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Biomedical subjects

P L Tan

Publications and source records attributed to P L Tan.

At least 19 recordsLinked to original sources
PubMed1995

The influence of a maternal chronic hepatitis B virus infection on the repertoire of transcribed T-cell receptor beta chain variable region genes in human cord blood.

We used an anchor polymerase chain reaction method to compare the repertoires of transcribed T-cell receptor beta chain variable region (V beta) genes in cord blood T cells from neonates of hepatitis B surface antigen (HBsAg) positive (n = 40) and HBsAg negative (n = 40) women. Fifteen of the HBsAg positive women were hepatitis B e antigen (HBeAg) positive, and 25 were HBeAg negative. The percentage of V beta 7.4 transcripts was lower in cord blood T cells from neonates of HBsAg-positive relative to HBsAg-negative women (9.7% +/- 0.5% vs. 12.7% +/- 0.6%, P = .002). The percent of V beta 5.1 transcripts was higher in cord blood T cells from neonates of HBeAg-positive relative to HBeAg-negative women (9.3% +/- 0.7% vs. 7.0% +/- 0.3%, P < .001). There were no correlations between neonatal maturity at birth and V beta repertoire. In summary, a maternal chronic hepatitis B virus (HBV) infection is associated with changes in the repertoire of transcribed T-cell receptor genes in neonatal cord blood T cells. It is possible that the T-cell response to the HBV is associated with a limited repertoire of V beta genes. The mechanism of vertical chronic HBV infection in human neonates may involve changes in the T-cell response to the virus that are induced in utero.

Adult↗
PubMed1995

Search for linkage disequilibrium between alleles in the T cell receptor alpha and beta chain loci and susceptibility to rheumatic fever.

A population-based linkage disequilibrium study was conducted to search for associations between alleles in T cell receptor alpha and beta chain polymorphic loci and susceptibility to rheumatic fever. The allele frequencies of four T cell receptor locus restriction fragment length polymorphisms were measured in 47 European and 51 Maori subjects with a history of rheumatic fever. These allele frequencies were compared to the allele frequencies in three or four independently recruited, race-matched control groups totalling 125 Europeans and 117 Maoris with no history of rheumatic fever. The polymorphisms studied were (locus/enzyme/probe) C alpha/Taq1/Y14, V alpha/Taq1/Y14, V beta 7/BAMHI/V beta 7.4 and V beta 8/BAMHI/V beta 8.1. There was no evidence for linkage disequilibrium between rheumatic fever and these Tcr alleles in either the Maori or European subjects.

Adult↗
PubMed1995

Peripheral blood T lymphocytes in systemic vasculitis: increased T cell receptor V beta 2 gene usage in microscopic polyarteritis.

Antigen recognition by T lymphocytes is mediated by cell surface receptors T cell specificity depends on the variable, diversity and junctional (VDJ) regions of the alpha and beta polypeptide chains of the T cell receptor (TCR). The expression of the variable region genes of the beta chain (V beta) has been analysed to study the involvement of peripheral blood T cells in systemic vasculitis. RNA was extracted from peripheral blood lymphocytes of 12 patients with microscopic polyarteritis, 10 with Wegener's granulomatosis, six with unclassified vasculitis, and 28 healthy age- and sex-matched individuals. Complementary DNA was made from RNA and amplified by the anchored polymerase chain reaction (PCR) using redundant oligonucleotide primers for the TCR V beta genes. To determine if the dominant usage of a V beta gene family reflected the presence of particular T cell clones, cDNA was amplified with primers for the specific V beta gene family. The product was screened for sequence homogeneity by single-stranded conformational polymorphism (SSCP) and cloned to sequence the adjoining TCR (D beta) J beta region. A significant increase in the mean percentage expression of the V beta 2.1 gene was seen in vasculitis patients (11.4 + 1.0% (mean + s.e.m.)) compared with controls (6.6 + 0.6%; P < 0.003). The most marked increase was seen in microscopic polyarteritis (13.9 + 1.7%; P < 0.0001). There were also increases in the expression of V beta 3, 13 and 14 in peripheral blood of vasculitis patients compared with controls. SSCP analysis of V beta 2.1 amplified products indicated the presence of oligoclonal bands in a smaller proportion of patients (8/27) than controls (12/28). There was no strong evidence for the conservation of the TCR V beta 2.1 junctional region sequence data from a sample group of three patients with oligoclonal bands. Thus, a subset of patients with systemic vasculitis, particularly those with microscopic polyarteritis, have increased TCR V beta 2.1 gene expression in their peripheral blood T cell repertoire. As superantigens binding V beta 2.1 are postulated to activate T cells with diverse CDR3 sequences, it is proposed that a superantigen is involved in the immunopathogenesis of vasculitis.

