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Biomedical subjects

K W Chan

Publications and source records attributed to K W Chan.

At least 217 records · Page 12Linked to original sources
PubMed1995

Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients.

To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-host disease (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10 children with leukemia received high-dose thiotepa, cyclophosphamide and total body irradiation followed by transplantation of CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to treatment with steroids. Five of nine evaluable patients developed chronic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD. This may have been due to the high number of T cells infused with the marrow.

Adolescent↗
PubMed1995

Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation.

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.

Acute Disease↗
PubMed1994

Obstructive lung disease in children after allogeneic bone marrow transplantation.

Obstructive lung disease (OLD) has been described as a significant complication after allogeneic bone marrow transplantation (BMT). The incidence of OLD in adults appears to be low (approximately 3%), but there is little data for children. We analyzed 89 consecutive pediatric allogeneic BMTs, > or = 1.5 years post-BMT, performed at British Columbia's Children's Hospital from 1980 to 1992 for evidence of OLD. Diagnosis of OLD was based on clinical findings (nonproductive cough, wheezing, and dyspnea with no evidence of infection), pulmonary function tests (FEV1 < 80% and FEF25-75% < 60% predicted), lung biopsy, and computed tomography scan. Sixty-seven of the 89 children evaluated survived > or = 90 days and were classified as at risk for OLD. Thirteen of 67 (19.4%), developed OLD, 3 of which were transient. The development of OLD was strongly associated with the following high-risk groups: chronic graft-versus-host disease (GVHD) (37.1% OLD), increased donor age, acute GVHD, and either mismatched related or matched unrelated donor transplants. No correlation was found with methotrexate prophylaxis for GVHD, total body irradiation, or cytomegalovirus reactivity in either donor or recipient and the development of OLD. Further analysis of only children with chronic GVHD showed that liver involvement by GVHD before the onset of OLD (57.9%) was the only other significant predictive factor. We observed an overall increased prevalence of OLD in children compared with that previously reported in adults. Further studies are required to confirm whether age is a risk factor for development of OLD after allogeneic BMT.

Acute Disease↗
PubMed1994

Protein tyrosine kinase p56-Lck regulates lymphocyte function-associated 1 adhesion molecule expression, granule exocytosis, and cytolytic effector function in a cloned T cell.

Elevated levels of p56-Lck kinase activity were achieved in an interleukin 2 (IL-2)-dependent cloned cytolytic T cell CTLL-2 through gene transfer approaches. CTLL-2-Lck cells remained dependent on IL-2 for growth and survival in culture but exhibited markedly elevated, IL-2-independent cytolytic activity against a variety of tumor targets. This immune cell effector function was similar to the non-major histocompatibility complex-restricted cytolytic activity previously described for lymphokine activated killer (LAK) cells, and involved a cytolytic mechanism that was independent of protein synthesis in either the T cells or the tumor targets. Characterization of CTLL-2-Lck cells revealed markedly elevated levels of both the alpha (CD11a) and beta (CD18) chains of the cell adhesion molecule lymphocyte function-associated 1 (LFA-1) and increased binding of these T cells to a recombinant protein representing the extracellular domain of the LFA-ligand, intercellular adhesion molecule 1 (ICAM-1). Antibodies to CD11a partially abrogated cytolytic killing of tumor target cells by CTLL-2-Lck cells, suggesting that the upregulation in LFA protein levels potentially accounts at least in part for the phenotype of these T cells. Gene transfer-mediated elevations in p56-Lck kinase activity in an IL-3-dependent myeloid cell clone 32D.3 also resulted in increased LFA-1 expression, demonstrating that the findings are not unique to CTLL-2 cells. In addition to upregulation of LFA-1 expression, CTLL-Lck cells also exhibited more efficient exocytosis of cytotoxic granules upon activation with Ca(2+)-ionophore and phorbol ester, relative to control transfected and untransfected CTLL-2 cells. The findings functionally link the Lck kinase to a T cell effector pathway involved in cell-mediated cytotoxicity.

