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Biomedical subjects

C Guo

Publications and source records attributed to C Guo.

At least 19 recordsLinked to original sources

Estradiol increases proteinuria and angiotensin II type 1 receptor in kidneys of rats receiving L-NAME and angiotensin II.

Prospective, placebo-controlled clinical trials suggest that estrogen may have adverse effects on the vascular system in women. The goal of this study was to determine if 17beta-estradiol (E2) would have adverse effects on the renovasculature in a rat model of renal injury characterized by low nitric oxide (NO) and high angiotensin II (AngII). We studied female Wistar rats that were sham-operated (sham), ovariectomized (OVX), or ovariectomized and replaced with E2 (OVX/E2). All rats were maintained on a high salt diet and renovascular injury was caused by treating rats with an inhibitor of NO synthase, N(omega)-nitro-L-arginine-methyl-ester (L-NAME), for 14 days, plus AngII on days 11 through 14. L-NAME/AngII treatment, as compared to placebo, caused proteinuria, glomerular injury, and fibrinoid necrosis of renal arterioles in sham-operated rats. Ovariectomy reduced L-NAME/AngII-induced renal damage, whereas E2 treatment increased L-NAME/AngII-induced damage in OVX rats. In rats treated with L-NAME/AngII, levels of AngII type 1 receptor (AT(1)R) protein were higher in the renal cortex of sham and OVX/E2 rats than in OVX rats. AT(1)R protein correlated with renal injury. E2 treatment also increased expression of AT(1)R mRNA. Thus, under conditions of low NO and high AngII, E2 exacerbated renal injury. E2-mediated increases in renal cortical AT(1)R expression may represent a novel mechanism for the adverse renovascular effects of estrogen.

Angiotensin II↗

Donor lymphoid organs are a major site of alloreactive T-cell priming following intestinal transplantation.

We hypothesized that lymphoid organs within intestinal allografts contribute to their immunogenicity. Consistent with this hypothesis recipient T cells rapidly migrated to the lymph nodes and Peyer's patches of syngeneic and allogeneic intestinal grafts such that at 24 h approximately 50% of the lymphocytes isolated from donor lymphoid organs were of recipient origin. However, only in the lymphoid organs of allografts did recipient T cells display an activated phenotype, proliferate and produce IFNgamma. Rejection of allogeneic intestines lacking lymphoid organs was dramatically impaired in splenectomized, lymph node-deficient recipients compared to lymph node bearing, wild-type allogeneic intestines. This demonstrates the important role of donor lymphoid organs in the rejection process. Furthermore, recipient T cells proliferated more extensively and produced more IFNgamma in donor lymphoid organs than in recipient lymphoid organs, indicating that donor lymphoid organs play a dominant role in initiating the recipient anti-donor immune response following intestinal transplantation.

Animals↗

Antinociceptive activity and chemical composition of constituents from Caragana microphylla seeds.

This investigation was undertaken to ascertain the antinociceptive activity of Caragana microphylla Lam. seeds and isolate and characterize the constituents. Antinociceptive activity was screened using acetic acid-induced abdominal constriction in ICR mice. The 75% ethanol extract and some fractions showed analgesic activity, but the antinociceptive activity of chloroform fraction was the strongest and was more productive than other fractions. Seven compounds were isolated from it and identified as: (1) machaeric acid, (2) beta-sitosterol, (3) stigmasterol, (4) pratol, (5) dehydrocavidine, (6) formononetin and (7) sucrose. Caragana microphylla Lam. seeds showed analgesic activity, with the chloroform fraction showing the strongest analgesic activity among the fractions.

Acetic Acid↗

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma.

