Biomedical subjects

G Wong

Publications and source records attributed to G Wong.

At least 145 records · Page 8Linked to original sources

PubMed1990

The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence.

MaxEPA (MA), a fish oil high in omega-3 fatty acids, was combined with various levels of corn oil (CO), rich in omega-6 fatty acids, and fed to female CF1 mice. The three fish oil blends with CO and the two CO levels of the diets studied were as follows: 16.0% CO + 4.4% MA (Diet 1); 10.2% CO + 10.2% MA (Diet 2); 4.4% CO + 16.0% MA (Diet 3); 20.4% CO (Diet 4); and 4.4% CO (Diet 5). The diets were provided 2 weeks before weekly subcutaneous injection of saline or azoxymethanol (AOM). Studies of epithelial cell proliferation and the incidence of focal areas of dysplasia (FAD) involved six weekly AOM injections. One week after the last AOM injection and 1 hour before killing, mice were injected with tritiated thymidine (3HTdR). No differences in any proliferative parameters were found among the five groups of saline-treated mice. Among the AOM-treated animals, those fed Diet 3 showed significantly fewer cells per crypt and significantly fewer labeled cells/gland than CO Diets 4 and 5. Additionally, the distribution of S-phase cells in crypts of AOM-treated mice fed Diet 3 most closely resembled that of the saline controls. The greatest alteration in the distribution of proliferative cells was observed in the high-CO diet (Diet 4) and the lowest MA level (Diet 1). Mice fed Diets 2 and 3 had significantly fewer FAD/500 microns of distal colonic serial sections than those fed the high CO diet (Diet 4). Mice involved in chronic tumor incidence studies received only three weekly injections of the same dose of AOM. Regardless of diet, approximately 88% of all tumors arose in the distal colon. A significantly larger tumor-bearing population was observed in both the high-CO Diet 4 and the lowest MaxEPA (MA) diet (Diet 1) compared with the incidence in MA Diets 2 and 3 and the low-CO Diet 5. A diet with a ratio of omega-6 to omega-3 fatty acids of approximately 1.0 apparently prevented the development of an adenoma-type proliferative pattern thereby reducing FAD numbers and subsequent tumor incidence.

Animals↗

PubMed1990

Phase I evaluation of a combination of monoclonal antibody R24 and interleukin 2 in patients with metastatic melanoma.

A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10(6) units/m2 i.v. over 6 h on days 1-5 and 8-12. R24 was given on days 8-12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 +/- 554/ml in patients treated at R24 doses of 8 and 12 mg/m2 versus 2239 +/- 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro.

Adult↗

PubMed1990

Production of human interleukin for DA cells (HILDA)/leukemia inhibitory factor (LIF) by activated monocytes.

We demonstrate mRNA accumulation and production of HILDA/LIF by human activated Mo, monocyte-derived macrophages and myelomonocytic cell lines. Among the various stimuli tested, the synergistic combination of phorbol diester and VD3 was the most potent inducer of HILDA/LIF gene expression. The kinetics of mRNA accumulation on activated Mo showed a stimulation peak at 24 hr which declined thereafter. HILDA/LIF activity in culture supernatants was detected at 24 hr and reached a plateau at 72 hr of culture. In contrast to Mo, PBL did not accumulate HILDA/LIF mRNA upon culture with PDBu and VD3, whereas PHA and the combination of PDBu and A23187 induced HILDA/LIF mRNA accumulation and secretion in the culture supernatant. To exclude the possibility that HILDA/LIF was produced by contaminating PBL, highly enriched Mo preparations were used, which were devoid of T cells as assessed by the absence of TCR-beta chain mRNA transcripts. HILDA/LIF production by monocytic cells was further documented by the capacity of stimulated U937 cell conditioned medium to compete with 125I-labeled nHILDA/LIF for binding to its receptor on murine M1 cells. Under the synergistic effect of PDBu and VD3 stimulation, Mo-derived macrophages as well as HL-60 and U937 cell lines accumulated HILDA/LIF mRNA and produced this cytokine with identical kinetics as for Mo. Finally, we show that HILDA/LIF mRNA accumulation in U937 cells upon stimulation with PDBu, or the combination of PDBu and VD3, was inhibited in the presence of the protein synthesis inhibitor CHX. These results document for the first time that human Mo, when stimulated appropriately in vitro, can express the HILDA/LIF gene and its product, and that intermediate proteins must be newly synthesized in this process.

Cell Differentiation↗

PubMed1990

A specific cis-acting element regulates in vitro transcription of sex-dependent mouse steroid 16 alpha-hydroxylase (C-P450(16 alpha)) gene.