Cell Adhesion↗
PubMed1994

Role of the TIGN sequence in E. coli tryptophanyl-tRNA synthetase.

Tryptophanyl-tRNA synthetase in E. coli does not have the HIGH sequence that is normally characteristic of class I aminoacyl-tRNA synthetases (EC 6.1.1.2), but instead contains a TIGN sequence at residues 17-20, which has been suggested to be equivalent to the HIGH sequence (Jones, M.D. et al. (1986) Biochemistry 25, 1887-1891). We have overexpressed E. coli Trp-tRNA synthetase and have used site-directed mutagenesis to mutate Thr-17 in the TIGN sequence to alanine. The mutant enzyme has the same Km values as the wild-type for tryptophan or tRNA(Trp), and a slightly increased Km for ATP, from 0.37 to 0.64 mM. On the other hand, the kcat for either the first step or the overall reaction is decreased by a factor of 30. In comparing the Thr-17 and Ala-17 enzymes, the delta delta G for the conversion of substrate to transition state is +9.6 kJ/mol (2.3 kcal/mol). Thr-17 is therefore important in binding the substrate in the transition state, thus supporting the suggestion that TIGN may fulfill the role of a HIGH sequence.

Amino Acid Sequence↗
PubMed1994

Somatic cell hybrid panel and NotI linking clones for physical mapping of human chromosome 3.

To identify by positional cloning the putative tumor-suppressor genes on the short arm of human chromosome 3 that are involved in the initiation or progression of several human malignancies, we have developed human mouse somatic cell hybrids and NotI linking libraries. The somatic cell hybrids contain either the intact human chromosome 3 or its derivatives as the only human genetic material in rodent background. The somatic cell hybrid panel defines five chromosomal regions on the short arm and two chromosomal regions on the long arm of chromosome 3. Two hundred sixty-one NotI linking probes from three independently constructed linking libraries were assigned to the seven chromosomal regions. The somatic cell hybrid panel and the regionally localized NotI linking probes should facilitate the construction of genetic linkage and physical maps to identify various tumor-suppressor and disease-related genes not only on the chromosome 3p, but on the entire chromosome.

Animals↗
PubMed1994

The lag time between onset of symptoms and diagnosis of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) may be biologically reversible if treated in the first several months, yet it is unknown whether patients are diagnosed that early. We investigated the lag time between symptom onset and diagnosis of RA in a population with excellent access to rheumatology care. METHODS: Using review of medical records, we evaluated all patients newly diagnosed as having RA from 1987 through 1990, at a health maintenance organization in central Massachusetts. Total lag time from symptom onset to first definite diagnosis was divided into medical encounter lag time (from symptom onset to first medical encounter) and diagnosis lag time (from first medical encounter to diagnosis). RESULTS: The median total lag time was 36 weeks (range 4 weeks to > 10 years). The median medical encounter lag time was 4 weeks (not all patients included in the analysis). The median diagnosis lag time was 18 weeks. Diagnosis lag time was shorter for patients with progressive disease and positive rheumatoid factor on the initial test. Of 25 patients with symmetric arthritis and positive rheumatoid factor, only 5 (20%) were diagnosed within 2 months, and 10 (40%) were diagnosed more than 6 months after symptom onset. CONCLUSION: RA diagnosis is usually delayed for several months after symptoms begin, in large part because of delay in diagnosis by the physician. Thus, the goal of initiating treatment extremely early may be unrealistic for most patients.

Arthritis, Rheumatoid↗
PubMed1994

Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies.

Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m2 by continuous infusion, and cyclophosphamide 2 g/m2 on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/microliters) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT.

Adolescent↗
PubMed1994

Bladder tumours in Chinese: a 6 year study.

