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Biomedical subjects

H Liang

Publications and source records attributed to H Liang.

At least 145 records · Page 8Linked to original sources
PubMed1997

A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer.

Endogenous murine angiostatin, identified as an internal fragment of plasminogen, blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. A recombinant protein comprising kringles 1-4 of human plasminogen (amino acids 93-470) expressed in Pichia pastoris had physical properties (molecular size, binding to lysine, reactivity with antibody to kringles 1-3) that mimicked native angiostatin. This recombinant Angiostatin protein inhibited the proliferation of bovine capillary endothelial cells in vitro. Systemic administration of recombinant Angiostatin protein at doses of 1.5 mg/kg suppressed the growth of Lewis lung carcinoma-low metastatic phenotype metastases in C57BL/6 mice by greater than 90%; administration of the recombinant protein at doses of 100 mg/kg also suppressed the growth of primary Lewis lung carcinoma-low metastatic phenotype tumors. These findings demonstrate unambiguously that the antiangiogenic and antitumor activity of endogenous angiostatin resides within kringles 1-4 of plasminogen.

Angiostatins↗
PubMed1997

Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.

Heterodimerization between members of the Bcl-2 family of proteins is a key event in the regulation of programmed cell death. The molecular basis for heterodimer formation was investigated by determination of the solution structure of a complex between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak. The structure and binding affinities of mutant Bak peptides indicate that the Bak peptide adopts an amphipathic alpha helix that interacts with Bcl-xL through hydrophobic and electrostatic interactions. Mutations in full-length Bak that disrupt either type of interaction inhibit the ability of Bak to heterodimerize with Bcl-xL.

Amino Acid Sequence↗
PubMed1997

Bcl-x(L) forms an ion channel in synthetic lipid membranes.

Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes. Here we demonstrate that Bcl-xL shares this functional feature. Like the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-xL display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-xL may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.

Cations↗
PubMed1997

Giant cell formation in cells exposed to 740 nm and 760 nm optical traps.

BACKGROUND AND OBJECTIVE: Optical trapping is becoming a useful and widespread technique for the micromanipulation of cells and organelles. Giant cell formation following optical trapping was studied to detect the potential adverse effects. STUDY DESIGN/MATERIALS AND METHODS: The nuclei of preselected single CHO cells were exposed to 740 nm and 760 nm laser microbeam generated by a titanium-sapphire tunable laser at 88 and 176 mW and different time exposures. The irradiated single cells were recorded and observed morphologically following exposure. Giant cells were tabulated and photographed. RESULTS: The irradiated cells either failed to divide, or they underwent nuclear proliferation to form giant cells through endoreduplication. CONCLUSION: Giant cells were induced by both 740 nm and 760 nm. The frequency of giant cell formation was higher for the longer time exposures and at the higher power densities. The use of an optical etalon to remove intracavity mode beating and high peak powers of the titanium-sapphire laser caused a significant reduction in the formation of giant cells.

Animals↗
PubMed1997

Aging- and ovariectomy-related skeletal changes in spontaneously hypertensive rats.

BACKGROUND: The skeletal impact of estrogen deficiency on subjects with hypertension has not been studied previously. In this study, we examined the skeletal characteristics of female spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto rat (WKY). We aimed to reveal: 1) the skeletal characters of female SHR, and 2) the response of SHR to ovariectomy (ovx) when compared to WKY and other strains. METHODS: Undecalcified double-fluorescent labeled cancellous (proximal tibial metaphysis, PTM) and cortical (tibial shaft, TX) bones from 23-weeks-old, and from rats 2 and 8 weeks post-ovx were studied. RESULTS: The SHR showed lower body weight, higher heart rate, and higher blood pressure than the WKY. Female SHR possessed more percent cancellous bone, less net cortical bone, smaller tissue area, and thinner cortex than WKY. Furthermore, SHR exhibited an age-related cancellous (-18%) and cortical (-7%) bone loss associated with a decrease in the longitudinal growth rate and bone balance and a decrease in periosteal bone formation in cortical bone. In contrast, the WKY maintained most of these parameters unchanged at their 23-week-old levels. Ovariectomy induced earlier and greater cancellous bone loss in the SHR than in the WKY, with greater increases in bone turnover rate, eroded surface, activation frequency, and a decrease in the ratio of labeled to eroded perimeter in PTM at 2 weeks postsurgery. However, the two groups exhibited no differences in bone loss at 8 weeks after ovx in PTM and TX. CONCLUSIONS: Spontaneously hypertensive rats were highly sensitive to estrogen deficiency. This might have clinical relevance to those postmenopausal women who suffer from hypertension, in that they may be more susceptible to osteopenia. If so, preventive measures should be initiated sooner than otherwise.

