Biomedical subjects

Hong Guo

Publications and source records attributed to Hong Guo.

At least 55 records · Page 3Linked to original sources

PubMed2005

Comparative gene genealogies indicate that two clonal lineages of Cryptococcus gattii in British Columbia resemble strains from other geographical areas.

Cryptococcus gattii has recently emerged as a pathogen of humans and animals in the temperate climate of Vancouver Island, British Columbia (B.C.). The majority (approximately 95%) of the isolates from the island belong to the VGII molecular type, and the remainder belong to the VGI molecular type. The goals of this study were to compare patterns of molecular variation among C. gattii isolates from B.C. with those from different areas of the world and to investigate the population structure using a comparative gene genealogy approach. Our results indicate that the C. gattii population in B.C. comprises at least two divergent lineages, corresponding to previously identified VGI and VGII molecular types. The genealogical analysis of strains suggested a predominantly clonal population structure among B.C. isolates, while there was evidence for sexual recombination between different molecular types on a global scale. We found no geographic pattern of strain relationships, and nucleotide sequence comparisons revealed that genotypes among isolates from B.C. were also present among isolates from other areas of the world, indicating extensive strain dispersal. The nucleotide sequence diversity among isolates from B.C. was similar to that among isolates from other areas of the world.

Animals↗

PubMed2005

New insight into the mechanism of cardiovascular dysfunction in the elderly: transfer function analysis.

This study sought to test the hypothesis that alterations in the relationships between (i) mean arterial pressure (MAP) and heart rate (HR), (ii) cardiac output (CO) and MAP, and (iii) total peripheral resistance (TPR) and MAP variability contribute to the diminished dynamic control of cardiovascular function with advanced age. Six-minute hemodynamic data were continuously recorded in 11 elderly (70 +/- 2 years) and 11 young (26 +/- 1 year) healthy volunteers under supine resting condition and during lower body negative pressure-induced orthostatic challenge. The data were converted using fast Fourier transform, and the ratio of cross-spectra to auto-spectra between two signals (i.e., MAP-HR, CO-MAP, TPR-MAP) was computed for transfer function analysis. In the low-frequency ranges (LF; 0.04-0.14 Hz) and high-frequency ranges (0.15-0.30 Hz), the gain and coherence of the transfer function describing the relationship between MAP-HR signals were significantly greater in younger than in older adults. The phase degree was significantly >0 in both groups under all conditions, suggesting that the MAP variability preceded the HR variability. In contrast, the coherence between CO-MAP signals in both age groups was <0.5, indicating that the beat-to-beat MAP variability was not significantly related to the CO signals. However, the transfer function gain and coherence of TPR-MAP signals were significantly greater in the young group (coherence >/=0.5 in the LF range), suggesting a more effective dynamic vasomotor control. In conclusion, the oscillations in CO-MAP signals are not significantly synchronized or not related in a simply linear fashion in both age groups. The MAP variability is more related to the oscillation of TPR signals in the young group only. Advanced age not only diminishes MAP-HR transfer function gain, but also weakens its coherence. Thus, alterations in the relationship between MAP-HR variability and TPR-MAP variability may significantly contribute to the diminished dynamic control of cardiovascular function manifest in the elderly.

Adult↗

PubMed2005

Design and evaluation of compound metformin/glipizide elementary osmotic pump tablets.

A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.

Delayed-Action Preparations↗

PubMed2005

[The erosion behaviour of matrix tablets using polyethylene oxide matrices as hydrophilic polymer].

AIM: To study the erosion behaviour during dissolution of matrices using different molecular weight polyethylene oxide (PEO) as hydrophilic polymer. METHODS: PEO hydrophilic matrix tablets with no added drug and excipients were prepared by direct compression method. The erosion rates of matrices comprised of pure or blending PEO polymers were evaluated in distilled water at (37 +/- 0.5) degrees C with rotating rate of 50 r x min(-1). The relationship between PEO molecular weight and erosion rate of matrices was investigated by experimental and mathematical model methods. RESULTS: The gravimetric erosion experimental results indicated that the power-law relationship which relates the polymer erosion rate and weight average molecular weight: k infinity (M(w)) -1.30 4 was proved to have great potential utility in predicting the degree of polymer erosion of matrices comprised of either intermediate molecular weight (97. 98 x 10(4) - 553. 36 x 10(4)) or blends of lower and higher molecular weight polymers. Based on the semiempirical equation for mass transfer rate: Jp = (fp < Dp > (2/3) v (-1/6) omega (1/2)) C(p,dis), a theoretical mathematic model was developed for describing the relationship between PEO erosion rate and PEO weight average molecular weight: Jp infinity M(-1.241), where the exponent of -1. 241 was very close to the exponent of - 1. 130 4 obtained from practical determination. CONCLUSION: PEO was proved to be a good candidate of hydrophilic polymer and appeared to have great potential for controlled release applications. The mathematic model presented together with the utilization of the erosion behaviour discussed in our study could provide a guide line to predict the degree of polymer erosion for other intermediate polymer grades and / or mixture of the polymers utilized in this study, which could play an active role in designing PEO hydrophilic sustained delivery systems.

