate (CR + PR) was 47.1% (32/68), with 2 patients giving CR and 30 PR. The response seemed to correlate with the intrahepatic tumor burden as 60.6% response rate was observed in intrahepatic tumor burden of less than 25% versus 34.3% response rate in those with more than 25% (P < 0.05). The median survival period was 15.2 months. The 1-, 2-year survival rates were 61.1% and 35.2% respectively in 54 patients who were followed. The therapeutic result was better in patients with liver metastasis originating from the gastrointestinal tract carcinoma than those from non-gastrointestinal tract carcinoma (P < 0.05). In patients with liver metastasis originating from the gastrointestinal tract carcinoma, the median survival was 17.6 months, with 1-, 2-year survival rates of 68.4% and 39.5%. There was no severe toxic side effects or complications. The toxic reaction in liver, biliary and gastrointestinal tract was mild. CONCLUSION: Continuous hepatic arterial infusion of 5-Fu/CF and dexamethasone via a subcutaneous drug delivery system is able to prolong the survival and improve the quality of life in patients with nonresectable liver metastasis.
OBJECTIVE: To evaluate the role of apoptosis mediated by Fas/FasL in the liver of hepatitis B and the expression status of Fas, FasL, and HBV antigens. METHODS: We studied the expression of Fas antigen, Fas-ligand (FasL) and hepatitis B virus(HBV) antigens(HBsAg and HBcAg) in the livers of 62 patients with hepatitis B using immunohistochemistry ABC method. Six normal liver samples were used as control. RESULTS: Hepatocytes in normal liver had no Fas/FasL expression, but in the cases of hepatitis B, Fas was expressed mainly in the cytoplasm in 58 cases(93.5%); FasL was observed in infiltrating mononuclear cells and in the cytoplasm of hepatocytes in 37 cases (59.7%). The expressions of Fas/FasL were closely related to the liver histological inflammation degrees. CONCLUSION: The apoptosis mediated by Fas/FasL may play an important role in the hepatocellular injury in hepatitis B. No correlation was found between the degrees of Fas/FasL expression and the presence of HBsAg and HBcAg in the liver.
PURPOSE: Older single African-American women are the population that is least likely to use screening procedures because of cognition-related, income-related, social-support-related and medical care-related barriers. This study aims to evaluate a breast screening intervention program developed according to socioeconomic, cultural, psychological and behavioral characteristics of older single African-American women.METHODS: Ten public housing complexes were randomly assigned to either intervention or control group. African-American women aged 65 and over were recruited into the study if they were widowed, divorced, separated or never-married in the preceding year, and did not have a history of breast cancer (n = 325). Delivered by lay health educators, the intervention program targeted increasing knowledge on breast health and breast screening, reducing emotional or psychological problems, and increasing support from the significant others of study women. Breast screening-related cognition and behavior were measured at pre-intervention and post-intervention.RESULTS: Comparisons of the pre-intervention and post-intervention measurements showed that while the proportion of women who had a clinical breast examination or mammogram in the preceding year was decreased at the post-intervention in the control group, it was increased in the intervention group. However, the differences did not reach a significant level. No consistent patterns could be found in changes of variables in knowledge, attitudes and beliefs. These results remained similar when potential confounding factors were adjusted using mixed model regression analyses.CONCLUSIONS: These results did not suggest significant effects of an intervention program which used lay health educators to promote breast cancer screening in older single African-American women.
