Biomedical subjects

T W Chin

Publications and source records attributed to T W Chin.

17 recordsLinked to original sources

PubMed1992

Recombinant human mullerian inhibiting substance inhibits human ocular melanoma cell lines in vitro and in vivo.

Since Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian duct, the anlagen of the uterus, vagina, and fallopian tube, we expected and have previously observed that purified recombinant human MIS causes regression of gynecological tumors. However, recent experiments indicating that neural crest derivatives might be responsive to MIS prompted study of a group of human ocular melanoma cell lines in 4 in vitro inhibition assays, and a subrenal capsule assay in vivo. Ocular melanoma cell lines that grew well in a respective assay were studied with MIS to determine whether this biological modifier could inhibit growth. Three human ocular melanomas, OM431 (P less than 0.01), OM467 (P less than 0.02), and OM482 (P less than 0.03), were growth-inhibited by highly purified human recombinant MIS in soft agarose. A dose-dependent tumor inhibition was noted when OM431 cells were incubated with MIS in a liquid colony inhibition assay (P less than 0.05). In addition, OM467 was inhibited (P less than 0.05) by MIS in a multicellular tumor spheroid assay. Cell cycle analysis indicated that OM431 cells were inhibited in monolayer by MIS while in G1. At 100-fold lower serum concentrations than required in the media of in vitro assays, MIS delivered via i.p. osmotic pumps inhibited (P less than 0.05) in vivo the growth of OM431 implanted beneath the renal capsule of nude and CD-1 irradiated mice when compared to mice given implants of pumps containing no MIS. The responsiveness of ocular melanoma to MIS broadens the spectrum of tumors that might be treated with MIS and suggests further investigation of other neural crest tumors.

Animals↗

PubMed1992

Detrimental effect of hypotonic cromolyn sodium.

In a randomized, double-blind, placebo-controlled, crossover study, inhalation of the commercially available nebulized form of cromolyn sodium resulted in a significant decrease in forced midexpiratory flow rate between the 25th and 75th percentile points, equivalent to that observed for distilled water, in children with chronic asthma. We conclude that inhalation of the current hypotonic concentration of cromolyn sodium may be detrimental.

Administration, Inhalation↗

PubMed1992

Familial pulmonary nodular lymphoid hyperplasia.

We describe three persons in one family with diffuse lung infiltrates, digital clubbing, and chronic hypoxia. Elevated immunoglobulin levels and antinuclear antibodies were found in all patients; pathologic findings included hyperplastic lymphoid follicles infiltrating the epithelium of the small airways. These cases may represent a familial systemic autoimmune disorder seen primarily with pulmonary compromise.

Adult↗

PubMed1992

Case report: treatment of blastomycosis with fluconazole.

The authors present two cases of systemic blastomycosis successfully treated with fluconazole. In one case, the disease involved the respiratory tract, and the central nervous system was presumed to be involved. The second case consisted only of pulmonary blastomycosis. Both patients were treated with oral fluconazole 200 mg twice per day for 9 and 6 months, respectively. Treatment with this new triazole antifungal agent resulted in the complete resolution of the disease in both patients. They have remained asymptomatic for more than 6 months after the completion of therapy.

Adult↗

PubMed1992

Catheter-related complications of continuous ambulatory peritoneal dialysis.

OBJECTIVE: To assess the effectiveness of continuous ambulatory peritoneal dialysis (CAPD) with particular reference to morbidity. DESIGN: Open study. SETTING: Two city general hospitals. SUBJECTS: 104 Adults and 11 children with end stage renal failure. MAIN OUTCOME MEASURE: Morbidity. RESULTS: There were 29 complications (25%), the most common being obstruction of the tube (n = 8, 7%), and migration of the tube (n = 7, 6%). Others were peritonitis (n = 5), haemorrhage (n = 4), infection at the exit site (n = 3), and leakage of fluid (n = 2). All were readily treatable. CONCLUSIONS: Fixing the catheter in two places may prevent its migration. The complication rate of CAPD is acceptable, and in children with end stage renal failure it is a suitable alternative to haemodialysis while they are waiting for renal transplantation.

Adult↗

PubMed1991

Human müllerian inhibiting substance inhibits tumor growth in vitro and in vivo.

