Biomedical subjects

X Xie

Publications and source records attributed to X Xie.

At least 73 records · Page 4Linked to original sources

PubMed2000

Combined gene therapy with suicide gene and interleukin-12 is more efficient than therapy with one gene alone in a murine model of hepatocellular carcinoma.

BACKGROUND/AIMS: Gene therapy has emerged as a new form of treatment for unresectable hepatocellular carcinoma (HCC). We evaluate here the effect of IL-12 and the suicide gene thymidine kinase as single agents and in combination to treat experimental liver cancer. METHODS: Recombinant adenoviruses expressing mouse interleukin-12 (AdCMVIL-12) or thymidine kinase of herpes simplex virus (AdCMVtk) or lacZ reporter gene (AdCMVlacZ) were constructed. The efficacy of the treatment was evaluated in a murine HCC model based on subcutaneous implantation of liver tumor cells (BNL). RESULTS: Transduction of BNL cells after in vitro infection with AdCMVlacZ was very low at multiplicity of infection (moi) of 100, whereas 10-15% of cells were transduced when using moi 1,000. Similarly, production of IL-12 was detectable only in BNL cells infected with AdCMVIL-12 at moi 1,000. In vitro infection of BNL cells with AdCMVIL-12 at moi 100 did not abrogate tumorigenicity, whereas moi 1,000 resulted in inhibition of tumor growth in all mice as well as in abrogation of tumor formation in 3 out of 8 animals. In vivo studies showed that intratumor injection of AdCMVIL-12 induced a dose-dependent effect on tumor regression. However, none of the animals exhibited complete tumor elimination with this treatment. We observed that suppression of tumor growth was more intense in animals treated with the combination of AdCMVIL-12 plus AdCMVtk than in animals which received AdCMVtk or AdCMVIL-12 alone. The combined treatment resulted in a significant increase in animal survival, and 25% of treated animals were free of tumor for over 100 days without recurrence of the disease. CONCLUSIONS: Combination of AdCMVIL-12 and AdCMVtk is more efficient than either of the two vectors alone for the treatment of the murine model of HCC used in this study.

Adenoviridae↗

PubMed2000

Effect of bile and pancreatic juice on adenoviral-mediated gene delivery: implications on the feasibility of gene delivery through ERCP.

Current research in gene delivery to the liver is focused on the intravenous, intraarterial, intraportal, or intratumoral route. Another possible route for gene delivery is via the common bile duct through endoscopic retrograde cholangiopancreatography (ERCP). Whether bile and pancreatic juice have any effect on gene delivery is not established. To evaluate the effect of bile and pancreatic juice on adenoviral-mediated gene delivery, liver and pancreatic cell lines were infected with a recombinant adenovirus expressing an E. coli beta-galactosidase gene under the control of a cytomegalovirus promoter (rAdCMVpLacZ) in the absence or presence of various concentrations of bile and pancreatic juice. The proportion of cells infected was evaluated through X-gal staining. The toxicity of bile and pancreatic juice was also evaluated through cell morphology and detachment. Bile appeared to induce significant cytotoxicity in HepG2 and Huh7 cells (50% viability with 15 min of incubation). Neither bile nor pancreatic juice affected transgene expression. In the absence of bile/pancreatic juice, HepG2 (15-25%) and PANC-1 cells (10-18%) were less susceptible to rAdCMVpLacZ compared to Huh7 cells (75-84%, vs HepG2, P < 0.001) and BxPc-3 (82-95%, vs PANC-1, P < 0.001) at a multiplicity of infection (MOI) of 5. Bile reduced the transduction efficiency, but 5-10% HepG2 and 5-42% of Huh7 cells were still transduced in the presence of 80% bile for up to 10 min. Adenoviral-mediated gene delivery was reduced in the presence of pancreatic juice with a low multiplicity of infection (MOI of 5), but this effect was negated with an MOI of 50. These data provide encouragement to develop adenoviral-mediated gene delivery through ERCP.

Adenoviridae↗

PubMed2000

Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two mechanisms.

