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Biomedical subjects

C Cheng

Publications and source records attributed to C Cheng.

At least 91 records · Page 5Linked to original sources

Diagnosis and management of acute alcohol withdrawal.

Alcohol abuse produces a considerable burden of illness in the Canadian population. The diagnosis of alcohol dependence and withdrawal can be difficult, particularly in the setting of covert intake or comorbidity. Two validated scales, the CAGE questionnaire to screen for alcohol abuse and dependence and the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale to assess the severity of withdrawal, are valuable tools for clinicians to use on a regular basis. For the treatment of alcohol withdrawal, compelling anecdotal evidence supports the routine administration of thiamine, but not necessarily other vitamins. Phenytoin has not been shown to be superior to placebo for uncomplicated withdrawal seizures. Neuroleptics are not recommended for routine use. Sedation with benzodiazepines guided by the CIWA-Ar results is recommended. There is good evidence that the management of alcohol withdrawal can be improved with the routine use of the CIWA-Ar scale to assess severity, treatment with adequate doses of benzodiazepines and follow-up monitoring of patients in alcohol withdrawal.

Acute Disease↗

Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves.

Nitric oxide may be liberated as an inflammatory mediator within injured peripheral nerve trunks. We evaluated the proximal stumps of injured peripheral nerve stumps that later form neuromas or regenerative nerve sprouts, for evidence of local nitric oxide elaboration and activity. Proximal stumps were created in male Sprague-Dawley rats by sectioning of the sciatic nerve and resection of its distal portions and branches. There was striking physiological evidence of nitric oxide activity at the tips of 48-h and 14-day-old proximal nerve stumps. We detected local nitric oxide-mediated hyperemia of both extrinsic plexus and endoneurial microvessels that was reversible, in a dose-dependent stereospecific fashion, by the broad-spectrum nitric oxide synthase inhibitors, Nomega-nitro-L-arginine-methyl ester or Nomega-nitro-L-arginine, but not by 7-nitroindazole, an inhibitor with relative selectivity for neuronal nitric oxide. Immunohistochemical studies provided evidence for the localization of nitric oxide generators at the same sites. In 48-h but not 14-day stumps increased expression of two isoforms of nitric oxide synthase was detected: endothelial nitric oxide and to a much lesser extent neuronal nitric oxide synthase. Both isoforms appeared in axonal endbulb-like profiles that co-localized with neurofilament immunostaining. Western immunoblots identified a band consistent with endothelial nitric oxide synthase expression. In 14-day stumps with early neuroma formation, but not 48-h stumps, there was staining for immunological nitric oxide synthase in some endoneurial and epineurial macrophages. Total nitric oxide synthase biochemical enzymatic activity, measured by labelled arginine to citrulline conversion, was increased in 14-day but not 48-h stumps. Injured peripheral nerves have evidence of early nitric oxide action, nitric oxide synthase expression and nitric oxide activity in proximal nerve stumps. Nitric oxide may have an important impact on the regenerative milieu.

Animals↗

Gender-role differences in susceptibility to the influence of support availability on depression.

Previous gender-role research on depression has revealed a consistent inverse relationship between masculinity and depression, but a non-significant relationship between femininity and depression. In light of the stronger affiliative needs for feminine individuals, received social support was speculated to moderate the relationship between femininity and depression in the present research. In a longitudinal study of a sample of Hong Kong college students, the relationships among gender-role orientation, received social support, and depression were examined. Consistent with previous findings, masculinity and androgyny were inversely related to depression. Moreover, the present study supplemented previous research by revealing that femininity was related to depression through its interaction with received social support. When the amount of received social support was increased, femininity was associated with a reduction in depression level over time. In contrast, when the amount of received social support was decreased, depression tended to increase with femininity over time. The findings are discussed in terms of their implications for the gender-role literature.

Adaptation, Psychological↗

Effects of VEGF administration following ischemia on survival of the gracilis muscle flap in the rat.

