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Biomedical subjects

H Shao

Publications and source records attributed to H Shao.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Clinical observation of palitaxel in the treatment of gynecologic malignant tumors].

OBJECTIVE: To observe the therapeutic effect of palitaxel. METHODS: Of 37 cases, 33 were treated when tumor recurrence occurred after surgery or chemotherapy. There were 27 cases with ovarian cancer, 6 with fallopian tube cancer. 3 with cervix cancer, and 1 with endometrium cancer. In all cases, diagnosis was confirmed by histopathology. Palitaxel (135-150 mg/m2) was administered i.v. or i.p. once every three werks in combination with cisplatin (PDD) 60 mg/m2 and cyclophosphamide (CTX) 60 mg/d. Antihistaminics and antiemetic were given prior to palitaxel. The results of treatment were compared with those in 37 cases treated in the some time period with PAC or VBP regimen. RESULTS: The overall median survival time of the control group was 4 months, and 8.5 months in the palitaxel treated group (P < 0.001). The response rate was 18.9% and 48.6% respectively (P < 0.005). The major toxic effects was myelosuppression and alopecia. CONCLUSION: Palitaxel is effective in the treatment of advanced gynecological tumors.

Adult↗
PubMed2000

[A comparison between latanoprost and timolol in treatment of patients with primary open-angle glaucoma and ocular hypertension].

OBJECTIVE: To evaluate the therapeutic value of latanoprost on glaucoma. METHODS: In an open-label fashion, multicenter, randomized control clinical trial, the efficacy and adverse drug reactions of topical application of 0.005% latanoprost once daily were compared with that of 0.5% timolol twice daily for 12 weeks in patients with open-angle glaucoma or ocular hypertension. RESULTS: The study included 128 patients (63 patients in latanoprost group and 65 patients in timolol group) and 117 patients remained at the end of the study (60 cases in latanoprost group and 57 cases in timolol group). Comparing 12 weeks with baseline diurnal intraocular pressure (IOP), the IOP reduction (mean +/- standard deviation) in latanoprost group was (7.5 +/- 0.3) mm Hg (1 mm Hg = 0.133 kPa) (32%, t = 22.73, P < 0.0001) greater than the reduction in timolol group (6.1 +/- 0.3) mm Hg (26%, t = 17.94, P < 0.0001), the difference between the two groups being significant (F = 9.54, P = 0.0026). Two patients treated with timolol and none treated with latanoprost were withdrawn from the study because of inadequate IOP control; 3 patients with latanoprost had foreign body sensation. In latanoprost group, there was one patient whose eyelashes became darker and longer at the last visit (the 12th week). No ocular and systemic adverse events related to the two drugs were found. CONCLUSION: It is demonstrated that 0.005% latanoprost topically applied once daily is well tolerated and more effective in reducing IOP than 0.5% timolol topically applied twice daily. Thus, latanoprost has the potential to be a new first-line antiglaucoma drug.

Adrenergic beta-Antagonists↗
PubMed1999

Biochemical characterization of the Ras-related GTPases Rit and Rin.

We report the biochemical characterization of Rit and Rin, two members of the Ras superfamily identified by expression cloning. Recombinant Rit and Rin bind GTP and exhibit intrinsic GTPase activity. Conversion of Gln to Leu at position 79 (for Rit) or 78 (for Rin) (equivalent to position 61 in Ras) resulted in a complete loss of GTPase activity. Surprisingly, significant differences were found when the guanine nucleotide dissociation constants of Rit and Rin were compared with the majority of Ras-related GTPases. Both proteins display higher k(off) values for GTP than GDP in the presence of 10 mM Mg(2+). These GTP dissociation rates are 5- to 10-fold faster than most Ras-like GTPases. Despite these unique biochemical properties, our data support the notion that both Rit and Rin function as nucleotide-dependent molecular switches. To begin to address whether these proteins act as regulators of distinct signaling pathways, we examined their interaction with a series of known Ras-binding proteins by yeast two-hybrid analysis. Although Rit, Rin, and Ras have highly related effector domain sequences, Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe but not with the Raf kinases, RIN1, or the p110 subunit of phosphatidylinositol 3-kinase. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors. Their biochemical properties and interaction with a subset of known Ras effector proteins suggest that Rit and Rin may play important roles in the regulation of signaling pathways and cellular processes distinct from those controlled by Ras.

