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Biomedical subjects

G He

Publications and source records attributed to G He.

At least 55 records · Page 3Linked to original sources

[Sequential intensified immunosuppressive therapy combining with hematopoietic growth factors in the treatment of severe aplastic anemia].

OBJECTIVE: To explore more effective regimen for reducing early mortality of severe aplastic anemia (SAA) and improving therapeutic effectiveness. METHODS: Antilymphocyte globulin/antithymocyte globulin (ALG/ATG) and cyclosporine A (CsA) (sequential intensified immunosuppressive therapy, SIIST), with or without hematopoietic growth factors (HGFs) were administered to 73 SAA patients in a prospective randomized clinical trial to test the effectiveness of the addition of HGFs for the patients. RESULTS: The response rate of SIIST with HGFs group was significantly higher than that of SIIST alone group (89.2% vs 63.9%), with lower rates of early infection (24.3% vs 55.3%) and mortality (4.0% vs 16.7%), shorter duration of cytopenia and blood transfusion dependence and faster recovery of bone marrow hematopoiesis. The addition of HGFs to SIIST was tolerated well in all patients. There was no difference in the treatment outcome of the two groups with GM-CSF plus Epo or G-CSF plus Epo. CONCLUSION: The use of HGFs in combination with SIIST could reduce early infection and mortality rates and, therefore, improve the response rates in SAA patients.

Adolescent↗

[Study on the transformation from myelodysplastic syndromes into acute leukemias].

OBJECTIVE: To study the patterns of transformation from myelodysplastic syndromes (MDS) into acute leukemias (AL). METHODS: Leukemic transformation of MDS patients was dynamically followed up and the clinical manifestations, peripheral blood and bone marrow pictures, karyotypes, immunophenotypes, response to treatment and prognosis of post MDS acute leukemia (postMDS-AL) were observed. RESULTS: During the past eight year and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia with a median interval of 5 (1 - 21) months. There were no significant differences among the rates of leukemia from RA, RAEB and RAEB-t groups. The transformation was developed either gradually or rapidly. There were five parameters related to the leukemic transformation: under 40 years of age, pancytopenia, more than 0.15 blasts in bone marrow, at least two types of abnormal karyotype and combined chemotherapy. All of the 21 post MDS-AL were acute myeloid leukemia (AML); and most of them were M(2), M(4) and M(5). Two (9.52%) post MDS-AML developed extramedullary infiltration. Leukopenia was found in 47.62% of patients. Two third of the patients, whose bone marrows were generally hypercellular, showed neutropenias. After evolving into AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD(33) (49.83 +/- 24.50)%, CD(13) (36.38 +/- 33.84)%, monocytic antigen CD(14) (38.50 +/- 24.60)%, and stem cell marker CD(34) (34.67 +/- 30.59)% were found on bone marrow mononuclear cells of post MDS-AML cases. In some cases, lymphoid antigens, such as CD(5), CD(7), CD(9) and CD(19) were coexisted with myeloid antigens. A low complete remission rate (31.25%) and short survival duration with median survival of 6 (1 - 28) months were found in patients with post MDS-AML treated by induction therapy. CONCLUSION: MDS was at high risk of evolving into AML, either gradually or rapidly. Patients with post MDS-AML had specific biologic features and worse prognoses.

Acute Disease↗

[A comparison of the kinetic characters of NT-3, NT-4 and BDNF retrogradely transported in facial nerve].

OBJECTIVE: To compare the kinetic characters of retrograde transport of neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) and brain-derived neurotrophin factor (BDNF) in facial nerve. METHODS: Radioactive tracer technique was used. After one lateral facial nerve trunk of adult rabbit was transected, a silicone chamber was inserted between the stumps, and 3.7 MBq of 125I-NT-3 or 125I-NT-4 or 125I-BDNF or 125I-HSA was administered into the chamber. At different time-points after injection, the facial nerve trunk and facial nerve motor neurone of brain-stem were collected and the uptake rates were measured. The kinetic parameters of each labeled compound were calculated using 3P87 program of kinetics. RESULTS: The transport amount of neurotrophin retrogradely transported by facial nerve is NT-3 > BDNF > NT-4 (P < 0.05), the transport rate is NT-4 > NT-3 > BDNF (P < 0.05). CONCLUSION: The findings could serve as the kinetic characters of retrograde transport of neurotrophins.

