Biomedical subjects

K Zhu

Publications and source records attributed to K Zhu.

At least 19 recordsLinked to original sources

PubMed2006

Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter.

Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

Acetylation↗

PubMed2004

History of diabetes mellitus and risk of prostate cancer in physicians.

Some studies have suggested that diabetes mellitus may decrease the risk of prostate cancer because of lower insulin levels. To further investigate the relation between diabetes and prostate cancer, a nested case-control study was conducted within the US Physicians' Health Study. Cases (n = 1,110) had been diagnosed with prostate cancer, confirmed on medical record review, during follow-up in 1982-1995. Controls (n = 1,110) were selected randomly from men free of prostate cancer and were matched on age and date of randomization. Information on personal history of diabetes and other diseases, lifestyle habits, and body weight/height was self-reported. Logistic regression analysis showed that the odds ratio for prostate cancer was 0.64 (95% confidence interval (CI): 0.43, 0.95) for men with diabetes, relative to those without the disease, after adjustment for potential confounders. Odds ratio estimates were 0.63 (95% CI: 0.35, 1.14), 0.77 (95% CI: 0.35, 1.72), 0.59 (95% CI: 0.21, 1.66), and 0.59 (95% CI: 0.27, 1.27) for diabetes diagnosed 1-5, 6-10, 11-15, and > or = 16 years prior to prostate cancer diagnosis (p for trend < 0.05). Adjusted odds ratios were 1.44 (95% CI: 0.34, 6.17) for stage A prostate cancer and 0.48 (95% CI: 0.28, 0.83) for stages B-D. Results suggest that history of diabetes may be associated with a decreased risk of prostate cancer, especially late-stage tumors.

Adult↗

PubMed2004

Physical and chemical processes for removing suspended solids and phosphorus from liquid swine manure.

A physical/chemical treatment train, that included 24-hour preliminary settling followed by coagulation/flocculation and sedimentation, was tested at a laboratory bench scale to treat liquid swine manure for the removal of total suspended solids (TSS) and total phosphorus (TP). Preliminary (i.e., natural) settling time had an effect on TSS removal within only the first 24 hours. TSS removal efficiency reached 75% (TSS concentration was reduced from 5,800 to 1,450 mg 1(-1)) after 24 hours of preliminary settling. Also, as a result of the 24-hour preliminary settling, TP concentration was reduced from 533 to 318 mg 1(-1), thus leading to a TP removal efficiency of 40%. When compared to ferric chloride, alum was more effective in reducing both TSS and TP. At a 95% confidence interval, alum dose, coagulation Gt (coagulation velocity gradient * rapid-mixing time), and flocculation Gt (flocculation velocity gradient * slow-mixing time) were not significant for TSS removal while alum dose was the only significant factor for TP removal. For the 24-hour settled liquid manure that had a TP concentration in the range of 362 to 401 mg l(-1)and as alum dose increased up to 1,600 mg 1(-1), TP removal efficiency increased up to 70%. Then, the rate of increase in TP removal efficiency per increase in alum dose started to decrease and TP removal efficiency reached about 93% at an alum dose of 3,000 mg 1(-1). Sequential alum dosing improved the TSS removal efficiency while it had no effect on TP removal efficiency. The mass ratio of removed TSS/applied alum increased from about 0.38, during a one-step dosing of alum at a concentration of 1,600 mg l(-1), to about 0.58 during a two-step dosing of alum at a concentration of 1,600 mg l(-1) (i.e., 800 mg l(-1) followed by another 800 mg l(-1)).

Alum Compounds↗

PubMed2001

Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4.

Sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC) are bioactive lipid molecules involved in numerous biological processes. We have recently identified ovarian cancer G protein-coupled receptor 1 (OGR1) as a specific and high affinity receptor for SPC, and G2A as a receptor with high affinity for LPC, but low affinity for SPC. Among G protein-coupled receptors, GPR4 shares highest sequence homology with OGR1 (51%). In this work, we have identified GPR4 as not only another high affinity receptor for SPC, but also a receptor for LPC, albeit of lower affinity. Both SPC and LPC induce increases in intracellular calcium concentration in GPR4-, but not vector-transfected MCF10A cells. These effects are insensitive to treatment with BN52021, WEB-2170, and WEB-2086 (specific platelet activating factor (PAF) receptor antagonists), suggesting that they are not mediated through an endogenous PAF receptor. SPC and LPC bind to GPR4 in GPR4-transfected CHO cells with K(d)/SPC = 36 nm, and K(d)/LPC = 159 nm, respectively. Competitive binding is elicited only by SPC and LPC. Both SPC and LPC activate GPR4-dependent activation of serum response element reporter and receptor internalization. Swiss 3T3 cells expressing GPR4 respond to both SPC and LPC, but not sphingosine 1-phosphate (S1P), PAF, psychosine (Psy), glucosyl-beta1'1-sphingosine (Glu-Sph), galactosyl-beta1'1-ceramide (Gal-Cer), or lactosyl-beta1'1-ceramide (Lac-Cer) to activate extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration- and time-dependent manner. SPC and LPC stimulate DNA synthesis in GPR4-expressing Swiss 3T3 cells. Both extracellular signal-regulated kinase activation and DNA synthesis stimulated by SPC and LPC are pertussis toxin-sensitive, suggesting the involvement of a G(i)-heterotrimeric G protein. In addition, GPR4 expression confers chemotactic responses to both SPC and LPC in Swiss 3T3 cells. Taken together, our data indicate that GPR4 is a receptor with high affinity to SPC and low affinity to LPC, and that multiple cellular functions can be transduced via this receptor.

3T3 Cells↗

PubMed2001

RETRACTED: Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A.

Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes. This finding implicates a role for LPC-G2A interaction in the etiology of inflammatory autoimmune disease and atherosclerosis.

Animals↗

PubMed2001

Impact of the tryptophan residues of Humicola lanuginosa lipase on its thermal stability.

Thermal stability of wild type Humicola lanuginosa lipase (wt HLL) and its two mutants, W89L and the single Trp mutant W89m (W117F, W221H, and W260H), were compared. Differential scanning calorimetry revealed unfolding of HLL at T(d)=74.4 degrees C whereas for W89L and W89m this endotherm was decreased to 68.6 and 62 degrees C, respectively, demonstrating significant contribution of the above Trp residues to the structural stability of HLL. Fluorescence emission spectra revealed the average microenvironment of Trps of wt HLL and W89L to become more hydrophilic at elevated temperatures whereas the opposite was true for W89m. These changes in steady-state emission were sharp, with midpoints (T(m)) at approx. 70.5, 61.0, and 65.5 degrees C for wt HLL, W89L, and W89m, respectively. Both steady-state and time resolved fluorescence spectroscopy further indicated that upon increasing temperature, the local movements of tryptophan(s) in these lipases were first attenuated. However, faster mobilities became evident when the unfolding temperatures (T(m)) were exceeded, and the lipases became less compact as indicated by the increased hydrodynamic radii. Even at high temperatures (up to 85 degrees C) a significant extent of tertiary and secondary structure was revealed by circular dichroism. Activity measurements are in agreement with increased amplitudes of conformational fluctuations of HLL with temperature. Our results also indicate that the thermal unfolding of these lipases is not a two-state process but involves intermediate states. Interestingly, a heating and cooling cycle enhanced the activity of the lipases, suggesting the protein to be trapped in an intermediate, higher energy state. The present data show that the mutations, especially W89L in the lid, contribute significantly to the stability, structure and activity of HLL.

Bacteria↗

PubMed2001

Controlling spatiotemporal chaos in coupled map lattices.

A simple method is presented for controlling spatiotemporal chaos in coupled map lattices to a homogeneous state. This method can be applied to many kinds of models such as coupled map lattices (CML), one-way open CML (the open-flow model), and globally coupled map. We offer the stability analysis of the homogeneous state. Simple and sufficient conditions are obtained for controlling the above mentioned models. Our theoretical results agree well with numerical simulations.