Although high-dose therapy and autologous stem cell transplant (ASCT) is superior to conventional chemotherapy for treatment of myeloma, most patients relapse and the time to relapse depends upon the initial prognostic factors. The administration of non-cross-resistant chemotherapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after single autologous peripheral blood stem cell transplant (auto-PBSCT) in 103 mostly newly diagnosed myeloma patients (67 patients were < or =6 months from the initial treatment). Patients received conditioning with BCNU, melphalan+/-gemcitabine and auto-PBSCT followed by two cycles of the DCEP+/-G regimen (dexamethasone, cyclophosphamide, etoposide, cisplatin+/-gemcitabine) at 3 and 9 months post-transplant and alternating with two cycles of DPP regimen (dexamethasone, cisplatin, paclitaxel) at 6 and 12 months post-transplant. With a median follow-up of 61.2 months, the median event-free survival (EFS) and overall survival (OS) are 26 and 54.1 months, respectively. The 5-year EFS and OS are 23.1 and 42.5%, respectively. Overall, 51 (49.5%) patients finished all CC, suggesting that a major limitation of this approach is an inability to deliver all planned treatments. In order to improve results following autotransplantation, novel agents or immunologic approaches should be studied in the post-transplant setting.

Adult↗

Enhanced immunogenicity and antitumour effects with heterologous prime-boost regime using vaccines based on MG7-Ag mimotope of gastric cancer.

MG7-Ag, gastric cancer-associated antigen, has been shown to be immunogenic and has been used as marker molecule for prognosis. In a previous study, we developed an oral DNA vaccine based on MG7-Ag mimotope. However, we failed to detect cellular immune response using the oral MG7-Ag mimotope DNA vaccine. To induce significant T cell response, we developed a recombinant adenovirus vaccine based on MG7-Ag mimotope and evaluated the efficacy and protective effects of heterologous prime-boost immunization protocol with an oral DNA vaccine previously developed. We found that both vaccines were able to elicit a significant humoral response against MG7-Ag, while the highest serum titre MG7 antibody was detected in mice immunized with the heterologous prime-boost immunization protocol. Enzyme-linked immunospot (ELISPOT) assay demonstrated that the heterologous prime-boost immunization strategy was more efficient in inducing T cell response than the homologous prime-boost strategy. In the tumour challenge assay, 2 of 5 mice immunized with the heterologous prime-boost protocol were tumour free, while none of the mice in homologous prime-boost groups or control groups was tumour free. Those tumour-bearing mice in the heterologous prime-boost regime had smaller tumour masses than their counterparts in the homologous prime-boost groups or control groups. Therefore, our study suggests that vaccines against MG7-Ag induce significant immune response against gastric cancer, and that the heterologous prime-boost protocol using different types of vaccines could achieve better protective effect than the homologous prime-boost protocol.

Adenoviridae↗

Cloning and molecular characterization of a gene coding D-xylulokinase (CmXYL3) from Candida maltosa.

AIMS: To clone and identify a gene (CmXYL3) coding D-xylulokinase from Candida maltosa Xu316 and understand its physiological function. METHODS AND RESULTS: Based on the conserved regions of the known D-xylulokinase-encoding genes, a pair of degenerate primers was designed to clone the CmXYL3 gene from C. maltosa Xu316. The coding region and sequences flanking the CmXYL3 gene were obtained by PCR-based DNA walking method. Southern blotting analysis suggested that there is a single copy of the CmXYL3 gene in the genome. The open reading frame starting from ATG and ending with TAG stop codon encoded 616 amino acids with a calculated molecular mass of 68889.743 Da. The CmXYL3 gene under the control of the GPD1 promoter was heterologously expressed in Saccharomyces cerevisiae deficient in D-xylulokinase (deltaScXKS1::LEU2) activity, and restored growth on D-xylulose. The specific activity of D-xylulokinase varied during xylose fermentation and was correlated with aeration level. After growth on different pentoses and pentitols as sole carbon sources, the highest specific activity of D-xylulokinase was observed on D-xylose. CONCLUSIONS: The CmXYL3 gene isolated from C. maltosa Xu316 encodes a novel D-xylulokinase that plays a pivotal role in xylulose metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that describes the isolation and cloning of D-xylulokinase gene (CmXYL3) from C. maltosa Xu316. D-xylulokinase is pivotal for growth and product formation during xylose metabolism. Better understanding of the biochemical properties and the physiological function of D-xylulokinase will contribute to optimizing fermentation conditions and determining the strategies for metabolic engineering of C. maltosa Xu316 for further improvement of xylitol yield and productivity.

Amino Acid Sequence↗

Screening and characterization of yeasts for xylitol production.