Animals↗

[A study of on the transport of neurotrophin-4 in facial nerve].

OBJECTIVE: This is a study on the transport information of neurotrophin-4 (NT-4) in facial nerve using radioactive tracer technique. METHODS: After one lateral facial nerve trunk of adult rabbit was transected, a silicone chamber was inserted between the stumps, and 7.4 MBq of 131I-NT-4 was administered into the chamber. At the distinct moment of post-injection, the head of one rabbit was imaged at coronary position, the bilateral facial nerve trunk and brain-stem of the others were collected and counted respectively. After 1 mg of brain-derived neurotrophic factor (BDNF) and 7.4 MBq of 131I-NT-4 were administered into the chamber of one rabbit, the rabbit was imaged at coronary position of head at distinct moment. RESULTS: 5.08% of 131I-NT-4 was transported into facial nerve trunk at 4 h of post-injection. 131I-NT-4 presented high peak in facial nerve trunk during the period of 8, 12 h, the peak values were 20.58% and 22.74% respectively. 34.75% and 45.57% of 131I-NT-4 were transported into the brain-stem of experimental side at 8 h and 12 h respectively. The transport of 131I-NT-4 was markedly restrained by BDNF in facial nerve. CONCLUSION: NT-4 displays a receptor-mediated retrograde transport in facial nerve.

Animals↗

[A comparative observation preoperatively and postoperatively of nasal mucosa in chronic sinusitis treated with endoscopic sinus surgery].

OBJECTIVES: To study morphologic and functional mucosal changes both preoperatively and postoperatively in chronic sinusitis (CS) treated with endoscopic sinus surgery (ESS). METHODS: 1. Saccharin test and light microscopic examination of nasal mucosa were taken preoperatively and postoperatively in 32 cases with CS and in 28 normal subjects as control. 2. Scanning and transmission electron microscopy were performed to exam preoperatively and postoperatively the nasal mucosa in 10 cases with CS and in 2 normal cases as control. RESULTS: 1. The preoperative saccharin test time (STT) in patients with CS was significantly longer than that in the controls (P < 0.001), and the postoperative STT became significantly shorter than that in preoperative one(P < 0.001). 2. The pathological changes of nasal mucosa, such as infiltration in inflammatory cells, edema, polypoid formations and pathologic glands were observed preoperatively. The infiltration in inflammatory cells, edema and polypoid formations were significantly released (P < 0.01) at four months after operation, and there was no significant difference comparing with the controls (P > 0.05). However, the pathologic glands were not reduced even after four months postoperatively. 3. The examination of electron microscopy demonstrated that the ultrastructure of nasal mucosa was impaired preoperatively and almost completely recovered at four months postoperatively. CONCLUSIONS: The normal structure and clearance function of nasal mucosa in patients with CS was impaired preoperatively, and the impaired structure and mucociliary clearing function of nasal mucosa were greatly improved after ESS and almost completely recovered at four months postoperatively. The pathologic glands and secretive function of nasal mucosa may need longer period for recovering.

Adolescent↗

Role of STAT4 and STAT6 signaling in allograft rejection and CTLA4-Ig-mediated tolerance.

STAT4(-/-) mice have impaired type 1 T cell differentiation, whereas STAT6(-/-) mice fail to generate type 2 responses. The role of type 1 and type 2 T cell differentiation in acute cardiac allograft rejection and in the induction of tolerance was examined in wild-type, STAT4(-/-), and STAT6(-/-) recipients. All recipients rejected the grafts promptly. Analysis of in situ cytokine gene expression in the allografts confirmed decreased levels of IFN-gamma in STAT4(-/-) recipients and undetectable levels of IL-4 and IL-5 in STAT6(-/-) mice. Blockade of the CD28/B7 costimulatory pathway prolonged cardiac graft survival for >100 days in 100% of wild-type and STAT4(-/-) mice. However, 14% of CTLA4-Ig-treated STAT6(-/-) mice rejected their grafts between 20 and 100 days. Moreover, of those animals followed past 100 days, 60% of the STAT6(-/-) mice rejected their grafts. Splenocytes harvested on day 145 posttransplant from CTLA4-Ig-treated rejecting STAT6(-/-) recipients were transfused into syngeneic SCID mice transplanted with donor or third party cardiac allografts. Both donor and third party grafts were rejected, indicating that the initial graft loss may be due to an immunological rejection. In contrast, when splenocytes from CTLA4-Ig-treated wild-type or nonrejecting STAT6(-/-) mice were transferred into SCID recipients, donor allografts were accepted, but third party hearts were rejected. Thus, long-term prolongation of cardiac allograft survival by CTLA4-Ig is STAT4-independent but, at least in part, STAT6-dependent. These data suggest that the balance of type 1 and type 2 T lymphocyte differentiation is not critical for acute rejection but influences the robust tolerance induced by CD28/B7 blockade in this model.