Journal Article↗

PubMed2001

ATP induces a conformational change in lipid-bound cytochrome c.

Resonance energy transfer studies using a pyrene-labeled phospholipid derivative 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphoglycerol (donor) and the heme (acceptor) of cytochrome c (cyt c) have indicated that ATP causes changes in the conformation of the lipid-bound protein (Rytömaa, M., Mustonen, P., and Kinnunen, P. K. J. (1992) J. Biol. Chem. 267, 22243-22248). Accordingly, after binding cyt c via its so called C-site to neat phosphatidylglycerol liposomes (mole fraction of PG = 1.0) has commenced, further quenching of donor fluorescence is caused by ATP, saturating at 2 mm nucleotide. ATP-induced conformational changes in liposome-associated cyt c could be directly demonstrated by CD in the Soret band region (380-460 nm). The latter data were further supported by time-resolved spectroscopy using the fluorescent cyt c analog with a Zn(2+)-substituted heme moiety. A high affinity ATP-binding site has been demonstrated in cyt c (Craig, D. B., and Wallace, C. J. A. (1993) Protein Sci. 2, 966-976) that is compromised by replacing the invariant Arg(91) to norleucine. Although no major effects on conformation and function of cyt c were concluded due to the modification, a significantly reduced effect by ATP on the lipid-bound [Nle(91)]cyt c was evident, implying that this modulation is mediated via the Arg(91)-containing binding site.

Adenosine Triphosphate↗

PubMed2001

Human RNA helicase II/Gu gene: genomic organization and promoter analysis.

Human RNA helicase II/Gu (hRH II/Gu) protein unwinds double-stranded RNA, folds single-stranded RNA, and may play important roles in ribosomal RNA biogenesis, RNA editing, RNA transport, and general transcription. The genomic organization and the regulation of expression of the hRH II/Gu gene were analyzed. The hRH II/Gu gene is over 29 kb in length, and includes 15 exons. All intron-exon junctions contain consensus GT-AG sequences. An 85 bp basic promoter was identified which lacks a functional TATA box. In LNCaP cells, the hRH II/Gu promoter was up to 50 times as active as pGL2-control vector which has an SV 40 early promoter. Mutation of a putative c-Myc/USF binding site in the region between -110 and -85 caused a decrease in the promoter activity by 2- to 3-fold. A negative regulatory region was also found between -324 and -264. Studies of transcriptional regulation of hRH II/Gu under different physiological and pathophysiological conditions may provide clues to its biological function.

Base Sequence↗

PubMed2001

Relationship between the increase of secretion of sTNF alpha induced by lipopolysaccharides and the enhanced expression of TACE mRNA in HL-60 cells and adhesive cells from human spleen.

In order to find out the potential modulators which influence the secretion of TNF alpha, the relationship between the amount of secreted TNF alpha (sTNF alpha) and the level of TNF alpha converting enzyme (TACE) gene expression was studied before and after the stimulation by lipopolysaccharides (LPS) to HL-60 cells and adhered cells isolated from human spleen using cytological and molecular biology techniques and methods (RT-PCR, Dot-blot hybridization, etc.). The experimental results showed that: (1) LPS could induce the increase of expression of TNF alpha mRNA and TACE mRNA, reaching the peak value at 6 h and 10 h respectively after addition of LPS into cell culture medium; (2) The anti-sense oligodeoxyribonucleotide (A-ODN) complementary to TACE mRNA sequence really inhibited the secretion of TNF alpha as a result of blocked translation of TACE gene; (3) Furthermore, it was also observed that RDQ, a kind of injection derived from Chinese traditional herb, had strongly inhibitory effects on the expression of TACE mRNA and secretion of sTNF alpha stimulated by LPS. The above results suggested that the TACE indeed involved in delivering and processing of pro-TNF alpha during the period of LPS stimulation and the study about the regulator/inhibitors of TACE gene expression would be very important to develop new types of therapy agents against toxic and side effects of sTNF alpha during the period of infection/inflammation to human body.