Aging↗
PubMed1997

The role of testosterone in cyclosporine-induced osteopenia.

Our laboratory has demonstrated that the immunosuppressants Cyclosporin A (CsA) and tacrolimus (FK506), in vivo in the rat, produce a high-turnover osteopenia. CsA is known to decrease serum testosterone (Test) levels both in the rat and in human transplant patients. Less is known of FK506's effect on androgens. CsA-induced hypogonadism may contribute to the aforementioned bone loss because hypogonadism itself is a risk factor for osteoporosis and fracture. The aim of this study was to assess serum androgen levels following CsA and FK506 therapy and to see wether Test replacement therapy, in the form of 28-day controlled release subcutaneous pellet implants, could prevent CsA-induced osteopenia. Two experiments were conducted. In experiment I, four groups of 6-month-old male Sprague-Dawley rats received the following: (A) CsA vehicle and placebo pellet, (B) Test 15 mg pellet and CsA vehicle, (C) CsA 10 mg/kg and placebo pellet, (D) Test 15 mg pellet and CsA 10 mg/kg. In experiment II, two groups of rats received (E) FK506 vehicle and (F) FK506 4 mg/kg. CsA, FK506, and vehicles were given for 28 days by daily oral gavage. The rats were weighted and bled on days 0, 14, and 28. All rats received double fluorescent labeling, and on day 28 the tibiae were removed for histomorphometry. Whole blood was assayed for CsA and FK506 levels. Serum was assayed for total and free Test as well as for osteocalcin (BGP), blood urea nitrogen (BUN), creatinine, and calcium. Whole blood monoclonal CsA levels measured by fluorescent immunoassay were in the therapeutic range, while a drug concentration profile showed good absorption of FK506. Those rats receiving Test and FK506 lost weight, while those receiving CsA remained constant. BUN was only marginally elevated in the CsA-treated groups on day 28 (p < 0.05), while creatinine was unchanged. On day 28, total and free Test was significantly reduced in the CsA-treated rats versus control (p < 0.05), while Test replacement therapy maintained total Test levels above vehicle (p < 0.01) and free Test levels similar to vehicle on day 28. FK506 did not lower total or free Test levels. BGP levels were significantly increased in the CsA (p < 0.01) and FK506 (p < 0.001) groups on day 28. BGP in the groups receiving Test alone and in combination with CsA remained similar to vehicle. Histomorphometry confirmed CsA- and FK506-induced high-turnover osteopenia. The Test alone group marignally increased bone formation. Test replacement failed to prevent the CsA-induced bone loss. In conclusion, immunosuppressive doses of CsA, but not FK506, lowers serum total and free Test. Hypoandrogenemia does not seem to be a major factor in CsA-induced osteopenia because bone loss occurs despite Test replacement.

Animals↗
PubMed1997

Organ-specific effects of 3,5,3'-triiodothyroacetic acid in rats.

In order to compare the effect of 3,5,3'-triiodothyroacetic acid (TRIAC) with those of triiodothyronine (T3) and thyroxine (T4), severely hypothyroid rats (n=56) were infused over 13 days with 1, 2 or 4 nmol/100 g body weight (BW) per day of T3 or 2, 4 or 8 nmol/100 g BW per day of T4 or TRIAC. The 8 nmol/100 g BW per day of T4 or TRIAC induced the same increase in resting metabolic rate, yet 4 nmol/100 g BW per day of T3 was more potent (P < 0.05). For inhibiting serum TSH levels, 2 nmol/100 g BW per day of TRIAC were significantly less active than 2 nmol/100 g BW per day of T4 or 1 nmol/100 g BW per day of T3 (TRIAC, serum TSH 35.5 +/- 5.7; T3 2.58 +/- 0.91; T4 2.12 +/- 0.59 ng/ml). At higher doses serum TSH and beta-TSH mRNA were unmeasurable. Using serum T3 levels as covariate, the action of T3 and T4 was identical on cardiac monodeiodinase type 1 (5'D1) activity and hepatic malic enzyme (Me) mRNA levels and similar for hepatic 5'D1 activity. The effect of TRIAC was compared with T3 by using increasing doses of 1, 2 and 4 nmol/100 g BW per day of T3 and 2, 4 and 8 nmol/100 g BW per day of TRIAC. ANOVA indicated that there was no major difference between the effects of the hormones since with increasing doses the response of hepatic 5'D1 mRNA levels and enzyme activity and Me mRNA remained parallel. However, when studying the effect on cardiac 5'D1 activity there was not only a difference for type of treatment (T3 > TRIAC) but this difference became greater with each increment in dose. Interestingly there was also only a small effect of TRIAC on increase in heart weight compared with T3 and T4. Brain cortex monodeiodinase type 2 (5'D2) was mainly inhibited by T4 infusions. Monodeiodinase type 3 (5'D3) was stimulated by T4, less so by TRIAC and least by T3, expressing probably the local T3 and TRIAC concentrations. In conclusion, despite apparently similar effects of TRIAC and T3 and T4 on hepatic parameters of thyroid hormone action, TRIAC differs considerably in terms of its effects on cardiac 5'D1 activity and possibly on other fundamental effects of thyroid hormones on the heart since heart weight increased significantly less with TRIAC than with T3 or T4.

