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Biomedical subjects

C S Chan

Publications and source records attributed to C S Chan.

At least 73 records · Page 4Linked to original sources
PubMed1992

Effect of experimentally-induced hypertension on angiotensin converting enzyme activity in the aortic endothelium and smooth muscle cum adventitia of the Sprague Dawley rat.

The effect of experimentally-induced hypertension on the angiotensin converting enzyme (ACE) activity in the endothelium and smooth muscle cum adventitia of the Sprague Dawley rats was investigated. The ACE activity in both tissues of the 1-clip 2-kidney renovascular hypertensive rats and the deoxycorticosterone acetate/salt hypertensive rats were significantly higher than those of the normotensive control. These findings (i) support the suggestion that the 1-clip 2-kidney renovascular hypertensive rat represents a model of renin- and angiotensin-dependent hypertension and that the increased vascular ACE activity could play a role in the maintenance of hypertension (ii) provide new information regarding the association of increased vascular ACE activity and hypertension in the mineralocorticoid/salt treated hypertensive rats which may account for the finding by others that captopril is effective in preventing the development of hypertension in this low renin model of hypertension. On the other hand, the data also bring forth the possibility that the observed increase in vascular ACE activity could be the result of hypertension.

Animals↗
PubMed1992

Direct detection of Molluscum contagiosum virus in clinical specimens by in situ hybridization using biotinylated probe.

Molluscum contagiosum virus (MCV) is an unclassified poxvirus which has recently become recognized as causing a major sexually transmitted disease. At present no assay is available for specific detection of MCV because the virus cannot be serially propagated in cell culture. Since MCV produces an abortive, limited growth with some cytopathic effect in certain cell lines, we were able to develop an in situ hybridization assay for detection of MCV genome in clinical specimens. Human fetal diploid lung cell monolayers were infected with clinical specimens, and after proper incubation and fixation in paraformaldehyde, hybridization was performed under full stringency conditions with a molecularly cloned biotinylated probe. Only MCV infected cells showed homology to the MCV probe with a purple-brown cytoplasmic staining. Additionally, we have described an in situ hybridization assay for direct detection of MCV genome in formalin-fixed, paraffin-embedded biopsies. Characteristic intracytoplasmic Molluscum bodies (Henderson-Paterson bodies) were detected in stratum spinosum cells of the epidermis. Striking staining similarities have been observed between in situ hybridization and haematoxylin-eosin cytostaining. These procedures are the first successful identification of MCV genome in clinical samples by molecular hybridization, with sensitivity and specificity equal to or greater than electron microscopy.

Blotting, Southern↗
PubMed1992

Conserved DNA binding and self-association domains of the Drosophila zeste protein.

The zeste gene product is involved in two types of genetic effects dependent on chromosome pairing: transvection and the zeste-white interaction. Comparison of the predicted amino acid sequence with that of the Drosophila virilis gene shows that several blocks of amino acid sequence have been very highly conserved. One of these regions corresponds to the DNA binding domain. Site-directed mutations in this region indicate that a sequence resembling that of the homeodomain DNA recognition helix is essential for DNA binding activity. The integrity of an amphipathic helical region is also essential for binding activity and is likely to be responsible for dimerization of the DNA binding domain. Another very strongly conserved domain of zeste is the C-terminal region, predicted to form a long helical structure with two sets of heptad repeats that constitute two long hydrophobic ridges at opposite ends and on opposite faces of the helix. We show that this domain is responsible for the extensive aggregation properties of zeste that are required for its role in transvection phenomena. A model is proposed according to which the hydrophobic ridges induce the formation of open-ended coiled-coil structures holding together many hundreds of zeste molecules and possibly anchoring these complexes to other nuclear structures.

Amino Acid Sequence↗
PubMed1991

Clonal rearrangement of the T-cell receptor beta-chain gene in hyperplastic lymphadenopathy associated with lung cancer.