ADAM Proteins↗

PubMed2001

Psoriasis scales contain C5a as the predominant chemotaxin for monocyte-derived dendritic cells.

Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.

Amino Acid Sequence↗

PubMed2001

Inhibition of dendritic cell differentiation by fumaric acid esters.

Fumaric acid esters have proved to be effective for the systemic treatment of severe psoriasis vulgaris. These compounds have been shown to induce a Th2-like cytokine secretion pattern in T cells and to reduce keratinocyte proliferation in vitro. Dendritic cells seem to be of major importance as regulatory cells driving the psoriatic tissue reaction. Monocytes or CD34-positive myeloid progenitor cells are precursors of dendritic cells that can be generated in vitro by culture with granulocyte-macrophage colony-stimulating factor and interleukin-4. Using this model the effect of fumaric acid esters on granulocyte-macrophage colony-stimulating factor/interleukin-4-induced differentiation of monocyte-derived dendritic cells was investigated. The results of this study show that dimethylfumarate as well as methylhydrogenfumarate-calcium-salt (0.01-100 microg per ml) concentration-dependently inhibit monocyte-derived dendritic cell differentiation. This was reflected by an inhibition of CD1a, CD40, CD80, CD86, and HLA-DR expression as well as by a reduced capacity of dimethylfumarate-treated monocyte-derived dendritic cells to stimulate lymphocytes in the allogeneic mixed lymphocyte reaction. Other fumaric acid esters showed no effect on monocyte-derived dendritic cell-differentiation. At higher concentrations (30-100 microg per ml) dimethylfumarate, but not methylhydrogenfumarate calcium-salt induced apoptosis in monocyte-derived dendritic cells as measured by expression of Apo 2.7 and DNA fragmentation (TUNEL assay). These data point to a high susceptibility of the monocyte/dendritic cell system to dimethylfumarate and its main metabolite methylhydrogenfumarate. Other fumaric acid esters investigated were without effect. As the effects of fumarates on monocyte-derived dendritic cells observed occur at concentrations 20-fold lower compared with lymphocytes, our data seem to be of relevance in explaining the possible mode of action of these compounds in psoriasis.

Adjuvants, Immunologic↗

PubMed2001

Risk factors for non-Hodgkin's lymphoma according to family history of haematolymphoproliferative malignancies.

BACKGROUND: Aetiological profiles of non-Hodgkin's lymphoma (NHL) may differ depending upon whether the disease is inheritance-related or sporadic. Because familial risk (a probable surrogate of inheritance-relatedness) of NHL is influenced by haematolymphoproliferative malignancies (HLPM), we evaluated whether non-familial risk factors differ between NHL with and without a family history of HLPM, using the Selected Cancers Study data. METHODS: Cases were 1511 men aged 31-59 and diagnosed with NHL during 1984-1988. Controls were men without NHL, frequency-matched to cases by age range and cancer registry (n = 1910). These groups were compared: cases with a family history of HLPM and without, and controls without such a family history. RESULTS: Polytomous logistic regression analyses showed that the odds ratio (OR) estimates of homosexual behaviour were 18.2 (95% confidence interval (CI) : 4.8-69.4) and 5.6 (95% CI : 3.3-9.5) for NHL with and without a family history of HLPM, respectively. The corresponding estimates were 3.9 (95% CI : 1.7-8.9) and 2.2 (95% CI : 1.5-3.1) for history of enlarged lymph nodes. Variables only related to NHL with a family history were use of heroin (OR = 15.6, 95% CI : 3.4-70.4), exposure to a chlorinated hydrocarbon pesticide (OR = 2.3, 95% CI : 1.0-5.0), occupational exposure to plywood, fibreboard or particleboard (OR = 2.0, 95% CI : 1.2-3.4) and history of liver diseases (other than hepatitis or cirrhosis) (OR = 6.5, 95% CI : 1.2-36.2). The association between homosexual behaviour and NHL among men with a family history was stronger for those aged 31-44, especially for B-cell type of the disease. CONCLUSIONS: This study suggests differences in the risk factor profiles between NHL with and without a family history of HLPM. The higher risks of NHL for homosexual behaviour and heroin use, surrogates of HIV infection, in men with a family history of HLPM imply that genetic susceptibility may be influential on the occurrence of HIV-related NHL.

