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Biomedical subjects

G Shi

Publications and source records attributed to G Shi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents.

BACKGROUND: Folate cofactors are essential for life. Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo. Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. RESULTS: The crystal structure of HPPK from Escherichia coli has been determined at 1.5 A resolution with a crystallographic R factor of 0.182. The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 A long, 10 A wide and 10 A deep. The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy. The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains. The ATP-binding site is located at the other end of the valley. The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP. CONCLUSIONS: The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer. Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents.

Adenosine Triphosphate↗
PubMed1999

Esophageal solid bolus transit: studies using concurrent videofluoroscopy and manometry.

OBJECTIVE: Our aim was to assess the efficacy and mechanism of solid bolus transit through the esophagus. METHODS: Eight healthy volunteers were studied with concurrent manometry and videofluoroscopy while swallowing 5 ml liquid barium, a 5-6 mm diameter bread ball, and 4 g chewed bread in both a supine and upright posture. As many as four successive swallows were performed until clearance was achieved. RESULTS: The esophageal clearance of liquid barium was 100% with the first swallow. Clearance of the unchewed bread ball occurred with the first swallow in only 6.7% of trials in the upright posture and 5.9% in the supine posture. After four swallows, clearance was 100% and 52.9% in the upright and supine postures, respectively. Chewed bread was more readily cleared than unchewed bread, with 100% clearance after two swallows in the upright posture and 91% clearance after four swallows in the supine posture. The most common locus of bread stasis was at the aortic arch and carina. The bread boluses were noted to move more effectively when localized in the head as opposed to the tail of the bolus composite. Nonocclusive contractions often occurred at the bolus tail despite the increased peristaltic amplitude seen with the chewed bread. Failed peristalsis, a frequent cause for solid clearance failure, was observed during 30% of all bread swallows. This usually occurred distal to the stopping point of the bolus, suggesting it to be the result rather than the cause of impaired transit. CONCLUSIONS: Although infrequently perceived by these normal subjects and in contradistinction to liquid clearance, bread is rarely cleared from the esophagus with a single swallow. Mastication and an upright posture facilitate the esophageal transport of solids. Bolus composition and impaired bolus transit alter the amplitude and conductance of peristalsis. Manometric data pertaining to liquid clearance through the esophagus do not readily apply to bread.

Adult↗
PubMed1999

[A light and scanning electron microscopic study of primary teeth in hypophosphatasia].

OBJECTIVE: To investigate the features of primary tooth structure in hypophosphatasia. METHODS: Three primary teeth from two patients at age of 3 yr-6 month and 4 yr-2 month, who were diagnosed hypophosphatasia. The structural changes of these teeth were examined by light microscopy, polarizing microscopy and scanning electron microscopy. RESULTS: The complete absence of cementum was a prominent feature in all the teeth, three small island-shape cementun areas were found in scanning electron microscopy. A large number of resorptions were found on the root surfaces, particularly near apical portions of roots. The main findings included disturbances of dentin mineralization, hypoplasia or aplasia of root cementum and external resorption of root dentin. CONCLUSION: The hypoplasia or aplasia of root cementum was thought to be the prime etiological factor in the early loss of primary teeth.

Child, Preschool↗
PubMed1999

Establishment of immunoglobulin M(IgM)-immunosorbent agglutination assay (ISAGA) for diagnosis of toxoplasmosis.

AIM: To establish an immunosorbent agglutination assay (ISAGA) for detection of IgM antibodies against Toxoplasma gondii. METHODS: In the ISAGA, wells of microtiter plates were coated with anti-human IgM antibodies and sealed with 1% bovine serum albumin. After the test sera were added and incubated, the plates were washed, T. gondii tachyzoite antigen suspension was added, and incubated overnight at 37 degrees C. The ISAGA results were evaluated by comparing with those detected by Danish ISAGA and ELISA and those detected by slide enzyme immunoassay (S-EIA). RESULTS: Forty-four sera from Danish pregnant women were tested by the IgM-ISAGA, 41(93.2%) were consistent with the Danish results. Sixty-seven sera from Danish and Shanghai pregnant women were detected by IgM-IgM-ISAGA and S-EIA, the total consistency rate was 92.5%. A significant correlation was found between the titers of the ISAGA and S-EIA, with a Pearson correlation coefficient of 0.589(P < 0.001). The titers of ISAGA were eighteen times higher than those of S-EIA. This method enables the detection of IgM antibodies as low as approximately 0.08 IU/ml. CONCLUSION: The IgM-ISAGA is therefore sensitive, specific, easy to perform, and is useful for mass screening and diagnosing recent Toxoplasma infection or reactivation.