Müllerian inhibiting substance (MIS) causes regression of the müllerian duct in the male fetus. Bovine MIS has been reported to inhibit the growth of some gynecological tumors. Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been highly purified by immunoaffinity chromatography. The introduction of a salt wash prior to elution of MIS from the affinity column removes a growth-stimulating factor(s) derived from Chinese hamster ovary cells. This immunopurified rhMIS caused significant inhibition (34-59% survival) of A431 (a vulvar epidermoid carcinoma), HT-3 (a cervical carcinoma), HEC-1-A (an endometrial adenocarcinoma), NIH:OVCAR-3 (an ovarian adenocarcinoma), and OM431 (an ocular melanoma) human cell lines in colony inhibition assays. Two cell lines, Hep 3B (a hepatocellular carcinoma) and RT4 (a bladder transitional cell papilloma), were unresponsive to immunopurified rhMIS. Using an in vivo subrenal capsule assay in irradiated CD-1 mice, the growth of A431 and OM431 cells was inhibited by immunopurified rhMIS. We conclude that rhMIS inhibits the growth of certain tumor cell lines in vitro and in vivo.

Animals↗

PubMed1991

Effects of herpes simplex virus on induced cell-mediated cytotoxicity in neonates and adults.

Deficient cellular cytotoxic mechanisms are present in neonates, contributing to their increased susceptibility to certain viruses, notably herpes simplex virus (HSV). Significant lymphokine-activated killer (LAK) cell activity has been described in cord blood, suggesting a possible role for LAK and/or interleukin-2 (IL-2) therapy in newborns with serious viral infections. The effect of HSV (type 1) on the activation of cord versus adult LAK cells was investigated by adding virus (multiplicity of infection, MOI = 10) to cells that had been previously incubated for 4-6 days with IL-2 (50-100 U/ml). The cells were then tested 24 h after virus exposure for cytotoxic activity against 51Cr-labelled K562 and Raji target cells. HSV inhibited LAK cytotoxicity of adult cells against K562 by 44% (72 +/- 2.4%, SEM; specific lysis to 40 +/- 6.2%, n = 15) and by 62% against Raji targets (50 +/- 5.6 to 19 +/- 4.4%). A similar degree of inhibition was observed for cord cells against K562 (76 +/- 2.0 to 46 +/- 5.3%) and Raji (60 +/- 4.6 to 24 +/- 6.2%). The degree of inhibition was correlated with the dose of virus in dose-response experiments. Inhibition was also noted with irradiated (10,000 rad) but not with heat-inactivated (56 degrees C for 60 min) virus. No inhibition was found when virus was added directly to the cytotoxic assay or when virus was added at the initiation or end of culture of cells with IL-2 (i.e. day 0 or day 5-7). In contrast, HSV stimulated cytotoxic activity against both the natural killer (NK)-sensitive (K562) and NK-resistant (Raji) targets in cells not incubated with IL-2. The cytotoxicity of adult cells incubated with infectious HSV (MOI = 10) for 5-7 days increased from 5.5 +/- 1.9% in the absence of virus to 25 +/- 6.0% against K562 in the presence of virus and from 3.5 +/- 1.0 (no virus) to 16 +/- 4.3% (with virus) against Raji targets (n = 8). The cytotoxicity of cord cells was also stimulated, but to a lesser degree. Irradiated virus also stimulated cytotoxic activity but to a lesser degree in cord cells. Virus-induced nonspecific cytotoxicity may represent an important component of the host's antiviral defense that is present at birth, but somewhat diminished compared to normal adults.

Antibodies, Monoclonal↗

PubMed1991

Computer-aided cell colony counting.

Counting cell colonies is a tedious task when performed with the light microscope. Moreover, unless strict double-blind protocols are adhered to, biased counts are difficult to avoid. Presented here is a computer software application that performs accurate, reproducible cell colony counts with a minimum of user generated bias. The application is based upon the Apple IICX computer system with Image software and AppleScan. Colonies are grown on 24-well plates and prepared in such a way as to permit good quality scanning. The scans are then transferred to Image and the individual colonies in each well are counted. Good correlation with counts done by light microscopy is achieved.

Clone Cells↗

PubMed1990

Mucosal intussusception to avoid ascending cholangitis.

Many methods have been devised to prevent ascending cholangitis following Kasai's hepatic portoenterostomy for biliary atresia. To investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis, 20 mongrel dogs were randomized to undergo Roux-en-Y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception. Aeromonas hydrophila was instilled into the gastrointestinal tract. Bacterial cultures were grown from samples taken from the gallbladders and lower jejunum, and blood chemistry and barium studies were performed. The barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception. Only two of them had positive cultures for Aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum. All ten dogs in the control group had positive cultures for Aeromonas from the gallbladder. Our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine (P less than 0.05). The method is worthy of clinical trial as a means of preventing or treating ascending cholangitis.