The influence of GM1 on the neuritogenic phase of neuronal differentiation has been highlighted in recent reports showing upregulation of this ganglioside in the plasma and nuclear membranes concomitant with axonogenesis. These changes are accompanied by alterations in Ca2+ flux which constitute an essential component of the signaling mechanism for axon outgrowth. This study examines 2 distinct mechanisms of induced neurite outgrowth involving plasma membrane GM1, as expressed in 3 neuroblastoma cell lines. Growth of Neuro-2a and NG108-15 cells in the presence of neuraminidase (N'ase), an enzyme that increases the cell surface content of GM1, caused prolific outgrowth of neurites which, in the case of Neuro-2a, could be blocked by the B subunit of cholera toxin (Ctx B) which binds specifically to GM1; however, the latter agent applied to NG108-15 cells proved neuritogenic and potentiated the effect of N'ase. With N18 cells, the combination was also neuritogenic as was Ctx B alone, whereas N'ase by itself had no effect. Neurite outgrowth correlated with influx of extracellular Ca2+, determined with fura-2. Treatment of NG108-15 and N18 cells with Ctx B alone caused modest but persistent elevation of intracellular Ca2+ while a more pronounced increase occurred with the combination Ctx B + N'ase. Treatment with N'ase alone also caused modest but prolonged elevation of intracellular Ca2+ in NG108-15 and Neuro-2a but not N18; in the case of Neuro-2a this effect was blocked by Ctx B. Neuro-2a and N18 thus possess 2 distinctly different mechanisms for neuritogenesis based on Ca2+ modulation by plasma membrane GM1, while NG108-15 cells show both capabilities. The neurites stimulated by N'ase + Ctx B treatment of N18 cells were shown to have axonal character, as previously demonstrated for NG108-15 cells stimulated in this manner and for Neuro-2a cells stimulated by N'ase alone.

Cell Membrane↗

PubMed2000

Cardiolipin provides specificity for targeting of tBid to mitochondria.

Recent evidence supports the theory that mitochondrial homeostasis is the key regulatory step in apoptosis through the actions of members of the Bcl-2 family. Pro-apoptotic members of the family, such as Bax, Bad and Bid, can induce the loss of outer-membrane integrity with subsequent redistribution of pro-apoptotic proteins such as cytochrome c that are normally located in the intermembrane spaces of mitochondria. The anti-apoptotic members of the family, such as Bcl-2 and Bcl-XL, protect the integrity of the mitochondrion and prevent the release of death-inducing factors. Bid normally exists in an inactive state in the cytosol, but after cleavage by caspase 8, the carboxy-terminal portion (tBid) moves from cytosol to mitochondria, where it induces release of cytochrome c. Here we address the question of what mediates specific targeting of tBid to the mitochondria. We provide evidence that cardiolipin, which is present in mitochondrial membranes, mediates the targeting of tBid to mitochondria through a previously unknown three-helix domain in tBid. These findings implicate cardiolipin in the pathway for cytochrome c release.

Apoptosis↗

PubMed2000

Erythropoietin receptors that signal through Stat5 or Stat3 support fetal liver and adult erythropoiesis: lack of specificity of stat signals during red blood cell development.

Erythropoietin (Epo) is essential for formation of mature red blood cells (RBC). However, the function of Epo receptor (EpoR)-dependent signaling pathways in the regulation of erythropoiesis remains unclear. To determine whether specific Stat signals are required for RBC development, we changed the Stat signaling specificity of the EpoR. The wild-type EpoR activates only Stat5. Thus, we substituted the major Stat5 binding sites (residues 343 and 401) in the EpoR cytoplasmic region with the Stat3 binding/activation motif from gp130. We demonstrated that activated EpoRs containing a single substitution stimulate Stat5 and Stat3, whereas an EpoR with both substitutions stimulates Stat3 but not Stat5. We then determined the ability of these receptors to support fetal liver and adult erythropoiesis. Our results show that erythropoiesis is stimulated by EpoRs that activate Stat5, both Stat5 and Stat3, or Stat3 in place of Stat5. These findings demonstrate that the specificity of EpoR Stat signaling is not essential for RBC development.

Animals↗

PubMed2000

A randomized, controlled crossover trial of two oral appliances for sleep apnea treatment.

