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Biomedical subjects

L Liang

Publications and source records attributed to L Liang.

At least 37 records · Page 2Linked to original sources

Examination of dietary methylmercury exposure in the Casa Pia Study of the health effects of dental amalgams in children.

This study examined methylmercury concentrations in blood of children participating in the Casa Pia Study of the Health Effects of Dental Amalgams in Children over a 1-yr period and related them to their diets in terms of fish and other seafood consumption. One hundred and fifty children between the ages of 8 and 10 yr who were residents of the Casa Pia School System of Lisbon, Portugal, participated. Parents or caregivers completed a food frequency questionnaire designed specifically for this study at baseline. Children provided urinary and blood samples for mercury determinations at baseline and at 1 yr following placement of dental tooth fillings. Mercury levels in fish samples from children's diets were also obtained. Mercury determinations in urine, blood, and fish were performed using cold vapor atomic fluorescence spectroscopy. The mean value of baseline methylmercury concentrations in blood increased as the report of seafood consumption increased, although not statistically significantly. However, blood methylmercury and total mercury concentrations were significantly lower at 1-yr follow-up than at baseline. Sixty-one percent of parents/caregivers reported that their children consumed fish on a weekly basis. The fish offered at a sample of the schools contained low levels of methylmercury (range 13.9-23.6 ng/g). Thus, children participating in the Casa Pia dental amalgam study are exposed to low dietary levels of methylmercury by way of fish consumption, and this finding was reflected in the low mean blood methylmercury concentrations observed. The present findings indicate that dietary methylmercury is not a significant source of mercury exposure and is not likely to confound the association of dental amalgam mercury with potential health effects in the present study.

Child↗

Targeting polymerised liposome vaccine carriers to intestinal M cells.

Due to their transcytotic capability, intestinal M cells may represent an efficient potential route for oral vaccine delivery. We previously demonstrated that the lectin Ulex europaeus agglutinin 1 (UEA1, specific for alpha-L-fucose residues) selectively binds to mouse Peyer's patch M cells and targets 0.5 microm polystyrene microparticles to these cells. Using a gut loop model we now demonstrate that covalently-membrane-bound UEA1 similarly targets polymerised liposomes (Orasomes, approximately 200 nm diameter), potential biocompatable oral vaccine delivery vehicles, to mouse M cells. Targeting was inhibited by alpha-L-fucose while the co-entrapped adjuvant, monophosphoryl Lipid A (MPL), failed to exert any detrimental effect on UEA1-mediated M cell targeting. Lectin-mediated M cell targeting may thus permit the efficacy of mucosal vaccines to be enhanced if cellular relationship between particle binding and immune outcome can be established.

Animals↗

Enhancement of CD8+ T cell responses by ICOS/B7h costimulation.

Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4(+) T cell responses, their ability to regulate CD8(+) responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8(+) T cells in the absence of CD4(+) T cells. Although responses of naive T cells were significantly augmented by priming with B7h, B7h was surprisingly effective in mobilizing recall responses of adoptively transferred T cells. To explore why secondary responses of CD8(+) T cells were particularly enhanced by B7h, kinetics of ICOS up-regulation, proliferative responses, and cytokine production were compared from both naive and rechallenged 2C-transgenic T cells costimulated in vitro. Although B7h costimulated proliferative responses from both CD8(+) populations, rechallenged cells were preferentially costimulated for IL-2 and IFN-gamma production. These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8(+) T cells.

Adjuvants, Immunologic↗

Identification and characterization of a melanin-concentrating hormone receptor.

Melanin-concentrating hormone (MCH), a neuropeptide expressed in central and peripheral nervous systems, plays an important role in the control of feeding behaviors and energy metabolism. An orphan G protein-coupled receptor (SLC-1/GPR24) has recently been identified as a receptor for MCH (MCHR1). We report here the identification and characterization of a G protein-coupled receptor as the MCH receptor subtype 2 (MCHR2). MCHR2 has higher protein sequence homology to MCHR1 than any other G protein-coupled receptor. The expression of MCHR2 has been detected in many regions of the brain. In contrast to MCHR1, which is intronless in the coding region and is located at the chromosomal locus 22q13.3, the MCHR2 gene has multiple exons and is mapped to locus 6q21. MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein. This discovery is important for a full understanding of MCH biology and the development of potential therapeutics for diseases involving MCH, including obesity.

Alternative Splicing↗

Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1 cultures.