The mouse steroid 16 alpha-hydroxylase (C-P450(16 alpha)) family consists of structurally similar genes with very divergent expressions (Wong, G., Itakura, T., Kawajiri, K., Skow, L., and Negishi, M. (1989) J. Biol. Chem. 264, 2920-2927). Of five family members, the C-P450(16 alpha) gene exhibits a male-specific expression whereas the P450cb gene is equally expressed in both males and females although the level of expression is much lower than that of the C-P450(16 alpha) gene. By DNase I footprinting and in vitro transcription of the C-P450(16 alpha) gene, we determined two cis-acting transcription elements. SDI (sex difference information) in the -84/-102 region from the transcription start site is one of the two cis-acting transcription elements, which is specific to the sex-specific C-P450(16 alpha) gene and confers a high transcription level of this gene. We substituted the nucleotide(s) in the SDI sequence to the corresponding base(s) in the P450cb gene promoter and tested each substituted gene promoter by in vitro transcription. The results indicate that the function of SDI as the transcription element depends most critically on the nucleotides at positions -100 to -98. Another cis-acting transcription element, CTE (common transcription element), is located between -44 and -68 in both C-P450(16 alpha) and P450cb genes. A column chromatography of nuclear extract indicates that the proteins bound to SDI and CTE are different. We speculate therefore that SDI is a specific and necessary element involved in the male-specific C-P450(16 alpha) gene transcription. The sequence comparisons of the corresponding regions of SDI and CTE among the mouse and the closely related rat P450 genes suggest that SDI is a newly evolved cis-acting element in the sex-specific C-P450(16 alpha) gene which arose through gene duplication and selective nucleotide substitution.

Animals↗

PubMed1990

PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex.

Platelet-derived growth factor (PDGF) stimulated the tyrosine phosphorylation of the GTPase activating protein (GAP) in 3T3 cells and in CHO cells expressing wild-type PDGF receptors, but not in several CHO cell lines expressing mutant receptors defective in transmitting mitogenic signals. Following PDGF treatment of cells, GAP physically associated with the PDGF receptor and with Raf-1, phospholipase c-gamma, and PI-3 kinase, suggesting that PDGF induced the formation of complexes of signaling molecules. The association of GAP with the PDGF receptor and the phosphorylation of GAP with the PDGF receptor and the phosphorylation of GAP were reconstituted in vitro using purified protein and in insect cells expressing murine PDGF receptor and human GAP. However, in cells transformed by activated c-Ha-ras, which are defective in certain responses to PDGF, GAP failed to associate with the PDGF receptor or increase its phosphotyrosine content in response to PDGF. The association of GAP with ligand-activated PDGF receptors may directly link PDGF and ras signaling pathways.

Animals↗

PubMed1990

Erythropoietin receptor: cloning strategy and structural features.

We recently isolated a cDNA clone encoding the murine erythropoietin (Epo) receptor from a PXM expression library made from uninduced murine erythroleukemia cells. The clone was identified by screening COS cell transfectants for internalization of radiolabeled recombinant human Epo. As inferred from the cDNA sequence, the murine Epo receptor (Epo-R) is a 507 amino acid polypeptide with a single membrane-spanning domain. Extensive homology was found between the Epo-R and the interleukin 2 receptor beta chain, both at the level of amino acid sequence and at the level of regional hydrophobicity.

Amino Acid Sequence↗

PubMed1990

Physical aspects of external beam radiotherapy for the treatment of malignant pleural mesothelioma.

The optimization of radiotherapy for the treatment of malignant mesothelioma highlights many of the currently outstanding problems in clinical radiation physics. The experimental investigation of an intuitively attractive irradiation technique with combined photon and electron beams using a specially constructed phantom has established that, due to the penetration in low density material of both primary electrons and those secondary to photon irradiation, the normal lung tissue is not spared to any significant degree by such a technique. Furthermore, great care needs to be exercised in the treatment planning calculations for this approach if absolute dosimetry errors as large as 50% are to be avoided.

Electrons↗

PubMed1990

A clinical evaluation of pulse oximetry during thoracic surgery.

To evaluate the utility of pulse oximetry for monitoring oxygenation during thoracic surgery, pulse oximeter oxygen saturation (SpO2) values from the Nellcor N-100 (Nellcor Inc, Haywood, CA) and Novametrix model 500 (Medical Systems Inc, Wallingford, CT) were compared with simultaneous arterial saturation values (SaO2) in 20 patients. A total of 255 matched observations were recorded, and the data were divided for statistical analysis into preinduction of anesthesia and postinduction groups. The preinduction group showed a good correlation between SpO2 and SaO2 values, with both pulse oximeters consistently overestimating the SaO2. However, once anesthesia was induced, there was no longer any correlation for either of the pulse oximeters versus simultaneous SaO2 values, although on average, the SpO2 values were significantly higher than the corresponding SaO2 values. It was concluded that pulse oximetry is useful in following trends of oxygenation in patients with preexisting lung pathology undergoing thoracic surgery, but it cannot replace arterial blood gas sampling for the intraoperative management of respiratory function.