Adult↗
PubMed1994

Natural killer cell function and expression of beta 7 integrin in psoriatic arthritis.

OBJECTIVE: To examine the cytotoxic activity of natural killer (NK) cells from peripheral blood (PB) and synovial fluid (SF) of patients with psoriatic arthritis (PsA). The influence of selected inflammatory mediators on the cytolytic function and integrin expression of NK cells was also studied. METHODS: Paired samples of PB and SF lymphocytes (PBL and SFL) were obtained from 8 patients with PsA for comparison of NK activity between PBL and SFL. In 6 patients the phenotype of NK cells was determined by flow cytometry using monoclonal antibodies (Mab) to natural killer associated antigen (NKH-1) and the beta 7 integrin, HML-1 (human mucosal lymphocyte adhesion molecule). RESULTS: NK activity of PB samples was significantly greater than paired SF (p = 0.015). SF NK activity was enhanced by overnight culture with interleukin 2 (IL-2) (p < 0.05). A trend towards reduction of NK activity by prostaglandin E2 (PGE2) was noted (p = 0.06) whereas interleukin 6 (IL-6) and indomethacin had no significant effect. NK activity did not correlate with the percentage of NK cells in PB or SF. However, all SF samples contained a greater proportion of monocytes than PB samples. The expression of HML-1 on NK cells correlated with expression HML-1 on CD3+ cells (r = 0.82) and was greater in SF than PB in PsA and RA patients. Effects of IL-2 on HML-1 expression by NK cells were variable in the 3 patients studied. CONCLUSION: In PsA, HML-1 is an activation marker on NK cells. IL-2 expands or maintains the population of HML-1/NKH1 positive cells and increases NK cytolytic activity. However, cytolytic activity of activated NK cells may be inhibited by monocyte derived PGE2.

Adult↗
PubMed1992

Lymphocyte responses to DR4/1-restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19-kd Mycobacterium tuberculosis protein.

OBJECTIVE: Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1-restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1-restricted lymphocyte responses in healthy volunteers and patients with RA were determined. METHODS: Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19-kd Mycobacterium tuberculosis (MT) protein. RESULTS: 3H-thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N-terminal peptide (residues 1-20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N-terminal peptide was not a common antibody-binding site, unlike several of the other peptides. CONCLUSION: Similar responses by RA and normal PBL to a DR4/1-restricted immunodominant T cell epitope on the 19-kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1-restricted peptide immunotherapy.

Adult↗
PubMed1992

Carbon dioxide absorption and gas exchange during pelvic laparoscopy.

Twelve ASA physical status I-II patients undergoing pelvic laparoscopy for infertility were enrolled in a study to quantify the effects of CO2 insufflation and the Trendelenburg position on CO2 elimination and pulmonary gas exchange, and to determine the minute ventilation required to maintain normocapnia during CO2 insufflation. Measurements of O2 uptake (VO2), CO2 elimination (VCO2), minute ventilation (VE), FIO2, and respiratory exchange ratio (RQ) were made during three steady states: control (C) taken after 15 min of normoventilation but before CO2 insufflation, after 15 min (L1) and 30 min (L2) of hyperventilation during CO2 insufflation. The FIO2 was controlled at 0.5 and arterial blood gases were used to calculate the oxygen tension-based indices of pulmonary gas exchange. After 15 min and 30 min of CO2 insufflation, the volume of CO2 absorbed from the peritoneal cavity was estimated at 42.1 +/- 5.1 and 38.6 +/- 6.6 (SEM) ml.min-1 respectively, increasing CO2 elimination through the lungs by about 30%. Hyperventilation of the lungs by a 20-30% increase in minute ventilation maintained normocapnia. Despite the CO2 pneumoperitoneum and Trendelenburg position, there was no impairment of pulmonary oxygen exchange as estimated by (A-alpha)DO2. This study demonstrated that a 30% increase in minute ventilation, achieved by increasing tidal volume to more than 10 ml.kg-1, is sufficient to eliminate the increased CO2 load and maintain normal pulmonary O2 exchange during pelvic laparoscopy.

Absorption↗
PubMed1992

Pressure controlled-inverse ratio ventilation and pulmonary gas exchange during lower abdominal surgery.