Cloning, Molecular↗
PubMed1999

Slow accumulation of active mitogen-activated protein kinase during thymocyte differentiation regulates the temporal pattern of transcription factor gene expression.

Thymocyte-positive selection is believed to result from low affinity/avidity interactions of TCR and MHC proteins, but how these weak interactions translate into downstream biochemical signals and how such signals modulate gene expression is unknown. Using a culture system where isolated immature thymocytes can be induced to differentiate along the CD4 lineage pathway, we show that sustained low level mitogen-activated protein/extracellular regulated kinase activity is required for cell differentiation and survival. Furthermore, induction of mitogen-activated protein/extracellular regulated kinase activity is surprisingly slow under conditions that induce differentiation. This pattern of kinase activity not only selects which genes are expressed but also regulates the temporal pattern of expression of transcription factor genes that are induced during double-positive thymocyte differentiation.

Animals↗
PubMed1999

Grafting of genetically modified human fetal fibroblasts to produce human butyrylcholinesterase in mice.

Human diploid fibroblast cultures were established from fetal skin tissue. Enzymic dissociation yielded cultures of higher growth capacity of fibroblasts than those prepared by mechanical dissociation followed by spontaneous outgrowth of cells. Transfer of recombinant human butyrylcholinesterase (BChE, EC 3.1.1.8) gene into primary human fibroblasts was achieved successfully using lipofection and retrovirus-mediated transfection. The analysis of drug-resistant colonies suggested the presence of the transcripted BChE mRNA in the cytoplasm of transfected cells. The secreted BChE protein in culture medium was assayed for enzyme activity using butyrylthiocholine as substrate. The genetically modified fibroblasts were mixed with rat tail collagen and transplanted subcutaneously and intraperitoneally to mice. Immunoreactive human BChE appeared in the plasma from the transplanted mice. reaching the top level at day 13. It was not present any longer in most of the mice 20 days later.

Animals↗
PubMed1999

Solution structures of micelle-bound amyloid beta-(1-40) and beta-(1-42) peptides of Alzheimer's disease.

The amyloid beta-peptide is the major protein constituent of neuritic plaques in Alzheimer's disease. The beta-peptide varies slightly in length and exists in two predominant forms: (1) the shorter, 40 residue beta-(1-40), found mainly in cerebrovascular amyloid; and (2) the longer, 42 residue beta-(1-42), which is the major component in amyloid plaque core deposits. We report here that the sodium dodecyl sulphate (SDS) micelle, a membrane-mimicking system for biophysical studies, prevents aggregation of the beta-(1-40) and the beta-(1-42) into the neurotoxic amyloid-like, beta-pleated sheet structure, and instead encourages folding into predominantly alpha-helical structures at pH 7.2. Analysis of the nuclear Overhauser enhancement (NOE) and the alphaH NMR chemical shift data revealed no significant structural differences between the beta-(1-40) and the beta-(1-42). The NMR-derived, three-dimensional structure of the beta-(1-42) consists of an extended chain (Asp1-Gly9), two alpha-helices (Tyr10-Val24 and Lys28-Ala42), and a looped region (Gly25-Ser26-Asn27). The most stable alpha-helical regions reside at Gln15-Val24 and Lys28-Val36. The majority of the amide (NH) temperature coefficients were less than 5, indicative of predominately strong NH backbone bonding. The lack of a persistent region with consistently low NH coefficients, together with the rapid NH exchange rates in deuterated water and spin-labeled studies, suggests that the beta-peptide is located at the lipid-water interface of the micelle and does not become inbedded within the hydrophobic interior. This result has implications for the circulation of membrane-bound beta-peptide in biological fluids, and may also facilitate the design of amyloid inhibitors to prevent an alpha-helix-->beta-sheet conversion in Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Perioperative cimetidine application modulates natural killer cells in patients with colorectal cancer: a randomized clinical study.