Our purpose was to compare the effectiveness and side effects of a novel, single-piece mandibular advancement device (OSA-Monobloc) for sleep apnea therapy with those of a two-piece appliance with lateral Herbst attachments (OSA-Herbst) as used in previous studies. An OSA-Monobloc and an OSA-Herbst with equal protrusion were fitted in 24 obstructive sleep apnea patients unable to use continuous positive airway pressure (CPAP) therapy. After an adaptation period of 156 +/- 14 d (mean +/- SE), patients used the OSA-Monobloc, the OSA-Herbst, and no appliance in random order, using each appliance for 1 wk. Symptom scores were recorded and sleep studies were done at the end of each week. Several symptom scores were significantly improved with both appliances, but to a greater degree with the OSA-Monobloc. Epworth Sleepiness Scale scores were 8.8 +/- 0.7 with the OSA-Herbst, and 8.6 +/- 0.8 with the OSA-Monobloc devices, and 13.1 +/- 0.9 without therapy (p < 0.05 versus both appliances). The apnea/hypopnea index was 8.7 +/- 1.5/h with the OSA-Herbst and 7.9 +/- 1.6/h with the OSA-Monobloc device, and 22.6 +/- 3.1/h without therapy (p < 0.05 versus both appliances). Side effects were mild and of equal prevalence with both appliances. Fifteen patients preferred the OSA-Monobloc, eight patients had no preference, and one patient preferred the OSA-Herbst device (p < 0.008 versus OSA-Monobloc). We conclude that both the OSA-Herbst and the OSA-Monobloc are effective therapeutic devices for sleep apnea. The OSA-Monobloc relieved symptoms to a greater extent than the OSA-Herbst, and was preferred by the majority of patients on the basis of its simple application.

Cross-Over Studies↗

PubMed2000

The direct and indirect relationships between alcohol prevention measures and alcoholic liver cirrhosis mortality.

OBJECTIVE: The objective of this article is to investigate direct and indirect relationships between prevention measures and alcoholic liver cirrhosis mortality in Canadian provinces from 1968 to 1986. METHOD: The data base that was assembled included alcoholic cirrhosis mortality rates, alcohol availability measures (rate of licensed premises, year in which the legal drinking age was reduced), per capita consumption of alcohol, rates of AA members and groups, and economic and demographic measures. This article develops a two-equation analytic model based on the availability theory of alcohol problems and prevention (Single, 1988). The distinction between direct and indirect effects of prevention measures can be made explicitly with this model. RESULTS: Alcohol availability measures, but not AA measures, had a significant direct potential impact on alcohol consumption. AA measures had a significant direct relationship to cirrhosis mortality rates. Alcohol consumption also had a significant direct relationship to cirrhosis mortality, and alcohol availability measures had an important indirect relationship through their influence on per capita alcohol consumption. CONCLUSIONS: While these observations need to be interpreted cautiously, the two-equation model shows promise as an approach to understanding direct and indirect influences on alcohol problems. As expected, AA measures and per capita alcohol consumption demonstrated significant direct relationship to cirrhosis mortality. In addition, important indirect influences of drinking-age changes and rates of licensed premises on cirrhosis mortality were observed through their relationships to per capita alcohol consumption.

Adult↗

PubMed2000

[Cytogenetics and clinical studies of hematologic malignancies with 11q23 abnormalities in China].

OBJECTIVE: To evaluate the association between 11q23 abnormalities and the clinical, hematologic, prognostic aspects of hematologic malignancies. METHODS: A total of 6000 cases of hematologic malignancies from our hospital and near regions in China were investigated between October 1985 and November 1998. Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding technique and expressed according to ISCN(1995). RESULTS: 11q23 abnormalities were found in 28 of 6000 cases with hematologic malignancies(0.47%). It may be separated into seven cytonetic categories: t(4;11)(q21;q23)(ten cases), t(11;19)(q23;p13)(five cases), t(9;11)(p12;q23)(two cases), t(10;11)(p15;q23)(two cases), t(6;11)(q27;q23) (one case), del(11)(q23)(seven cases), and t(11;?)(q23;?)(one case). The diagnoses included acute myeloid leukemia in 14 cases (M(2a), three; M(4), two; M(5a), one; M(5b), eight), acute lymphoblastic leukemia(ALL) in 10 cases, myelodysplastic syndrome in three cases and malignant histiocytosis in one case. All 10 cases with t(4;11) anomaly were ALL. Follow-up data were available for 22 of them. Their median survival was 113 days. The patients may be grouped according to the presence or absence of additional abnormalities and/or normal karyotype. The median survival was 75 days for five patients with 11q23 anomaly only, 18 days for two patients with 11q23 and additional abnormalities, 135 days for 10 patients with 11q23 anomaly, additional abnormalities and normal karyotype, and 150 days for 5 patients with 11q23 anomaly and normal karyotype. CONCLUSION: 11q23 abnormalities were mainly seen in ALL and acute monocytic leukemia. Their prognosis was very poor. Both additional abnormalities and lack of normal karyotype had adverse effects on the survival of patients. Thus, they represent a unique clinical-cytogenetic association. 11q23 abnormality; hematologic malignancy; acute monocytic leukemia; acute lymphoblastic leukemia; prognosis