Animals↗
PubMed1997

Impact of antihypertensive therapy on the skeleton: effects of moexipril and hydrochlorothiazide on osteopenia in spontaneously hypertensive ovariectomized rats.

Skeletal effects of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ), a thiazide diuretic, were studied in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Moexipril (10 mg/kg per day), HCTZ (10 mg/kg per day), alone or in combination, as well as 17 alpha-estradiol (30 micrograms/kg per day) were given to OVX SHR immediately after surgery and studied for short- and long-term effects (14 and 56 days respectively). All drugs were given orally. Histomorphometric data on the secondary spongiosa of proximal tibial metaphyses (cancellous bone) and tibiofibular junctions of tibial shafts (cortical bone) were analyzed. Ovariectomy induced cancellous bone loss in SHR by inducing negative bone balance. Estrogen prevented ovariectomy-induced cancellous bone loss in the SHR by reducing bone turnover and partially suppressing the coupling of bone formation to resorption on the endocortical surface. HCTZ reduced blood pressure after 1 week of treatment, yet this effect was no lower than that seen in controls after 3 weeks of treatment. Two weeks of HCTZ transiently prevented ovariectomy-induced increases in bone turnover rate and eroded surface. This delayed ovariectomy induced trabecular bone loss in the proximal tibial metaphysis, but had no effect on the tibial shaft. Like HCTZ, moexipril also reduced blood pressure after the first week of treatment but it had no apparent effect on either the proximal tibial metaphysis or the tibial shaft. A combination of moexipril and HCTZ exhibited a much more potent hypotensive effect and had the same effect on bone mass and dynamic end-points as HCTZ alone. Our data indicate that (1) HCTZ treatment has some transient beneficial effects on both antihypertension and osteoprotection in hypertensive osteopenic rats, (2) the combination of moexipril with HCTZ improved the antihypertensive effect but did not potentiate or hamper the osteoprotective effect of HCTZ, and (3) the skeletal effect of estrogen is not impacted by the hypertensive state. These findings are relevant for the use of ACE inhibitor and thiazide diuretics, alone or in combination, in antihypertensive therapy in postmenopausal women.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

[Effect of superoxide dismutase on membrane fluidity and functions of lymphocytes in traumatized mice].

Effect of superoxide dismutase (SOD) on membrane fluidity and functions of lymphocytes in traumatized mice was studied. The results showed that in vivo administration of SOD (10,000 U/kg.d, from 0 to 3 days posttrauma) could significantly decrease malondialdehyde (MDA) contents in serum, lymphatic tissues from spleen, thymus, mesenteric lymph nodes and T cells plasmalemma, mitochondria, microsome, restore decreased T lymphocytes and T cells in traumatized mice, elevate membrane fluidity of lymphocytes transformation (TLT), reduce interleukin 2 (IL-2) production, supprssed IL-2 receptor (IL-2R) expression and depress IL-2 mediated lymphocyte proliferation response (IL 2MLPR) after trauma in various degress. It is suggested that SOD may protect lymphocytes post trauma from damage of oxygen free radical, and elevate lymphocytes functions.

Animals↗
PubMed1997

[Separation and identification of the compounds from Achyranthes bidentata Bl].

Eight compounds were separated from the roots of Achyrathes bidentata by repeated chromatography. On the basis of physicochemical properties and spectral analysis their structures were elucidated as alpha-spinasterol (1), beta-sitosterol (2), chrysophanol (3), dibutyl phthalate (4), palmitic acid (5), alpha-spinasterol-3-O-beta-D-glucoside (6), daucosterol (7) and ecdysterone (8). Compounds 1-7 were isolated from the plant for the first time.

Anthraquinones↗
PubMed1997

[Early observation of healing of rabbit mandibular defects with porous blocks consisting of polylactic acid and recombinant human bone morphogenetic protein-2].

The effects of bone morphogenetic protein (BMP) which can induce bone formation have been surely proved, Porous polylactic-acid blocks were prepared by a freeze-drying method. During preparation of the blocks, recombinant human bone morphogenetic protein-2(rhBMP-2) was mixed with the polylactic-acid(4 mg per block). PLA-rhBMP-2 was implanted in the mandibular defects of rabbit and retrieved after 2 or 4 weeks. The results showed that: with the PLA-rhBMP-2 blocks, new bone formation was observed in 2 weeks after implantation, and plain PLA blocks produced a little of new bone formation in the edges of defect even in 4 weeks after implantation. Calcium content of the retrieved PLA-rhBMP-2 block was statistically higher than that of plain PLA blocks. These results suggest that PLA may be effective delivery system for BMP and the PLA/rhBMP-2 block may potentially have usefulness as a bone graft substitute.

