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Biomedical subjects

S H Chan

Publications and source records attributed to S H Chan.

At least 163 records · Page 9Linked to original sources
PubMed1993

Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: intravenous bolus administration.

Based on the tail-flick response to noxious thermal stimuli, we determined in the present study that the minimal effective antinociceptive dose of propofol in adult, male Sprague-Dawley rats, given in an intravenous bolus manner, was 10 mg/kg. Simultaneous power spectral analysis of the electroencephalographic (EEG) and systemic arterial pressure signals further revealed a concomitant transient suppression of the EEG activity, primarily in the theta and sigma bands, alongside minor hypotensive and negative inotropic and chronotropic actions, but with maintained vasomotor tone. These alterations followed a time course that paralleled the plasma concentration of propofol in the arterial blood, as detected by high-performance liquid chromatography.

Anesthesia, Intravenous↗
PubMed1993

Another view of the selective model of thymocyte selection.

Thymocyte commitment to the CD4 helper versus CD8 cytotoxic lineage has not been satisfactorily established. Two models have been elaborated: one based on instruction, the other on selection. Most previous results support the instructive model, but our comparison of thymocyte differentiation in MHC class II-, class I- and double-deficient mice provides data challenging it. There exists a significant population of CD4 single positive cells in class II-deficient animals that is intermediate in maturity between CD4+CD8+ and end-stage CD4+CD8- thymocytes and is selected on class I molecules; an equivalent CD8+CD4- population occurs in class I-deficient animals. We propose a selective model entailing two TCR-MHC molecule engagements: the first provokes random down-modulation of either CD4 or CD8 and a degree of differentiation; the second, requiring participation of the appropriate coreceptor, permits end-stage differentiation.

Animals↗
PubMed1993

Spinal cord localization of the motoneurons innervating the sacrococcygeus dorsi lateralis muscle and their noradrenergic nerve terminals in rats.

We examined in the present study the spinal cord localization of motoneurons innervating the caudal portion of the sacrococcygeus dorsi lateralis (SCDL) muscle and their noradrenergic nerve terminals in Sprague-Dawley rats, using horseradish peroxidase (HRP) and dopamine-beta-hydroxylase (DBH) double-labeling techniques. Retrogradely HRP-labeled motoneurons innervating the caudal part of the SCDL muscle were located ipsilaterally in the ventromedial aspect of the ventral horn (lamina IX) in spinal segments of S2-S4. These cells were polygonal in shape, with an average soma diameter of 37.0 +/- 1.1 microns (mean +/- S.E.M., n = 95) and amounted to 33.6 +/- 5.7 (n = 7) in the horizontal plane. Of note was the presence of abundant DBH-positive nerve terminals arborizing on the soma and dendrites of HRP-labeled motoneurons. These results provided anatomical evidence to further support our previous findings that the coerulospinal noradrenergic neurotransmission is involved in the mediation of fentanyl-induced muscular rigidity.

Animals↗
PubMed1993

Graft rejection by T cells not restricted by conventional major histocompatibility complex molecules.

The appropriate crosses of mice lacking conventional major histocompatibility complex (MHC) class I or class II molecules generate single- and double-deficient offspring. These were used as donors for skin grafts across major plus minor, or just minor, histocompatibility differences. Surprisingly, in the two circumstances, there was a rapid rejection of grafts lacking both MHC class I and class II molecules. Rejection was mediated by thymically derived CD4+ T cells of the host. We provide evidence that these T cells recognize an unconventional ligand, capable of activating a pre-formed T cell compartment but incapable of positively selecting it. The existence of this unexpected rejection phenomenon should serve to caution those aiming to engineer "universal donor" cells by simply abrogating expression of MHC class I and class II molecules.

Animals↗
PubMed1993

A monoclonal antibody with specificity to the HLA-DR1 and -DR51 antigens.

A monoclonal antibody 137BL7 raised against purified DR1 protein was shown to bind specifically to 5/5 DR1, 18/18 DR2 cells and 0/23 non-DR1,2 cells by cell-EIA. Further analysis by FACS using HLA-transfectants revealed that 137BL7 also bound specifically to the DRB5 transfectants in addition to the expected DR1 transfectants. However, it did not bind to the DR2 (DR15) transfectants, showing that cross-reactivity with DR2 cells lies with the DRB5 (DR51) rather than the DRB1 gene product. A comparison of the HLA-DR amino acid sequences of DR1 and DR51 antigens revealed a common glutamic acid residue at position 96, which may form the putative binding epitope of this mAb.