PURPOSE: Depression-related symptoms, such as despair and loneliness, may prevent women from using preventive screening for diseases. This study aimed to assess if depression-related variables affect the likelihood of implementation of breast self-examination (BSE) in single African-American women aged 65 and older.METHODS: Subjects for this study included 325 African-American women, aged 65 and older, who were widowed, divorced, separated, or never-married, and lived in ten public housing tenements in Nashville, Tennessee. In-person interviews were conducted to collect information on breast screening behavior, knowledge and attitudes, social networks and activities, medical care use and depression. Depression variables included 19 factors, such as feeling guilty, feeling sad or blue, and feeling worthless.RESULTS: Using logistic regression with adjustment for potential confounders, we found that, compared with women who did not perform BSE, those who performed BSE were less likely to have felt guilty in the preceding year (p < 0.05, odds ratio (OR) = 0.3, confidence interval (CI) = 0.13-0.71). However, the other depression-related variables were not associated with BSE. For example, women who performed BSE and those who did not perform BSE reported feeling sad or blue in equal frequencies (OR = 0.93, CI 0.49-1.7).CONCLUSIONS: In general, this study suggests that there is no overall association between depression-related symptoms and breast self-examination in single African-American women aged 65 and older.
The Dbl family guanine-nucleotide exchange factors (GEFs) for Rho GTPases share the structural array of a Dbl homology (DH) domain in tandem with a Pleckstrin homology (PH) domain. For oncogenic Dbl, the DH domain is responsible for the GEF activity, and the DH-PH module constitutes the minimum structural unit required for cellular transformation. To understand the structure-function relationship of the DH domain, we have investigated the role of specific residues of the DH domain of Dbl in interaction with Rho GTPases and in Dbl-induced transformation. Alanine substitution mutagenesis identified a panel of DH mutants made in the alpha1, alpha6, and alpha9 regions and the PH junction site that suffer complete or partial loss of GEF activity toward Cdc42 and RhoA. Kinetic and binding analysis of these mutants revealed that although most displayed decreased k(cat) values in the GEF reaction, the substrate binding activities of T506A and R634A were significantly reduced. E502A, Q633A, and N673A/D674A, on the other hand, retained the binding capability to the Rho GTPases but lost the GEF catalytic activity. In general, the in vitro GEF activity of the DH mutants correlated with the in vivo Cdc42- and RhoA-activating potential, and the GEF catalytic efficiency mirrored the transforming activity in NIH 3T3 cells. Moreover, the N673A/D674A mutant exhibited a potent dominant-negative effect on serum-induced cell growth and caused retraction of actin structures. These studies identify important sites of the DH domain involved in binding or catalysis of Rho proteins and demonstrate that maintaining a threshold of GEF catalytic activity, in addition to the Rho GTPase binding activity, is essential for efficient transformation by oncogenic Dbl.
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Detergent (pentaoxyethylene octyl ether, C(8)E(5))-induced conformational changes of Humicola lanuginosa lipase (HLL) were investigated by stationary and time-resolved fluorescence intensity and anisotropy measurements. Activation of HLL is characterized by opening of a surface loop (the "lid") residing directly over the enzyme active site. The interaction of HLL with C(8)E(5) increases fluorescence intensities, prolongs fluorescence lifetimes, and decreases the values of steady-state anisotropy, residual anisotropy, and the short rotational correlation time. Based on these data, we propose the following model. Already below critical micellar concentration (CMC) the detergent can intercalate into the active site accommodating cleft, while the lid remains closed. Occupation of the cleft by C(8)E(5) also blocks the entry of the monomeric substrate, and inhibition of catalytic activity at [C(8)E(5)] less than or equal to CMC is evident. At a threshold concentration close to CMC the cooperativity of the hydrophobicity-driven binding of C(8)E(5) to the lipase increases because of an increase in the number of C(8)E(5) molecules present in the premicellar nucleates on the hydrophobic surface of HLL. These aggregates contacting the lipase should have long enough residence times to allow the lid to open completely and expose the hydrophobic cleft. Concomitantly, the cleft becomes filled with C(8)E(5) and the "open" conformation of HLL becomes stable.