Aeromonas↗

PubMed1990

Lip and intraoral tumours: a local perspective.

Lip and intra-oral cancer is an uncommon disease in Singapore among the local population. The incidence is less than 1.5% of all cancers reported to the Singapore Cancer Registry which recorded a total of 18,049 cases of all types of cancer in a 5-year period from 1978 to 1982. The Department of Plastic Surgery at Singapore General Hospital has been conducting a multidisciplinary clinic for the management of head and neck tumours since 1984. The results of the distribution, age, sex and racial differences, risk factors and modalities of treatment of the various types of cancer affecting the lip and intraoral region were analysed in a prospective study. A total of 69 cases were analysed and of these 59 (85.5%) were squamous cell carcinoma (SCC) of varying grades of malignancy, the remaining comprising adenoidcystic and mucoepidermoid carcinoma, malignant melanoma and a single case of ameloblastoma. A number of predisposing factors such as smoking, alcohol and the chewing of betel nuts could be identified in the history of patients suffering from cancers involving the buccal mucosa and tongue. As the numbers involved in non-SCC are small in this study, the discussion will be confined to patients presenting with squamous cell carcinoma only.

Adult↗

PubMed1989

Lymphokine-activated killer cells in primary immunodeficiencies and acquired immunodeficiency syndrome.

Cytotoxic mechanisms (e.g., natural killer (NK) lysis, antibody-dependent cellular cytotoxicity, and cytotoxic T lymphocyte lysis) play an important role in host defense against various infections and neoplasms. Lymphokine-activated killer (LAK) cytotoxicity, induced in vitro by incubating mononuclear cells with interleukin 2 (IL-2) for 2-5 days, may also represent an important component of the body's cytotoxic repertoire. In 10 patients with congenital cellular immunodeficiencies, including 5 with severe combined immunodeficiency, the mean LAK activity in a 3-hr chromium release assay against Raji target cells was 44 +/- 8.1%, which is equivalent to that observed in normal adults and neonates. In only one case, a patient with reticular dysgenesis, was there absent LAK cell generation. Haploidentical T cell-depleted bone marrow transplantation (BMT) restored LAK activity in this patient. LAK activity was first observed in this patient and two others 3-6 weeks following BMT, prior to other evidence of immunologic engraftment such as lymphocyte proliferation to mitogens, NK activity, or interferon-gamma production. One patient with adenosine deaminase deficiency showed normal levels of LAK activity despite absent NK activity. Three patients with chronic granulomatous disease also had normal LAK activity (57 +/- 14% specific lysis). In 9 patients with acquired immunodeficiency syndrome (AIDS), IL-2 activation resulted in a mean cytotoxic activity of 56 +/- 8.7% toward Raji targets. In addition, 9 patients with pre-AIDS complex also showed normal levels of cytotoxicity (37 +/- 3.3% toward Raji targets), equivalent to that of 8 normal controls, including two healthy homosexual males (mean lysis 38 +/- 3.9%). These results indicate that LAK cells appear early in immunologic ontogeny. Further, the mechanism of lysis is not oxygen dependent since LAK activity was present in the 3 patients with chronic granulomatous disease. The ability to generate LAK in a wide spectrum of immunodeficiencies may indicate that IL-2 could be used in therapy of such disorders.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Enhanced interferon production and lymphokine-activated cytotoxicity of human placental cells.