Anesthesia, General↗

PubMed1990

Characterization and regulation of sex-specific mouse steroid hydroxylase genes.

We characterized the genes of the male-specific mouse steroid 16 alpha-hydroxylase (C-P-45016 alpha) and the female-specific mouse steroid 15 alpha-hydroxylase (P-45015 alpha) within two distinct gene families. In spite of the high structural identities within each family, the expression of the hydroxylase genes is uniquely regulated. Moreover, the other family members encode the P-450s which are structurally very similar to the hydroxylases but are not able to catalyze steroid hydroxylase activities. For example, only a single amino acid substitution creates steroid 15 alpha-hydroxylase activity in another family-member P-450coh, which catalyzes coumarin 7-hydroxylase but little steroid hydroxylase activity. It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions.

Amino Acid Sequence↗

PubMed1990

Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.

Adolescent↗

PubMed1989

Gene family of male-specific testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) in mice. Organization, differential regulation, and chromosome localization.

Three genes in the testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) family, ca, cb, and cc, are characterized. The sizes of the genes are approximately 4.5 to 5.2 kilobase pairs, and all three consist of nine exons with junctions at identical sites. Gene ca is identified as the male-specific, androgen-dependent C-P-450(16 alpha) gene in adult mice, since the exonic sequence matched 100% to the cDNA, pc16 alpha-2 (Wong, G., Kawajiri, K., and Negishi, M. (1987) Biochemistry 26, 8683-8690). Gene cb and cc are organized in tandem within 18-kilobase pair DNA. Their encoded P-450s contain an approximate 94% nucleotide sequence similarity to the C-P-450(16 alpha). The high similarity in gene nucleotide sequences, including the introns and flanking regions, suggests a combination of an ancestral gene duplication and gene conversion as a mechanism for evolution of the C-P-450(16 alpha) family. Gene ca shows male-specific expression in mouse kidney as well as in liver; gene cb, neither sex-specific nor androgen-dependent, is seen only in liver; gene cc is not expressed in either adult mouse liver or kidney. Expression of these three genes is not detected in adult mouse lung. It appears, therefore, that the C-P-450(16 alpha) gene family includes a large number of genes whose expressions are differentially regulated. Southern hybridization of C-P-450(16 alpha) cDNA to genomic DNAs from mouse-hamster somatic hybrid cells localizes tentatively this gene family on mouse chromosome 15. The recombination frequency in BXD recombinant inbred mice suggests that the C-P-450(16 alpha) gene family is approximately 16M from the 55-kDa locus.

Animals↗

PubMed1989

RAS enzyme-linked immunoblot assay discriminates p21 species: a technique to dissect gene family expression.

The members of the RAS gene family of protooncogenes are of implied biological significance in oncogenesis. The precise role of these genes is unclear. One difficulty has been the inability to discriminate the individual p21 protein products of various ras genes in cell lines, de novo human tumors, and related normal tissues. In this report, specific proteins of the human c-Ha-ras-1, c-Ki-ras-2, and c-N-ras genes have been detected and discriminated by the differential use of various antisera recognizing these p21s. This enzyme-linked immunoblot assay utilizes a double antibody system in which monoclonal antibodies are initially used to immunoprecipitate the p21ras proteins. Immunoprecipitates are then subjected to one-dimensional Western blot analysis utilizing other antibodies raised against p21s, coupled with nonradiolabeled enzyme-linked colorimetric detection. By direct detection, the specific products of the three human ras genes can be discriminated. In addition, we describe the generation and characterization of a new anti-p21c-N-ras-specific antibody. The simultaneous expression into protein of multiple ras genes is unequivocally demonstrated in both homogeneous cell lines and heterogeneous human tissues. This new technique is also applicable for discrimination of the protein products of other gene families.

Animals↗

PubMed1989

Macrophage colony-stimulating factor enhances monocyte and macrophage antibody-dependent cell-mediated cytotoxicity.

In vitro culture of either human peripheral blood monocytes or murine peritoneal macrophages for 72 hr in the presence of macrophage colony-stimulating factor (M-CSF) dramatically increased their subsequent ability to mediate antibody-dependent cellular cytotoxicity (ADCC). The M-CSF-treated cells were more effective in ADCC at lower effector to target cell ratios and in the presence of lower concentrations of tumor-specific monoclonal antibody than the untreated control cells. Two other hematopoietic cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-3, reported to enhance other macrophage effector functions were ineffective in promoting the development of ADCC by cultured human monocytes. All three hematopoietic growth factors were capable of enhancing the ability of the cultured monocytes to secrete TNF alpha; however, TNF alpha is unlikely to be an important cytotoxic factor in ADCC because neutralizing antibodies against TNF alpha had no affect on ADCC in vitro. Further, much higher concentrations of M-CSF were required to augment monocyte TNF alpha release (20-100 ng/ml) than ADCC capacity (1-10 ng/ml). These results suggest that M-CSF administration might prove effective in increasing the tumoricidal activities of tumor-specific monoclonal antibodies by enhancing the capacity of monocytes and macrophages to mediate ADCC.