Delayed-Action Preparations↗

PubMed2004

Chinese version of the M. D. Anderson Symptom Inventory: validation and application of symptom measurement in cancer patients.

BACKGROUND: Symptom management is an essential component of cancer treatment for patients of every culture and nationality. Symptom assessment depends on subjective reporting, mandating linguistically equivalent versions of symptom assessment scales. Because disease-related and treatment-related symptoms most often occur in clusters, there is a global need for a standardized multiple-symptom assessment tool. METHODS: The authors sought to validate the Chinese version of the M. D. Anderson Symptom Inventory (MDASI-C) by enrolling patients who had received various diagnoses of and different types of treatment for cancer (n = 249) in a cross-sectional symptom study conducted at an urban cancer center in China. RESULTS: Factor analysis identified 2 underlying constructs, general symptoms and gastrointestinal symptoms, which had Cronbach alpha coefficients of 0.86 and 0.84, respectively. These results were consistent with English- and Japanese-language MDASI validation studies. Known-group validity was supported by the MDASI-C's ability to detect significant differences in symptom and interference levels according to Eastern Cooperative Oncology Group performance status (ECOG PS; P < 0.001) and chemotherapy status (P < 0.05). Fifty-five percent of the study cohort had > or = 1 symptom that was considered severe (score > or = 7 on a 0-10 scale). ECOG PS was strongly associated with symptom burden (total interference score: R(2) = 0.26; P < 0.001). Fatigue, sadness, drowsiness, and lack of appetite accounted for most of the variability in the total interference score (R(2) = 0.49; P < 0.05). CONCLUSIONS: The authors demonstrated that the MDASI-C is a valid, reliable, and concise tool for measuring symptom severity and interference with functioning in Chinese cancer patients.

Adolescent↗

PubMed2004

Association of excitatory amino acid transporters, especially EAAT2, with cholesterol-rich lipid raft microdomains: importance for excitatory amino acid transporter localization and function.

In the present study, we investigated the role of membrane cholesterol in the function of glutamate transporters. Depletion of membrane cholesterol by methyl-beta-cyclodextrin resulted in reduced Na(+)-dependent glutamate uptake in primary cortical cultures. Glial glutamate transporter EAAT2-mediated uptake was more sensitive to this effect. Cell surface biotinylation and immunostaining experiments revealed that the loss of cholesterol significantly altered the trafficking of EAAT2 to the plasma membrane as well as their membrane distribution. These effects were also observed in neuronal glutamate transporter EAAT3 but to a lesser extent. Furthermore, the treatment of mouse brain plasma membrane vesicles with methyl-beta-cyclodextrin resulted in a significant reduction in glutamate uptake, suggesting that cholesterol depletion has a direct effect on the function of the glutamate transporters. Plasma membrane cholesterol is localized within discreet microdomains known as lipid rafts. Analyses of purified lipid raft microdomains revealed that a large portion of total EAAT2 and a minor portion of total EAAT1, EAAT3, and EAAT4 were associated with lipid rafts. Artificial aggregation of lipid rafts in vivo resulted in the formation of larger EAAT2-immunoreactive clusters on the cell surface. The purified lipid raft-associated fractions were capable of Na(+)-dependent glutamate uptake. Our data suggest that the glutamate transporters, especially EAAT2, are associated with cholesterol-rich lipid raft microdomains of the plasma membrane and that the association with these cholesterol-rich microdomains is important for excitatory amino acid transporter localization and function.

Amino Acid Transport System X-AG↗

PubMed2004

Clinical value of Helicobacter pylori stool antigen test, ImmunoCard STAT HpSA, for detecting H pylori infection.