A patient presenting with marked inflammatory lymphadenitis and Jaccoud's arthritis was found to have a rearranged gene for the beta-chain of the T-cell receptor (TCR-beta) antigen in the lymph node DNA digests and normal germ line DNA in the peripheral blood lymphocytes. Four months later, the patient was diagnosed to have poorly differentiated adenocarcinoma of the lung with small foci of metastatic tumor in lymph nodes that contained the same extensive lymphocytic and inflammatory cell infiltrates noted earlier. Rearranged TCR-beta chain genes were detected in both lymph node and peripheral blood lymphocyte DNA at this time. The most likely explanation for the florid lymph node reaction and the unusual arthropathy appears to be a paraneoplastic immune response. The rearranged TCR-beta genes indicate a clonal T-cell expansion that most likely resulted from the aberrant immunologic response to the lung cancer.

Aged↗
PubMed1991

H-ras-1 polymorphism in leukemia.

We have examined leukocyte DNAs obtained from 21 patients with various types of leukemia for the Sacl polymorphism of H-ras-1. The patients included ten with B-lineage leukemia, two with T-cell leukemia, and nine with acute myelogenous leukemia. Using a genomic probe for H-ras-1 in Southern hybridizations, we found that 78% of the DNA from leukemias of myeloid origin were heterozygous. In contrast, only three of ten B-cell-derived leukemias showed heterozygosity. This difference in the number of heterozygotes vs. homozygotes in the two patient samples studied is statistically significant (P = 0.04 by Fisher's exact test). These results suggest the possibility that the H-ras-1 allelic pattern that is associated with acute myelogenous leukemia is distinct from that found in B-cell-derived malignancies.

Genes, ras↗
PubMed1991

Advantages of a human immunodeficiency virus type 1 (HIV-1) persistently infected HeLa T4+ cell line for HIV-1 indirect immunofluorescence serology.

A HeLa T4+ cell line persistently infected with human immunodeficiency virus type 1 (HIV-1) was used in an indirect immunofluorescent antibody assay (IFA) system to explore its potential suitability as an alternative source of viral antigen for confirmatory IFA in HIV serology. In a study of 121 serum samples chosen because they were reactive on repeat examination by enzyme immunoassay but nonspecific by IFA by using HIV-1-infected H9 cells (H9 IFA) or gave discrepant results by enzyme immunoassay and H9 IFA, the specificity and sensitivity of the HeLa T4+ IFA were comparable to those of Western blot (immunoblot), and identification of the true positive samples among these discrepant or nonspecific samples by HeLa T4+ IFA was approximately twice that by H9 IFA. The primary advantages of using the HeLa cell line rather than lymphoid cell lines in IFA are that cells can be grown as a monolayer and that the individual cells are much larger. The cell membrane, cytoplasm, and nucleus are easily discernible; this allows specific and nonspecific staining to be distinguished. At least eight different nonspecific nuclear and cytoplasmic staining patterns were identified in this study by using T4+ cells.

Evaluation Studies as Topic↗
PubMed1991

Direct detection of molluscum contagiosum virus in clinical specimens by dot blot hybridization.

A dot blot hybridization protocol was developed for the direct detection of molluscum contagiosum virus (MCV) DNA in clinical specimens submitted for virus isolation. Samples were concentrated by high-speed centrifugation and treated with proteinase K; this was followed by a single phenol-chloroform extraction step. The DNA was denatured, and the entire volume was spotted onto a nitrocellulose membrane. A biotinylated DNA probe specific for the BamHI-C region of MCV type 1 was used for hybridization. Evidence of MCV DNA was visualized by using streptavidin alkaline phosphatase conjugate and 5-bromo-4-chloro-3-indolyl phosphate-nitroblue tetrazolium as the substrate. Results showed that nonspecific hybridization does not occur with herpes simplex virus- or orf virus-infected clinical specimens and that dot blotting is more sensitive and reproducible than electron microscopy.

DNA Probes↗
PubMed1991

A comparison of two-lung high frequency positive pressure ventilation and one-lung ventilation plus 5 cm H2O non-ventilated lung CPAP, in patients undergoing anaesthesia for oesophagectomy.

