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S H Chan

Publications and source records attributed to S H Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Trichosanthin interacts with acidic ribosomal proteins P0 and P1 and mitotic checkpoint protein MAD2B.

Trichosanthin is a ribosome-inactivating protein with multiple pharmacological properties. By a yeast two-hybrid system, ribosomal phosphoproteins P0 and P1 and a putative mitotic checkpoint protein, MAD2B, were found to interact with an active-site mutated trichosanthin (TCS). The interactions were verified by an in vitro binding assay of recombinant wild-type TCS and target proteins. The interaction domain of P0 was mapped to amino acids 220-273, which had been previously reported to be involved in the interaction with P1 and P2 in yeast. Consistent with our previous finding that the last seven residues of TCS are not essential for an active conformation, the same deletion did not affect the interaction with P0. Our present study suggests that TCS may disrupt the binding of elongation factors to the P-complex, in addition to the well-known N-glycosidase activity for ribosome inactivation.

Binding Sites↗
PubMed2001

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Antibodies, Viral↗
PubMed2001

Does intensive rehabilitation improve the functional outcome of patients with traumatic brain injury? Interim result of a randomized controlled trial.

To evaluate the effects of intensive rehabilitation on the functional outcome in patients with traumatic brain injury (TBI), we carried out a randomized controlled assessor-blind trial, comparing two groups of patients receiving different intensities of rehabilitation treatment (2 versus 4 h per day). Patients with moderate and severe TBI, aged from 12 to 65 years, were included. Glasgow Outcome Scale (GOS) and Functional Independent Measurement (FIM) were assessed monthly. The interim results of 36 cases showed that there was a trend of more patients in the study group achieving full FIM scores, and good GOS at 2 and 3 months, but the control group appeared to be catching up towards 6 months. Intensive rehabilitation may improve the early functional outcome of TBI patients. The interim results indicate that the study should be continued.

Adolescent↗
PubMed2001

Spectral changes in systemic arterial pressure signals during acute mevinphos intoxication in the rat.

We investigated the cardiovascular consequences of acute intoxication by the organophosphate poison, mevinphos (Mev), and delineated the underlying mechanism. Based on on-line power spectral analysis of systemic arterial pressure (SAP) signals in rats anesthetized and maintained by propofol, we identified two distinct phases after intravenous administration of Mev (160 or 320 microg/kg). Phase I was characterized by transient hypertension and mild tachycardia, concurrent with an increase in the very high-frequency (BVHF; 5-9 Hz), high-frequency (BHF; 0.8-2.4 Hz), low-frequency (BLF; 0.25-0.8 Hz),and very low-frequency (BVLF; 0-0.25 Hz) components of SAP signals. Phase II exhibited significant hypotension, a reversal of the BVHF and BVLF power to control levels, and further reduction in the power density of both BHF and BLF components to below baseline. Microinjection of Mev (2 microg) into the bilateral nucleus reticularis ventrolateralis (NRVL), the medullary origin of sympathetic neurogenic vasomotor tone, essentially duplicated those phasic cardiovascular changes. Similarly, sympathoexcitatory NRVL neurons exhibited respectively an elevation and a decline in their spontaneous activities during Phase I and Phase II Mev intoxication. We conclude that the progressive accumulation of acetylcholine over time induced by a direct inhibition of Mev on cholinesterase in the NRVL may be responsible for the phasic changes in cardiovascular events over the course of acute Mev intoxication. Whereas the initial amount of acetylcholine is excitatory to NRVL neurons, overstimulation by the amassed acetylcholine results instead of an inhibitory action.

Animals↗
PubMed2001

Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat.

We investigated the differential contribution of inducible and neuronal nitric oxide synthase (iNOS and nNOS) at the rostral ventrolateral medulla (RVLM) to endotoxemia induced by E. coli lipopolysaccharide (LPS). In Sprague-Dawley rats maintained under propofol anesthesia, i.v. administration of LPS (15, 30, or 45 mg/kg) induced a reduction (phase I), followed by an augmentation (phase II) and a secondary decrease (phase III) in the power density of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP) signals. LPS also induced an immediate hypotension, followed by a rebound increase and a secondary decrease in SAP. In addition, the level of iNOS mRNA exhibited a significant surge that began with phase I endotoxemia, reaching progressively its peak at phase III. Discernible down-regulation of nNOS mRNA was not detected until the last phase of endotoxemia. Pretreatment with microinjection of the selective iNOS inhibitor, aminoguanidine (250 pmol), into the bilateral RVLM significantly prolonged phases II and III endotoxemia, blunted the initial and secondary hypotension, and antagonized the upregulation of iNOS mRNA. Similar pretreatment with the selective nNOS inhibitor, 7-nitroindazole (1 pmol), on the other hand, discernibly shortened phase II and prolonged phase III endotoxemia, and induced progressive hypotension by antagonizing the rebound increase in SAP. We conclude that the relative prevalence of functional expression and molecular synthesis of iNOS over nNOS in the RVLM may be a crucial determinant for the reduction or loss in power density of the vasomotor components of SAP signals during experimental endotoxemia.

