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Biomedical subjects

H R Chang

Publications and source records attributed to H R Chang.

At least 55 records · Page 3Linked to original sources
PubMed1993

Human monoclonal antibody SK1-mediated cytotoxicity against colon cancer cells.

PURPOSE: Human monoclonal antibody (HuMAb) SK1, a human monoclonal IgM, has previously been shown to react selectively with a wide range of human carcinomas. In this study, the complement-dependent cytotoxicity (CDC) mediated by the HuMAb SK1 was investigated. METHODS: The presence of AgSK1 on the two studied cell lines, HT29 and PANC-1, was evaluated by the immunocytochemical staining. The intracellular and surface locations of the targeting antigen of HuMAb SK1 were further characterized by the study of flow cytometry. The specific lysis of target cells by the HuMAb SK1 in the CDC assay was studied. RESULTS: In the presence of human complement, the HuMAb SK1 was shown to be effective in the lysis of cultured human gastrointestinal cancer cells as well as the fresh colon cancer cells derived from the patient's specimens. In addition, our data suggested that HuMAb SK1 activated the mouse complement in a similar magnitude. CONCLUSIONS: We concluded that HuMAb SK1 showed some promise for future clinical trials. The in vitro CDC effect of HuMAb SK1 with mouse complement suggested that the antitumor effect of HuMAb SK1 might be successfully studied in the nude mouse model bearing xenografts of human colon cancer as a part of the preclinical evaluation.

Animals↗
PubMed1992

Expression of disialogangliosides GD2 and GD3 on human soft tissue sarcomas.

METHODS: Fifty-six freshly frozen human sarcomas were studied for expression of disialogangliosides by avidin-biotin immunohistochemical staining with purified monoclonal antibodies (MoAb) 3F8 (antidisialoganglioside GD2) and R24 (antidisialoganglioside GD3). RESULTS: Ninety-three percent of the tumors tested by the immunohistochemical staining expressed GD2 and 88% expressed GD3. The intensity of expression varied among sarcomas of different histologic types. Liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma reacted strongly with 3F8 and R24. Embryonal rhabdomyosarcoma and synovial sarcoma demonstrated substantially weaker staining by either MoAb. Weakly reactive or nonreactive tumors were, in general, high-grade or metastatic sarcomas. Ganglioside extraction and thin-layer chromatography/immunothin-layer chromatography of two liposarcomas confirmed the identities of these gangliosides. CONCLUSIONS: GD2 and GD3 may indicate sites for MoAb-targeted imaging and therapy for sarcomas. The association of a diminished stainability by 3F8 and R24 with aggressive sarcomas may indicate prognostic significance.

Gangliosides↗
PubMed1992

Disseminated "Mycobacterium genavense" infection in patients with AIDS.

We describe 18 patients with advanced HIV infection, most of whom had a chronic illness characterised by fever, diarrhoea, and massive loss of weight. Biopsy and necropsy samples revealed abundant acid-fast microorganisms in intestines, liver, spleen, lymph nodes, and many other tissues, which did not grow on solid media, although limited growth was observed in liquid blood cultures. Using primers complementary to bacterial 16S rRNA we amplified DNA sequences from tissue and leucocyte extracts and from blood-culture bottles. The sequences obtained were unique and suggest that the microorganism is a new member of the genus Mycobacterium, for which we propose the name "Mycobacterium genavense". Disseminated infection with "M genavense" should be considered in the differential diagnosis of HIV-infected patients with extreme immunosuppression, wasting, and fever.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium.

Mortality rate in mice fed fish oil for 4 weeks was remarkably higher after a very low peroral (PO) challenge with Salmonella typhimurium, as compared with those fed diets rich in either corn oil or hydrogenated coconut oil, or a low fat (chow) diet. None of the surviving mice fed the fish oil diet showed bacterial counts in their spleens, unlike 45.4% to 66.6% of surviving mice fed high fat or low fat diets. The spleens of mice fed fish oil presented the highest number of bacteria 7 days after intraperitoneal infection with the same bacterial strain. Thus, the current studies demonstrate that a diet rich in fish oil decreases host resistance to infection.

Adipose Tissue↗
PubMed1992

Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor.