The incidence of free flap transplantation failure is only 3% to 5%, yet still occurs in cases in which the flap suffers prolonged ischemia. The purpose of the current study was to determine the effects of vascular endothelial growth factor (VEGF)--a potent angiogenic agent with a suspected role in the protection of endothelium--on flap survival in a model of ischemia-reperfusion injury. The model chosen was the rat gracilis muscle flap. A total of 36 adult male Sprague-Dawley rats were divided into three groups (N = 12). One experimental group received VEGF treatment and the other received heparin. A third group was treated with saline and served as the control. The gracilis muscle flap was dissected and isolated based on a vascular pedicle originating at the femoral vessels. Following 3.75 hours of ischemia, induced by clamping the femoral vessels, either VEGF, heparin, or saline was infused directly into the pedicle of the flap via a cannula. The flaps were evaluated both grossly and histologically after 72 hours of reperfusion. Eleven of the 12 flaps from the VEGF group survived, whereas the survival rate was 6 of 12 and 5 of 12 flaps for the heparin- and saline-treated groups respectively. Flap survival was significantly greater in the VEGF-treated group compared with the heparin- and saline-treated groups (p < 0.025, p < 0.01 respectively). Furthermore, there was no significant difference between the heparin and saline groups. These results indicate that VEGF plays a role in reducing the damage that occurs in ischemia-reperfusion injury, and that the use of VEGF holds promise as a potential therapy for increasing flap survival.

Animals↗

The role of the bladder tumour antigen test in the management of gross haematuria.

BACKGROUND: The bladder tumour antigen (BTA) test has been found to be more sensitive than urine cytology for the detection of recurrent bladder cancer. We chose to evaluate the role of the bladder tumour antigen test in the management of gross haematuria on initial presentation. METHODS: A prospective analysis over a 3-month period of consecutive cases of gross haematuria was conducted. Routine investigations including intravenous urogram, flexible cystoscopy, urine cytology testing and BTA testing were performed. Results were correlated with the final diagnosis, and also with histology and tumour stage in the cases of malignant outcome. RESULTS: The prevalence of malignancy in our series was 25.5%. Sensitivity of the BTA test was 67% and specificity 66%. This was compared to cytology which yielded a sensitivity of 66% and specificity of 100%. There were 12 cases of falsely positive results on BTA testing, giving a positive predictive value of 40%. Four cases of falsely negative results were all from superficial tumours. CONCLUSION: In view of its poor sensitivity and positive predictive value, the BTA test has a limited role in the initial management of gross haematuria.

Adult↗

Intelligent visualization and exploration of time-oriented clinical data.

Physicians and other care providers often need to quickly browse and interpret large numbers of time-oriented clinical data. Reducing the information overload involving such tasks is a major goal for medical information systems. We describe a conceptual architecture and software implementation specific to the task of interpretation, summarization, visualization, explanation, and interactive exploration of time-oriented clinical data and the multiple levels of meaningful concepts that can be derived from these data. We build on our work on abstraction of time-oriented clinical data using a knowledge base, acquired from expert physicians, of temporal properties of the data. The core module of the new framework is called KNAVE (Knowledge-based Navigation of Abstractions for Visualization and Explanation). Health care providers can manipulate the display though several visualization and exploration operators. These operators have semantics that are domain independent but that are customized automatically for the application by access to the domain-specific knowledge base. The display, which reflects data and derived interpretations in the patient's database, changes when the user explores key relations (e.g., the dependency hierarchy) in the knowledge base of the relevant clinical domain. Preliminary assessment of the initial prototype with several clinical users has been encouraging. The KNAVE methodology has broad ramifications for reducing the load that large numbers of time-oriented clinical data put on care providers.

Artificial Intelligence↗

Transpelvic rectus abdominis flap for perineal reconstruction following abdominal perineal resection with en bloc partial cystectomy and prostatectomy for locally advanced rectal cancer.