Animals↗
PubMed2001

Evaluation of Etest for direct antifungal susceptibility testing of yeasts in positive blood cultures.

The performance of the Etest (AB BIODISK, Solna, Sweden) for direct antifungal susceptibility testing of yeasts in positive blood cultures was compared with that of the macrodilution method for determining the MICs of five antifungal agents. Culture broths with blood from bottles positive for yeasts were inoculated directly onto plates for susceptibility testing with the Etest, and the MICs were read after 24 and 48 h of incubation. A total of 141 positive blood cultures (72 cultures of Candida albicans, 31 of Candida tropicalis, 14 of Candida glabrata, 11 of Candida parapsilosis, 3 of Candida krusei, and 3 of Cryptococcus neoformans, 4 miscellaneous yeast species, and 3 mixed cultures) were tested, and the rates of MIC agreement (+/-1 log(2) dilution) between the direct Etest (at 24 and 48 h, respectively) and macrodilution methods were as follows: amphotericin B, 81.8 and 93.5%; flucytosine, 84.8 and 87.7%; fluconazole, 89.4 and 85.5%; itraconazole, 69.7 and 63.8%; ketoconazole, 87.9 and 79.0%. By a large-sample t test, the difference in log(2) dilution between the direct Etest and the macrodilution method was found to be small (P < 0.05). The lone exceptions were ketoconazole at 48 h of incubation and itraconazole at both 24 and 48 h of incubation (P > 0.05). By Tukey's multiple comparisons, the difference between the direct Etest (48 h) and reference methods among different species was found to be less than 1 log(2) dilution. When the MICs were translated into interpretive susceptibility, the minor errors caused by the direct Etest (at 24 and 48 h, respectively) were as follows: flucytosine, 2.3 and 1.4%; fluconazole, 3.0 and 3.6%; itraconazole, 21.2 and 21.3%. Itraconazole also produced an additional 3.0 and 3.6% major errors as determined by the direct Etest at 24 and 48 h, respectively. It was concluded that, except for itraconazole, the Etest method was feasible for direct susceptibility testing of blood cultures positive for yeasts. The method is simple, and the results could be read between 24 and 48 h after direct inoculation, whenever the inhibition zones were discernible.

Antifungal Agents↗
PubMed2001

Inhibition of baroreflex by angiotensin II via Fos expression in nucleus tractus solitarii of the rat.

We evaluated the modulatory action of angiotensin II at the nucleus tractus solitarii on spontaneous baroreceptor reflex response, the angiotensin subtype receptors involved, and the role of Fos protein in this process, using Sprague-Dawley rats anesthetized with pentobarbital sodium. Microinjection bilaterally of angiotensin (Ang ) II (5, 10, 20, or 40 pmol) into the nucleus tractus solitarii significantly suppressed the spontaneous baroreceptor reflex, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. There also was a concomitant increase in Fos-like immunoreactivity in the nucleus tractus solitarii. Both the suppression of spontaneous baroreceptor reflex and Fos expression in nucleus tractus solitarii neurons elicited by Ang II were discernibly attenuated by pretreatment with or comicroinjection into the bilateral nucleus tractus solitarii of a 15-mer antisense c-fos oligonucleotide that targets against the initiation codon of c-fos mRNA. In addition, those 2 actions of Ang II were reversed by the coadministration of the nonpeptide Ang II type 1 (AT(1)) receptor antagonist losartan (1.6 nmol) but not by the nonpeptide AT(2) receptor antagonist PD 123,319 (1.6 nmol). Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotide with a scrambled sequence were ineffective. We conclude that under minimal cardiovascular perturbation, Fos expression mediated via activation of AT(1) subtype receptors may underlie the inhibitory modulation of beat-to-beat baroreflex control of blood pressure by Ang II at the nucleus tractus solitarii.

Angiotensin II↗
PubMed2001

Blocking L-selectin and alpha4-integrin changes donor cell homing pattern and ameliorates murine acute graft versus host disease.