Myostatin, a new TGF-beta family member, is known as a muscle growth inhibitor, but its role in adipocyte development has not been studied. To test the role of Myostatin in 3T3-L1 preadipocyte differentiation, we treated cultured 3T3-L1 preadipocytes with Myostatin dissolved in 0.1% trifluoroacetic acid (TFA) during differentiation after they had become confluent. Myostatin treatment significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity and oil Red-O staining compared to controls that did not receive Myostatin. Western blot analysis showed that the expression levels of CCAAT/enhancer binding protein alpha (C/EBP alpha) and peroxisome proliferator-activated receptor gamma (PPAR gamma) were significantly decreased by Myostatin treatment (P < 0.05). However, the expression of C/EBP beta was not significantly changed by the treatment (P > 0.05). From RT-PCR result, the relative level of leptin mRNA in Myostatin-treated cells was not significantly different (P > 0.1) from the level in cells without Myostatin treatment. Our data show that Myostatin, a secreted protein from muscle, inhibits preadipocyte differentiation in 3T3-L1 cells, which is mediated, in part, by altered regulation of C/EBP alpha and PPAR gamma.

3T3 Cells↗

Src homology 3 domain-dependent interaction of Nck-2 with insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is a multi-domain protein that mediates signal transduction from receptors for insulin and other growth factors to a variety of downstream molecules through both tyrosine-phosphorylation-dependent and -independent interactions. While the tyrosine-phosphorylation-dependent interactions mediated by IRS-1 have been well characterized, the molecular basis underlying the tyrosine-phosphorylation-independent IRS-1 interactions is largely unknown. We previously detected, in an in vitro binding assay, interactions of Nck-2 Src homology (SH) 3 domains with IRS-1. We show here that IRS-1 associates with Nck-2 in vivo. Additionally, we have investigated the molecular basis underlying the IRS-1-Nck-2 complex formation. We have found that (i) mutations at the highly conserved tryptophan within the Nck-2 SH3 domains markedly reduced the association with IRS-1, (ii) interactions mediated by multiple SH3 domains enhance the complex formation of Nck-2 with IRS-1, (iii) deletion of either the phosphotyrosine-binding/Shc and IRS-1 NPXY-binding (PTB/SAIN) domains or the Pre-C-terminal domain of IRS-1, but not the pleckstrin homology (PH) domain, reduced the Nck-2 binding, (iv) PTB/SAIN domains or the Pre-C-terminal domain alone is capable of interacting with Nck-2, and (v) the IRS-1-Nck-2 interaction occurs in the absence of other proteins and therefore is direct. These results establish that IRS-1 is a bona fide target of the Nck-2 SH3 domains and reveal that IRS-1 forms a complex with Nck-2 via direct interactions mediated by multiple domains from both binding partners.

Adaptor Proteins, Signal Transducing↗

Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa.

Factor Xa (fXa) plays a critical role in the coagulation cascade, serving as the point of convergence of the intrinsic and extrinsic pathways. Together with nonenzymatic cofactor Va and Ca2+ on the phospholipid surface of platelets or endothelial cells, factor Xa forms the prothrombinase complex, which is responsible for the proteolysis of prothrombin to catalytically active thrombin. Thrombin, in turn, catalyzes the cleavage of fibrinogen to fibrin, thus initiating a process that ultimately leads to clot formation. Recently, we reported on a series of isoxazoline and isoxazole monobasic noncovalent inhibitors of factor Xa which show good potency in animal models of thrombosis. In this paper, we wish to report on the optimization of the heterocyclic core, which ultimately led to the discovery of a novel pyrazole SN429 (2b; fXa K(i) = 13 pM). We also report on our efforts to improve the oral bioavailability and pharmacokinetic profile of this series while maintaining subnanomolar potency and in vitro selectivity. This was achieved by replacing the highly basic benzamidine P1 with a less basic benzylamine moiety. Further optimization of the pyrazole core substitution and the biphenyl P4 culminated in the discovery of DPC423 (17h), a highly potent, selective, and orally active factor Xa inhibitor which was chosen for clinical development.

Administration, Oral↗

Comparison between EPI and HASTE for ultra-fast MR imaging of the human brain.