We report a case of locally advanced carcinoma of the rectum invading the bladder and prostate in a young man treated initially with neoadjuvant chemoradiotherapy. This was followed by an en bloc resection of the tumour, partial cystectomy and prostatectomy and an abdominal perineal resection. The urinary bladder was reconstructed and a new bladder neck reimplanted into the proximal urethra where the sphincter had been preserved. There was extensive radiation changes to the perineal skin where a wide excision had been performed. The pelvic defect was reconstructed with a pedicled transpelvic rectus abdominis myocutaneous flap. The patient recovered uneventfully and remains well with no clinical evidence of recurrence 18 months post-operatively. In very selected cases there is a definite role for neoadjuvant therapy and enbloc resection of the tumour followed by reconstruction of the perineum.

Adult↗

[Time effect of restraint stress-induced suppression of lymphocyte transformation].

In the present study, restraint, which caused no direct tissue damage, was selected as a method of stress to investigate time effect of stress-induced suppression of lymphocyte transformation in rats. The lymph node and spleen extract or the serum from rats restrained for 3, 6, 12, 18 h or 12, 24, 48, 72, 96 h after restraint, with concanavalin A (Con A), was added to the lymphocyte suspension of rat mesenteric lymph node and was incubated for 72 h. The optical density (OD) value indicating the level of lymphocyte transformation was determined by colorimetric assay of methylthiazol tetrazolium bromide (MTT). The results are as follows. (1) The lymph node and spleen extract or the serum from the rats restrained for 3 or 6 h did not markedly affect the lymphocyte transformation. (2) The lymph node and spleen extract or the serum from the rats restrained for 12 h or 18 h significantly inhibited the lymphocyte transformation and stronger inhibition occurred at 18 h. (3) Up to 96 h after restraint, the suppressive effect of the lymph node or spleen extract on the lymphocyte transformation still existed, but the suppression of the serum on the lymphocyte transformation almost disappeared. These results suggest that the restraint of rats may cause lymphoid tissues to produce some immune suppressive protein of stress, which is released into blood leading to a generalized suppression of cellular immunity.

Animals↗

[A minitype acceleration circulation device].

This devices uses the circular pulsating air pressure to apply the contracting and stretching actions to the patient's extremities section by section, for promoting the back flow of vein blood and lymph in the extremities. It has better functions in prevention and cure of extremities' edema and vein twist expansion in lower limbs that caused by various block of circulation as well as the forming of vein thrombus in the bedfast patients for a long time.

Equipment Design↗

Complete structural elucidation of triacylglycerols by tandem sector mass spectrometry.

We developed a method to elucidate the complete structure of triacylglycerols by means of high-energy collisional activation tandem mass spectrometry (MS/MS). Both ESI- and FAB-produced [M + NH4]+ and [M + met.]+ ions (where met. = Li, Na, and Cs) of triacylglycerols undergo charge-remote and charge-driven fragmentations. We emphasize the study of fragment ions from ESI-produced [M + NH4]+ and [M + Na]+ ions and FAB-produced [M + Na]+ ions. ESI-produced [M + NH4]+ ions fragment to produce four types of ions, [M + NH4 - RnCOONH4]+, [RnCO + 128]+, [RnCO + 74]+, and RnCO+ ions, from which the carbon number and the degree of unsaturation of each acyl group are obtained. In addition, three series of ions are produced by charge-remote fragmentations (CRFs), and analysis of their patterns gives the position and the number of double bonds on the acyl groups. Information about the position of each acyl group on the glycerol backbone, however, is not provided by collisionally activated dissociation of [M + NH4]+ ions. On the other hand, ESI- and FAB-produced [M + Na]+ ions fragment to form eight types of ions (named A-J ions) that, like those produced by CRF, are highly structurally informative. The absence of certain series members also carries useful structural information. Interpretation of these patterns enables one to obtain the number of carbons, degrees of unsaturation, and location of double bonds, as well as the positions of acyl groups on the glycerol backbone.