AIMS: To discover novel naturally occurring xylitol producing yeast species with potential for industrial applications. METHODS AND RESULTS: Exactly 274 strains were cultivated on both solid and liquid screening medium with xylose as the sole carbon resource. Five strains were selected on the basis of significant growth and high degree of xylose assimilation. Their phylogenetic position was confirmed by the PCR-RFLP and sequence analysis of the D1/D2 domain of the 5' end of the large subunit rDNA gene (5'-LSU rDNA). Enzymatic analysis was conducted to compare xylose metabolism in each strain. Candida guilliermondii Xu280 and Candida maltosa Xu316 were found to have high xylose consumption rates and xylitol yields in the batch fermentation under micro-aerobic condition. The effect of the different media with high initial xylose concentration on biosynthesis of xylitol by both strains was investigated. CONCLUSIONS: We have identified Candida spp. strains, which exhibit high levels of xylitol production from xylose suggesting that these may have potential for industrial applications. SIGNIFICANCE AND IMPACTS OF THE STUDY: Microbial species are of importance for xylitol production. Xylitol production involves complicated metabolic regulation including xylose transport, production of key enzymes and cofactor regeneration. Thus, screening of naturally occurring xylose-utilizing micro-organisms is a viable and effective mean to obtain xylitol producing organisms with industrial application. Moreover, the research on selected strains will contribute to a better understanding of regulatory properties of xylose metabolism in different yeasts.

Bioreactors↗

Self-assembled silicon nanotubes under supercritically hydrothermal conditions.

Self-assembled silicon nanotubes with one-dimensional structure have been synthesized from silicon monoxide powder under supercritically hydrothermal conditions with a temperature of 470 degrees C and a pressure of 6.8 MPa. The silicon nanotubes were identified by transmission electron microscopy and high-resolution transmission electron microscopy. The results show that the silicon nanotubes (SiNT) have closed caps. The structures of the silicon nanotubes are hollow inner pore, crystalline silicon wall layers with a 0.31 nm interplanar spacing and 2-3 nm amorphous silica outer layers. Pure crystalline silicon nanotubes survive after etching the silicon nanotubes with 5% HF acid for enough time to imply that the self-assembled silicon nanotubes are stable. A possible theoretical reason for the growth of SiNTs from SiO under supercritically hydrothermal conditions was also proposed.

Journal Article↗

Concentration, temperature, and salt-induced micellization of a triblock copolymer Pluronic L64 in aqueous media.

The effect of copolymer concentration, temperature, and sodium halides (NaI, NaBr, NaCl, and NaF) on micellization and micellar properties of a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) amphiphilic copolymer (Pluronic L64: EO13PO30EO13), was examined by different methods such as dye spectral change, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), small angle neutron scattering (SANS), dynamic light scattering (DLS), viscosity, and cloud point (CP). Temperature/polymer concentration/salt dependent aggregation behavior of L64 was observed. The data on critical micelle concentration (CMC), critical micelle temperature (CMT), (CP), micelle size, and shape are reported. The Fourier transform infrared (FTIR) showed temperature dependent changes in C-O-C stretching variation band towards higher wave numbers and broadening of band width during the micellization process; this was attributed to increase in proportion of the anhydrous methyl groups, while the proportion of the hydrated methyl groups was decreased. Differential scanning calorimetry (DSC) provides CMTs and CPs from the same experiment. CMC values derived from dye spectral change, decrease significantly with the addition of salt. The increases in salt/copolymer concentration lower the onset temperature of micellization (CMT). Halide anions influence both CMT and CP in the order of F- > Cl- > Br- > I- when total salt and copolymer concentration kept constant. SANS results show the increase of inter-micellar interaction due to the increase in temperature/salt concentration; this is supported by viscosity data.

Calorimetry, Differential Scanning↗

A pilot study of fatty acid metabolism in oral squamous cell carcinoma.