Adolescent↗

PubMed2000

Secondary near-pentaploidy and/or near-tetraploidy characterized by the duplication of 8;21 translocation in the M2 subtype of acute myeloid leukemia.

Hyperploidy, especially near-tetraploidy, is rare in acute myeloid leukemia (AML). We report 2 cases with secondary hyperploidy characterized by double 8;21 translocations. Morphologic observation of bone marrow smears revealed numerous giant blasts in both cases. Chromosome analyses with R-banding technique showed a karyotype of 46,XX,t(8;21)(2%)/92,XXXX, add(7)(q31)x2,t(8;21)x2(7%)/100-117,XXX,-X,-X,-1,+4,+4,-7,+add(7)(q31)x3 , t(8;21)x2,+der(21)t(8;21),+22(90.6%)/46,XX(0.3%) in case 1 and a karyotype of 45,X,-Y,t(8;21)(15%)/90,XX,-Y,-Y,t(8;21)x2(80%)/46,XY(5%) in case 2. DNA ploidy analyses by flow cytometry showed triple peaks (diploid, tetraploid [DI 2.09] and near-pentaploid [DI 2.59]) in case 1, and double peaks (diploid and near-tetraploid [DI 2.07]) in case 2. Reverse-transcriptase polymerase chain reaction detected an AML1/ETO fusion transcript (152 bp) in both cases. This paper brings the total number of cases of secondary hyperploid t(8;21) AML to 6 and further emphasizes a correlation between hyperploidy and t(8;21) translocation.

Bone Marrow↗

PubMed2000

[Study on 515 anti-tumor recipe in inducing leukemic HL-60 cells apoptosis].

OBJECTIVE: To observe the efficacy of 515 anti-tumor recipe on inducing human myeloid leukemic HL-60 cells apoptosis. METHODS: The morphological change of apoptotic cells was observed by light microscopy and transmission electromicroscopy (TEM), and flow cytometry and TUNEL reaction to further confirm the apoptosis of HL-60 cells. RESULTS: Typical apoptosis appeared such as marginal nuclei, chromatin condensation and nuclear fragmentation could be seen by light microscopy and TEM. The drug concentration was between 0.013-0.04 g/ml. The apoptosis rate is 30% in 0.04 g/ml group at the 72nd hour, but it was only 0.8% in the control group at the same time (P < 0.01). CONCLUSIONS: The 515 anti-tumor recipe can induce apoptosis in HL-60 cells. The apoptosis rate increased as the time extended. There was an enhanced efficiency of apoptosis in a dose-dependent manner.

Antineoplastic Agents, Phytogenic↗

PubMed2000

[The expression of glial cell derived neurotrophic factor and its receptor GDNFR-alpha and GDNFR-beta mRNA in spinal cord, brainstem and frontal cortex during morphine withdrawal in rats].