Although pressure controlled-inverse ratio ventilation (PC-IRV) has been used successfully in the treatment of respiratory failure, it has not been applied to the treatment of respiratory dysfunction during anaesthesia. With PC-IRV the inspiratory wave form is fundamentally altered so that inspiratory time is prolonged (inverse I:E), inspiratory flow rate is low, and the peak inspiratory pressure is limited. Positive end-expiratory pressure (PEEP) can be applied and the mean airway pressure is higher than with conventional ventilation. To assess the clinical efficacy of this new mode of ventilation we studied ten patients having lower abdominal gynaecologic surgery in the Trendelenburg position under general anaesthesia. Pulmonary O2 exchange was determined during four steady states: awake control (AC), after 30 and 60 min of PC-IRV during surgery, and at the end of surgery. Patients' lungs were ventilated with air/O2 by a Siemens 900C servo ventilator in the PC-IRV mode with an I:E ratio of 2:1 and 5 cm H2O of PEEP. The FIO2 was controlled at 0.5 and arterial blood gases were used to calculate the oxygen tension-based indices of gas exchange. There were significant increases of (A-a) DO2 at 30 and 60 min (41 and 43%). These changes were less than those reported in a previous study using conventional tidal volume ventilation (7.5 ml.kg-1) and were similar to those in patients whose lungs were ventilated with high tidal volumes (12.7 ml.kg-1). Thus, in this clinical model of compromised gas exchange, arterial oxygenation was better with PC-IRV than with conventional ventilation, but not better than with large tidal volume ventilation.

Abdomen↗
PubMed1990

Expression of the interleukin 6 gene in rheumatoid synovial fibroblasts.

A number of fibroblastoid synovial cell lines have been established from rheumatoid joints. These cell lines were shown to express the interleukin 6 (IL-6) gene constitutively, and exposure of these cells to 5 ng/ml of recombinant human interleukin 1 beta (IL-1 beta) increased IL-6 gene expression. Other recombinant human lymphokines, namely interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor had no enhancing effect on IL-6 gene expression. Dexamethasone added to the cultures at 10(-7) M concentration suppressed the constitutive expression of the IL-6 gene. At a concentration of 10(-5) M, dexamethasone partially suppressed the IL-1 enhanced expression of IL-6. The IL-6 gene probe also hybridized to RNA from unfractionated synovial fluid cells, peripheral blood T cells and non-T cells but not Epstein-Barr virus transformed peripheral blood B cells of patients with rheumatoid arthritis. Our results suggest that in rheumatoid arthritis, synovial fibroblasts actively participate in joint inflammation by lymphokine production. The coexpression of both IL-1 and IL-6 by one synovial fibroblast line suggests a mechanism for the perpetuation of synovitis.

Arthritis, Rheumatoid↗
PubMed1989

Effects of aminobisphosphonate infusion on biochemical indices of bone metabolism in rheumatoid arthritis.

In a phase 1 study, seven patients with classical rheumatoid arthritis were treated with intravenous 3-amino-1-hydroxypropylidene-1-1-bisphosphonate (APD). Following this treatment, bone resorption as measured by fasting urine calcium/creatinine and hydroxyproline/creatinine ratios, was reduced. This was sustained for 6 months in only three patients. Elevations of these ratios often coincided with flares of active arthritis in the remaining four patients. Bone turnover as measured by serum osteocalcin levels was reduced in all patients but serum alkaline phosphatase levels remained unchanged. There was no consistent improvement in clinical indices of disease activity.

Adult↗
PubMed1989

B cell lymphokines in human systemic lupus erythematosus.

B lymphocytes of patients with systemic lupus erythematosus were studied to determine if they were intrinsically hyperresponsive to lymphokine mediators. Peripheral blood B cells from 25 lupus patients and 16 normal individuals matched for age and sex were cultured with recombinant lymphokines. B cells both from patients and normal subjects did not show increased [3H]thymidine uptake when cultured with interleukins 1, 2, and 4. The addition of Staphylococcus aureus Cowan I as costimulant increased [3H]thymidine uptake by B cells of patients and normal subjects. In the absence of T cells these recombinant lymphokines did not increase in vitro IgG or IgM production by lupus or normal B cells. Other recombinant lymphokines, interleukin 3, interferon gamma, lymphotoxin, tumour necrosis factor, and colony stimulating factors for granulocytes and macrophages were tested on lymphocytes from smaller numbers of patients and controls. Most patients in this study had inactive disease and all data suggested that B cells from patients with inactive lupus were not hyperresponsive to the lymphokines tested. In addition, the use of lymphokine gene probes for interleukins 2, 3, and 4 did not show spontaneous expression of these genes in circulating lymphocytes.

Adult↗
PubMed1988

Aminobisphosphonate inhibition of interleukin-1-induced bone resorption in mouse calvariae.