AIM: To evaluate the reliability of the Helicobacter pylori stool antigen test, ImmunoCard STAT HpSA, for detecting H pylori infection. METHODS: Stool specimens were collected from 53 patients who received upper endoscopy examination due to gastrointestinal symptoms. ImmunoCard STAT HpSA was used to detect H pylori stool antigens. H pylori infection was detected based on three different tests: the urease test, Warthin-Starry staining and culture. H pylori status was defined as positive when both the urease test and histology or culture alone was positive. RESULTS: Sensitivity, specificity, positive predictive and negative predictive values and the total accuracy of ImmunoCard STAT HpSA for the diagnosis of H pylori infection were 92.6% (25/27), 88.5% (23/26), 89.3% (25/28), 92% (23/25) and 90.6% (48/53), respectively. CONCLUSION: The stool antigen test, ImmunoCard STAT HpSA, is a simple noninvasive and accurate test for the diagnosis of H pylori infection.

Adult↗

PubMed2004

The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons.

DNA topoisomerase I (Top1p) catalyzes changes in DNA topology via the formation of an enzyme-DNA covalent complex that is reversibly stabilized by the antitumor drug, camptothecin (CPT). During S-phase, collisions with replication forks convert these complexes into cytotoxic DNA lesions that trigger cell cycle arrest and cell death. To investigate cellular responses to CPT-induced DNA damage, a yeast genetic screen identified conditional tah mutants with enhanced sensitivity to self-poisoning DNA topoisomerase I mutant (Top1T722Ap), which mimics the action of CPT. Mutant alleles of three genes, DOA4, SLA1 and SLA2, were recovered. A nonsense mutation in DOA4 eliminated the catalytic residues of the Doa4p deubiquitinating enzyme, yet retained the rhodanase domain. At 36 degrees C, this doa4-10 mutant exhibited increased sensitivity to CPT, osmotic stress, and hydroxyurea, and a reversible petite phenotype. However, the accumulation of pre-vacuolar class E vesicles that was observed in doa4Delta cells was not detected in the doa4-10 mutant. Mutations in SLA1 or SLA2, which alter actin cytoskeleton architecture, induced a conditional synthetic lethal phenotype in combination with doa4-10 in the absence of DNA damage. Here actin cytoskeleton defects coincided with the enhanced fragility of large-budded cells. In contrast, the enhanced sensitivity of doa4-10 mutant cells to Top1T722Ap was unrelated to alterations in endocytosis and was selectively suppressed by increased dosage of the ribonucleotide reductase inhibitor Sml1p. Additional studies suggest a role for Doa4p in the Rad9p checkpoint response to Top1p poisons. These findings indicate a functional link between ubiquitin-mediated proteolysis and cellular resistance to CPT-induced DNA damage.

Carrier Proteins↗

PubMed2004

End-of-life care in urban areas of China: a survey of 60 oncology clinicians.

Although cancer is a leading cause of death, little is known about cancer-related end-of-life care in China. We surveyed 60 Chinese oncology clinicians' practices and attitudes toward end-of-life care. Fewer than half reported available hospital-based hospice service, although mast urban cancer patients die in the hospital. Most clinicians reported they felt competent to care for dying patients--more competent in controlling pain, constipation, nausea, and vomiting, but less competent in managing depression, anorexia, and dyspnea. Regarding disclosure, most believed that patients should know and want to know their diagnosis and stage, whereas families strongly resist informing patients. Unrealistic family expectations, fears of depressing patients, and physician reluctance to stop treatment were barriers to disclosing prognosis to patients, to ending anti-cancer therapy, and to starting palliative care. Results of the survey suggest specific training and research in symptom management that might improve end-of-life care for Chinese cancer patients.

Attitude of Health Personnel↗

PubMed2004

Validation study of the Chinese version of the Brief Fatigue Inventory (BFI-C).

A cross-sectional study was conducted among 249 Chinese cancer patients with multiple diagnoses to validate a Chinese version of the Brief Fatigue Inventory (BFI-C). Cronbach's coefficient alpha was 0.92 for fatigue severity items and 0.90 for fatigue interference items. Construct validity was explored by principal factor analysis and suggested a two-factor solution: fatigue severity and fatigue interference. Internal consistency reliability was excellent. Convergent validity was examined by correlating the BFI-C with 2 subscales and 2 component scores of the MOS 36-Item Short-Form Health Survey (coefficients ranged between -0.44 and -0.71, P<0.001). Known-group validity was examined by comparing fatigue severity in patients having different scores on the Eastern Cooperative Oncology Group Performance Status Scale. Approximately 60% of patients experienced moderate to severe fatigue (4 or greater on the 0-10 scale of the BFI-C "fatigue worst" item). The BFI-C is a valid, reliable instrument to measure the severity and impact of cancer-related fatigue among Chinese patients.

Adult↗

PubMed2004

Polyprotein cleavage mechanism of SARS CoV Mpro and chemical modification of the octapeptide.