L-selectin, LFA-1 and alpha(4) integrins play important roles in the homing of naïve T cells into peripheral lymphoid tissues. L-selectin- or LFA-1-deficient lymphocytes cannot effectively home to lymph nodes (LN), and antibody blockade of alpha(4) integrins also hinders lymphocytes homing. The present study was initiated to explore whether it is feasible to ameliorate acute graft-versus-host disease (aGVHD) by modulating the homing process of donor cells in the recipient in a mouse model. Using a fluorescence labeling method, we found that two monoclonal antibodies directed at L-selectin and alpha(4) integrins, respectively, when used in combination, could delay half of the donor C57BL/6J mouse spleen cells homing into the LN of recipient BALB/c mouse 15 h after injection. Spleen cells (1 x 10(7)) derived from C57BL/6J (H-2(b)) mice were injected into each C.B-17 SCID recipient mouse (H-2(d)) with or without prior incubation with 10 microg each of the two antibodies. T cell repopulation in the blood was observed in both groups of mice at a comparable level 14 days after injection of the donor cells. Eight control mice started to show aGVHD signs 7 - 14 days after the injection, and all died by day 31. However, among the ten mice that received the antibody-treated donor cells, two died before day 29, four survived between 36 and 78 days, and the remaining four survived more than 150 days, with two of them aGVHD free. It is apparent that the temporarily reduced lymphocyte homing into LN reduced the alloreactivity of the donor T cells, thus providing a simple way of modifying aGVHD. This novel approach may shed light on the prevention of aGVHD associated with clinical bone marrow transplantation.

Acute Disease↗
PubMed2001

Education and cognitive decline in Parkinson's disease: a study of 102 patients.

OBJECTIVE: To understand the correlation between low education level (EL) and the cognitive impairment in Parkinson's disease (PD). PATIENTS AND METHODS: This is a cross-sectional study of cognitive function in 102 non-demented PD patients, from a special clinic (behavioral neurology) in a referral medical center. PD patients were divided into low, middle and high EL groups. We used the Chinese version of the Cognitive Ability Screening Instrument as a neuropsychological test, which covers nine domains of cognitive function. A full score is 100. When determining the abnormality rate of each item of CASI, we used age/education stratified normal control groups as reference to obliterate the influence of education and age on cognitive decline. RESULTS: Recent memory, language and attention are the three items in which there were differences between the groups, in terms of abnormal performance rates. The high EL group is at less risk of recent memory impairment, but at more risk of impairment in language and attention. The other six items and total score showed no differences among the groups. Thirty-eight percent of the patients had a total score below 1.5 SD of the means of the general population. CONCLUSION: This study shows that high EL exerts no protective effect on the cognitive decline in PD patients in general, except in recent memory. The rate of cognitive dysfunction in PD patients is high. This deserves more attention.

Aged↗
PubMed2001

Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder.

In vitro experiments have demonstrated that epidermal growth factor (EGF)-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities. The implications of cross-talk among ErbB family receptors in human cancer, however, remain to be clarified. This cohort study was performed to examine the expression patterns of ErbB receptors by immunohistochemistry in primary human bladder cancer (n = 245) and compared with conventional biological indicators for their prognostic significance. Expression of individual EGF receptor (EGFR) and ErbB2, ErbB3, or ErbB4 receptors was detected in 72.2, 44.5, 56.3, and 29.8% of bladder cancer cases, respectively. Expression of two of the receptors varied from 14.7 to 42.4%, of three of the receptors between 11.0 and 22.0%, and of all four of the ErbB receptors by 8.6%. Important indicators in association with patient survival were tumor staging (P = 0.017), ErbB2 (P = 0.018), EGFR-ErbB2 (P = 0.023), and ErbB2-ErbB3 (P = 0.042). In the subset of grade-2 tumors, EGFR-ErbB2-ErbB3 and EGFR-ErbB2 predicted the development of second recurrence (P = 0.026 and 0.039, respectively), and ErbB2-ErbB3 tended to correlate with patient survival (P = 0.09). The results indicate that a combination of EGFR, ErbB2, and ErbB3 expression profile may be a better prognostic indicator than any family member alone. Given that ErbB2 is the preferred coexpression partner of ErbB family members, expression of other ErbB receptors may significantly affect the prognostic implication of ErbB2 for bladder cancer patients.

Carcinoma, Transitional Cell↗
PubMed2000

Engineering of a mini-trichosanthin that has lower antigenicity by deleting its C-terminal amino acid residues.