Our purpose was to evaluate and compare the performance of ultra-fast single-shot T2-weighted sequences: echo-planar imaging (EPI) versus half-Fourier single-shot turbo spin-echo (HASTE) and to assess the usefulness of their combined reading. Comparative experiments on a phantom as well as a prospective clinical study in 47 patients were done. Axial images acquired with the following methods were compared: (a) HASTE; (b) segmented HASTE (s-HASTE); (c) single-shot spin-echo EPI (SE-EPI); and (d) gradient-echo EPI (GREEPI). Quantitative and qualitative criteria as well as lesion detectability were analyzed against the "gold standard" fast spin-echo (FSE) sequence. For contrast and contrast-to-noise ratio (CNR) between gray and white matter, GRE-EPI was best. The visibility of small markedly hyperintense lesion was best with HASTE and s-HASTE in the clinical study. Small hyperintense lesions were detected equally well with all four sequences, although all performed significantly worse than FSE. The two HASTE variants were better than the EPIs for the extraaxial lesions. The combination of the GRE-EPI and s-HASTE was judged best, and sometimes superior to the FSE image. HASTE or EPI alone cannot substitute for FSE in the screening evaluation of the brain. However, together, EPI and HASTE could provide comparable diagnostic information to that of FSE because their combination compensates for their individual limitations.

Adolescent↗

The zygotic expression of zebrafish trebf during embryogenesis is restricted to the embryonic shield and its derivatives.

We have identified a zebrafish gene trebf that shows an overall similarity of 51.5% and 55.1% in amino acid sequence with human and mouse TREB5/hXBP-1/HTF, respectively. Northern hybridization reveals that trebf mRNA is expressed throughout the life cycle of zebrafish. Whole-mount in situ hybridization detects an expression pattern of trebf in zebrafish that is very different from that of mammalian TREB5. Just before the onset of gastrulation, trebf transcripts are accumulated in the dorsal blastoderm margin and subsequently in the forming organizer. During gastrulation, the trebf-positive cells in the organizer migrate toward the animal pole and form two distinct domains. The cells in the anterior leading expression domain ultimately differentiate into hatching gland, whereas those in the following domain form the notochord.

Amino Acid Sequence↗

Temporal and rate representations of time-varying signals in the auditory cortex of awake primates.

Because auditory cortical neurons have limited stimulus-synchronized responses, cortical representations of more rapidly occurring but still perceivable stimuli remain unclear. Here we show that there are two largely distinct populations of neurons in the auditory cortex of awake primates: one with stimulus-synchronized discharges that, with a temporal code, explicitly represented slowly occurring sound sequences and the other with non-stimulus-synchronized discharges that, with a rate code, implicitly represented rapidly occurring events. Furthermore, neurons of both populations displayed selectivity in their discharge rates to temporal features within a short time-window. Our results suggest that the combination of temporal and rate codes in the auditory cortex provides a possible neural basis for the wide perceptual range of temporal information.

Acoustic Stimulation↗

Sequential analysis of kidney stone formation in the Aprt knockout mouse.

BACKGROUND: We have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified in kidney sections from male and female mice (strain 129) aged one day to eight months and this parameter was correlated with changes in renal histopathology. Aprt heterozygous and wild-type mice were used as controls. METHODS: Following anesthesia, the left kidney was removed and immediately frozen in dry ice. Unstained cryosections were examined by polarized light to determine total area of birefringent particles. The right kidney was perfused and embedded in plastic, and stained sections were viewed by light microscopy to examine the histopathology and to determine the location of the birefringent particles. A pathological score was assigned to the histological findings. The scores from the right kidney were compared with crystal/particle area in the left kidney, and the data were analyzed using two-way analysis of variance. The chemical composition of the particles was determined by x-ray diffraction analysis. Several stone fragments from the bladder were also examined by scanning electron microscopy (SEM). RESULTS: Crystals were detected in kidney sections from one- to two-day-old Aprt knockout mice. The crystal burden remained low in both sexes throughout the study except in males at the 120- to 240-day period. Furthermore, there was a substantial degree of renal pathology, primarily seen as interstitial fibrosis, in those males with a very high level of stone formation. The crystalline material was identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM indicated that the crystals were spherical, with a diameter of 10 to 20 microm. Tissue staining and fixation procedures dramatically reduced the amount of birefringent material in kidney sections. Aprt heterozygotes of both sexes had low levels of crystalline material in the kidneys and no pathology. Birefringent material or pathological changes were not seen in kidneys from wild-type mice. CONCLUSIONS: Both male and female Aprt knockout mice accumulate DHA. However, the area occupied by DHA crystals was significantly greater in 120- to 240-day-old males compared with the females of similar age. Also, substantial renal pathology was detected in kidneys of male mice that had very high levels of stone material.