This study was undertaken to determine the characteristics of fatty acid synthesis in squamous carcinoma cells and to assess the possibility of exploiting this synthesis pathway in anticancer therapy. Incorporation of [(3)H]acetate into total lipids of the TCA-83 squamous carcinoma cell line and normal gingival fibroblasts was measured. The effects of cerulenin, a specific, potent, noncompetitive inhibitor of fatty acid synthase (FAS), on growth of TCA-83 cells and normal gingival fibroblasts was determined by the MTT method, and the effect of cerulenin on apoptosis was determined by electrophoresis of cellular DNA. Incorporation of [(3)H]acetate into total lipids was significantly higher in TCA-83 cells (68 +/- 12.7 cpm per 2 x 10(5) cells) than in normal gingival fibroblasts (13 +/- 4.2 cpm per 2 x 10(5) cells; P = 0.011). Cerulenin inhibited TCA-83 cell growth in a dose-dependent manner, even at 2.5 microg/ml, a concentration at which normal gingival fibroblasts were not inhibited. After exposure to cerulenin, TCA-83 cells showed typical apoptotic DNA ladders. These results indicate that cerulenin exerts selective cytotoxic effects on squamous carcinoma cells and can induce their apoptosis. These findings suggest that targeting of fatty acid synthesis may be useful in the treatment of squamous cell carcinomas.

Apoptosis↗

Overexpression of DARPP-32 in colorectal adenocarcinoma.

Dopamine and cAMP-regulated phosphoprotein (DARPP)-32 is a phosphoprotein that is centrally involved in dopamine signalling pathways. It may play an important role in gastric tumorigenesis. Our aim is to investigate the expression of DARPP-32 protein in colorectal adenocarcinoma. The expression of DARPP-32 was evaluated by immunohistochemical SABC staining and Western blotting. DARPP-32 was specifically localised in colorectal epithelium. The expression of DARPP-32 in colorectal adenocarcinoma tissues 33/42, 78.57% was higher than that in normal colon epithelial tissues (31/60, 51.67%, p <0.05). There was no significant relationship between the expression of DARPP-32 and the differentiation, metastasis and Dukes' stage of colorectal adenocarcinoma (p >0.05). Both DARPP-32 and its truncated isoform t-DARPP were overexpressed in colorectal adenocarcinoma (t=2.306, p=0.028), while t-DARPP was more frequently detected. These results showed that DARPP-32 may play an important role in the regulation of normal colorectal epithelial biology and carcinogenesis.

Adenocarcinoma↗

An enzymatic assay for metabolites of perfluoro-tagged 5-hydroxytryptophan.

l-5-hydroxytryptophan (5-HTP) with two types of multiple (19)F-atom tags bonded at various positions onto the indole ring (positions 4, 6, or 7) was exposed to aromatic l-amino acid decarboxylase (AADC) in lysates of Escherichia coli JM109 which had been transformed with the plasmid pKKAADCII. Resulting samples were analyzed with HPLC. In the first study, which investigated a straight-chain seven-atom tag, a novel peak, putatively perfluoro-tagged serotonin, was detected. A second study demonstrated that 5-HTP was converted to 5-HT in transformed E.coli lysate but not in untransformed lysate. A third study, investigating a tag with nine fluorine atoms all in the same nuclear environment, identified the isomer serving as the best substrate for AADC. This novel molecule had the tag bonded at the 6 position on the indole ring. Isomers that fit into the active site of AADC are likely to follow the biosynthetic path for serotonin in vivo and are potentially useful in (19)F magnetic resonance spectroscopy studies. The enzymatic assay described here provides an efficient and cost-effective tool for screening new compounds.

5-Hydroxytryptophan↗

High-dose cyclophosphamide with or without etoposide for mobilization of peripheral blood progenitor cells in patients with multiple myeloma: efficacy and toxicity.