A randomised prospective controlled study was conducted during a one-year period on patients scheduled for oesophagectomy via a right thoracotomy approach. Twenty-two patients received one-lung ventilation (OLV group) and twenty patients received high frequency positive pressure ventilation (HFPPV group). Episodic hypoxaemia (SaO2 less than 90% for greater than 30 seconds, FiO2 1.0) occurred in eleven patients in the OLV group and six patients in the HFPPV group. No patient in the HFPPV group had a severe desaturation episode (SaO2 less than 80%, FiO2 1.0) compared with nine patients in the OLV group (P less than 0.05). The mean peak inspiratory pressure and average mean airway pressure were significantly lower in the HFPPV group 28.8 (SD 7.7) and 7.2 (SD 2.4) cm H2O respectively, compared with the OLV group, 40.0 (SD 9.9) and 11.9 (SD 4.9) cm H2O (P less than 0.05). Two-lung high frequency positive pressure ventilation has some advantages over one-lung ventilation during the thoracotomy phase of oesophagectomy because it is easy to administer, does not significantly compromise the surgical exposure and is associated with fewer severe undesirable physiological disturbances.

Aged↗
PubMed1991

Postoperative analgesia for oesophageal surgery: a comparison of three analgesic regimens.

Sixty-four patients undergoing oesophageal surgery were randomly allocated to receive either a continuous lumbar epidural infusion of morphine or fentanyl, or, intramuscular morphine for postoperative analgesia. There was no statistical difference in analgesic requirements between the patients who underwent a thoracotomy for their procedure (n = 50) and those who did not (n = 14), as assessed by the total dose of opioid administered, visual analogue scale (VAS) and pain score (PS) comparison. However, by these criteria, epidural morphine infusion provided the most satisfactory analgesia (P less than 0.05). Despite the variable quality of analgesia achieved with the three regimens, the postoperative lung function tests were similar for all groups, and we conclude that routine lung function tests are not an appropriate method of comparing analgesic efficacy. Prophylactic administration of loratadine to 15% of our patients was not shown to be effective in diminishing the incidence of pruritus.

Adult↗
PubMed1990

Differential response of malignant human B-cells to anti-IgM immunoglobulin (anti-mu) and B-cell growth factor: unique direct cytotoxicity of anti-mu on prolymphocytic leukemia cells.

We examined in vitro tritiated thymidine uptake by B cells from seven prolymphocytic leukemia (PLL), seven chronic lymphocytic leukemia (CLL), and four plasma cell leukemia (PCL) patients in response to culture with anti-human IgM antibody (anti-mu) and B-cell growth factor (BCGF). In contrast to the stimulatory effect observed in normal B-cell cultures, the divalent F(ab')2 anti-mu antibody uniquely inhibited the autonomous proliferation and induced marked cytotoxicity in six of seven PLL cell cultures independent of complement or Fc-receptor-mediated mechanisms. There was neither stimulation or inhibition of the slgM+ CLL or the slgM- PCL cells. The inhibitory effect on the PLL cells was observed at an anti-mu concentration below the stimulatory threshold for normal B cells. Significant impairment of trypan blue exclusion was delayed until 48 hours, with morphological cellular changes suggestive of a programmed cell death mechanism or apoptosis. The cytotoxicity was independent of the slgM-staining intensity or the autonomous and BCGF-augmented DNA synthetic activity of the PLL cells and was similar in patients with de novo PLL or with prolymphocytic transformation of CLL. Cells from a PLL patient were separated by elutriation into two fractions, a BCGF-unresponsive large "transformed" cell fraction with marked autonomous DNA synthesis and a smaller lymphoid cell subset with low 3H-thymidine uptake that could be augmented by BCGF. Both fractions were equally susceptible to the cytotoxic effect of anti-mu. These data suggest that certain slgM-bearing malignant B cells are susceptible to anti-mu-triggered cytotoxicity. They may represent the malignant counterpart of a "tolerogenic" normal B-cell subset, and the unique direct cytotoxicity of anti-mu may provide a therapeutic strategy specifically for PLL.

Antibodies, Anti-Idiotypic↗
PubMed1990

B-cell surface phenotypes of proliferating myeloma cells: target antigens for immunotherapy.