Trichosanthin is a ribosome-inactivating protein that possesses antitumor and antiviral activities. Clinical trials of trichosanthin on AIDS patients, however, elicit anaphylactic reactions. To reduce the antigenicity of trichosanthin as a drug while preserving its biological activity, the C-terminal domain (residues 203 to 247), which contains a putative antigenic site, was systemically deleted. We have found that the minimum length of trichosanthin that can fold into an active conformation is residue 1 to 240. The mini-trichosanthin (C7) generated by deleting the last seven C-terminal amino acid residues has 2.7-fold decrease in antigenicity, 10-fold reduction in in vitro ribosome-inactivation activity, and in vivo cytotoxicity toward K562 cells, and 2-fold reduction in abortificient activity. Structural analyses of C7 indicate decrease in the helix content, increased exposure of Trp192, and lower thermodynamic stability. The deletion of the C-terminal residues (Leu241 to Ala247) probably perturbs local structure of the C-terminal antigenic epitope that results in the decrease in antigenicity and activities of C7.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Role of calcium/calmodulin-dependent protein kinases in expression of Fos protein in the nucleus tractus solitarii after sustained hypertension.

We investigated the role of calcium/calmodulin-dependent protein kinases in the phosphorylation of cyclic AMP response element binding protein and subsequent induction of c-fos gene elicited by sustained hypertension in neurons of the nucleus tractus solitarii of anesthetized rats. Activation of glutamate receptors in the nucleus tractus solitarii significantly increased the number of neurons that were immunoreactive to phosphorylated cyclic AMP response element binding protein and Fos protein. Microinjection bilaterally into the nucleus tractus solitarii of the calcium/calmodulin-dependent protein kinase inhibitor, 1-[N,O-bis(5-isoquinolinesulfonyl-N-methyl-L-tyrosyl]-4-phenylpiperazine , appreciably blunted such an increase. This inhibitor also attenuated the augmented immunoreactivity for phosphorylated cyclic AMP response element binding protein or Fos protein in the same nucleus induced by sustained hypertension. These results were comparable to those observed after blockade of either N-methyl-D-aspartate or non-N-methyl-D-aspartate ionotropic glutamate receptors in the nucleus tractus solitarii. Reverse transcription-polymerase chain reaction further indicated that the calcium/calmodulin-dependent protein kinase blocker attenuated the expression of Fos protein induced by sustained hypertension in the nucleus tractus solitarii by suppressing the transcription of c-fos messenger RNA. The present results suggest that activation of calcium/calmodulin-dependent protein kinases may represent an important step in the cascade of intracellular events that leads to phosphorylation of cyclic AMP response element binding protein and subsequent induction of c-fos gene after activation of ionotropic glutamate receptors by baroceptive signals in the nucleus tractus solitarii.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Hippocampal noradrenergic neurotransmission in concurrent EEG desynchronization and inhibition of penile erection induced by cocaine in the rat.

We previously reported that cocaine may induce activation of cortical (cEEG) and hippocampal (hEEG) electroencephalographic signals, concurrent with inhibition of penile erection, via an action on the hippocampal formation. The present study further evaluates the role of noradrenergic neurotransmission at the hippocampal formation in this process, using adult, male Sprague-Dawley rats anaesthetized and maintained by chloral hydrate. Unilateral microinjection of cocaine (100 nmoles) into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited significant activation of both cEEG and hEEG activity. At the same time, the intracavernous pressure (ICP), our experimental index for penile erection, underwent a discernible reduction. Co-administration of equimolar doses (250 pmoles) of prazosin, naftopidil, yohimbine or rauwolscine significantly reversed those effects elicited by cocaine on cEEG, hEEG and ICP. Microinjection unilaterally of equimolar doses (5 nmoles) of norepinephrine, phenylephrine or BHT 933 into the hippocampal formation, similar to cocaine, also induced appreciable cEEG and hEEG excitation, with a simultaneous decrease in ICP. We conclude that cocaine may activate cEEG and hEEG and decrease ICP via noradrenergic neurotransmission, possibly engaging at least alpha(1A/D)-, alpha(2B)- and alpha(2C)-adrenoceptors at the hippocampal formation.

Adrenergic alpha-Agonists↗
PubMed2000

Spectral analysis of systemic arterial pressure and heart rate signals of patients with acute respiratory failure induced by severe organophosphate poisoning.