Adenine↗

Calcium fortification of breakfast cereal enhances calcium absorption in children without affecting iron absorption.

OBJECTIVES: Provision of calcium-fortified foods may represent an important component of improving the calcium intake of children. We sought to determine whether the addition of calcium to cereal would have a net positive effect on calcium absorption without decreasing iron absorption. METHODS: Twenty-seven children, 6 to 9 years of age, were provided two servings per day (30 g of cereal per serving) of either a low (39 mg/serving) or fortified (156 mg/serving) calcium-containing cereal product for 14 days. Calcium absorption was measured by using stable isotopes added to milk (extrinsically labeled) and to the calcium-fortified cereal (intrinsically labeled). RESULTS: Fractional calcium absorption from the fortified cereal was virtually identical to that from milk. Fractional absorption of calcium from milk did not differ significantly when given with enriched or low-calcium-containing cereal. Total calcium absorption increased from 215 +/- 45 mg/d to 269 +/- 45 mg/d with the addition of the calcium-fortified cereal (P <.001). Iron absorption was similar when children received the calcium-fortified cereal or unfortified cereal. CONCLUSIONS: The addition of a moderate amount of calcium to a cereal product was beneficial to calcium absorption and did not interfere with iron absorption. Use of calcium-fortified food products may be considered a practical approach to increasing the calcium intake of children.

Absorption↗

U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids.

The herpes simplex virus type 1 (HSV-1) U(L)34 protein is likely a type II membrane protein that localizes within the nuclear membrane and is required for efficient envelopment of progeny virions at the nuclear envelope, whereas the U(L)31 gene product of HSV-1 is a nuclear matrix-associated phosphoprotein previously shown to interact with U(L)34 protein in HSV-1-infected cell lysates. For these studies, polyclonal antisera directed against purified fusion proteins containing U(L)31 protein fused to glutathione-S-transferase (U(L)31-GST) and U(L)34 protein fused to GST (U(L)34-GST) were demonstrated to specifically recognize the U(L)31 and U(L)34 proteins of approximately 34,000 and 30,000 Da, respectively. The U(L)31 and U(L)34 gene products colocalized in a smooth pattern throughout the nuclear rim of infected cells by 10 h postinfection. U(L)34 protein also accumulated in pleiomorphic cytoplasmic structures at early times and associated with an altered nuclear envelope late in infection. Localization of U(L)31 protein at the nuclear rim required the presence of U(L)34 protein, inasmuch as cells infected with a U(L)34 null mutant virus contained U(L)31 protein primarily in central intranuclear domains separate from the nuclear rim, and to a lesser extent in the cytoplasm. Conversely, localization of U(L)34 protein exclusively at the nuclear rim required the presence of the U(L)31 gene product, inasmuch as U(L)34 protein was detectable at the nuclear rim, in replication compartments, and in the cytoplasm of cells infected with a U(L)31 null virus. When transiently expressed in the absence of other viral factors, U(L)31 protein localized diffusely in the nucleoplasm, whereas U(L)34 protein localized primarily in the cytoplasm and at the nuclear rim. In contrast, coexpression of the U(L)31 and U(L)34 proteins was sufficient to target both proteins exclusively to the nuclear rim. The proteins were also shown to directly interact in vitro in the absence of other viral proteins. In cells infected with a virus lacking the U(S)3-encoded protein kinase, previously shown to phosphorylate the U(L)34 gene product, U(L)31 and U(L)34 proteins colocalized in small punctate areas that accumulated on the nuclear rim. Thus, U(S)3 kinase is required for even distribution of U(L)31 and U(L)34 proteins throughout the nuclear rim. Taken together with the similar phenotypes of the U(L)31 and U(L)34 deletion mutants, these data strongly suggest that the U(L)31 and U(L)34 proteins form a complex that accumulates at the nuclear membrane and plays an important role in nucleocapsid envelopment at the inner nuclear membrane.

Animals↗

Neural representations of temporally asymmetric stimuli in the auditory cortex of awake primates.