Thirty-eight colorectal cancer patients were randomly assigned to treatment group, which took cimetidine in the perioperative period, and control group to which no drug was given. Twenty healthy volunteers served as normal controls. NK cells were measured by immunocytochemical technique. The results showed that NK percentages before treatment in both groups of patients were significantly lower than those in normal controls (P < 0.05). NK cell percentages at admission, before operation, on the 2nd and the 10th postoperative days were 14.84 +/- 4.41, 15.74 +/- 3.75, 17.21 +/- 3.69, 21.05 +/- 4.54, respectively, for the treatment group, and 15.00 +/- 2.77, 13.05 +/- 2.46, 14.21 +/- 2.19, 15.58 +/- 1.68, respectively, for control group. The difference was statistically significant (P < 0.01), suggesting that the perioperative administration of cimetidine could help restore NK cells in colorectal cancer patients.

Cimetidine↗
PubMed1999

Martin-Gruber communicating branch: anatomical and histological study.

We dissected 72 upper limbs of fresh cadavers and found 17 cases with a Martin-Gruber communicating branch (23.6%). These were classified into 4 types: type I (n = 5, 29.4%): communicating branch between the anterior interosseous and ulnar nn, type II (n = 3, 17.6%): Communicating branch between the median and ulnar nn., type III (n = 3, 17.6%): Communicating branch between the muscular branches to the flexor digitorum profundus m., type IV (n = 6, 35.3%): combination of type I or II and type III. At histologic examination the number and size of the nerve bundles each communicating branch contained proved to be very different. In one case of type II only a single nerve bundle was found. We suggest that the different numbers of nerve bundles innervate different amounts of the intrinsic hand musculature. The communicating branch with a single nerve bundle probably innervated only the first dorsal interosseous muscle.

Aged↗
PubMed1999

Long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.

The Wyoming strain of equine infectious anaemia virus (EIAV) is a highly virulent field strain that replicates to high titre in vitro only in primary equine monocyte-derived macrophages. In contrast, Wyoming-derived fibroblast-adapted EIAV strains (Malmquist virus) replicate in primary foetal equine kidney and equine dermis cells as well as in the cell lines FEA and Cf2Th. Wyoming and Malmquist viruses differ extensively both in long terminal repeat (LTR) and envelope region sequences. We have compared the promoter activities of the Wyoming LTR with those of LTRs derived from fibroblast-adapted viruses by examining their abilities to drive a luciferase reporter gene as well as by construction of infectious molecular clones differing only in LTR sequence. Our results indicate that LTR sequences are a major restriction for growth of the Wyoming strain of EIAV in fibroblasts.

Animals↗
PubMed1999

[Anatomic study and review of the literature on the Martin Gruber anastomosis].

We dissected 72 upper limbs of fresh cadavers and found 17 cases of the Martin-Gruber anastomosis. The incidence was 23.6%. They can be classified into 5 types. Type I (n = 5, 29.4%): Communication between the anterior interosseous and the ulnar nerves. Type II (n = 3, 17.6%): Communication between the median and the ulnar nerves. Type III (n = 3, 17.6%): Communication between the muscular branches of the flexor digitorum profundus muscle (FDP). Type IV (n = 3, 17.6%): Communication between the anterior interosseous and the ulnar nerves, the muscular branches of the flexor digitorum profundus muscle (FDP) originated from the connection. Type V (n = 3, 17.6%): The anastomotic branch originated from the median nerve and joined the ulnar at two different points as well as connecting with the ulnar branch of the FDP. Through histologic examination, we found the number and size of nerve fascicles which every connection contained to be very different. In one case of type II only one single nerve fascicle was found. We propose the hypothesis that the different amounts of nerve fascicles innervate different amounts of intrinsic hand musculature. The communication which contained one single nerve fascicle only innervate the first dorsal interosseous muscle (FDI).