PURPOSE: To determine preventable risk factors for cancers of the nasal cavity and paranasal sinuses in the United States, we analyzed data from the population-based, case-control Selected Cancers Study. METHODS: Cases were men born between 1929 and 1953 who were diagnosed with primary nasal cancer between 1984 and 1988 and identified from population-based cancer registries; we narrowed the cohort to 70 subjects whose diagnosis of nasal cancer was confirmed by pathology review. All living controls interviewed for the Selected Cancers Study were included as the comparison group (n = 1910); they were recruited by random-digit dial telephone and were frequency-matched to the lymphoma cases of the Selected Cancers Study by geographic area and age. Both cases and controls were interviewed by telephone. RESULTS: Logistic regression analyses showed that cases were 2.5 times more likely than controls to have smoked cigarettes [95% confidence interval (CI) = 1.1-5.3], and 2.2 times more likely to have worked in selected occupations, including lawn care, forestry, and maintenance of highway right-of-way areas (CI = 1.2-3.7). These occupations may cause workers to be exposed to pesticides or herbicides. The population attributable risk (PAR) was 53% for having ever smoked cigarettes. CONCLUSIONS: The study results suggest that among U.S. men, some nasal cancer may be preventable by avoiding cigarette smoking.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid that acts as an intracellular and extracellular signalling molecule in numerous biological processes. Many of the cellular actions of SPC are believed to be mediated by the activation of unidentified G-protein-coupled receptors. Here we show that SPC is a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1). In OGR1-transfected cells, SPC binds to OGR1 with high affinity (Kd = 33.3 nM) and high specificity and transiently increases intracellular calcium. The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation. In addition, SPC causes internalization of OGR1 in a structurally specific manner.
Effects of guanidine hydrochloride (GdnHCl) on the structure and dynamics of wild-type Humicola lanuginosa lipase (HLL) and its two mutants were studied. The latter were S146A (with the active site Ser replaced by Ala) and the single Trp mutant W89m, with substitutions W117F, W221H, and W260H. Steady-state, stopped-flow, and time-resolved laser-induced fluorescence spectroscopy were carried out as a function of [GdnHCl]. The maximum emission wavelength and fluorescence lifetimes revealed the microenvironment of the tryptophan(s) in these lipases to become more polar upon increasing [GdnHCl]. However, significant extent of tertiary structure in GdnHCl is suggested by the observation that both wild-type HLL and W89m remain catalytically active at rather high GdnHCl concentrations of >6 and 4.0 M, respectively. Changes in steady-state emission anisotropy, as well as variation in rotational correlation times and residual anisotropy values, demonstrate that upon increasing [GdnHCl] the structure of the lipases became more loose, with increasing amplitude of structural fluctuations. Finally, intermediate states in the course of exposure of the proteins to GdnHCl were revealed by stopped-flow fluorescence measurements.
This study examines the effects of xenografts of microencapsulated bovine chromaffin cells (BCCs) on the rotational behavior of hemiparkinsonian monkey recipients. In addition, it determines the content of monoamine neurotransmitters and their major metabolites in the neostriatum in hemiparkinsonian monkeys. The hemiparkinsonian model in monkeys was induced by a unilateral intracarotid injection of methyl-phenyl-tetrahydropyridine (MPTP). Unencapsulated BCCs, BCCs microencapsulated in alginate-polylysine-alginate (ALA) membranes as well as empty microencapsules were grafted into the neostriatum of the hemiparkinsonian monkeys. Following the transplantation the hemiparkinsonian symptoms subsided and the number of rotations induced by apomorphine decreased for up to nine months in the group of recipients grafted with microencapsulated BCCs, while only a temporary improvement (one month) was detected in the recipients of the unencapsulated BCCs. No change was observed in the recipients of empty microencapsules. Dopamine and its metabolites were found considerably depleted in the MPTP-lesioned side versus the unlesioned side of the neostriatum in the hemiparkinsonian monkeys(P<0.05).