The representation of rapid acoustic transients by the auditory cortex is a fundamental issue that is still unresolved. Auditory cortical neurons have been shown to be limited in their stimulus-synchronized responses, yet the perceptual performances of humans and animals in discriminating temporal variations in complex sounds are better than what existing neurophysiological data would predict. This study investigated the neural representation of temporally asymmetric stimuli in the primary auditory cortex of awake marmoset monkeys. The stimuli, ramped and damped sinusoids, were systematically manipulated (by means of half-life of the exponential envelope) within a cortical neuron's presumed temporal integration window. The main findings of this study are as follows: 1) temporal asymmetry in ramped and damped sinusoids with a short period (25 ms) was clearly reflected by average discharge rate but not necessarily by temporal discharge patterns of auditory cortical neurons. There was considerable response specificity to these stimuli such that some neurons were strongly responsive to a ramped sinusoid but almost completely unresponsive to its damped counterpart or vice versa. Of 181 neurons studied, 140 (77%) showed significant response asymmetry in at least one of the tested half-life values of the exponential envelope. Forty-six neurons showed significant response asymmetry over all half-lives tested. Sustained firing, commonly observed under awake conditions, contributed to greater response asymmetry than that of onset responses in many neurons. 2) A greater proportion of the neurons (32/46) that exhibited significant overall response asymmetry showed stronger responses to the ramped sinusoids than to the damped sinusoids, possibly contributing to the difference in the perceived loudness between these two classes of sounds. 3) The asymmetry preference of a neuron to ramped or damped sinusoids did not appear to be correlated with its characteristic frequency or minimum response latency, suggesting that this is a general phenomenon that exists across populations of cortical neurons. Moreover, the intensity of the stimuli did not have significant effects on the measure of the asymmetry preference based on discharge rate. 4) A population measure of response preference, based on discharge rate, of cortical neurons to the temporally asymmetric stimuli was qualitatively similar to the performance of human listeners in discriminating ramped versus damped sinusoids at different half-life values. These findings suggest that rapid acoustic transients embedded in complex sounds can be represented by discharge rates of cortical neurons instead of or in the absence of stimulus-synchronized discharges.

Acoustic Stimulation↗

Evaluation of the intracranial dural sinuses with a 3D contrast-enhanced MP-RAGE sequence: prospective comparison with 2D-TOF MR venography and digital subtraction angiography.

BACKGROUND AND PURPOSE: The diagnosis of dural sinus thrombosis is often difficult because of its variable and nonspecific clinical presentation and the overlapping signal intensities of thrombosis and venous flow on conventional MR images and MR venograms. We compared 3D contrast-enhanced magnetization-prepared rapid gradient-echo (MP-RAGE) sequences with 2D time-of-flight (TOF) MR venography, digital subtraction angiography (DSA), and conventional spin-echo (SE) MR imaging for the assessment of normal and abnormal dural sinuses. METHODS: In a phantom study, a plastic tube with pulsating flow was used to simulate the intracranial dural sinus. With 3D MP-RAGE, a variety of flow velocities, contrast material concentrations, and angulations between the phantom flow tube and the plane of acquisition were tested to measure their relationship to signal-to-noise ratio (SNR). In a clinical study, 35 patients, including 18 with suspected dural sinus thrombosis, were studied with both MR imaging and DSA. Receiver operating characteristic (ROC) analysis was performed in a blinded fashion using DSA as the reference standard. RESULTS: With the phantom, the SNR of flow increased with increasing contrast concentration, but was not affected by the angle between the tube and scan slab. There was no relationship between SNR and velocity when the contrast concentration was 1.0 mmol/L or greater. In the clinical study, dural sinus thrombosis as well as the normal anatomy of the dural sinuses were seen better with 3D contrast-enhanced MP-RAGE than with 2D-TOF MR venography. Three-dimensional contrast-enhanced MP-RAGE showed the highest diagnostic confidence on ROC curves in the diagnosis of thrombosis. CONCLUSION: Three-dimensional contrast-enhanced MP-RAGE is superior to 2D-TOF MR venography and conventional SE MR imaging in the depiction of normal venous structures and the diagnosis of dural sinus thrombosis, and is a potential alternative to DSA.

Adult↗

[The effect of p53 gene on p-glycoprotein expression and chemotherapeutic cytotoxicity of hepatocellular carcinoma].