Agglutination Tests↗
PubMed1999

[Dynamic changes in the expression of type VI collagen in mice with schistosomal liver fibrosis].

AIM: To clarify the dynamic changes in type VI procollagen mRNA expression and collagen content in mice with schistosomal liver fibrosis. METHODS: Northern blot hybridization and immunohistochemical technique. RESULTS: The expression of alpha 1(VI) procollagen mRNA measured by Northern blot hybridization in the liver of schistosome infected mice was elevated significantly at 8 wk post infection, peaked at 10 wk pi, slightly decreased at 12-16 wk pi, and sustained at high levels until 20 wk pi. Immunohistochemical assay revealed that the staining pattern of type VI collagen first appeared in the walls of central veins and liver sinusoids at 8 wk pi, then extended gradually to the egg granuloma and the portal tract, within and surrounding the egg granuloma to form dense reticular septum at the 12, 16 and 20 wk pi, respectively. The VI collagen content as indicated by the intensity of stain peaked at 16 wk pi. CONCLUSION: Both the expression of alpha 1(VI) procollagen and the content of collagen VI were significantly increased in the liver of mice with early schistosomal fibrosis, suggesting that the type VI collagen detection might be of importance for evaluating the intensity of schistosomal liver fibrosis.

Animals↗
PubMed1999

[6A8 cDNA encodes A type of alpha-mannosidase].

OBJECTIVE: To find the nature of the protein encoded by 6A8 cDNA. METHODS: In the light of that the ligand of Con A is mannoses and that the function of alpha-mannosidase is trimming of mannoses in the oligosaccharide chains of glycoproteins, COS-7 cells and CNE-2L2 cells, a cloned cell line of human nasopharyngeal carcinoma, were transfected with pRc/CMV-sense 6A8 cDNA or pRc/CMV-antisense 6A8 cDNA and the Con A binding to the cells was examined upon a lazer scan confocal microscope. RESULTS: The data demonstrated that with transfection of pRc/CMV-sense 6A8 cDNA the binding of Con A to the cells was decreased, but the staining of the cells with mAb 6A8 was enhanced, and vise versa for the cells with transfection of pRc/CMV-antisense 6A8 cDNA. CONCLUSIONS: The protein encoded by 6A8 cDNA might be a type of alpha-mannosidase recognized by mAb 6A8.

Animals↗
PubMed1999

[Simultaneous determination of tungsten, molybdenum and titanium by k-factor dual-wavelength standard addition method].

In this paper, a new method for simultaneous spectropthotometric determination of tungsten, molybdenum and titanium is proposed. The method is based on the difference of absorption spectra of the three elements forming coloured complexes with PF in acidic medium and in the presence of nonionic surfactant Tween-80. The absorbance of sample was measured at wavelengths of 503, 530 and 560 nm, and the data were treated by the principle of the k coefficients and dual-wavelength standard addition method. The method has been applied to the determination of tungsten, molybdenum and titanium in steels, and satisfactory results were obtained.

English Abstract↗
PubMed1998

Neuroendocrine synaptic vesicles are formed in vitro by both clathrin-dependent and clathrin-independent pathways.

In the neuroendocrine cell line, PC12, synaptic vesicles can be generated from endosomes by a sorting and vesiculation process that requires the heterotetrameric adaptor protein AP3 and a small molecular weight GTPase of the ADP ribosylation factor (ARF) family. We have now discovered a second pathway that sorts the synaptic vesicle-associated membrane protein (VAMP) into similarly sized vesicles. For this pathway the plasma membrane is the precursor rather than endosomes. Both pathways require cytosol and ATP and are inhibited by GTPgammaS. The second pathway, however, uses AP2 instead of AP3 and is brefeldin A insensitive. The AP2-dependent pathway is inhibited by depletion of clathrin or by inhibitors of clathrin binding, whereas the AP3 pathway is not. The VAMP-containing, plasma membrane-derived vesicles can be readily separated on sucrose gradients from transferrin (Tf)-containing vesicles generated by incubating Tf-labeled plasma membrane preparations at 37 degreesC. Dynamin- interacting proteins are required for the AP2-mediated vesiculation from the plasma membrane, but not from endosomes. Thus, VAMP is sorted into small vesicles by AP3 and ARF1 at endosomes and by AP2 and clathrin at the plasma membrane.