Studies reported here investigate the influence of dietary fat types on cytokine production in response to endotoxin (LPS) challenge. Tumor necrosis factor (TNF) serum levels were markedly higher (by 10-fold) in mice fed chronically a diet rich in fish oil rather than either a diet rich in corn or coconut oil or a low fat diet. This in vivo hyper-responsiveness in LPS-induced TNF production following fish oil consumption concorded with similar exaggerated in vitro TNF release from macrophages exposed to LPS. These data suggest that high consumption of fish oils, by virtue of their high content of omega-3 polyunsaturated fatty acids, can lead to an exaggerated production of mediators of inflammation with potentially adverse consequences on the outcome and severity of infectious diseases.

Animals↗
PubMed1991

Activity of minocycline against Toxoplasma gondii infection in mice.

The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10(5) tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8.5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1.8 mg/l and 10 mg/l after 1 h, respectively, and showed an extended half-life.

Acute Disease↗
PubMed1991

Assignment of a Chinese xeroderma pigmentosum patient from Taiwan to complementation group C.

A 2 years and 7 months-old Chinese boy with severe skin symptoms was diagnosed as xeroderma pigmentosum (XP) at Chang Gung Memorial Hospital in Taipei, Taiwan. Skin fibroblasts derived from the patient (patient identification number, XP1CTA) were used for genetic complementation analysis by the conventional cell-fusion technique followed by measurement of ultraviolet light (UV)-induced unscheduled DNA synthesis (UDS). The level of UDS in XP1CTA cells measured by autoradiography was about 20% of that in normal cells. When XP1CTA cells were fused with cells of a representative strain from each of the complementation groups A, D, E, F, G, and H, binuclear cells showed UDS levels in the range of normal cells, demonstrating a clear complementation between XP1CTA strain and either one of these strains. XP1CTA cells failed to complement with all the five reference strains belonging to group C. From these results, the XP1CTA was unambiguously assigned to complementation group C. Sensitivity of XP1CTA cells to UV, as measured by colony-forming ability, also fell within a range of variation in UV sensitivities of these group C XP cell strains.

Asian People↗
PubMed1990

Generation of human monoclonal antibodies against colon cancer.

Lymphocytes from regional lymph nodes of patients with colon cancer were fused with a human lymphoblastoid cell line with or without in vitro immunization. The efficacy of these two protocols for the generation of human monoclonal antibodies against colon cancer was investigated. The hyperplastic lymph nodes adjacent to the tumor were the best source of B lymphocytes. Fusion frequency and the number of tumor-reactive clones were markedly increased when the in vitro immunization protocol was applied prior to fusion. As a stimulant in in vitro immunization, the supernatant of pokeweed mitogen-stimulated T lymphocytes was superior to the supernatant of mixed lymphocytes culture. Carcinoembryonic antigen at 20 micrograms/L seemed to be the optimal dose for in vitro immunization. The reactivities of human monoclonal antibodies thus generated were measured by enzyme-linked immunosorbent assay and confirmed by immunoperoxidase staining. Combining in vitro immunization with lymphocytes of cancer patients may lead to the successful production of clinically useful human monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1990

Expression of host resistance to Salmonella typhi and Salmonella typhimurium: bacterial survival within macrophages of murine and human origin.

Cell-association of various strains of Salmonella typhi and Salmonella typhimurium with different populations of macrophages was studied. Macrophages were infected, exposed to gentamicin, washed, and counts of viable bacteria protected from gentamicin killing were made. J774A.1 cells, a continuous macrophage-like cell line, were the most permissive, all strains tested achieving similar high recoveries. Virulent S. typhimurium 779C-Sms, but not avirulent S. typhimurium 779C-SmD, survived well in mouse peritoneal macrophages and human monocyte-derived macrophages. Virulent S. typhi Ty2 were killed by mouse peritoneal macrophages, but were able to survive within human monocyte-derived macrophages. Viable counts of clinical isolates of S. typhi within the human monocyte-derived phagocytes were lower as compared with those of S. typhi Ty2. Phagocytosis of opsonized and non-opsonized virulent S. typhi Ty2 and S. typhimurium 779C-SmS by mouse peritoneal macrophages failed to trigger their respiratory burst as assessed by the intracellular reduction of nitroblue tetrazolium dye (NBT). These experiments support the view that the intracellular survival of Salmonella is in part host dependent and specific in nature. They also suggest that virulence influences the survival and intracellular multiplication of Salmonella within macrophages, and that their ultimate fate within macrophages may not be related to oxygen-dependent mechanisms.

Animals↗
PubMed1990

Effects of ampicillin, ceftriaxone, chloramphenicol, pefloxacin and trimethoprim-sulphamethoxazole on Salmonella typhi within human monocyte-derived macrophages.