PL and PLEG are biodegradable, biocompatible polymers. They have been widely used for controlled release of drugs. We synthesized PLEG copolymers containing PEG segments with various molecular weight and prepared hCG-loaded PL/PLEG blend microspheres to improve hCG entrapment efficiency. It was shown that the hCG entrapment effciency of PL/PLEG microspheres was higher than that of PL or PLEG microspheres when P(L-co-PEG6000)(90:10) was used. In vitro release test showed that the release of hCG was a burst-slow process, which was thought to be good for antigens to produce antibodies.
Barriers to engaging African Americans as research participants may be accentuated among older single African-American women partly because of financial, social, physical, and cognitive factors. This article shows our multifaceted strategies and experiences in the recruitment of single African-American women aged 65 and older in a cancer prevention and control study. The study was conducted in 10 public housing complexes in Nashville, Tennessee. Out of 367 eligible women, 325 participated in the study, resulting in a rate of 89%. The result suggests that a strategy, which targets the cultural, perceptive, and cognitive characteristics of the population, was effective for increasing the enrollment of study subjects in this population. Because the single constitute 75% of African-American women aged 65 and older; and the incidence and mortality of cancer are especially high in elderly African Americans, our experiences are encouraging for cancer prevention and control research in the population.
OBJECTIVE: Using baseline data from an intervention study, we examined cognitive, psychological, social and medical care factors in relation to the use of a mammogram in the preceding year among single African-American women aged 65 and older. METHODS: Study subjects were 325 African-American women aged 65 and older who were divorced, widowed, separated or never-married, and lived in ten public housing complexes in Nashville, Tennessee. In-person interviews were conducted to collect information on breast screening behavior, knowledge and attitude, social network and activities, emotional and psychological symptoms and signs, and medical care use. RESULTS: Compared with those who had not had a mammogram in the preceding year, women who had had a mammogram in the preceding year were three times more likely to have a regular doctor (95% confidence interval [CI] 1.4-5.0) and about six times more likely to have a doctor's recommendation for a mammogram (95%CI 3.4-11.1). In addition, they were more likely to: (a) have attended a meeting on breast health or received educational materials on breast cancer; (b) agree that a woman needs a mammogram even though she has no breast problem; (c) agree that a woman can have breast cancer without having symptoms; (d) have living children and grandchildren; and (e) attend social activities more frequently. CONCLUSIONS: While access to regular medical care and receiving a physician's recommendation are strongly associated with mammography among these older, single African-American women, education on breast health and social networks also appear to be influential.
OBJECTIVE: To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC-CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte-derived dendritic cells (MoDCs). The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was also studied. METHODS: In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratory ability was assessed by a micromultiwell chemotaxis chamber assay. RESULTS: IL-8, MCP-1, RANTES and their corresponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable after 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. CONCLUSION: Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.
OBJECTIVE: To analyse the treatment-related complications of busulphan and cyclophosphamide (BU-CY) as the conditioning regimen for allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: The clinical data of 40 leukemia patients undergoing allo-PBSCT between June 1997 and May 1999 in our BMT center were retrospectively analysed. RESULTS: Recovery of neutrophil and platelet was achieved at a median of day +13 (9 - 28) and day +12 (7 - 60) respectively. Acute GVHD occurred in 17 of 40 patients (42.5%) with grade II-IV in 10 patients (25%). Chronic GVHD developed in 21 out of 30 evaluable patients (70%). Mild to severe mucositis occurred in 30 patients (75%), and 4 of them had severe esophagitis with bleeding. Haemorrhagic cystitis developed in 8/40 (20%) patients, the median time of its onset was day +100 (+7 to +165). Six of 40 patients (15%) developed interstitial pneumonia (IP), 5 of them were due to cytomegalovirus infection, and the remaining one due to pneumocystis carinii infection. No hepatic veno-occlusive disease was observed and no seizure occurred. During the median follow-up of 480 (300 - 1000) days, 4 (10%) patients relapsed and 8 (20%) patients died of the transplant-related complications. The 3 year leukemia-free survival rate was 70%. CONCLUSION: BU (domestic busulfan)-CY regimen is relatively easy to administer and well tolerated, with low extramedullary toxicities.