Acylation↗

Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1.

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-beta1 (TGF-beta1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6) cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-beta1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-beta1. The transduced cells secreted 2-4 ng/ml of latent TGF-beta1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-gamma were similar before and after transduction; interleukin-4 and -10 were absent. TGF-beta1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-beta1-transduced, antigen-activated cells, contained detectable amounts of TGF-beta1 cDNA. We conclude that latent TGF-beta1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.

Animals↗

Assembly of the epithelial Na+ channel evaluated using sucrose gradient sedimentation analysis.

Three subunits, alpha, beta, and gamma, contribute to the formation of the epithelial Na+ channel. To investigate the oligomeric assembly of the channel complex, we used sucrose gradient sedimentation analysis to determine the sedimentation properties of individual subunits and heteromultimers comprised of multiple subunits. When the alpha subunit was expressed alone, it first formed an oligomeric complex with a sedimentation coefficient of 11 S, and then generated a higher order multimer of 25 S. In contrast, individual beta and gamma subunits predominately assembled into 11 S complexes. We obtained similar results with expression in cells and in vitro. When we co-expressed beta with alpha or with alpha plus gamma, the beta subunit assembled into a 25 S complex. Glycosylation of the alpha subunit was not required for assembly into a 25 S complex. We found that the alpha subunit formed intra-chain disulfide bonds. Although such bonds were not required to generate an oligomeric complex, under nonreducing conditions the alpha subunit formed a complex that migrated more homogeneously at 25 S. This suggests that intra-chain disulfide bonds may stabilize the complex. These data suggest that the epithelial Na+ channel subunits form high order oligomeric complexes and that the alpha subunit contains the information that facilitates such formation. Interestingly, the ability of the alpha, but not the beta or gamma, subunit to assemble into a 25 S homomeric complex correlates with the ability of these subunits to generate functional channels when expressed alone.

Animals↗

NF-kappa B is activated and ICAM-1 gene expression is upregulated during reoxygenation of human brain endothelial cells.

Reperfusion injury is mediated, in part, by the upregulated expression of genes in microvascular endothelial cells that encode for inflammatory cytokines and adhesion molecules. The redox-regulated transcription factor, nuclear factor kappa B (NF-kappaB), may play a major role in the induced expression of these genes. In this study we use cultured human brain microvascular endothelial cells (HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the activation of NF-kappaB and the upregulation of the adhesion molecule, ICAM-1. When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia alone, an NF-kappaB complex composed of p65 and p50 Rel proteins was rapidly activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the proteasome inhibitor, n-Tosyl-Phe-chloromethyl ketone, blocked both the activation of NF-kappaB and the upregulation of the ICAM-1 gene. These results indicate that NF-kappaB is activated in HBMEC by reoxygenation and may play a significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF-kappaB activation may be potential therapeutic agents in acute ischemic stroke.

Brain↗

A catalytic domain of eukaryotic DNA topoisomerase I.

Eukaryotic type IB topoisomerases catalyze the cleavage and rejoining of DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate. The 314-amino acid vaccinia topoisomerase is the smallest member of this family and is distinguished from its cellular counterparts by its specificity for cleavage at the target sequence 5'-CCCTT downward arrow. Here we show that Topo-(81-314), a truncated derivative that lacks the N-terminal domain, performs the same repertoire of reactions as the full-sized topoisomerase: relaxation of supercoiled DNA, site-specific DNA transesterification, and DNA strand transfer. Elimination of the N-terminal domain slows the rate of single-turnover DNA cleavage by 10(-3.6), but has little effect on the rate of single-turnover DNA religation. DNA relaxation and strand cleavage by Topo-(81-314) are inhibited by salt and magnesium; these effects are indicative of reduced affinity in noncovalent DNA binding. We report that identical properties are displayed by a full-length mutant protein, Topo(Y70A/Y72A), which lacks two tyrosine side chains within the N-terminal domain that contact the DNA target site in the major groove. We speculate that Topo-(81-314) is fully competent for transesterification chemistry, but is compromised with respect to a rate-limiting precleavage conformational step that is contingent on DNA contacts made by Tyr-70 and Tyr-72.