The immunologic competence of human placental mononuclear cells was compared to that of adult and cord blood mononuclear cells. Mononuclear cells were isolated from fresh placentas by digestion with collagenase and DNase, followed by Ficoll-Hypaque and discontinuous Percoll separation. Placental cells incubated with phytohemagglutinin (PHA) synthesized significantly more interferon-gamma (IFN-gamma) at 2 days (29 +/- 5.5 IU/ml) and 5 days (46 +/- 8.5 IU/ml) than PHA-activated cord cells (3.6 +/- 0.6 IU/ml at 2 days and 2.7 +/- 0.7 IU/ml at 5 days) but less than PHA-activated adult cells (81 +/- 20 IU/ml at 2 days and 270 +/- 161 IU/ml at 5 days). Placental and adult cells, but not cord cells, also synthesized significant quantities of IFN-gamma following incubation with interleukin-2 (IL-2). There was synergism between IL-2 and PHA activation for IFN-gamma production for some cord samples. After a 5- to 7-day incubation with IL-2, the lymphocyte-activated killer (LAK cell) cytotoxicity of placental cells (measured in a 3-hr chromium-release assay at an E:T ratio of 40:1) was enhanced 13-fold against K562 target cells (6 +/- 2% to 77 +/- 4%) compared to a 4-fold increase in cord cells (16 +/- 4% to 68 +/- 3%) and a 2-fold increase in normal adult cells (35 +/- 4% to 65 +/- 3%. Against the natural killer (NK)-resistant Raji target, placental cells increased their LAK cytotoxic activity (3 +/- 1% to 59 +/- 7%) compared to a 7-fold increase with cord cells (6 +/- 1% to 43 +/- 3%) and a 3-fold increase with adult cells (11 +/- 2% to 38 +/- 4%). A notable degree of cytotoxic activity in the absence of IL-2 against Molt targets was noted in 11 of 14 (79%) placental cell samples at 5 days. Only 10 of 24 (42%) adult and 17 of 37 (40%) cord samples showed spontaneous cytotoxic activity equal to or greater than 10%. Some placental samples actually showed an increase in cytotoxic activity when incubated without IL-2. The ability of placental cells to produce significant levels of IFN-gamma, to develop considerable LAK activity, and to maintain or develop cytotoxic activity in the absence of IL-2 suggests a vigorous, active immune system of the placenta compared to the relatively dormant immune system of the neonate. These observations suggest that placental cells may have a primary role in fetal defense.

Adult↗

PubMed1987

Corticosteroids in treatment of obstructive lesions of chronic granulomatous disease.

Two patients with chronic granulomatous disease had obstructive lesions of the gastrointestinal tract, esophagus, and genitourinary tract, which were successfully treated with corticosteroids. These obstructive lesions, caused by local granuloma formation, have been reported in 18 other patients with chronic granulomatous disease, none of whom received steroids. Our first patient, a 3-year-old boy, had emesis and weight loss associated with antral narrowing and delayed gastric emptying at age 2 years. Antibiotic therapy was ineffective, but intravenous and oral corticosteroid therapy for 10 weeks resulted in clinical cure. One year later, dysuria associated with bladder neck obstruction was also treated successfully with corticosteroids. The second child, a 10-year-old boy, had dysphagia caused by distal esophageal stenosis. Corticosteroid therapy (with concomitant antibiotics) on two occasions reversed this obstruction. Granulomatous cystitis with ureteropelvic obstruction then developed, which also responded to treatment with corticosteroids and antibiotics. Despite the risk of increased susceptibility to infection, corticosteroid therapy is justified in preventing life-threatening obstruction of vital organs.

Child↗

PubMed1986

Absence of tachyphylaxis in gastric acid secretion during pentagastrin infusion.

Tachyphylaxis to stimulation of gastric juice secretion during intravenous pentagastrin (PG) infusion has been reported in animal studies. We assessed the course of gastric response to PG 2 micrograms/kg/hr over eight hours in eight healthy subjects. Peak H+, pepsin, and volume secretions occurred during the second half hour of stimulation. Peak H+ output was 11.6 +/- 1.3 mmol/0.5 hr or 7.6 +/- 0.8% of the total eight-hour secretion. During subsequent half-hour collection intervals, there was no significant decline in response, and the average output was 10.3 +/- 0.4 mmol/0.5 hr (6.5 +/- 0.1%). Peak pepsin and volume secretions were respectively 10.0 +/- 1.4% (74.8 +/- 11.6 mg/0.5 hr) and 8.8 +/- 1.1% (146.3 +/- 17.4 mL/0.5 hr) of the total eight-hour secretion. Although there was a significant decline in pepsin and volume response subsequent to the peak output, the decline was not continuous, and pepsin and volume secretions were maintained, respectively, at 6.0 +/- 0.2% (46.1 +/- 2.5 mg/0.5 hr) and 6.2 +/- 0.1% (107.5 +/- 3.0 mL/0.5 hr) of the total eight-hour secretion. Our study did not demonstrate any tachyphylaxis in H+ response to continuous PG stimulation. This model appears to be a valid tool for the assessment of histamine-H2 antagonist effects on stimulated gastric juice secretion over 8 hours in humans.

Adult↗

PubMed1986

Pharmacokinetics of cimetidine after subchronic administration.