Specimens from 334 Chinese patients who underwent surgical treatment for bladder tumours over a 6 year period were studied retrospectively. Transitional cell carcinoma (TCC) accounted for 91.3% of all the bladder tumours. The male to female ratio was 3:1 and the mean age was 69 years. Papillary TCC, which represented 67.5% of all TCC, were more often of a lower grade compared to non-papillary tumours. The staging of tumours was done for the 102 cystectomy specimens with TCC only. Among these, 28% were superficial while 72% were muscle-invasive and the papillary TCC usually presented at an earlier stage. Infiltration into the prostate gland was identified in 11% of male patients while coexisting adenocarcinoma of the prostate was observed in another 4.2%. Other types of carcinoma were uncommon. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma accounted for 2.7, 1.8 and 0.6% of all bladder tumours, respectively. A rare case of sarcomatoid carcinoma was also found, but no true sarcoma was documented in this series. Benign lesions included five inverted papillomas, three nephrogenic adenomas, two paragangliomas and one haemangioma.

Adenocarcinoma↗
PubMed1994

Cranial neuropathy, polyneuropathy and thrombocytopenia with Epstein-Barr virus infection.

Neurological involvement is an uncommon complication of Epstein-Barr virus infection, and the long incubation period may complicate the diagnosis. A 15-year-old boy is described with Epstein-Barr virus infection complicated by prolonged life-threatening thrombocytopenia, cranial neuropathy and peripheral sensorimotor neuropathy. The abnormal platelet count was unresponsive to multiple-drug therapy and splenectomy, but normalized 13 months after presentation. Neurological recovery was slow; the patient continues to have a mild peripheral sensorimotor neuropathy three years after the onset of the illness. Infection with Epstein-Barr virus should be considered in patients with acute neurological problems associated with thrombocytopenia. Measurement of antibodies to individual Epstein-Barr virus proteins facilitates the diagnosis of Epstein-Barr virus infection.

Adolescent↗
PubMed1994

Prevalence of human papillomavirus types 16 and 18 in penile carcinoma: a study of 41 cases using PCR.

AIMS: To determine retrospectively the prevalence of human papillomavirus (HPV) types 16 and 18 in penile carcinomas. METHODS: Forty one surgically resected penile carcinomas from the archives at Queen Mary Hospital, Hong Kong, were reviewed and classified into verrucous carcinoma, and well, moderately, and poorly differentiated squamous cell carcinomas. Paraffin wax embedded tumour tissue was sectioned and analysed for HPV 16 and HPV 18 using the polymerase chain reaction with type specific internal probes. RESULTS: There were seven verrucous carcinomas, and 11 well, 17 moderately, and six poorly differentiated squamous cell carcinomas. Six of the 41 (15%) patients had penile carcinoma containing HPV 16 or HPV 18 DNA, or both, with HPV 16 found in four (10%) and HPV 18 in four (10%). The mean ages of HPV positive and HPV negative groups of patients were 68.5 and 57.6 years, respectively (p < 0.05). None of the seven verrucous and 11 well differentiated squamous cell carcinomas was positive for HPV. The mean age of patients who had these carcinomas was 52.4 years. As a group, these low grade carcinomas occurred in patients younger by more than a decade than those who had carcinomas of the higher grades (mean age 64.4 years; p < 0.01). CONCLUSIONS: Penile carcinomas had much lower rates of infection by HPV 16 or HPV 18 than cervical carcinomas in this Hong Kong population. Based on our findings and on data collated from published findings, it is concluded that penile verrucous carcinomas are not associated with HPV 16 and HPV 18. The overall low prevalence of HPV 16 and HPV 18 in penile carcinomas suggests that other HPV types might be important in the pathogenesis of these tumours.