The cleavage mechanism of severe acute respiratory syndrome (SARS) coronavirus main proteinase (M(pro) or 3CL(pro)) for the octapeptide AVLQSGFR is studied using molecular mechanics (MM) and quantum mechanics (QM). The catalytic dyad His-41 and Cys-145 in the active pocket between domain I and II seem to polarize the pi-electron density of the peptide bond between Gln and Ser in the octapeptide, leading to an increase of positive charge on C(CO) of Gln and negative charge on N(NH) of Ser. The possibility of enhancing the chemical bond between Gln and Ser based on the "distorted key" theory [Anal. Biochem. 233 (1996) 1] is examined. The scissile peptide bond between Gln and Ser is found to be solidified through "hybrid peptide bond" by changing the carbonyl group CO of Gln to CH(2) or CF(2). This leads to a break of the pi-bond system for the peptide bond, making the octapeptide (AVLQSGFR) a "distorted key" and a potential starting system for the design of anti SARS drugs.

Amino Acid Sequence↗

PubMed2004

Expression of members of the 28-kilodalton major outer membrane protein family of Ehrlichia chaffeensis during persistent infection.

The 28-kDa immunodominant outer membrane proteins (P28 OMPs) of Ehrlichia chaffeensis are encoded by a multigene family. As an indirect measure of the in vivo expression of the members of the p28 multigene family of E. chaffeensis, sera from two beagle dogs experimentally infected with E. chaffeensis were evaluated for the presence of specific antibodies to P28 OMPs by enzyme-linked immunosorbent assay. Antigenic peptides unique to each of the P28s were identified within the first hypervariable region of each P28 OMP. Serological responses to peptides derived from all P28 OMPs were detected from day 30 postinoculation to day 468 and from day 46 until day 159 in the two beagles. Although antibody titers to the peptides fluctuated, the peak response to all of the peptides appeared simultaneously in each dog. The antibody responses to another outer membrane protein of E. chaffeensis (GP120) showed similar temporal and quantitative changes. These data suggest that the P28 OMPs are expressed concurrently during persistent Ehrlichia infection.

Amino Acid Sequence↗

PubMed2004

[The clinical and pathological features of rhinocerebral mucormycosis].

OBJECTIVE: To investigate the clinical and pathological features of rhinocerebral mucormycosis. METHODS: The clinical data of three cases of mucormycosis were collected and analyzed. Pathological examination was conducted by autopsy or biopsy. RESULTS: All the three cases of mucormycosis had diabetic ketoacidosis. The early symptoms were fever, periocular and temporal headache. Gradually, orbital apex syndrome, periocular skin cellulitis and necrosis developed. Examination of nose revealed black necrotic turbinates. Meningeal signs and hemiplegia may also occur. Frontal hemorrhagic infarction was seen in pathology. A large amount of mucor fungi were found in the mucosa of nasal sinuses necrotic brain tissue under microscope. CONCLUSIONS: Rhinocerebral mucormycosis is a rare complication which was mainly seen in patients with diabetic ketoacidosis. The lesion invaded nose, eyes and brain with a high mortality.

Biopsy↗

PubMed2004

[An analysis about the safe range of thickness of the residual corneal stroma bed after LASIK].

OBJECTIVE: To ascertain the safe range of thickness of the residual corneal stroma bed and the length of stable time after LASIK operation. METHODS: Two hundred and twenty seven eyes were randomly selected from cases treated with LASIK in 2000. The posterior curvature of cornea was measured by Obscan II preoperatively and 1, 2, 3, 6 months, 1 year and 2 year postoperatively. These data were compared and analyzed. RESULTS: Ectasia of central corneal posterior surface was detected at different degrees in all cases at the early postoperative period after LASIK. Ectasia was more prominent in eyes with thinner corneal stroma bed (< 300 microm). In eyes with thicker corneal stroma, ectasia remained stable or reverting obviously during the first year. The posterior curvature of cornea had no significant difference between 1 year and 2 year after operation in all cases. CONCLUSIONS: Ectasia of corneal posterior surface presents in the early postoperative period after LASIK. It is safer to reserve more than 300 microm of the corneal stroma bed. The posterior curvature of cornea of all cases remains stable after one year postoperatively.

Adolescent↗

PubMed2003

Analyzing antibody specificity with whole proteome microarrays.