Alleles↗
PubMed1993

Continuous, on-line, real-time spectral analysis of systemic arterial pressure signals.

We present in this communication an algorithm that offers continuous, on-line, real-time analysis of the power spectrum (CORAPS) of systemic arterial pressure (SAP) signals. Based on direct fast Fourier transform of raw SAP signals into power spectral density, it is suitable for the delineation of acute SAP spectral changes over time after physiological or pharmacological perturbations. Thus it is an improvement over most current methods, which only generate the spectra off-line or from intermittent data. Furthermore, all executions can be accomplished economically with a general-purpose personal computer. We demonstrated and quantified vivid sequential alterations in the low-frequency components (< 3 Hz) of the SAP spectrum, which purportedly reflect the influence of vasomotor, baroreceptor, and respiratory activity on SAP during pentobarbital administration or transient hypertension. Three window options incorporated into the algorithm further improved the frequency or temporal resolution and discrimination of the spectral changes during abrupt hypertension or hypotension. Thus our CORAPS algorithm may be useful as an on-line monitor for acute hemodynamic changes.

Algorithms↗
PubMed1993

HLA and Singaporean Chinese myasthenia gravis.

Chinese Singaporean myasthenia gravis (MG) patients are associated with three HLA haplotypes: Cw1 B46 DRB1*0901 DQB1*0303 DQA1*03, DRB1*14 DRB3*0202 DQB1*0503 DQA1*0101 and DRB1*1202 DRB3*0301 DQB1*0301 DQA1*0601. The B46 haplotype was associated with the total group of MG patients but in particular with those with younger onset, low antiacetylcholine receptor (anti-AchR) titres, with only ocular lesions and with normal thymuses. The DRB1*14 haplotype was associated with thymic hyperplasia, younger onset patients, with high anti-AchR titres and with generalised MG. The DRB1*1202 haplotype was associated with thymoma, older onset patients, ocular lesions, and mid to high anti-AchR titres.

Adult↗
PubMed1993

Reappraisal of the biological role of epidermal growth factor receptor in transitional cell carcinoma.

Retrospective immunohistochemical and flow cytometric DNA analyses were performed on 56 cases of transitional cell carcinoma (TCC) to examine the biologic implications of epidermal growth factor receptor (EGFR) expression. A total of 28 (50%) cases were reactive for EGFR immunostaining. The receptor expression increased from 41.7 to 56.3% with tumor stage. There was a significant association between EGFR expression and tumor stage (p < 0.0005), but not tumor grade. The flow DNA content and the Ki-67 proliferating index had no relation to the status of EGFR (p = 1, respectively). For those receptor-positive tumors (n = 28), there was a significant association (p < 0.0001) between receptor expression and tumor proliferation. Interestingly, the DNA content was not correlated with EGFR expression (p = 0.69). We support the possible role of EGFR in cell proliferation and the potential significance for tumor growth in TCCs. However, the biology of TCC in half the cases could not be explained by this mechanism. The interaction between EGFR and DNA ploidy status necessitates further evaluation.

Adult↗
PubMed1993

Unsustained dipsogenic response to chronic central infusion of angiotensin-III in spontaneously hypertensive rats.

We evaluated the chronic effect of angiotensin-III (AIII) in the promotion of drinking behavior in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, using conscious, freely moving, male, adult animals that had been instrumented with an intracerebroventricular (icv) cannula connected to an osmotic mini-pump for 7-day infusion. Chronic icv infusion of AIII (5 or 10 pmol/min) elicited robust, dose-dependent, and Ile7-AIII (100 pmol/min; as specific antagonist)-reversible dipsogenesis in both SH and WKY rats, with higher water intake in the former strain. However, the drinking response in the SHRs exhibited a sharp drop after 3 days of AIII infusion, during which acute AIII (80 pmol, icv) challenges also failed to induce dipsogenesis. Chronic icv infusion of bestatin (150 pmol/min), an aminopeptidase-B inhibitor, did not by itself discernibly affect basal drinking. When combined with AIII (5 or 10 pmol/min), however, bestatin, respectively, suppressed and augmented the dipsogenic response of SH and WKY rats to the heptapeptide. These results suggest that chronic administration of AIII did not produce sustained drinking behavior in SHRs, possibly because of the development of early desensitization of the angiotensin receptors.

Aminopeptidases↗
PubMed1993

Comparison of two different trauma assessment scores in predicting trauma outcome.