Aged↗
PubMed1998

A role for p21ras/MAP kinase in TCR-mediated activation of LFA-1.

LFA-1 is a beta2 integrin that plays well-characterized roles in adhesion of T lymphocytes to APC, T cell-mediated cytolysis, and leukocyte-endothelial cell interactions. Although it is clear that LFA-1 must undergo affinity or avidity changes to bind its cellular ligand ICAM-1, the intracellular signaling pathways involved are not well characterized. Here, we show that the Ras-mitogen-activated protein kinase (MAPK) signaling pathway is also involved in TCR-activated LFA-1 adhesion. Expression of a dominant negative form of p21ras in a thymocyte cell line inhibits, while constitutively active p21ras both enhances and sustains, subsequent TCR-triggered adhesion to isolated ICAM-1. However, the Ras/MAPK pathway alone is not sufficient for activating T cell LFA-1, as inhibition of both downstream MAPK/extracellular regulated kinase kinase (MEK) activity and phosphatidylinositol 3-kinase activity is required for complete inhibition of adhesion.

Animals↗
PubMed1998

Inhibition of Alzheimer beta-fibrillogenesis by melatonin.

It is generally postulated that the amyloid beta protein (Abeta) plays a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathologic properties of this protein, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of Abeta to form beta-sheet structures or amyloid fibrils. We report that melatonin, a hormone recently found to protect neurons against Abeta toxicity, interacts with Abeta1-40 and Abeta1-42 and inhibits the progressive formation of beta-sheets and amyloid fibrils. These interactions between melatonin and the amyloid peptides were demonstrated by circular dichroism and electron microscopy for Abeta1-40 and Abeta1-42 and by nuclear magnetic resonance spectroscopy for Abeta1-40. Inhibition of beta-sheets and fibrils could not be accomplished in control experiments when a free radical scavenger or a melatonin analog were substituted for melatonin under otherwise identical conditions. In sharp contrast with conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential new therapeutic agent in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Gangliosides enhance apoptosis of thymocytes.

Monosialogangliosides, normal components of cell membranes, regulate cell development and differentiation in several organs. Our previous observation of dramatic premature thymic involution in cats with feline GM1 gangliosidosis, whose thymocytes have abnormally high cell surface gangliosides, suggested that excess GM1 ganglioside (GM1) could modulate thymocyte apoptosis in this disease (Cox et al., "Thymic Alterations in Feline GM1 Gangliosidosis," submitted). In these studies, we added exogenous GM1 to murine primary thymocyte cultures and demonstrated enhanced apoptosis in treated cells by DNA fragmentation, apoptotic body, and electrophoretic analyses. GM1-enhanced apoptosis was blocked by common apoptotic pathway inhibitors including aurintricarboxylic acid (inhibitor of endonuclease activity), actinomycin D (inhibitor of RNA transcription), and cycloheximide (inhibitor of protein synthesis). GM1 treatment primarily affected the immature CD4+ CD8+ subset, as shown by flow cytometric evaluation of fetal thymic organ culture and primary thymocyte cultures. Apoptosis also could be induced by GM2, GM3, and GT1b, whereas asialo-GM1 failed to do so, suggesting that the sialic acid moiety may play an important role in the induction of thymocyte apoptosis.

Animals↗
PubMed1998

Moment analysis of multibreath nitrogen washout in healthy preterm infants.