The purpose of the study was to examine the yield of CD34(+) cells, response rates, and toxicity of high-dose cyclophosphamide with or without etoposide in patients with multiple myeloma. In total, 77 myeloma patients received either cyclophosphamide 4.5 g/m(2) (n=28) alone or with etoposide 2 g/m(2) (n=49) in a nonrandomized manner, followed by G-CSF 10 microg/kg/day for the purpose of stem cell mobilization. The effects of various factors on CD34(+) cell yield, response rate and engraftment were explored. A median of 22.39 x 10(6) CD34(+) cells/kg were collected on the first day of leukapheresis (range 0.59-114.71 x 10(6)/kg) in 71 (92%) of patients. Greater marrow plasma cell infiltration (P=0.02) or prior radiation therapy (P=0.02) adversely affected CD34(+) cell yield. In total, 45% of patients receiving cyclophosphamide and 56% of those receiving cyclophosphamide/etoposide had at least a minimum response by EBMT criteria. In all, 25% of patients who received cyclophosphamide alone vs 75.5% of patients who received combined chemotherapy required hospitalization mainly for treatment of neutropenic fever. Cyclophosphamide alone is associated with impressive CD34(+) cell yields and clear antimyeloma activity. The addition of etoposide resulted in increased toxicity without significant improvement in CD34(+) cell yield or response rates.

Adult↗

Autologous stem cell transplantation followed by consolidation chemotherapy for relapsed or refractory Hodgkin's lymphoma.

Relapse remains a major cause of treatment failure after autotransplantation (auto-PBSCT) for Hodgkin's disease (HD). The administration of non-crossresistant therapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after auto-PBSCT in 37 patients with relapsed or refractory HD. Patients received high-dose gemcitabine-BCNU-melphalan and auto-PBSCT followed by involved-field radiation and up to four cycles of the DCEP-G regimen, which consisted of dexamethasone, cyclophosphamide, etoposide, cisplatin, gemcitabine given at 3 and 9 months post transplant alternating with a second regimen (DPP) of dexamethasone, cisplatin, paclitaxel at 6 and 12 months post transplant. The probabilities of event-free survival (EFS) and overall survival (OS) at 2.5 years were 59% (95% CI=42-76%) and 86% (95% CI=71-99%), respectively. In all, 17 patients received 54 courses of CC and 15 were surviving event free (2.5 years, EFS=87%). There were no treatment-related deaths during or after the CC phase. Post-transplant CC is feasible and well tolerated. The impact of this approach on EFS should be evaluated in a larger, randomized study.

Adolescent↗

Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat.

We examined the hypothesis that activation of the apoptosis cascade occurs relatively early in diabetes mellitus affecting three distinct neuronal populations that are involved in regulating gut function: (i) dorsal root ganglion (DRG), (ii) vagus nodose ganglion and (iii) colon myenteric plexus. A validated streptozotocin-induced diabetic rat model and age-matched healthy controls were studied. After 4-8 weeks of diabetes the animals were anaesthetized, fixed in situ and the relevant tissues removed. After 1 month of diabetes some animals were treated with insulin for 2 weeks to restore euglycaemia. Apoptosis was measured using immunohistochemical detection of activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)-positive cells in adjacent sections in neurones (PGP 9.5-positive cells). The level of apoptosis was confirmed using double-label assessment of caspase-3 and TUNEL in DRG preparations. Caspase-3 immunoreactive neurones demonstrated a range in staining intensity. When all grades of staining were included, 6-8% of the DRG, nodose ganglia and myenteric neurones were immunoreactive in the preparations from diabetic rats compared with 0.2-0.5% in controls. Neurones staining positive for both caspase-3 and TUNEL accounted for 1-2% of the total neuronal population in all three preparations in diabetic rats compared with 0.1-0.2% in controls (P < 0.05). Insulin treatment reversed the percentage of TUNEL-positive neurones in diabetic rats to control levels. Activation of the apoptosis cascade occurs relatively early in diabetic autonomic neuropathy and may contribute to the pathophysiology of this disorder.

Animals↗

Enzymatic assay for perfluoro-tagged metabolites of l-DOPA using crude lysate from E. coli transformed with pKKAADCII.

Isomers of l-DOPA and dopamine with a nine-atom 19F atom tag were exposed to aromatic acid decarboxylase (AADC) in the lysate of Escherichia coli JM109 that had been transformed with the plasmid pKKAADCII. The resulting samples were analyzed with HPLC. The first study investigated the conversion of the tagged l-DOPA into tagged dopamine, using the tagged dopamine as a standard. A second study was undertaken to identify the source of peaks seen in the enzymatic assays. l-DOPA with the tag bonded at position 5 served as the best substrate for AADC. Isomers that fit into the active site of AADC are likely to follow the biosynthetic path for dopamine in vivo and are potentially useful in magnetic resonance studies. The enzymatic assay described here provides an efficient and cost-effective tool for screening new compounds for use in the fluorine imaging of neural pathways.