Abatacept↗

Absence of host B7 expression is sufficient for long-term murine vascularized heart allograft survival.

CD28 antagonists have been shown to promote long-term graft survival and induce donor-specific tolerance. In this study, the role of CD28/B7 costimulation and the relative importance of host versus donor B7 expression in allograft rejection was assessed in a murine abdominal vascularized heterotopic heart transplant model. Wild-type, CD28-deficient, or B7-1/B7-2-deficient C57BL/6 (B6) mice were grafted with allogeneic wild type or B7-1/B7-2-deficient hearts. The results demonstrate allogeneic heart grafts survive long-term in mCTLA4Ig-treated B6 and untreated B7-1/B7-2-deficient B6 recipients but not CD28KO B6 mice. B7-1/B7-2KO B6 recipients treated with anti-CD28 (PV-1) or recombinant human IL-2 rejected the heart transplants indicating that these mice are immunologically competent to reject grafts if costimulatory signals are supplied or bypassed. Finally, there was no difference in rejection between normal animals transplanted with wild-type versus B7-1/B7-2-deficient hearts. These results support a critical role for B7-expressing host antigen presenting cells in the rejection of heart allografts in mice and differences among B7KO and CD28KO animals.

Animals↗

[Clinical study of weaning predictors in COPD patients with prolonged mechanical ventilation].

OBJECTIVE: To evaluate the combined pulmonary function test at bedside as a predicting parameter of weaning in prolonged mechanically ventilated (MV) patients with chronic obstructive pulmonary disease (COPD). METHODS: 58 patients [mean duration of MV (18.4 +/- 9.2) d] who were divided into two groups were enrolled in this study. Group I included 43 patients [male 30, female 13, mean age (65 +/- 12) y] were successful in weaning, group II included 15 patients [male 10, female 5, mean age (64 +/- 10) y] were failed. ABGs, APACHEII, pulmonary function test and respiratory mechanics were measured in both groups after 30 minutes stable spontaneous breathing. RESULTS: There were no significant difference in ABGs, APACHEII, oxygenation index (OI), dynamic compliance (Cdyn) and airway resistance (Raw) between two groups (all P values > 0.05). There were significant differences in the following parameters between two groups: vital capacity/tidal volume (VC/VT, 2.10 +/- 0.20 vs. 1.30 +/- 0.20), maximal inspiratory pressure (Pimax), (-21 +/- 4) vs. (-13 +/- 3) cm H2O, rapid shallow breath index (RSBI), f/VT, (74 +/- 30) vs. (115 +/- 20) times.min-1.L-1, all P values < 0.05. By the use of VC/VT(> 1.8), Pimax(< -18 cm H2O) and f/VT(< 105 times.min-1.L-1) as the criteria of weaning, the specificity (90%) was significantly higher than each of the above three parameters. CONCLUSION: The bedside combined pulmonary function test (VC/VT, Pimax and f/VT) was a valuable weaning predictor in prolonged mechanically ventilated COPD patients.

Aged↗

[Modification of facial mask on the dead space effect in non-invasive mask ventilation].