Binding Sites↗

Conservation of structure and mechanism between eukaryotic topoisomerase I and site-specific recombinases.

Vaccinia DNA topoisomerase breaks and rejoins DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate. A C-terminal catalytic domain, Topo(81-314), suffices for transesterification chemistry. The domain contains a constellation of five amino acids, conserved in all eukaryotic type IB topoisomerases, that catalyzes attack of the tyrosine nucleophile on the scissile phosphate. The structure of the catalytic domain, consisting of ten alpha helices and a three-strand beta sheet, resembles the catalytic domains of site-specific recombinases that act via a topoisomerase IB-like mechanism. The topoisomerase catalytic pentad is conserved in the tertiary structures of the recombinases despite scant sequence similarity overall. This implies that the catalytic domains of type IB topoisomerases and recombinases derive from a common ancestral strand transferase.

Binding Sites↗

Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits.

Members of the DEG/ENaC protein family form ion channels with diverse functions. DEG/ENaC subunits associate as hetero- and homomultimers to generate channels; however the stoichiometry of these complexes is unknown. To determine the subunit stoichiometry of the human epithelial Na+ channel (hENaC), we expressed the three wild-type hENaC subunits (alpha, beta, and gamma) with subunits containing mutations that alter channel inhibition by methanethiosulfonates. The data indicate that hENaC contains three alpha, three beta, and three gamma subunits. Sucrose gradient sedimentation of alphahENaC translated in vitro, as well as alpha-, beta-, and gammahENaC coexpressed in cells, was consistent with complexes containing nine subunits. FaNaCh and BNC1, two related DEG/ENaC channels, produced complexes of similar mass. Our results suggest a novel nine-subunit stoichiometry for the DEG/ENaC family of ion channels.

Animals↗

Getting the right kind of support: functional differences in the types of social support on depression for Chinese adolescents.

The present study adopted a prospective design to explore relationships among various types of social support and depression. Four types of social support, namely network support, instrumental enacted support, socio-emotional enacted support, and perceived support, were assessed in a sample of Chinese adolescents. Results revealed that perceived support was related to a reduction of subsequent depression for both male and female adolescents. In addition, instrumental enacted support was a significant predictor of subsequent depression for male adolescents, whereas socioemotional enacted support was a significant predictor of subsequent depression for female adolescents. Functional differences in the types of social support for Chinese male and female adolescents, as well as implications for clinical intervention, are discussed.

Adolescent↗

Results of termino-lateral neurorrhaphy to original and adjacent nerves.

In this comprehensive investigation, we studied three different neurorrhaphy models in an attempt to elucidate the potential of termino-lateral nerve repair to original and adjacent nerves. In experimental group 1, the peroneal nerve was sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experiment group 2, the motor nerves to the gastrocnemius muscle were sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experimental group 3, the obturator nerve (L2-4) was sectioned and attached to the sciatic nerve (L4-6) in a termino-lateral fashion. For the control in each group, the same type of nerve used in each respective group was transected without repair. Experimental groups 1 and 2 showed viable axons in the peroneal nerve distal to the neurorrhaphy site. Experimental group 3 showed no viable axons at these sites. No regeneration was observed in the transected nerve without repair in all three control groups. This study suggests that termino-lateral neurorrhaphy is a viable means of repairing damaged nerves if the distal segment of the sectioned nerve is reattached to its original trunk distal to its original branch point. However, the results from experimental group 3 demonstrate that termino-lateral neurorrhaphy cannot be used to repair nerves when the donor and recipient nerves originate from different spinal cord levels.

Anastomosis, Surgical↗