The killing effect of various antimicrobial agents used in the therapy of Salmonella typhi infection was tested against Salm. typhi strain Ty2 after phagocytosis by human monocyte-derived macrophages. The macrophages, cultured in 96-well microtitre plates, were infected for 1 h at 37 degrees C by opsonized Salm. typhi Ty2 at a bacteria-cell ratio of 9:1. When added to the infected macrophage monolayers, at one and ten times the MIC, ampicillin, ceftriaxone and pefloxacin appeared to be highly bactericidal (less than 0.25 log10 cfu/well after 20 h, against 4 log10 cfu/well in antibiotic-free controls). Trimethoprim-sulphamethoxazole was bactericidal at ten times the MIC, but not at the MIC. Chloramphenicol was mostly bacteriostatic at the concentrations tested. As a control, gentamicin (10 mg/l) did not exhibit any significant antibacterial effect, indicating that most or all the bacteria recovered from lysed cells were intracellular. Other controls for phagocytosis were also performed with heat-killed Candida albicans. Our results seem to correlate with the known clinical effect of some antimicrobials in human Salm. typhi infection. The in-vitro assay described here may be useful for assessing the activity of antimicrobial agents against Salm. typhi infection.

Ampicillin↗
PubMed1990

In vitro and in vivo effects of doxycycline on Toxoplasma gondii.

We investigated the effects of doxycycline on Toxoplasma gondii infections in vitro and in vivo. Resident peritoneal macrophages were infected with the virulent RH strain of T. gondii and exposed to doxycycline at different concentrations. The antitoxoplasmic activity of doxycycline was first assessed with [3H]uracil, which is incorporated by the parasite but not the host cell. The concentration of doxycycline that inhibited 50% of the radioactive uptake was calculated to be 6.4 micrograms/ml (95% confidence limits, 5.07 to 8.06 micrograms/ml); the concentration of doxycycline that inhibited 90% of the radioactive uptake was 14 micrograms/ml. Tetracycline was ineffective up to 40 micrograms/ml. Furthermore, microscopic examination of the infected macrophages after treatment with doxycycline confirmed the inhibition of intracellular growth of T. gondii. Mice acutely infected by the intraperitoneal route with 5 x 10(3) tachyzoites of T. gondii were protected against death with a dose of 300 mg of doxycycline per kg (body weight) administered by the oral route for 10 days, starting 24 h after challenge. When mice were infected with 10(5) tachyzoites of T. gondii and treated 12 days starting 2 h after challenge, the protection and the cure rates were, respectively, 100 and 0% after doxycycline alone (300 mg/kg per day), 0 and 0% after pyrimethamine alone (12.5 mg/kg per day), and 100 and 60% after the combination of these two drugs at the same dosages given above. These results suggest that doxycycline may prove to be useful in the treatment of toxoplasmic infections.

Animals↗
PubMed1990

Role of TNF and IL-1 in infections with Toxoplasma gondii.

Mice lethally infected with the C56 strain of Toxoplasma gondii and treated with purified recombinant murine tumour necrosis factor (TNF, 1 microgram/day/mouse for 8 days), recombinant human interleukin-1 (IL-1 alpha or IL-1 beta, 100 ng/day/mouse for 5 days) or a single dose of a combination of TNF (1 microgram/mouse) and IL-1 alpha or IL-1 beta (100 ng/mouse) were significantly protected against death (P less than 0.05-0.001, as compared with untreated infected controls). Mice infected with 100,000 tachyzoites of the highly virulent RH strain of T. gondii released serum TNF in relation to the time after infection and were primed to secrete an enhanced level of serum TNF upon stimulation with bacterial lipopolysaccharide (LPS). In vitro studies showed that interferon-gamma (IFN-gamma) increased the antimicrobial activity of murine peritoneal macrophages whereas TNF, IL-1 alpha and IL-1 beta did not. TNF, however, synergized with the anti-toxoplasmic effect provided by IFN-gamma and this activity was blocked by anti-TNF antibodies. IFN-gamma induced the production of TNF and the anti-toxoplasmic effect provided by IFN-gamma seemed to be dependent partly on the production of TNF. We conclude that TNF and IL-1 may play a significant role in modulating the host's immune defence against T. gondii infection.

Animals↗
PubMed1990

[A case of xeroderma pigmentosum treated by oral etretinate].