Adult↗

PubMed2001

Effects of i-propanol on the structural dynamics of Thermomyces lanuginosa lipase revealed by tryptophan fluorescence.

Influence of isopropanol (iPrOH) on the structural dynamics of Thermomyces lanuginosa lipase (TLL) was studied by steady-state, time-resolved, and stopped-flow fluorescence spectroscopy, monitoring the intrinsic emission of Trp residues. The fluorescence of the four Trps of the wild-type enzyme report on the global changes of the whole lipase molecule. To monitor the conformational changes in the so-called "lid," an alpha-helical surface loop, the single Trp mutant W89m (W117F, W221H, W260H) was employed. Circular dichroism (CD) spectra revealed that iPrOH does not cause major alterations in the secondary structures of the wild-type TLL and W89m. With increasing [iPrOH], judged by the ratio of emission intensities at 350 nm and 330 nm, the average microenvironment of the Trps in the wild-type TLL became more hydrophobic, whereas Trp89 of W89m moved into a more hydrophilic microenvironment. Time-resolved fluorescence measurements revealed no major changes to be induced by iPrOH neither in the shorter fluorescence lifetime component (tau(1) = 0.5--1.2 ns) for the wild-type TLL nor in the longer fluorescence lifetime component (tau(2) = 4.8--6.0 ns) in the wild-type TLL and the W89m mutant. Instead, for W89m on increasing iPrOH from 25% to 50% the value for tau(1) increased significantly, from 0.43 to 1.5 ns. The shorter correlation time phi(1) of W89m had a minimum of 0.08 ns in 25% iPrOH. Judged from the residual anisotropy r(infinity) the amplitude of the local motion of Trp89 increased upon increasing [iPrOH] 10%. Stopped-flow fluorescence spectroscopy measurements suggested the lid to open within approximately 2 ms upon transfer of W89m into 25% iPrOH. Steady-state anisotropies and longer correlation times revealed increasing concentrations of iPrOH to result also in the formation of dimers as well as possibly also higher oligomers by TLL.

2-Propanol↗

PubMed2001

Oligomerization of DH domain is essential for Dbl-induced transformation.

The dbl oncogene product (onco-Dbl) is the prototype member of a family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. The Dbl homology (DH) domain of onco-Dbl is responsible for the GEF catalytic activity, and the DH domain, together with the immediately adjacent pleckstrin homology (PH) domain, constitutes the minimum module bearing transforming function. In the present study, we demonstrate that the onco-Dbl protein exists in oligomeric form in vitro and in cells. The oligomerization is mostly homophilic in nature and is mediated by the DH domain. Mutagenesis studies mapped the region involved in oligomerization to the conserved region 2 of the DH domain, which is located at the opposite side of the Rho GTPase interacting surface. Residue His556 of this region, in particular, is important for this activity, since the H556A mutant retained the GEF catalytic capability and the binding activity toward Cdc42 and RhoA in vitro but was deficient in oligomer formation. Consequently, the Rho GTPase activating potential of the H556A mutant was significantly reduced in cells. The focus-forming and anchorage-independent growth activities of onco-Dbl were completely abolished by the His556-to-Ala mutation, whereas the abilities to stimulate cell growth, activate Jun N-terminal kinase, and cause actin cytoskeletal changes were retained by the mutant. The ability of onco-Dbl to oligomerize allowed multiple Rho GTPases to be recruited to the same signaling complex, and such an ability is defective in the H556A mutant. Taken together, these results suggest that oligomerization of onco-Dbl through the DH domain is essential for cellular transformation by providing the means to generate a signaling complex that further augments and/or coordinates its Rho GTPase activating potential.