Dual-parameter flow cytometric analysis of B-cell antigens and DNA content was used to determine the phenotypes of proliferating tumor cells (S-phase cells) from 30 patients with multiple myeloma. B4 (CD19), J5 (CALLA, CD10), B1 (CD20), and monotypic surface immunoglobulin (Slg) were expressed heterogeneously in 24 patients. J5 and monotypic Slg were found most frequently but were always expressed on a significantly lower percentage of cells than the antigens typically associated with plasma cells, cytoplasmic immunoglobulin (Clg) and T10 (CD38). S-phase cells were found in each antigen(+) subset. B antigen(+) cycling cells were demonstrated in 16 patients whose marrow or blood cells expressed B antigens exclusively in the hyperdiploid fraction and therefore were certainly part of the myeloma clone. Similar to the low level of proliferative activity of the T10(+), Clg(+), and PCA1(+) subsets, the percentages of cycling cells of the preplasma cell B-antigen-bearing myeloma subsets ranged from less than 1% to 12%. The tumor cells of four patients were also studied with dual-color surface antigen analysis and demonstrated independent expression of B antigens, with only rare coexpression of T10 and monotypic Slg, J5, or B4. These findings are consistent with the presence of distinct myeloma subsets bearing differing B phenotypes in the same tumor and provide evidence that the proliferation in myeloma is occurring at various developmental stages in the malignant B lineage. These antigens may be important targets for immunologic therapy aimed at eliminating the entire proliferating compartment of this B-cell tumor.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1990

Eucapnia and hypercapnia in patients with chronic airflow limitation. The role of the upper airway.

In this study, we examined two groups of patients with chronic airflow limitation (CAL) separated according to their awake, stable arterial CO2 level. The aim was to identify factors that may contribute to the development of chronic hypercapnic respiratory failure. Patients with obstructive sleep apnea were excluded from the study. Detailed lifetime histories of smoking, alcohol, and snoring were obtained from all patients together with measurements of lung function and of upper airway size. Thirty-three patients with FEV1 less than 1.5 L were studied, of whom 19 were eucapnic and 14 were hypercapnic. Both groups had a similar degree of chronic airflow limitation and similar lung volumes and DLCO. The hypercapnic group had more hypopneas and desaturated more severely during sleep. The greatest differences between the groups were in their alcohol consumptions, snoring histories, and upper airway dimensions. The eucapnic patients were characterized by lower lifetime alcohol intake, minimal snoring, and large upper airway size. In contrast, the hypercapnic patients were characterized by excessive lifetime alcohol consumption, habitual snoring over many years, and a small upper airway size. Our findings suggest that chronic, heavy alcohol use and upper airway dysfunction are important factors in the development of hypercapnic respiratory failure.

Aged↗
PubMed1989

In vitro evidence for dose-dependent cytotoxicity as the predominant effect of low dose Ara-C on human leukemic and normal marrow cells.

To determine whether cytosine arabinoside (Ara-C) has a differentiating effect in vitro, marrow cells from nine patients with acute non-lymphocytic leukemia or myelodysplastic syndrome and eight non-leukemic controls were exposed to drug concentrations comparable to those achieved in vivo with low-dose Ara-C therapy. In soft agar cultures, the predominant effect of Ara-C at concentrations between 10(-8) M and 10(-6) M was cytotoxicity with a dose-dependent decrement in Colony Forming Unit of the granulocyte and monocyte lineage (CFUg/m) at 14 days. Growth in liquid cultures containing Giant Cell Tumor(GCT)-conditioned media without Ara-C resulted in a significant increment in the recovery of mature cells at day 10 from the non-leukemic cultures (P = 0.03), while only a minor increase was found in the leukemic cultures (P = 0.09). All liquid cultures exposed to greater than or equal to 10(-9) M Ara-C showed a marked reduction in the immature proliferating cell pool, with a concomitant increase in the percentage of mature non-dividing cells at 10 days. However, the absolute number of differentiated cells recovered remained constant or decreased in all non-leukemic and eight of nine leukemic cultures, compared with cultures without Ara-C. Enhanced recovery of differentiated cells was also never observed in any culture exposed to the relatively non-toxic 10(-9) M Ara-C. These in vitro findings support clinical observations suggesting that cytotoxicity rather than differentiation is the major mechanism involved in the therapeutic effect of low-dose Ara-C in acute leukemia and myelodysplasia.

Bone Marrow↗
PubMed1989

Dual parameter analysis of myeloma cells by flow cytometry. DNA content of cells containing monotypic cytoplasmic immunoglobulin.