OBJECTIVE: Spectral analysis of systemic arterial pressure (BP) and heart rate (HR) signals may be an alternative prognostic tool for predicting patient outcome in the intensive care unit (ICU). We evaluated the applicability of the same analysis in the emergency department for predicting mortality in patients with acute respiratory failure induced by severe organophosphate poisoning. DESIGN: Prospective collection of data from 14 emergency service patients. SETTING: Emergency service at a large, university-affiliated medical center. PATIENTS: Consecutive patients who, after attempting suicide by ingesting organophosphates, were admitted to the ICU of the emergency service with acute respiratory failure and remained for > or =2 days INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and survival data and day 1 Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale scores were recorded. Continuous, on-line, real-time spectral analysis of BP and HR signals was carried out during the first 12 hrs after admission. We then computed the total sum of power density during this period of the low-frequency (0.04-0.15 Hz) and very low-frequency (0.004-0.04 Hz) components in the BP and HR spectra, along with the averaged values of mean BP and HR. Eight patients who recovered exhibited vigorous power in the low-frequency and very low-frequency components of their BP and HR signals. There was a significant reduction in the power density of those four spectral components in three patients who eventually died. Three patients discharged in a vegetative state manifested significantly reduced power in the low-frequency component in their BP spectra, with maintained power in the other three spectral components. APACHE II and Glasgow Coma Scale scores of the recovered patients were discernibly different from those of patients who eventually died or who became vegetative. None of the 14 patients showed appreciable differences in mean BP, mean HR, erythrocyte or plasma cholinesterase concentration, or atropine requirement during the first 24 hrs. CONCLUSION: The low-frequency and very low-frequency components of BP and HR signals may be a sensitive alternative index for early prediction of mortality in patients with acute respiratory failure induced by severe organophosphate poisoning.

Acute Disease↗
PubMed2000

Variability in CD34+ cell counts in umbilical cord blood: implications for cord blood transplants.

OBJECTIVE: To determine if total nucleated cell counts alone are sufficient for predicting the efficacy of cord blood units for transplant from neonatal umbilical cord blood samples. METHODS: Umbilical cord blood samples were collected from 200 mothers at delivery and the cord blood units processed. The total nucleated cells and CD34+ cells were enumerated and compared for each sample. RESULTS: Despite an apparent linear correlation between total nucleated cell counts and CD34+ cell counts, each group of total nucleated cell counts demonstrated a high degree of variation in CD34+ cell counts and could be as low as 0.1% of total nucleated cell counts. CONCLUSIONS: Large variations in CD34+ cell counts per total nucleated cell count are present for cord blood units from neonatal umbilical cord samples. Hence a CD34+ cell count for each cord blood unit would improve selection of samples for transplant.

Antigens, CD34↗
PubMed2000

The role of nm23-H1 in the progression of transitional cell bladder cancer.

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23-H1 as a metastasis suppressor or prognostic indicator for human cancers remains enigmatic. Given that gene expression is regulated at the tissue-specific level, we studied the molecular mechanisms of nm23-H1 expression in human bladder cancer cell lines and the clinical importance of protein product (NM23-H1) in association with patient outcome (n = 257) by immunohistochemistry. We demonstrated that nm23-H1 is expressed in bladder cancer cells without genomic alterations. High NM23-H1 expression was found in 39 cases (15.2%), intermediate expression in 119 cases (46.3%), and low NM23-H1 in 99 cases (38.5%). NM23-H1 was inversely related to staging classification or tumor size (P < 0.05), with the most significant difference being observed between pTa tumors and those of pT1-pT3 bladder cancer (P = 0.01). Reduced NM23-H1, defined as intermediate and low levels of expression, tended to have a higher risk of tumor metastasis (P = 0.06) or poor longtime survival (P = 0.07). In the subset of grade 2 bladder tumors, reduced NM23-H1 significantly correlated with the occurrence of tumor metastasis or poor patient survival (P < 0.05). These findings overall suggest that nm23-H1 may play an important role in suppressing the early step of carcinogenesis and thus act as an invasion suppressor for human bladder cancer. A prospective study is required to clarify the potential of the molecular marker in prediction of disease progression.

Carcinoma, Papillary↗
PubMed1999

Transient elevation in plasma prolactin level in rats with temporal lobe status epilepticus.

Microinjection of kainic acid into the CA3 subfield of hippocampus in anesthetized rats elicited seizure-like hippocampal EEG activity that persisted for more than 180 minutes. There was a concomitant rise in plasma prolactin level that peaked at 15 to 20 minutes but endured less than 60 minutes. We conclude that plasma prolactin exhibited only transient elevations during experimental temporal lobe status epilepticus in rats.

Animals↗