We reviewed 1,455 trauma cases admitted through the Emergency Department of National Cheng Kung University Hospital from June 1988 to December 1991. Of these, 1,251 patients had Revised Trauma Scores (RTS) and 1,452 cases had Injury Severity Scores (ISS) available for analysis of final trauma outcome. Several statistical methods such as simple logistic regression, the contingency table approach, and stepwise logistic regression were adopted to obtain the critical regions of major trauma which satisfied the requirements for sensitivity and specificity with the largest probability of a correct classification. We found that RTS < or = 5.7 and ISS > or = 17 were the best critical regions for defining major trauma. These patients deserve more attention during prehospital and interhospital disposition. Moreover, RTS contributes more to the prediction of patient outcome than ISS, indicating the power of RTS at the time of field evaluation in predicting patients' survival probability. The ISS is calculated retrospectively and is of limited value in acute settings. Therefore, based on our trauma database, we recommended that the RTS be used as a triage tool to select severely ill patients. We also urge that a generalized trauma registry be established in order to validate its usefulness.

Humans↗
PubMed1993

Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves' disease.

Human Leucocyte Antigen (HLA) A, B, C, DR, DQ and DP locus alleles in 35 Chinese patients with Graves' disease and 80 controls were typed for using serological and DNA polymerase chain reaction/sequence specific oligonucleotide (PCR/SSO) methods. B46 was found to be strongly associated with male patients (p = 0.0002; RR = 8.2, 95% confidence interval 2.1-32.2). In HLA class 1 alleles, besides B46, the frequencies of A2 and Cw1 were increased and A24 and B63 decreased in patients compared to controls. In HLA class 2 alleles, the frequencies of DRB1*1602, *0301, *1405, DRB5*02, DQB1*0502 were increased and DRB1*1501, DQB1*0301 decreased in patients.

Adult↗
PubMed1992

Tonic suppression of baroreceptor reflex response by endogenous neuropeptide Y at the nucleus tractus solitarius of the rat.

We evaluated the potential participation of endogenous brain neuropeptide Y (NPY) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Bilateral microinjection of NPY (4.65 pmol) into the caudal one-third level of the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferent fibers, promoted a significant suppression of the baroreceptor reflex (BRR) response. The maximal inhibition occurred at 30-40 min postinjection, and amounted to -42.7 +/- 8.6% (mean +/- S.E.M., n = 9). The same treatment, however, only caused transient (approximately 5 min) hypotension and bradycardia. Blocking the endogenous NPY activity at the NTS with its antiserum appreciably enhanced the sensitivity of BRR response (+ 59.2 +/- 18.8%, mean +/- S.E.M., n = 6), but had no appreciable effect on systemic arterial pressure or heart rate. These results suggest that neurons that contain NPY may participate in central cardiovascular regulation by tonically suppressing the BRR response, possibly by exerting an influence on the baroreceptive neurons at the NTS.

Afferent Pathways↗
PubMed1992

Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells.

We have analyzed the effects of NK cell stimulatory factor/IL-12, on proliferation of PBL and their subsets. IL-12 synergizes with lectins and phorbol diesters to induce proliferation of CD4+ and CD8+ peripheral blood T lymphocytes. In the case of phorbol-diester-induced proliferation, the effect of IL-12 is in part mediated by induced IL-2 production, as suggested by the observation that IL-12 enhances IL-2 production in these cultures and that anti-IL-2 antibodies inhibit proliferation. IL-12 synergizes also with anti-CD3 antibodies and with allogeneic stimulation in MLC in inducing T cell proliferation. IL-12 alone is mitogenic for preactivated T and NK lymphoblasts. This mitogenic effect is observed with similar doses of IL-12 on NK lymphoblasts as well as on CD4+ and CD8+ TCR-alpha beta+ and on TCR-gamma delta+ lymphoblasts. On TCR-alpha beta+ T lymphocytes the effect of IL-12 is always additive to that of IL-2 over a wide dose range. The same effect is observed on highly activated, actively proliferating NK cells. However, on NK and TCR-gamma delta+ lymphoblasts reverting to a resting state after stimulation and on a TCR-gamma delta+ acute leukemia-derived T cell line, IL-12 inhibits significantly the proliferation induced by moderate to high doses (10 to 100 U/ml) of IL-2. This inhibitory effect is, at least in part, indirect, and depends on IL-12-induced production of TNF. Neutralizing anti-TNF antibodies, but not anti-IFN-gamma and anti-transforming growth factor antibodies, restore by more than 70% the inhibition of proliferation induced by IL-12 in these cultures. However, TNF alone cannot mimic the inhibitory effect of IL-12 on the IL-2-induced proliferation of NK and TCR-gamma delta+ lymphoblasts, suggesting the involvement of additional mechanisms. The relevance of these findings for the biology of lymphocyte subsets mediating MHC nonrestricted cytotoxicity is discussed.