Aged↗
PubMed1994

Thalidomide in the management of chronic graft-versus-host disease in children following bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is the major complication in patients surviving > 100 days post-allogeneic bone marrow transplantation and occurs in 30% of pediatric patients. It is most prevalent 1-2 years post-transplant. Treatment involves corticosteroids and other immunosuppressive therapy which may affect growth and increase the likelihood of infectious complications. We report five children with severe corticosteroid-dependent chronic GVHD treated with thalidomide 12-25 mg/kg/day. Response to therapy was based on resolution of symptoms of chronic GVHD and withdrawal of other immunosuppressive therapy. All the children showed clinical response to thalidomide with cessation or diminution in other immunosuppressive medication. Side-effects were minimal and no patient developed peripheral neuropathy. All patients are alive 48-65 months post-transplantation. Thalidomide is a safe and effective drug for the treatment of chronic GVHD in children and may avoid the use of long-term corticosteroid therapy.

Adolescent↗
PubMed1994

Primary pulmonary lymphoma: report of three cases and a brief review of the literature.

We report three patients with primary pulmonary non-Hodgkin's lymphoma which is a rare extranodal lymphoid neoplasm. In these patients, both the history and physical findings were vague and minimal. The laboratory findings were normal apart from chest radiographic abnormalities and serum gammopathy in two cases. All three patients underwent several diagnostic procedures before conclusive results were obtained from thoracotomy specimens. Histology revealed small lymphocytic infiltrate of the pulmonary parenchyma with nodal involvement in all three cases. All three patients had surgical resection and two received adjuvant chemotherapy. They are all alive and symptom-free at 92, 51 and 12 months, respectively, after diagnosis.

Diagnosis, Differential↗
PubMed1994

A study of bond strength of dentin bonding agents to human dentin.

BACKGROUND: Marginal leakage of restoration induced by polymerization shrinkage of composite resin can be prevented if the dentin bonding agent is strong enough to counteract the force of polymerization shrinkage. METHODS: Fifty molar teeth obtained due to periodontal problem were used in this investigation. Crown portion of the teeth was grounded perpendicular to the long axis of the teeth until a complete layer of dentin surrounded by enamel was created. The teeth were then mounted with dental stone, and divided into five groups randomly. Dentin bonding agent was applied to the dentinal surface and a gelatin capsule mold was used to apply composite resin material. After incubation, the bonded composite specimens were tested with Instron universal testing machine in order to determine the shear strength of the composite bonding result. The fracture patterns were examined with scanning electron microscope. RESULTS: The Universal bond 3 combined with the AP.H composite exhibited the highest shear bond strength (10.76 MPa). The fracture pattern of the Universal Bond 3 combined with AP.H was mainly that of cohesive failure in the composite resin part instead of adhesive failure in the other groups tested. CONCLUSIONS: The shear bond strength of these five dentin bonding agents ranged from 2.89MPa to 10.76MPa. The fracture pattern of the tested groups was mainly that of adhesive failure at the interface between dentin bonding agent and its corresponding composite resin instead of cohesive failure disclosed in the composite resin part of Universal Bond 3 combined with AP.H group.

Biomechanical Phenomena↗
PubMed1994

Bone marrow transplantation in Gaucher's disease: effect of mixed chimeric state.

The effective dose and schedule of enzyme replacement therapy for Gaucher's disease have not been definitely established. We report a case of mixed chimeric state in an allogeneic BMT patient and followed her clinical and laboratory progress. The result shows that a low but sustained glucocerebrosidase level may provide symptomatic relief for this lysosomal disorder.

Bone Marrow Transplantation↗
PubMed1994

Simple aspiration of pneumothorax.

The effectiveness of simple aspiration of pneumothorax with an intravenous cannula was evaluated in 34 patients who would otherwise have been treated by intercostal tube drainage with underwater seal. The procedure was successful in 25 patients (73.5%). The following features were associated with a successful outcome: (a) age below 50 years, (b) absence of underlying lung disease, (c) pneumothorax size not exceeding 50%, (d) volume of air aspirated less than 3000 ml, and (e) no previous pneumothorax. There were no complications encountered. Successfully treated patients benefitted from a shorter hospitalisation stay. The potential use of this procedure in treating selected patients in an outpatient setting should be explored.

Adult↗