OBJECTIVE: There were reports concerning the CO2 rebreathing during non-invasive positive pressure ventilation (NIPPV) with full face mask. It is our hypothesis that modification of the mask from one way connection to two ways connection by making a side hole in the mask makes it possible that CO2 inside the mask could be washed out by a constant flow through the mask. METHODS: A randomized self-control study on CO2 rebreathing was conducted in 7 COPD patients to compare the modified set-up with the conventional one. A BiPAP-30 ventilator and a plateau exhaustion valve (Respironics USA) were employed in the study. In the modified two ways set-up, the exhaustion valve (with distal end blocked) was connected to the side hole of the mask, so that a constant base flow could pass through the mask to the exhaustion valve. The average base flow was 0.43 LPS. The parameters were set as following: S/T mode, f: 15 BPM, pressure support level: 8 cm H2O. Three different levels of PEEP (2, 3 and 5 cm H2O) were used to investigate the PEEP level on CO2 rebreathing. Flow and CO2% were constantly recorded with computer data acquisition and analysis system (Microcal Origin). RESULTS: In conventional set-up, there was obvious CO2 rebreathing (rebreathing volume: 83.1 +/- 32.9 ml). In modified connection, the rebreathing volume was only (0.1 +/- 0.4) ml (P < 0.001). CONCLUSION: There was obvious CO2 rebreathing during full face mask NIPPV in conventional set-up. A modified two ways connection could reduce CO2 rebreathing to be near zero, which might be important in the management of hypercapnic respiratory failure with NIPPV.

Aged↗

[Study on clinical and laboratory features of preleukemia patients].

OBJECTIVE: To explore prospective diagnostic criteria for preleukemia. METHODS: A case control study of the discrepancies of clinical and laboratory features between patients with preleukemia and those with chronic aplastic anemia (CAA) or atypical paroxysmal nocturnal hemoglubinuria (a-PNH). RESULTS: There were eight variables of significance: (1) lymphocytoid micromegakaryocytes in marrow; (2) immature granulocytes in peripheral blood; (3) >or= 2% myeloblasts in marrow; (4) positive periodic acid schiff (PAS) staining of nucleated erythrocytes; (5) myeloid differentiation index >or= 1.8; (6) clonal karyotypic abnormalities; (7) negative sister chromatid differentiation; (8) > 4.0 cluster/colony ratio of granulocyte-macrophage colony-forming units (CFU-GM). The following criteria was assigned: A: To meet (1) and at least two of the other seven variables; B: To meet at least four of the eight variables. All of the patients with preleukemia met A or B and none of the patients with CAA or a-PNH did. CONCLUSION: Preleukemia is different from CAA or a-PNH. It has its own clinical and laboratory features, which may be useful for prospective diagnosis.

Adolescent↗

Identification of two novel mutations in the hypoglycemic phenotype of very long chain acyl-CoA dehydrogenase deficiency.

Very long chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial step of long chain fatty acid oxidation in the mitochondria. Patients with VLCAD deficiency have recently been observed with two clinical phenotypes. The cardiac form presents with an early onset cardiomyopathy and a high incidence of infant death, while the hypoglycemic form resembles medium chain acyl-CoA dehydrogenase (MCAD) manifesting with hypoketotic hypoglycemia. In our investigation on the molecular basis for these phenotypes, we identified two novel mutations in one VLCAD patient with the hypoglycemic form, a C953T (Pro318Leu) mutation in exon 10 resulting in a substitution of proline 318 by leucine on one allele, and a C1194A (Tyr398Stop) mutation in exon 12 which created a premature stop codon TAA on another allele. The Tyr398Stop mutation may result in a truncated protein or instable messenger RNA.

Acyl-CoA Dehydrogenase, Long-Chain↗

Cutting edge: blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells.

The effect of blocking the CD28/B7 costimulatory pathway on intestinal allograft rejection was examined in mice. Murine CTLA4Ig failed to prevent the rejection of allografts transplanted into wild-type or CD4 knockout (KO) mice but did inhibit allograft rejection by CD8 KO recipients. This effect was associated with decreased intragraft mRNA for IFN-gamma and TNF-alpha and increased mRNA for IL-4 and IL-5. This altered pattern of cytokine production was not observed in allografts from murine CTLA4Ig-treated CD4 KO mice. These data demonstrate that blockade of the CD28/B7 pathway has different effects on intestinal allograft rejection mediated by CD4+ and CD8+ T cells and suggest that these T cell subsets have different costimulatory requirements in vivo. The results also suggest that the inhibition of CD4+ T cell-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines.