ADP-Ribosylation Factor 1↗
PubMed1998

Total synthesis of brevetoxin A.

Brevetoxin A is the most potent neurotoxin secreted by Gymnodinium breve Davis, a marine organism often associated with harmful algal blooms known as 'red tides'. The compound, whose mechanism of action involves binding to and opening of sodium channels, is sufficiently toxic to kill fish at concentrations of nanograms per ml and, after accumulation in filter-feeding shellfish, to poison human consumers. The precise pathway by which nature constructs brevetoxin A is at present unknown, but strategies for its total synthesis have been contemplated for some time. The synthetic challenge posed by brevetoxin A reflects the high complexity of its molecular structure: 10 oxygen atoms and a chain of 44 carbon atoms are woven into a polycyclic macromolecule that includes 10 rings (containing between 5 and 9 atoms) and 22 stereogenic centres. Particularly challenging are the 7-, 8- and 9-membered rings which allow the molecule to undergo slow conformational changes and force a 90 degrees twist at one of its rings. Here we describe the successful incorporation of methods that were specifically developed for the construction of these rings into an overall strategy for the total synthesis of brevetoxin A in its naturally occurring form. The convergent synthesis reported here renders this scarce neurotoxin synthetically available and, more importantly, allows the design and synthesis of analogues for further biochemical studies.

Animals↗
PubMed1998

Inhibition of prostaglandin-induced intestinal secretion by igmesine in healthy volunteers.

BACKGROUND & AIMS: Igmesine, a final sigma ligand, has been shown to inhibit intestinal secretion and diarrhea in animal models. The purpose of this study was to measure the inhibitory effect of igmesine on basal and prostaglandin E2 (PGE2)-induced jejunal secretion in normal volunteers. METHODS: Jejunal absorption of water and electrolytes was measured with a three-lumen open-segment perfusion method in 16 volunteers. A double-blind crossover study was performed involving intraluminal infusion of PGE2 after oral administration of placebo or igmesine at two doses. RESULTS: PGE2 induced net secretion of water and electrolytes (P < 0.01 vs. basal conditions). The effect of PGE2 on water and electrolytes was not changed by 25 mg of igmesine but was suppressed by 200 mg of igmesine. This effect lasted at least 3 hours after a single oral dose. Igmesine at a dose of 200 mg also produced a significant decrease in basal rates of water and electrolyte absorption. CONCLUSIONS: Igmesine, a final sigma ligand, inhibits PGE2-induced intestinal secretion in normal humans. Evaluating the drug in chronic diarrheas may be of interest.

Adult↗
PubMed1998

On-demand treatment of gastro-oesophageal reflux symptoms: a comparison of ranitidine 75 mg with cimetidine 200 mg or placebo.

AIM: To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro-oesophageal reflux disease during a 15-day period. METHODS: A total of 1336 patients (aged > or = 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end-point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h). RESULTS: Analysis was performed in an intention-to-treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end-point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group. The three treatment groups did not differ in terms of tolerability. CONCLUSION: On-demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux-related symptoms.

Adolescent↗
PubMed1998

Lower esophageal sphincter relaxation characteristics using a sleeve sensor in clinical manometry.