Although approximately 10,000 antibodies are available from commercial sources, antibody reagents are still unavailable for most proteins. Furthermore, new applications such as antibody arrays and monoclonal antibody therapeutics have increased the demand for more specific antibodies to reduce cross-reactivity and side effects. An array containing every protein for the relevant organism represents the ideal format for an assay to test antibody specificity, because it allows the simultaneous screening of thousands of proteins for possible cross-reactivity. As an initial test of this approach, we screened 11 polyclonal and monoclonal antibodies to approximately 5,000 different yeast proteins deposited on a glass slide and found that, in addition to recognizing their cognate proteins, the antibodies cross-reacted with other yeast proteins to varying degrees. Some of the interactions of the antibodies with noncognate proteins could be deduced by alignment of the primary amino acid sequences of the antigens and cross-reactive proteins; however, these interactions could not be predicted a priori. Our findings show that proteome array technology has potential to improve antibody design and selection for applications in both medicine and research.

Antibodies↗

PubMed2003

Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects.

Nonimmunosuppressant ligands, exemplified by GPI 1046 (1), for the peptidyl-prolyl isomerase FKBP12 have been found to unexpectedly possess powerful neuroprotective and neuroregenerative effects in vitro and in vivo. We have extensively explored the therapeutic utility of FKBP12 ligands based on analogues of proline and pipecolic acid. As part of our ongoing program to explore novel structural classes of FKBP12 ligands, we herein wish to report a new class of FKBP12 ligands containing aza-proline and aza-pipecolic acid analogues. Details of the synthetic studies, together with biological activity will be presented.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality.

Eukaryotic DNA topoisomerase I (Top1) is a monomeric protein clamp that functions in DNA replication, transcription, and recombination. Opposable "lip" domains form a salt bridge to complete Top1 protein clamping of duplex DNA. Changes in DNA topology are catalyzed by the formation of a transient phosphotyrosyl linkage between the active-site Tyr-723 and a single DNA strand. Substantial protein domain movements are required for DNA binding, whereas the tight packing of DNA within the covalent Top1-DNA complex necessitates some DNA distortion to allow rotation. To investigate the effects of Top1-clamp closure on enzyme catalysis, molecular modeling was used to design a disulfide bond between residues Gly-365 and Ser-534, to crosslink protein loops more proximal to the active-site tyrosine than the protein loops held by the Lys-369-Glu-497 salt bridge. In reducing environments, Top1-Clamp was catalytically active. However, contrary to crosslinking the salt-bridge loops [Carey, J. F., Schultz, S. J., Sission, L., Fazzio, T. G. & Champoux, J. J. (2003) Proc. Natl. Acad. Sci. USA 100, 5640-5645], crosslinking the active-site proximal loops inhibited DNA rotation. Apparently, subtle alterations in Top1 clamp flexibility impact enzyme catalysis in vitro. Yet, the catalytically active Top1-Clamp was cytotoxic, even in the reducing environment of yeast cells. Remarkably, a shift in redox potential in glr1Delta cells converted the catalytically inactive Top1Y723F mutant clamp into a cellular toxin, which failed to induce an S-phase terminal phenotype. This cytotoxic mechanism is distinct from that of camptothecin chemotherapeutics, which stabilize covalent Top1-DNA complexes, and it suggests that the development of novel therapeutics that promote Top1-clamp closure is possible.

Camptothecin↗

PubMed2003

Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice.

The glial glutamate transporter EAAT2 is primarily responsible for clearance of glutamate from the synaptic cleft and loss of EAAT2 has been previously reported in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. The loss of functional EAAT2 could lead to the accumulation of extracellular glutamate, resulting in cell death known as excitotoxicity. However, it is still unknown whether it is a primary cause in the cascade leading to neuron degeneration or a secondary event to cell death. The goals of this study were to generate transgenic mice overexpressing EAAT2 and then to cross these mice with the ALS-associated mutant SOD1(G93A) mice to investigate whether supplementation of the loss of EAAT2 would delay or rescue the disease progression. We show that the amount of EAAT2 protein and the associated Na+-dependent glutamate uptake was increased about 2-fold in our EAAT2 transgenic mice. The transgenic EAAT2 protein was properly localized to the cell surface on the plasma membrane. Increased EAAT2 expression protects neurons from L-glutamate induced cytotoxicity and cell death in vitro. Furthermore, our EAAT2/G93A double transgenic mice showed a statistically significant (14 days) delay in grip strength decline but not in the onset of paralysis, body weight decline or life span when compared with G93A littermates. Moreover, a delay in the loss of motor neurons and their axonal morphologies as well as other events including caspase-3 activation and SOD1 aggregation were also observed. These results suggest that the loss of EAAT2 may contribute to, but does not cause, motor neuron degeneration in ALS.

Amyotrophic Lateral Sclerosis↗