OBJECTIVE: To test the hypothesis that wild-type p53 regulates the expression of p-glycoprotein. METHODS: Hep3B cells which lack the expression of both p53 and retinoblastoma tumor suppressor genes because of deletions, were transfected with a wild-type (wt) p53 cDNA and control vector by a liposome method. RESULTS: After G418 selection, stable wt-p53 transformants and control vector transformants (pNeo) were obtained. Northern and Western blot analysis determined the expression of p53 mRNA and protein in wt-p53 transformants, respectively. In wt-p53 transformants, induction of transcriptionally active p53 was confirmed by the increase of P21(waf1/cip1) protein. Levels of P-gp reduced in the cells expressing wild-type p53 were linked to wt-p53 activity. Cytotoxicity assays revealed that the wt-p53 transfectants were more sensitive to doxorubicin and mitomycin compared with the pNeo transformants. Flow cytometry showed that the accumulation of doxorubicin in wt-p53 transfectants was as 13 times as that of the pNeo transformants. CONCLUSIONS: Restoration of wt-p53 activity in Hep3B leads to sensitiveness to chemotherapeutic agents because of the decrease of p-glycoprotein expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Appraisal of renal failure reversing therapies in lupus nephritis].

OBJECTIVE: This study aimed to explore the therapies of reversing renal failure in lupus nephritis. METHODS: The research strategy was a retrospective cohort study. 173 patients were included in the study. All of them were consecutive in-patients of newly diagnosed renal failure (serum creatinine > 180 micromol/L) with lupus nephritis from 1991 to 1999 in the university hospital. The research factors included steroids, cyclophosphamide and cyclosporin. Steroids were divided to oral prednisone, intravenous dexamethasone and intravenous methylprednisolone pulse; cyclophosphamide dose intensity was divided into three grades: none, low dose (average dose 0.25 g/m(2) body surface area per week). 51 demographic, clinical and laboratory data were included in the study as possible confounding factors. The study end-point was recovery of renal function that was defined as a level of serum creatinine <or= 116 micromol/L in the azotemia patients or a 50% reduction of serum creatinine and discontinuation of dialysis in the uremic patients. The improvement had to be maintained for at least three months. Collection of the study factors and outcome variable was conducted by two separate, blinded groups of clinical specialists with two structured abstracting forms. RESULTS: The number of complete following up patients was 142 (82.1%). After over 6 months of following up, 93 cases (65.5%) recovered their renal function and 17 cases (12.0%) died. In COX proportional hazard regression model, cyclophosphamide therapy was significantly associated with the recovery of renal function. The adjusted hazard ratio (HR) to recovery of renal function was 4.41, 95% CI = 1.03 - 18.94 in low dose; and the HR was 13.29, 95% CI = 3.11 - 56.82 in high dose cyclophosphamide therapy. The gender, duration of renal dysfunction, small renal size, severe anemia and serum creatinine were also significantly associated with renal function recovery. Cyclophosphamide therapy was not significantly associated with death. The variables associated with death were low level of serum albumin and edema. CONCLUSION: Cyclophosphamide pulse was an efficient therapy in reversing renal failure of lupus nephritis, especially in the patients with short duration of renal failure, non-small in renal size, and non-severe anemia.

Administration, Oral↗

[The expression of growth factors in filtering area following sclerectomy and the interaction between growth factors and interferon].

OBJECTIVE: To study the expression of beta-Fibroblastic Growth Factor (bFGF) and Transforming Growth Factor beta 1 (TGF beta 1) in filtering area following sclerectomy and the interaction between growth factors and interferon alpha-2b (IFN alpha-2b). METHODS: Immunohistochemical technique were applied to test the expression bFGF and TGF beta 1 in frozen sections of filtration area following sclerectomy on postoperative day three, five, seven and 14 in white rabbits, respectively. 16 eyes of eight rabbits in all were randomly and equally divided into two groups. The experimental eyes had subconjunctivally been administered IFN alpha-2b 5 x 10(5) IU 0.2 ml each time at filtering bleb following operation whereas the control eyes hadn't taken. RESULTS: In control group, positive cell and substance expressing bFGF and TGF beta 1 on postoperative day three were revealed in the filtration area, on postoperative day five and seven, they were gradually increased. On the postoperative day 14, all significant cells and substance markly decreased. In experimental group only small amount of positive cell and bFGF or TGF beta 1-expressing substance were sparely distributed in the filtration area. CONCLUSION: The filtration area after glaucoma filtering surgery was "bathed" in growth factors such as bFGF and TGF beta 1 which well-known play an important role in stimulating wound healing response, IFN alpha-2b had an inhibitory effect on bFGF or TGF beta 1 expression in wound environment.

Animals↗