3T3 Cells↗

PubMed2001

Autoinhibition mechanism of proto-Dbl.

The dbl oncogene encodes a prototype member of the Rho GTPase guanine nucleotide exchange factor (GEF) family. Oncogenic activation of proto-Dbl occurs through truncation of the N-terminal 497 residues. The C-terminal half of proto-Dbl includes residues 498 to 680 and 710 to 815, which fold into the Dbl homology (DH) domain and the pleckstrin homology (PH) domain, respectively, both of which are essential for cell transformation via the Rho GEF activity or cytoskeletal targeting function. Here we have investigated the mechanism of the apparent negative regulation of proto-Dbl imposed by the N-terminal sequences. Deletion of the N-terminal 285 or C-terminal 100 residues of proto-Dbl did not significantly affect either its transforming activity or GEF activity, while removal of the N-terminal 348 amino acids resulted in a significant increase in both transformation and GEF potential. Proto-Dbl displayed a mostly perinuclear distribution pattern, similar to a polypeptide derived from its N-terminal sequences, whereas onco-Dbl colocalized with actin stress fibers, like the PH domain. Coexpression of the N-terminal 482 residues with onco-Dbl resulted in disruption of its cytoskeletal localization and led to inhibition of onco-Dbl transforming activity. The apparent interference with the DH and PH functions by the N-terminal sequences can be rationalized by the observation that the N-terminal 482 residues or a fragment containing residues 286 to 482 binds specifically to the PH domain, limiting the access of Rho GTPases to the catalytic DH domain and masking the intracellular targeting function of the PH domain. Taken together, our findings unveiled an autoinhibitory mode of regulation of proto-Dbl that is mediated by the intramolecular interaction between its N-terminal sequences and PH domain, directly impacting both the GEF function and intracellular distribution.

3T3 Cells↗

PubMed2001

Mechanisms of mechanical heart valve cavitation: investigation using a tilting disk valve model.

BACKGROUND AND AIM OF THE STUDY: The induction of mechanical heart valve (MHV) cavitation was investigated using a 27 mm Medtronic Hall (MH27) tilting disk valve. METHODS: The MH27 valve was mounted in the mitral position of a simulating pulse flow system, and stroboscopic lighting used to visualize cavitation bubbles on the occluder inflow surface at the instant of valve closure. MHV cavitation was monitored using a digital camera with 0.04 mm/pixel resolution sufficient to render the tiny bubbles clearly visible on the computer monitor screen. RESULTS: Cavitation on MH27 valve was classified as five types according to the time, site and shape of the cavitation bubbles. Valve cavitation occurred at the instant of occluder impact with the valve seat at closing. The impact motion was subdivided into three temporal phases: (i) squeezing flow; (ii) elastic collision; and (iii) leaflet rebound. MHV cavitation caused by vortices was found to be initiated by the squeezing jet and/or by the transvalvular leakage jets. By using a tension wave which swept across the occluder surface immediately upon elastic impact, nuclei in the vortex core were expanded to form cavitation bubbles. CONCLUSION: Analysis of the shape and location of the cavitation bubbles permitted a better understanding of MHV cavitation mechanisms, based on the fluid dynamics of jet vortex and tension wave propagations.

Biomechanical Phenomena↗

PubMed2001

Allogeneic peripheral blood stem cell transplantation for leukemia.

OBJECTIVE: To observe engraftment kinetics, the incidence and severity of graft-versus-host disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: From June 1997 to May 1999, forty leukemia patients with a median age of 35 years underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 micrograms/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0-16.8) x 10(6) CD34+ cells/kg was infused into the recipients. Busulfan-cyclophosphamide (BU-CY) was used as the 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 13 days (9-28 days) and 12 days (7-60 days) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5%), with grade II-IV acute GVHD in 10 patients (25%). Chronic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients (21/30, 70%) with a median follow up of 380 days (180-900 days). Transplant related mortality was 17.5% and the relapse rate was 10%. The probability of leukemia free survival at 3 years was 72.5%. CONCLUSION: Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD.

Adult↗