Moment analysis (MA) of multibreath nitrogen washout (MBNW) has not previously been applied to newborn infants. The aim of the present study was to adapt this method to healthy preterm infants using an improved technique suitable for small infants, and to determine reference values of MA. Twenty healthy preterm infants with a mean birth weight (+/-SD) of 1,666+/-402 g and a mean gestational age of 31.3+/-2.1 weeks were studied during their first 7-28 days of life. Computerized bedside equipment with very low dead space was constructed. The limits of normal variability were determined from results of duplicate studies. Outcome variables included functional residual capacity (FRC), the first-to-zeroth moment ratio (M1/M0), the second-to-zeroth moment ratio (M2/M0), and the lung clearance index (LCI). The starting point for MA had considerable impact on the results. Mean M1/M0 and M2/M0 were 2.18+/-0.18 and 8.71+/-1.24, respectively. No significant relation between moment ratios and weight, gender or age was found. Intrasubject coefficients of variation (CV) for M1/M0 (7.9+/-5.9%) and for M2/M0 (12.1+/-9.1%) and intersubject CV for M1/M0 (8%) and M2/M0 (14%) were similar to those reported in children and adults. Mean lung clearance index was 10.8+/-1.4 and intra- and intersubject CVs were 11.3+/-8.9% and 13%, respectively. Mean functional residual capacity (FRC) was 22.5+/-2.1 ml/kg. Mean intra- and intersubject CVs for FRC were 8.3% and 9%, respectively. We conclude that the MBNW test can be performed by a simple bedside method and that MA appears to be a suitable method for measuring gas mixing in preterm infants.

Breath Tests↗
PubMed1998

Disease induction by virus derived from molecular clones of equine infectious anemia virus.

Equine infectious anemia virus (EIAV), a macrophage-tropic lentivirus, causes persistent infections of horses. A number of biologic features, including the rapid development of acute disease, the episodic nature of chronic disease, the propensity for viral genetic variation, and the ability for many infected animals to eventually control virus replication, render EIAV a potentially useful model system for the testing of antiretroviral therapies and vaccine strategies. The utility of the EIAV system has been hampered by the lack of proviral clones that encode promptly pathogenic viral stocks. In this report, we describe the generation and characterization of two infectious molecular clones capable of causing acute clinical syndromes similar to those seen in natural infections. Virus derived from clone p19/wenv17 caused severe debilitating disease at 5 to 7 days postinfection; initial febrile episodes were fatal in two of three infected animals. Virus derived from a second clone, p19/wenv16, caused somewhat milder primary febrile episodes by 10 to 12 days postinfection in two of two infected animals. Virus derived from both clones caused persistent infections such that some animals exhibited chronic equine infectious anemia, characterized by multiple disease episodes. The two virulent clones differ in envelope and rev sequences.

Acute Disease↗
PubMed1998

Impaired gas mixing and low lung volume in preterm infants with mild chronic lung disease.

The aim of this study was to assess the possible role of gas mixing inefficiency in spontaneously breathing infants with mild chronic lung disease (CLD) of prematurity in relation to changes in other functional parameters. A simple bedside technique for recording and analysis of multiple breath nitrogen washout curves was applied together with occlusion mechanics. Fifteen preterm infants with mild or moderately severe CLD were studied at a mean postconceptional age of 35 wk, together with 15 healthy preterm infants at the same maturity. All infants breathed spontaneously, and the test was performed by a continuous bypass flow system, connected to a face mask, a pneumotachograph, and a nitrogen meter. The results showed impaired gas mixing with moment ratios above the 95th percentile of the normal group in 11/15 infants with CLD. Functional residual capacity (FRC) was low in 13/15 infants, but specific compliance and resistance of the respiratory system did not differ between the groups. As FRC and moment ratios were not correlated, it is suggested that they may reflect different aspects of the pathophysiology in CLD. It is concluded that low FRC and disturbed gas mixing are characteristic disturbances in CLD at different degrees of severity. The multiple breath nitrogen washout test, followed by moment analysis of end-tidal nitrogen concentrations, is a simple and sensitive method for detection of these disturbances and for monitoring purposes.

Breath Tests↗