Abatacept↗

Adsorbed layers and the origin of static friction

Analytic results and experiments in ultrahigh vacuum indicate that the static friction between two clean crystalline surfaces should almost always vanish, yet macroscopic objects always exhibit static friction. A simple and general explanation for the prevalence of static friction is proposed. "Third bodies," such as small hydrocarbon molecules, adsorb on any surface exposed to air and can arrange to lock two contacting surfaces together. The resulting static friction is consistent with experimental behavior, including Amontons' laws.

Journal Article↗

Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging.

EPR imaging has emerged as an important tool for noninvasive three-dimensional (3D) spatial mapping of free radicals in biological tissues. Spectral-spatial EPR imaging enables mapping of the spectral information at each spatial position, and, from the observed line width, the localized tissue oxygenation can be mapped. We report the development of EPR imaging instrumentation enabling 3D spatial and spectral-spatial EPR imaging of small animals. This instrumentation, along with the use of a biocompatible charcoal oximetry-probe suspension, enabled 3D spatial imaging of the gastrointestinal (GI) tract, along with mapping of oxygenation in living mice. By using these techniques, the oxygen tension was mapped at different levels of the GI tract from the stomach to the rectum. The results clearly show the presence of a marked oxygen gradient from the proximal to the distal GI tract, which decreases after respiratory arrest. This technique for in vivo mapping of oxygenation is a promising method, enabling the noninvasive imaging of oxygen within the normal GI tract. This method should be useful in determining the alterations in oxygenation associated with disease.

Animals↗

Mitogen-activated protein/extracellular signal-regulated kinase inhibition attenuates angiotensin II-mediated signaling and contraction in spontaneously hypertensive rat vascular smooth muscle cells.

This study investigates the role of extracellular signal-regulated kinases (ERKs) in angiotensin II (Ang II)-generated intracellular second messengers (cytosolic free Ca2+ concentration, ie, [Ca2+]i, and pHi) and in contraction in isolated vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY) using the selective mitogen-activated protein (MAP)/ERK inhibitor, PD98059. VSMCs from mesenteric arteries were cultured on Matrigel basement membrane matrix. These cells, which exhibit a contractile phenotype, were used to measure [Ca2+]i, pHi, and contractile responses to Ang II (10(-12) to 10(-6) mol/L) in the absence and presence of PD98059 (10(-5) mol/L). [Ca2+]i and pHi were measured by fura-2 and BCECF methodology, respectively, and contraction was determined by photomicroscopy. Ang II-stimulated ERK activity was measured by Western blot analysis using a phospho-specific ERK-1/ERK-2 antibody and by an MAPK enzyme assay. Ang II increased [Ca2+]i and pHi and contracted cells in a dose-dependent manner. Maximum Ang II-elicited contraction was greater (P<0.05) in SHR (41.9+/-5.1% reduction in cell length relative to basal length) than in WKY (28.1+/-3.0% reduction in cell length relative to basal length). Basal [Ca2+]i, but not basal pHi, was higher in SHR compared with WKY. [Ca2+]i and pHi effects of Ang II were enhanced (P<0.05) in SHR compared with WKY (maximum Ang II-induced response [Emax] of [Ca2+]i, 576+/-24 versus 413+/-43 nmol/L; Emax of pHi, 7.33+/-0.01 versus 7.27+/-0.03, SHR versus WKY). PD98059 decreased the magnitude of contraction and attenuated the augmented Ang II-elicited contractile responses in SHR (Emax,19. 3+/-3% reduction in cell length relative to basal length). Ang II-stimulated [Ca2+]i (Emax, 294+/-55 nmol/L) and pHi (Emax, 7. 27+/-0.04) effects were significantly reduced by PD98059 in SHR. Ang II-induced ERK activity was significantly greater (P<0.05) in SHR than in WKY. In conclusion, Ang II-stimulated signal transduction and associated VSMC contraction are enhanced in SHR. MAP/ERK inhibition abrogated sustained contraction and normalized Ang II effects in SHR. These data suggest that ERK-dependent signaling pathways influence contraction and that they play a role in vascular hyperresponsiveness in SHR.

Angiotensin II↗