OBJECTIVE: To investigate the expression of glial cell derived neurotrophic factor (GDNF) and its receptor GDNFR-alpha (GFRalpha-1) and GDNFR-beta (Ret) genes and the effects of muscarinic receptor antagonists, NMDA receptor antagonist, inhibitor of nitric oxide synthase on the expression of these genes in the spinal cord, brainstem and frontal cortex during morphine withdrawal, and to observe the effects of GDNF antisense oligoneucleotide (i.c.v) on the morphine withdrawal symptoms in rats. METHODS: The levels of GDNF, GDNFR-alpha and GDNFR-beta mRNA were assayed by reverse transcription polymerase chain reaction (RT-PCR) with the beta-actin mRNA as an internal control. RESULTS: The GDNF mRNA levels were increased, and GDNFR-alpha and GDNFR-beta mRNA levels was slightly increased in the spinal cord and brainstem during morphine dependence. These genes were decreased at 1 h, increased at 2 h after administration of naloxone in morphine dependent rats. While the GDNF, GDNFR-alpha and GDNFR-beta levels in the frontal cortex were increased significantly at 1, 2 and 4 h after the injection of naloxone during morphine withdrawal. The pre-treatment with L-N-nitric arginine methylester (10 mg/kg), the expressions of GDNF and GDNFR-beta in the spinal cord, both GDNFR-alpha and GDNFR-beta in the frontal cortex were decreased. The expressions of both GDNF and GDNFR-alpha in the frontal cortex were decreased by treatment with MK801 (0.5 mg/kg), and the expressions of GDNF in both the stem and cortex, and GDNFR-beta in the brainstem decreased by treatment with the methyl-scopolamine (0.5 mg/kg). The beta-actin mRNA levels were not different in each group. Moreover, the morphine withdrawal symptoms were attenuated by intracerebroven tricular injection of GDNF antisense oligoneucleotide in 6 hour and 24 hour before naloxone administration in morphine dependent rats. CONCLUSION: The results not only provide direct evidence that the expressions of GDNF and its receptors mRNA in glial cells play an important role in mediating the process of morphine dependence and may be account for the long-term neuro-adaptation associated with morphine dependence, but also suggest that muscarinic receptor, NMDA receptor and nitric oxide pathways may be involved in the expression of GDNF and GDNF receptor genes during morphine withdrawal.

Animals↗

PubMed2000

[The relationship between effects and radiation doses of intra-arterial phosphorus-32 glass microspheres embolization therapy for patients with advanced liver cancer].

OBJECTIVE: To evaluate the relationship between effects and internal radiation of phosphorus-32 glass microspheres embolization therapy for liver cancer patients. METHODS: From 1994 to 1998, 44 patients with unresectable liver cancer received intra-arterial radio-embolization therapy using (32)P-GMS. Preoperative and postoperative function and energy level of the liver were tested by liver function test and arterial blood ketone body ratio (AKBR). CT, single photon emission computer tomography (SPECT), and AFP were used to judge the effect of the therapy; multivariate analysis was made. RESULTS: In the moderate dose group, low incidence of complication, high tumor shrinking rate and AFP decreasing rate, and long-term survival rate were observed. In the larger dose group, high incidence of liver failure, high tumor shrinking rate and AFP decreasing rate, and long-term survival rate were also observed. In the low dose group, low incidence of complication, but low tumor shrinking rate and AFP decreasing rate and long-term survival rate were not observed. CONCLUSIONS: The reasonable radiation doses for liver cancer patients may be about 30 Gy; if liver cirrhosis is serious, the doses can be reduced.

Adult↗

PubMed2000

[Chromosome t (4; 11) acute lymphoblastic leukemia: an analysis of 10 cases].

OBJECTIVE: To characterize morphologically, immunophenotypically, cytogenetically and clinically the acute lymphoblastic leukemia (ALL) with t (4; 11) (q21; q23). METHODS: Ten cases of t (4; 11) ALL were reported. Of them, eight patients were de novo and two relapsed. The patients were treated with combination chemotherapy of DOPL or VP regimen. Immunophenotypic analysis was performed by flow cytometry in seven cases. Cytogenetic analysis was performed using bone marrow cells prepared directly and/or after 24h culture (case 7 using peripheral blood). RHG banding was used for karyotypic analysis. RESULTS: Ten (3.5%) of 285 ALL patients were found to be t (4; 11) ALL. In these 10 patients, increased WBC (> 100 x 10(9)/L) was found in 6 cases. Liver, spleen and/or lymph nodes were involved in all. t (4; 11) was detected as a single abnormality in 5 karyotypes whereas the other 5 showed additional aberration besides t (4; 11). Six patients were CD(19) (+), five were CD(22) (+) and one was HLA-DR (+), CD(5) (+), supporting that most cases of t (4; 11) ALL were B cell origin. Median survival time was 5.5 months in the present series. CONCLUSION: t (4; 11) ALL was a subtype with unique clinical and cytogenetic features, and had a poor prognosis.

Adolescent↗

PubMed2000

[Acute myeloid leukemia M2and t (8; 19) (q22; q13)].