The influence of cimetidine on its own pharmacokinetics after subchronic administration was assessed in 8 healthy volunteers, aged 26-29 years. On control Day 1, each subject received cimetidine 300 mg i.v., and serum and urine samples were obtained. Each subject was initiated on cimetidine 600 mg b.i.d. orally for 2 weeks. There were 3 further study days repeated after 1 and 2 weeks of cimetidine dosing and 1 week after stopping cimetidine. There was no significant difference in the mean total body clearance of cimetidine among the 4 study days. Mean elimination t1/2 beta and V beta were similarly unchanged. However mean renal clearance (CLR) and fe were significantly increased following 2 weeks of drug dosing (CLR 5.41 ml X min-1 X kg-1; fe 0.61) compared to control (CLR 4.00 ml X min-1 X kg-1; fe 0.48). Although the non renal clearance was reduced from control values of 4.29 to 3.51 ml X min-1 X kg-1 following 2 weeks of dosing the difference was not significant. Dosage adjustment of cimetidine appears unnecessary after short-term dosing in the presence of normal renal function.

Administration, Oral↗

PubMed1986

Cytotoxic studies in human newborns: lessened allogeneic cell-induced (augmented) cytotoxicity but strong lymphokine-activated cytotoxicity of cord mononuclear cells.

Nonspecific cytotoxic responses such as natural killer activity can be increased in vitro by incubating effector cells with soluble factors or allogeneic cells. We sought to determine if newborn cells, known to be deficient in most cytotoxic responses, including resting NK activity, could develop enhanced cytotoxic responses following incubation with allogeneic cells (augmented cytotoxicity) or with lymphokines (lymphokine-activated cytotoxicity). Cord whole mononuclear cells (WMC) incubated with irradiated Raji cells for 5 days develop lower levels of cytotoxicity toward K562 targets at both a 20:1 effector:target (E:T) ratio (39 +/- 2.7% vs 49 +/- 3.6%) and a 10:1 E:T ratio (29 +/- 2.6% vs 40 +/- 3.6%) than do adult cells. Lessened specific cytotoxicity of cord cells developed toward the sensitizing Raji cells was also observed at both E:T ratios. Attempts to enhance the induced cytotoxicity by incubation with interferon or isoprinosine were unsuccessful. In contrast, lymphokine (i.e., interleukin 2)-activated killer (LAK) cytotoxicity is not deficient in cord WMC. Indeed, the level of LAK cytotoxicity is equivalent to that observed with similarly treated adult cells despite a lower baseline level of cytotoxicity toward the target cells. In the presence of purified IL-2 for 5 days, cord WMC cytotoxicity against K562 cells increased from 12 +/- 2.6 to 71 +/- 4.2% and against Raji cells increased from 9.6 +/- 2.5 to 48 +/- 6.7%. Similarly treated adult cells increased their killing against K562 from 23 +/- 4.2 to 61 +/- 4.5% and against Raji from 12 +/- 3.0 to 36 +/- 5.3%. This substantial lymphokine-activated cytotoxicity of newborn cells suggests the possibility of therapeutic intervention with purified lymphokines in neonatal infections or neoplasms.

Cytotoxicity, Immunologic↗

PubMed1986

Infectious complications of the primary immunodeficiencies.

The primary manifestation of the immunodeficiencies is undue susceptibility to infection. This means too many, too severe, too prolonged, too complicated and too unusual infections. Infections in immunodeficiency have a characteristic cause depending on the nature of the immune deficiency. Antibody deficiencies are associated with infections with gram-positive infections. Cellular immune deficiencies are associated with mycobacterial, protozoan, fungus, virus, and opportunistic bacterial infection. Phagocytic disorders are associated with staphylococcal, fungal, and gram-negative organisms. Complement disorders are associated by neisserial infections. Infections have also been implicated in the pathogenesis of some immunodeficiencies in some circumstances. These include human T lymphotropic virus type III (HTLV-III), rubella virus, cytomegalovirus, and Epstein-Barr virus. Several infectious syndromes in specific immunodeficiencies have been identified. Examples include enteric cytopathic human orphan (ECHO) virus encephalitis in agammaglobulinemia, and meningococcal meningitis in C6 deficiency. Infections can also be induced by live vaccines given in immunodeficiency (e.g., paralytic polio in agammaglobulinemia.) Unusual infectious syndromes will be illustrated including parainfluenza infection in severe combined and immunodeficiency, Legionella pneumonia in chronic granulomatous disease, and Cryptosporidium infection in hyper-IgM immunodeficiency.

Antibody Formation↗