Dual-parameter flow cytometric analysis of monotypic cytoplasmic immunoglobulin (CIg) and DNA content on 15 myeloma marrows allowed S-phase determination of the CIg(+) tumor separately from the CIg(-) hematopoietic cell pool. The median percentage of the CIg(+) cells in S-phase was 2% compared with 5% for the CIg(-) cells. The median survival of patients with more than 2%, and those with 2% or less CIg(+) S-phase cells was 2 months and more than 13 months, respectively, from the time of study. Ploidy analysis identified four patterns of plasma cell DNA content: entirely hyperdiploid, entirely diploid, combined diploid and tetraploid stemlines, and tumors containing diploid and aneuploid CIg(+) cells. A monotypic CIg(+) double stemline myeloma was distinguished from two aneuploid tumors containing admixed normal, diploid polyclonal plasma cells. This technique provides an improved and expedient means for determining the proliferating fractions of myeloma cells and enhances recognition of double stemline tumors and clonal evolution in myeloma.

Cytoplasm↗
PubMed1989

Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients.

The mechanism of sustained awake hypercapnia in the obstructive sleep apnea syndrome (OSA) is unknown. Recent work has implicated coexisting chronic airflow limitation (CAL) as an important contributing factor. We approached this question by studying consecutive patients with both OSA syndrome and severe CAL in detail and comparing those with and without retention of CO2 while awake. Of 28 patients with both severe OSA (mean NREM apnea index = 48 +/- 9, SEM) and severe CAL (mean FEV1 = 1.07 +/- 0.07 L), 14 had persistent awake hypercapnia (mean PaCO2 = 50 +/- 1 mm Hg), and 14 were normocapnic (mean PaCO2 = 40 +/- 1 mm Hg). When separated according to their PaCO2 level, there was no difference in the apnea indices in both non-rapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep, although the hypercapnic group had lower average levels of oxyhemoglobin saturation in both NREM (SaO2 = 77 +/- 2% versus 85 +/- 3%, p less than 0.05) and REM (SaO2 = 60 +/- 4% versus 82 +/- 3%, p less than 0.001) sleep. The mean values for FEV1, VC, lung volumes, and diffusing capacity for CO measured while awake did not differ. The hypercapnic group had lower awake PaO2 levels (p less than 0.001), were heavier (p less than 0.05), had narrower upper airway size on CT scan measurements (p less than 0.01), and gave a history of much heavier alcohol intake (p less than 0.05). Our results demonstrate that some patients with severe OSA and severe CAL can maintain normal awake arterial CO2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1988

Nocturnal asthma: role of snoring and obstructive sleep apnea.

In this study, we documented the clinical features of patients who had obstructive sleep apnea (OSA) and coexisting asthma and assessed the safety of nocturnal nasal continuous positive airway pressure (nCPAP) therapy on the stability of asthma. Nine patients (8 men and 1 woman) with asthma and OSA confirmed on all-night sleep study were studied. All patients suffered from frequent nocturnal asthma attacks, resulting in hospitalizations and respiratory arrests in 3. All patients had symptoms of heavy snoring, nocturnal choking, frequent sleep arousals, and excessive daytime sleepiness. They recorded their daily peak expiratory flow rates (PEFR) in the mornings and evenings, before and after bronchodilator in three 2-wk periods consisting of control, nCPAP, and control. During the period of nCPAP therapy, all patients recorded improvement in their PEFR. The mean prebronchodilator and postbronchodilator PEFR for the 9 patients were significantly higher during nCPAP therapy than during both control periods. This study confirms that nCPAP therapy can be used safely in treating patients with OSA and coexisting asthma. Furthermore, nCPAP treatment improves the asthma control and, in particular, the nocturnal attacks in this group of patients. These results also suggest that recurrent upper airway obstruction and snoring may be important triggering mechanisms of nocturnal asthma attacks.

Adult↗
PubMed1988

Psychological effects of running loss on consistent runners.

This study examined the psychological effects of running loss upon consistent runners. We compared a group of 30 "Prevented Runners" who were unable to run for at least two weeks with a group of 30 "Continuing Runners" who ran without interruption on the Profile of Mood States (POMS), Rosenberg Self-esteem Scale, Zung Depression Scale, and a Running Information questionnaire. We found that Prevented Runners displayed significantly greater symptoms of psychological distress, including depression, anxiety, confusion, over-all mood disturbance, and lower self-esteem than did Continuing Runners. Deprivation of running may result in withdrawal symptoms of psychological distress for consistent runners who rely on running as a coping strategy for stress reduction and who feel dependent upon the psychological reinforcements of running.

Adaptation, Psychological↗