OBJECTIVE: Report for the first time of two cases of acute myeloid leukemia (AML) M(2) with t (8; 19) (q22; q13). METHODS: Chromosome specimens were prepared by short-term culture of bone marrow cells and karyotype analyses were carried out using R-and G-banding techniques. Immunophenotyping of the blast cells was analyzed by flow cytometry with a panel of monoclonal antibodies. AML1/ETO fusion gene was tested by "nested" reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Karyotype analyses showed 46, XX, t (8; 19) (q22; q13) [28]/46, XX [2] in case 1 and t (8; 19) (q22; q13), del (9) (q12q22) [23]/46, XY [2] in case 2. In case 2, the blast cells expressed CD(13) (38.8%), CD(33) (31.8%), CD(34) (80.9%), and CD(19) (63.9%) and RT-PCR assay revealed no AML1/ETO fusion gene transcript. CONCLUSION: t (8; 19) (q22; q13) is a variant form of t (8; 21) (q22; q22). Its molecular entity remains to be elucidate.

Adolescent↗

PubMed2000

[Detection of trisomy 8 with interphase fluorescence in situ hybridization in myelodysplastic syndromes].

OBJECTIVE: To explore the value of interphase fluorescence in situ hybridization (FISH) in the detection of trisomy 8 in myelodysplastic syndromes (MDS). METHODS: Conventional cytogenetics (CC) and interphase FISH using SpectrumGreen labelled chromosome 8 centromere specific probe were simultaneously carried out to detect trisomy 8 in 69 MDS and 6 normal individuals. RESULTS: Two hundred interphase cells were counted and cells with three green hybridization spots > 3% was assigned. Eleven cases displayed trisomy 8 by CC and were confirmed in 10 by FISH. In 7 cases, the percentage of trisomy 8 cells was significantly lower by FISH than by CC. Seven cases displayed trisomy 8 by FISH in 58 cases who did not show trisomy 8 by CC. Of the 7 cases, two had 2 and 3 marker chromosomes respectively, 4 had normal karyotypes. CONCLUSIONS: Interphase FISH was a useful method for the detection of trisomy 8 in MDS, especially in patients with normal karyotype or marker chromosome. It was a important complement to CC.

Adult↗

PubMed2000

[Determination of the composition distribution of polymer blend films by using microscopic FTIR].

In this paper, PS/PC blend film (about 120 microns thick) and PS/PMMA (about 90 microns thick) blend film were prepared by evaporation the solvent very slowly from polymer blend solution. Different FTIR methods were used to determine the composition distribution along the vertical direction of the films. PS/PC film was firstly sectioned by ultramicrotomy, then the vertical section was measured to determine the composition of every 16 microns width unit from the surface-side to the bottom-side by Microscopic transmission-FTIR. The results showed that the concentration of PS was significantly greater in the vicinity of the surface of the film than that in the bulk, i.e., the component of PS enriched to the surface. Focusing the reflecting infrared light on different layer of the film, we can detect the composition of the different depth region in the PS/PMMA blend film. As the result, PMMA aggregated to the bottom of the film. It was considered that this effect was related to the different affinity and wetting prosperities of the blend component to the substrate or air.

English Abstract↗

PubMed1999

Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis.

Animal cells divide into two daughter cells by the formation of an actomyosin-based contractile ring through a process called cytokinesis. Although many of the structural elements of cytokinesis have been identified, little is known about the signaling pathways and molecular mechanisms underlying this process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTPases, RhoA, Rac1, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other known guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nuclear localization in interphase, spreads throughout the cytoplasm in prometaphase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH(2)-terminal domain required for the midbody localization but lacking the COOH-terminal catalytic domain, strongly inhibits cytokinesis. Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis. These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division.

Antibodies↗

PubMed1999

Erythropoietin receptor mutations associated with familial erythrocytosis cause hypersensitivity to erythropoietin in the heterozygous state.

Inherited mutations in the erythropoietin receptor (EPOR) causing premature termination of the receptor cytoplasmic region are associated with dominant familial erythrocytosis (FE), a benign clinical condition characterized by hypersensitivity of erythroid progenitor cells to EPO and low serum EPO (S-EPO) levels. We describe a Swedish family with dominant FE in which erythrocytosis segregates with a new truncation in the negative control domain of the EPOR. We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5. These results demonstrate that FE is caused by hyperresponsiveness of receptor-mediated signaling pathways and that this is dominant with respect to WT EPOR signaling.

DNA-Binding Proteins↗