Interleukin-1 (IL-1) is probably an important lymphokine mediator of inflammation and bone resorption. IL-1 derived from mononuclear cells, a melanoma cell line (MM96 cells), and recombinant human IL-1 (rHuIL-1 beta) increased in vitro bone resorption, as measured by the release of 45Ca from cultured mouse calvariae. The 50% maximum active resorption was observed with 0.125 ng/ml or approximately 10(-11) M rHuIL-1 beta. The resorptive action of IL-1 was not entirely dependent on prostaglandin mediation, since its effect was evident when prostaglandin synthesis was inhibited in the cultures by indomethacin. IL-1-induced resorption has been shown to be inhibited by 10(-5) M 3-amino-1-hydroxypropylidene-1-1-bisphosphonate (APD). This inhibition was partially reversed by increasing doses of IL-1. In vitro toxicity studies showed that at concentrations of 10(-4) M, APD inhibited the growth of cultured MM96, murine myelomonocytic P388D1, and rat osteosarcoma UMR 106 cells, but not other mast and lymphoid cell lines. These in vitro observations may have relevance to the use of APD in bone and joint diseases in which inflammation and bone resorption are prominent.

Animals↗
PubMed1986

Current topical corticosteroid preparations.

A brief review of the development, desirability, potency, and side effects of topical corticosteroids is presented. Because of potential sensitizing agents present in vehicles delivering corticosteroids and because new products are constantly being marketed, a detailed listing of single and combination products, as well as the constituents of their vehicles, has been compiled to aid the practicing physician.

Administration, Topical↗
PubMed1985

Induction of antibody responses to influenza virus in human lymphocyte cultures. I. Role of interleukin 2.

The in vitro T cell-dependent antibody response of human lymphocytes to influenza virus X31 was used to study the role of T cell-derived lymphokines in antigen-specific responses. Supernatant from cultures of phytohaemagglutinin-stimulated, pooled human tonsil cells (PHA-MLR) was capable of replacing T cells and inducing T-depleted tonsil cells to secrete influenza-specific antibody. The T cell-replacing activity of PHA-MLR supernatant co-purified with interleukin 2 (IL 2) on Ultrogel AcA54 gel filtration and reversed phase-high performance liquid chromatography. PHA-MLR supernatant and IL 2 also enhanced B cell proliferation induced by anti-mu or Staphylococcal aureus strain Cowan I (SAC). A murine monoclonal antibody directed against the human IL 2 receptor (Mab 2A3) was used to completely block the enhancement of influenza-specific antibody production mediated by PHA-MLR supernatant, purified IL 2, and recombinant human IL 2. Mab 2A3 did not affect the T-independent B cell proliferation induced by anti-mu or SAC, but abrogated the enhancing effect of the PHA-MLR supernatant and IL 2 in this culture system. Immunofluorescence studies failed to demonstrate binding of Mab 2A3 to B cells activated by the X31 influenza virus and IL 2, or by SAC. By using Mab 2A3 to mask out IL 2 effects in the influenza-specific culture system, no other B cell differentiating activities were revealed in supernatants from lymphocytic cultures stimulated with a variety of mitogens. Thus, our results indicate that the production of influenza-specific antibodies by T-depleted human lymphocyte cultures is absolutely dependent on the presence of both antigen and IL 2.

Antibodies, Monoclonal↗
PubMed1984

Thymosin induces helper function in OKT3-positive, E-rosette-negative human cord blood T cells.

E-rosette-negative lymphocytes (TE-), which express monoclonal T-cell markers (OKT3+) were found in higher frequencies in human cord blood (CB) (30% by phenotype and 11.7% by sequential rosette isolation) than in adult peripheral blood lymphocytes (13% by phenotype and 3.7% by isolation). TE- cells had very low levels of 5'-nucleotidase, a lymphocyte maturational marker low in thymocytes. Like other CB T cells, TE- cells possessed marked suppressor capability. Irradiated TE- cells from two cord blood samples demonstrated helper activity for Ig production by adult B cells. In six cord blood samples, however, irradiated TE- cells lacked helper activity. When incubated with thymosin, these TE- cells E+ and differentiated into inducer-helper T cells. These observations confirm previous assumptions that CB T cells are not fully differentiated. Furthermore, T cells from different CB samples may be at various stages of ontogeny. We have also shown that thymosin fraction 5 is able to confer a new immunoregulatory function.

5'-Nucleotidase↗
PubMed1983

Genetic predisposition to two rheumatic diseases.

The co-existence of ankylosing spondylitis and rheumatoid arthritis is uncommon and usually occurs in a male with a long history of back pain followed by the appearance of clinical features of ankylosing spondylitis, while features of rheumatoid arthritis develop in the third or fourth decade of life. Recently, histocompatibility (HLA) antigens have partially elucidated the genetic factors predisposing to both diseases. We report a patient with ankylosing spondylitis and rheumatoid arthritis who had the associated HLA genes.

Aged↗