Animals↗

PubMed1989

Monoclonal antibodies that specifically inhibit GM-CSF- and IL-3-dependent growth of human monocytic leukemia cells.

We describe monoclonal antibodies (mAbs: anti-MaG-1, TGI-1, TGI-5, and TGI-6) that block the proliferation of AML-193 cells in response to GM-CSF or IL-3 and do not affect the proliferation of AML-193 cells in response to G-CSF and IL-2-driven proliferation of Kit 225 cells. However, none of the mAbs tested had any stimulative effect on the proliferation of AML-193 cells. The mAbs (anti-MaG-1, TGI-1, -5, and -6) could inhibit the binding of [125I]GM-CSF to AML-193 cells. We were able to purify MaG-1 Ag by anti-MaG-1 affinity chromatography. Thus, the MaG-1 Ag and the Ags recognised by mAbs (TGI-1, -5, and -6) may be associated with the receptor for GM-CSF or IL-3 or a structure close to the receptor for GM-CSF or IL-3.

Animals↗

PubMed1989

Esmolol for potentiation of nitroprusside-induced hypotension: impact on the cardiovascular, adrenergic, and renin-angiotensin systems in man.

Esmolol infusion at rates of 200, 300, and 400 micrograms.kg-1.min-1 was used to potentiate hypotension (mean arterial pressure = 60 mm Hg) induced with sodium nitroprusside (SNP) in 10 male patients undergoing radical cancer surgery during nitrous oxide-oxygen and fentanyl anesthesia. Heart rate (HR), blood pressure (radial arterial catheter), and plasma levels of renin activity (PRA), norepinephrine (N), epinephrine (E), and dopamine (D) were measured: 1) while patients were awake; 2) after induction of anesthesia (nitrous oxide, 60% in oxygen, fentanyl = 5 micrograms/kg followed by an infusion at 10 micrograms.kg-1.hr-1); 3) after surgery had begun; 4) after 20 minutes of SNP-induced hypotension; 5) after 20 minutes of esmolol at each of the above infusion rates; and 6) after the completion of surgery. Compared to awake values, SNP-induced hypotension (mean infusion rate = 3.1 micrograms.kg-1.min-1 +/- 0.6 SE) during surgery resulted in significant (P less than 0.05) increases in heart rate, PRA, N, and D. Infusion of esmolol resulted in significant (P less than 0.05) dose-dependent reductions in SNP requirement to maintain MAP = 60 mm Hg. At 200 micrograms.kg-1.min-1, SNP requirement was 2.1 micrograms.kg-1.min-1 +/- 0.4, at 300 micrograms.kg-1.min-1, it was 1.0 micrograms.kg-1.min-1 +/- 0.2, and at 400 micrograms.kg-1.min-1, was 0.5 micrograms.kg-1.min-1 +/- 0.3. Concomitant with the decrease in SNP requirement, there were significant reductions in HR and PRA at all infusion rates of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1988

Molecular cloning of two types of GAP complementary DNA from human placenta.

The ras p21 GTPase-activating protein (GAP) was purified from human placental tissue. Internal amino acid sequence was obtained from this 120,000-dalton protein and, by means of this sequence, two types of complementary DNA clones were isolated and characterized. One type encoded GAP with a predicted molecular mass of 116,000 daltons and 96% identity with bovine GAP. The messenger RNA of this GAP was detected in human lung, brain, liver, leukocytes, and placenta. The second type appeared to be generated by a differential splicing mechanism and encoded a novel form of GAP with a predicted molecular mass of 100,400 daltons. This protein lacks the hydrophobic amino terminus characteristic of the larger species, but retains GAP activity. The messenger RNA of this type was abundantly expressed in placenta and in several human cell lines, but not in adult tissues.

Amino Acid Sequence↗

PubMed1988

Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium.

We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.

Adult↗

PubMed1988

Intracerebral haematoma mimicking intracranial neoplasm at computed tomography.

The diagnosis of a typical acute intracerebral haematoma is comparatively specific with computed tomography. Three cases are presented to illustrate computed tomographic similarities between intracerebral haematomas and intracranial neoplasms. In the appropriate clinical setting, an incorrect diagnosis may be reached unless these similarities are borne in mind.

Acute Disease↗