Flow Cytometry↗
PubMed1992

Isolation and characterization of COX12, the nuclear gene for a previously unrecognized subunit of Saccharomyces cerevisiae cytochrome c oxidase.

We have cloned and sequenced COX12, the nuclear gene for subunit VIb of Saccharomyces cerevisiae cytochrome c oxidase. This subunit, which was previously not found in cytochrome c oxidase purified from S. cerevisiae, has a deduced amino acid sequence which is 41% identical to the sequences of subunits VIb of bovine and human cytochrome c oxidases. The chromosomal copy of COX12 was replaced with a plasmid-derived copy of COX12, in which the coding region for the suspected cytochrome oxidase subunit was replaced with the yeast URA3 gene. The resulting Ura+ deletion strain grew poorly at room temperature and was unable to grow at 37 degrees C on ethanol/glycerol medium, whereas growth was normal at both temperatures on dextrose. This temperature-dependent, petite phenotype of the deletion strain was complemented to wild-type growth with a single copy plasmid carrying COX12. Cytochrome c oxidase activity in mitochondrial membranes from the cox12 deletion strain is decreased to 5-15% of that in membranes from the wild-type parent, and this activity is restored to normal when the cox12 deletion strain is complemented by the plasmid-borne COX12. Optical spectra of mitochondrial membranes from the cox12 deletion strain revealed that optically detectable cytochrome c oxidase is assembled at room temperature and at 37 degrees C, although the heme a + a3 absorption is diminished approximately 50%. The N-terminal amino acid sequence of the protein encoded by COX12 is identical to the N-terminal sequence of a subunit found in yeast cytochrome c oxidase purified by a new procedure (Taanman, J.-W., and Capaldi, R. A. (1992) J. Biol. Chem. 267, 22481-22485). We conclude that COX12 encodes a subunit of yeast cytochrome c oxidase which is essential during assembly for full cytochrome c oxidase activity but apparently can be removed after the oxidase is assembled, with retention of oxidase activity. This is the first instance in which deletion of a subunit of cytochrome c oxidase results in assembly of optically detectable cytochrome c oxidase but having markedly diminished activity.

Amino Acid Sequence↗
PubMed1992

Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.

Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35. NKSF/IL-12 has multiple effects on T and NK cells and was originally identified and purified from the supernatant fluid of Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cell lines. We have produced a panel of monoclonal antibodies against both chains of NKSF/IL-12. Some of these antibodies have neutralizing activity, and several combinations of them have been used to establish sensitive radioimmunoassays detecting the free p40 chain, the free p35 chain, or the p70 heterodimer. Using these reagents, we have determined that most EBV-transformed human B lymphoblastoid cell lines constitutively produce low levels of the p70 heterodimer and an excess of the free p40 chain, whereas Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived cell lines produce neither. Production of both p40 and p70 is increased several-fold upon stimulation of the EBV-transformed cell lines with phorbol diesters. The ability of supernatant fluids from unstimulated and phorbol diester-stimulated cell lines to induce interferon gamma (IFN-gamma) production from T and NK cells, one of the effects of NKSF/IL-12, parallels the levels of production of the p70 heterodimer, known to be the biologically active form of NKSF/IL-12. Staphylococcus aureus Cowan I strain (SAC) and other stimuli induce accumulation of p40 mRNA and production of both p40 and p70 by peripheral blood mononuclear cells (PBMC). The producer cells appear to include both adherent cells and nonadherent lymphocytes, possibly B cells. The supernatant fluids from SAC-stimulated PBMC mediate the typical functions of NKSF/IL-12 (i.e., IFN-gamma induction, mitogenic effects on T/NK blasts, enhancement of NK cell cytotoxicity) at concentrations of p70 similar to those at which recombinant NKSF/IL-12 mediates the same functions. Moreover, these activities are significantly inhibited by anti-NKSF/IL-12 antibodies. The neutralizing anti-NKSF/IL-12 antibodies also inhibit 85% of the IFN-gamma production in response to SAC, an NKSF/IL-12 inducer, and approximately 50% of the IFN-gamma production in response to non-NKSF/IL-12-inducers such as IL-2, phytohemagglutinin, and anti-CD3 antibodies. These results indicate that induced or constitutively produced NKSF/IL-12 has a major role in facilitating IFN-gamma production by peripheral blood lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