Aromatic-L-Amino-Acid Decarboxylases↗

Hyaluronate for temporomandibular joint disorders.

BACKGROUND: Temporomandibular joint disorders (TMD) refer to a group of heterogeneous pain and dysfunction conditions involving the masticatory system, reducing life quality of the sufferers. Intra-articular injection of hyaluronate for TMD has been used for nearly two decades but the clinical effectiveness of the agent has not been summarized in the form of a systematic review. OBJECTIVES: To assess the effectiveness of intra-articular injection of hyaluronate both alone and in combination with other remedies on temporomandibular joint disorders. SEARCH STRATEGY: Intensive electronic and handsearches were carried out. The Oral Health Group's Trials Register (September 2001), The Cochrane Library CENTRAL database (Issue 3, 2001), MEDLINE (1966- May 2001), PubMed ( up to March 2002), EMBASE (1974 - August 2001), SIGLE (1980 - December 2001), CBMdisc (1983 - July 2001, in Chinese) and Chinese Medical Library were searched. All the Chinese professional journals in the oral health field were handsearched and conference proceedings consulted. There was no language restriction. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials (RCTs), with single or double blind, design testing the effectiveness of hyaluronate for patients with temporomandibular joint disorders. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, and three reviewers independently assessed the quality of included studies. The first authors of the selected articles were contacted for additional information. MAIN RESULTS: Seven studies were included in the review. Three studies, including 109 patients with temporomandibular disorders, compared hyaluronate with placebo. Long term effects (three months or longer) are in favour of hyaluronate for the improvement of clinical signs/overall improvement of TMD (RR=1.71, 95%CI: 1.05, 2.77) from two of the studies (n=71). However, this conclusion was not stable enough at sensitivity analysis. Three studies provided data from 124 patients for the comparison of hyaluronate with glucocorticoids (one study also included a placebo group). Hyaluronate had the same short term and long term effects on the improvement of symptoms, clinical signs or overall conditions of the disorders as glucocorticoids. When comparing the effect of arthroscopy or arthrocentesis with and without hyaluronate, results were inconsistent. Hyaluronate had a potential in improving arthroscopic evaluation scores. Mild and transient adverse reactions such as discomfort or pain at the injection site were reported in the hyaluronate groups. No quality of life data were reported REVIEWER'S CONCLUSIONS: There is insufficient, consistent evidence to either support or refute the use of hyaluronate for treating patients with TMD. Further high quality RCTs of hyaluronate need to be conducted before firm conclusions with regard to its effectiveness can be drawn.

Glucocorticoids↗

Influence of preapheresis clinical factors on the efficiency of CD34+ cell collection by large-volume apheresis.

We evaluated 120 leukapheresis procedures (93 patients), in order to detect clinical factors that influence the efficiency of CD34+ collection using Cobe Spectra trade mark cell separators. Hematocrit was >27% and platelet count >30 000/microl in >95% of patients. Platelet transfusions were given if the postprocedure count was &<20 000/microl. Multiple regression analysis was used to analyze putative factors, and a predictive equation defined by stepwise regression modeling. The mean efficiency was 0.59 (s.d. 0.27). Sex (M>F; P=0.01), the volume processed (inversely; P=0.01) and CD34+ cell count (inversely; P=0.04) were associated with efficiency, whereas hematocrit, platelet or leukocyte count, catheter type and patient weight were not. The effect size for predictive factors was small (R(2)=0.21). Adverse events were limited to hypocalcemia. We conclude that female sex, volume processed and CD34+ cell count adversely influence the efficiency of CD34+ cell leukapheresis. However, the impact of volume and CD34+ cell count is small, and likely to be offset by the influence of these same factors on overall yield. Leukapheresis appears to be safe and efficient for autologous blood and marrow transplantation patients with hematocrit >27% and platelet count >30 000/microl.

Antigens, CD34↗