OBJECTIVE: We undertook this study to determine the characteristics of swallow-induced lower esophageal sphincter (LES) relaxation in the setting of clinical manometry using a standardized methodology. METHODS: We reviewed 170 manometric recordings performed using a perfused manometric assembly with a sleeve sensor and a computer polygraph. Patients were categorized as patient controls, gastroesophageal reflux disease (GERD), diffuse esophageal spasm (DES), or achalasia. Tracing were semiautomatically analyzed for basal LES pressure, LES pressure during deglutitive relaxation (relaxation LES pressure), duration of LES relaxation, timing of LES relaxation, and the success rate of primary peristalsis. RESULTS: Forty-six patient controls, 93 with GERD, five with DES, and 26 with achalasia were identified. GERD and achalasia patients had lower or higher basal LES pressures than patient controls, respectively. Compared with patient controls, achalasia patients had higher relaxation LES pressures, lower percent LES relaxation, and shorter durations of LES relaxation. The best single measure for distinguishing achalasia was the relaxation LES pressure; using the 95th percentile value of patient controls (12 mm Hg) as the upper limit of normal, its sensitivity and positive predictive value for the diagnosis of achalasia were 92% and 88%, respectively. Coupled with the finding of aperistalsis, a relaxation LES pressure > or = 10 mm Hg achieved 100% sensitivity and positive predictive value among these patients. CONCLUSIONS: Sleeve sensor recording is a practical method for clinical manometry that reliably records LES relaxation characteristics and is amenable to both a standardized manometry protocol and a semiautomated analysis routine. Relaxation LES pressure has a high diagnostic value for achalasia.

Deglutition↗
PubMed1998

Immunohistochemical study of Fas antigen expression in synovial tissues from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the location and expression of Fas (Apo-1, CD-95) antigen in synovial tissue from rheumatoid arthritis (RA). METHODS: Immunohistochemical technique was used to identify the location and expression of Fas antigen in synovial tissues from 27 RA, 11 osteoarthritis (OA), 7 ankloysing spondylitis (AS), 3 pigmented villo-hyperplastic synovitis, 1 juvenile rheumatoid (JRA) patients and 5 "normal" control subjects. RESULTS: Fas was strongly expressed by synoviocytes and infiltrated lymphocytes in approximately two-thirds of RA patients (16/27). However, only weak expression occurred on lymphocytes in 3 of 11 OA, 1 of 7 AS patients and 1 of 5 "normal" subjects. The stain-positive substance in the forms of rings, granules, or dust was deposited on the cell membrane and in cytoplasm. CONCLUSION: The expression of Fas may be involved in the mechanism of synovium proliferation and abnormal activation of local lymphocytes in RA.

Adult↗
PubMed1998

[Weight gain pattern in normal pregnant women].

OBJECTIVE: The purpose of this study was to determine the maternal weight gain pattern of normal pregnant women. METHODS: One thousand five hundred and sixty-two (1,562) women, with 11,059 records, received prenatal care and had their babies delivered at the Second Hospital of West China University of Medical Sciences during the period of Jan. 1-Dec. 31, 1995. All the women without complications and with their babies weighted between 2,500-3,999 g were included, and data was analyzed. RESULTS: The average age was 26.49 +/- 3.02 and height 158.69 +/- 4.85 cm. The women were divided into three categories according to their prepregnant body mass index (BMI): underweight (< 16.75), normal weight (16.75-23.71) and overweight (> 23.71). The BMIs of each categories increased as gestational week approached to the term, with total BMI increase as 8.07, 5.37, 3.82 for underweight, normal weight and overweight, respectively. CONCLUSION: BMI, calculated with weight and height, is more accurate to assess maternal weight gain than weight alone do, and above results and accompanied charts could be used to monitor maternal weight gain as a reference.

Adult↗
PubMed1998

[Molecular analysis of HLA-DR beta polymorphism in Han nationality patients with rheumatoid arthritis].

OBJECTIVE: To analyze the molecular basis for HLA-DR associations with rheumatoid arthritis(RA) in the han nationality of Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to dertermine DRB1 alleles in 35 unrelated patients with RA and 100 healthy controls from the Han nationality. RESULTS: The frequency of DR4(DRB1 * 04) was 51.4% in RA patients and 24.0% in the healthy controls(P < 0.01, RR = 3.3). There was a significant increase in the presence of the amino acid sequences QKRAA or QRRAA both in the RA patients overall compared with the healthy group(65.7% vs 30.0%, P < 0.001) and in DR4+ RA patients compared with DR4+ healthy individuals(100% vs 75.0%, P < 0.05). Substitution of residues in QKRAA, V85 and G86 appeared to correlate with relative risk for RA, among the subjects having 0-1 amino acid substitution, RA occurred in 48.8%, whereas in subjects with 2-3 amino acid changes, RA was present in only 16.7%. CONCLUSION: These results suggest that DR4 is strongly associated with RA in the Han nationality, and the dominant effect that determines susceptibility to RA is associated with QKRAA or QRRAA as well as V85 and G86.

Adult↗