A case of xeroderma pigmentosum (XP) with neurological disorders is reported. The patient is a 16 year old male who presented a marked photosensitivity from his early infancy. The family history is negative for XP with no consanguinity being observed. He displayed neurological symptoms such as a low IQ and audiological disturbances. He developed six basal cell epitheliomas (BECEs) on his face at age of 14. We tried oral etretinate for 4 years at a initial dosage of 30 mg per day for the possible prevention of new skin cancers. Efficacy of the drug for prevention of cancers has not been confirmed, but evidence is obtained that the drug might prevent the growth of tumors. We also reviewed the chemoprevention of skin cancers with retinoids, in patients with xeroderma pigmentosum.

Administration, Oral↗
PubMed1989

The prognostic value of histologic subtypes in primary extremity liposarcoma.

Patients with a localized primary liposarcoma of the extremity who were treated in Memorial Sloan-Kettering Cancer Center between 1968 and 1978 were studied. The prognosis of patients with extremity liposarcoma was analyzed according to histopathologic subtypes. A system of five subtypes was used; well-differentiated, myxoid, fibroblastic, lipoblastic, and pleomorphic liposarcomas. The 5-year treatment failure rates and survival rates were, respectively, 30% and 100% for well-differentiated, 25% and 88% for myxoid, 60% and 58% for fibroblastic, 100% and 40% for lipoblastic, and 64% and 56% for pleomorphic liposarcomas. Although local recurrence was present in all five subtypes, a significant increment in local failure was seen in patients with high-grade liposarcomas. Distant metastasis after the initial operation was not found in patients with well-differentiated liposarcoma and rare in the patients with myxoid liposarcoma. In contrast, 50% of the patients with fibroblastic, lipoblastic, and pleomorphic liposarcoma had a distant relapse within 5 years.

Adolescent↗
PubMed1989

Macrophage oxidative metabolism and intracellular Toxoplasma gondii.

We explored the mechanisms by which Toxoplasma gondii avoids destruction by the oxidative metabolism of normal macrophages. Unelicited murine peritoneal macrophages were infected with T. gondii and exposed to different experimental conditions. As endpoints we used measurement of hydrogen peroxide (H2O2) release and intracellular reduction of nitroblue tetrazolium dye (NBT). Three main observations were made. Firstly, different T. gondii preparations (live or dead, opsonized or not) failed to trigger the respiratory burst. Combined challenges also showed that a primary T. gondii infection was able to block H2O2 release triggered by heat-killed (HK)-Candida albicans. The H2O2 release, however, once triggered by HK-C. albicans, was not inhibited by a subsequent challenge with T. gondii. Secondly, when a respiratory burst was obtained in T. gondii-infected macrophages--for instance by stimulation with phorbol myristate acetate (PMA)--the toxic oxygen metabolites (as determined by the NBT reduction test) did not seem to reach the vacuoles containing the parasite. Thirdly, when a respiratory burst occurred in T. gondii-infected macrophages, the intracellular development of T. gondii did not seem to be affected. In conclusion, we hypothesize that T. gondii is not damaged by the macrophage oxidative metabolism because the parasite fails to encounter toxic oxygen metabolites. The killing of intracellular T. gondii, as it is commonly observed in activated macrophages, does not appear oxygen-dependent.

Animals↗
PubMed1989

Hypersensitivity of human tumor xenografts lacking O6-alkylguanine-DNA alkyltransferase to the anti-tumor agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea.

Human tumor cell strains having different activities of O6-alkylguanine-DNA alkyltransferase (ATR) were transplanted into nude mice and chemotherapeutic responses of tumor xenografts were compared after intraperitoneal injection of the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). The tumor strains used were four Mer+ strains possessing high ATR activity and three Mer- strains lacking this activity. Included in these Mer+ strains was a clone 5'dD which expresses the Escherichia coli ATR in Mer- HeLa cells and thus shows the Mer+ phenotype. All the Mer- tumor xenografts were much more sensitive than tumors of Mer+ strains, including the clone 5'dD; after the highest ACNU dose (three injections of 50 mg/kg), some Mer- tumors disappeared completely and the growth of other tumors was severely retarded, whereas all Mer+ tumors continued to grow. These results demonstrate that ATR activity in tumor cells is a major determinant of tumor response to ACNU, and further suggest that measurement of ATR activity in biopsy specimens may provide a useful guide to predict the response to chemotherapy.

Animals↗