Animals↗
PubMed1997

[Studies on sultamicillin hydrolysis].

Sultamicillin is an oral mutual pro-drug composed of double esters of formaldehyde hydrate in which one of the hydroxyl groups is esterified with ampicillin and the other with sulbactam. It is hydrolyzed fast in neutral or weakly alkaline condition. When hydrolyzed, it forms ampicillin and hydroxylmethyl sulbactam or sulbactam and hydroxylmethyl ampicillin by different routes. Usually, the former has priority as the two ester bonds have different activities. The ratio of ampicillin to sulbactam in the products is about 3:1. Both the hydroxylmethyl sulbactam and the hydroxylmethyl ampicillin can be further catalyzed by esterase to produce formaldehyde.

Ampicillin↗
PubMed1997

[The inhibitory effect of recombinant human C3 fragment on murine endotoxic shock].

OBJECTIVE: To study the potentially practical use of C3 inactive fragment in anti-inflammation. METHODS: A vector expressing RGD polypeptide derived from the alpha chain segment of human C3 was constructed by using PCR and genetic engineering methods and a recombinant protein (namely C 33) was expressed with high efficiency in E. coli. RESULTS: The analysis of SDS-PAGE showed the molecular weight of C 33 was about 15 KD. Its purity was above 95% after purification. The amino acid composition was inconsistent with the theoretical values. U937 cells stimulated by low dosage PMA adhered with coated C 33, and the adhesion was blocked by anti-CD 11b monoclonal antibody. After injection of purified C 33 into mice which were consequently challenged by dead E. coli, the mortality of the endotoxic shock was significantly reduced. CONCLUSION: C 33 can specifically bind to CD 11b/CD 18. C 33 as a ligand for CD 11b/CD 18 might be potentially used as an anti-inflammatory agent.

Animals↗
PubMed1996

Translocations and deletions of 5q13.1 in myelodysplasia and acute myelogenous leukemia: evidence for a novel critical locus.

Acquired partial and complete deletions of chromosome 5 (5q-, -5) are common cytogenetic anomalies associated with myelodysplasia (MDS) and acute myeloid leukemia (AML). A critical region of consistent loss at 5q31.1 (in > 90% of cases) has led us and others to postulate the presence of a key negative regulator(s) of leukemogenesis. Although the interstitial deletion limits vary among patients, del(5) (q13q33) and del(5)(q13q35) constitute major subsets. Furthermore, it is not rare to encounter deletions, translocations, or paracentric inversions involving 5q11 to 5q13, which indicates inactivation or disruption of important gene(s) at that locus. In this report, we have localized a novel locus at 5q13.1 to a 2.0-Mb interval between the anonymous markers D5S672 and GATA-P1804. This locus resided within the region of loss in 12 of 27 patients with anomalies of chromosome 5; one of these cases had apparent retention of both alleles of all the telomeric loci. Fluorescence in situ hybridization (FISH) studies demonstrate that the AML cell line ML3 is disrupted at 5q13.1 by a translocation involving chromosome 3, with apparent retention of the entire chromosome 5 sequence. Our results suggest that this novel proximal locus encodes a critical gene that may be deleted or disrupted in a subset of MDS/AML patients with chromosome 5 anomalies.

Adult↗
PubMed1996

Characterization of SH2-ligand interactions via library affinity selection with mass spectrometric detection.

Synthetic combinatorial libraries have proven to be a valuable source of diverse structures useful for large-scale biochemical screening. Their use has greatly facilitated the study of protein-protein interactions. We have developed a practical technique for screening such libraries by integrating affinity chromatography selection with electrospray ionization mass spectrometric detection, referred to as library affinity selection-mass spectrometry (LAS-MS). The process allows for rapid and efficient screening of solution phase libraries and provides detailed information such as the relative affinities of substrates. The method is generally applicable to include nonpeptide libraries; moreover, electrospray tandem mass spectrometry (ES-MS/MS) yields sequence-specific identification of individual components without the need for chemical tags. This technique is demonstrated using the Src homology 2 (SH2) domain of phosphatidylinositol 3-kinase (PI 3-kinase). The critical importance of methionine in the position +3 (relative to the phosphotyrosine position) is demonstrated in a library built with a phosphotyrosine mimic, (phosphonodifluoromethyl)phenylalanine. The described method has broad applicability to combinatorial library screening.

Amino Acid Sequence↗