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Biomedical subjects

W Wong

Publications and source records attributed to W Wong.

At least 181 records · Page 10Linked to original sources
PubMed1986

Hormonal therapies for breast cancer: can progestogens stimulate growth?

The human breast cancer cell line, MCF-7, displays many of the properties of breast tumours in vivo and, in particular, shows similar responses to hormones. Medroxyprogesterone acetate significantly inhibited cell proliferation, but, following continued treatment, this effect was lost and further exposure to the drug stimulated cell proliferation and increased polyamine content while tamoxifen inhibited growth. Prolonged administration of progestogens may thus have adverse effects and should be assessed critically.

Breast Neoplasms↗
PubMed1986

Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin.

Anthracyclines such as Adriamycin (ADR) and daunomycin markedly inhibit cell growth in vivo and in vitro. These studies demonstrate that 30 microM hemin, which induces hemoglobin synthesis in human and murine erythroleukemia cells in culture, markedly decreases the cytotoxicity of ADR in a variety of hemopoietic cell lines (K562, HEL-1, MEL-745, HL-60, and U937) and in erythroid burst-forming cells from normal human marrow. Hemin failed to protect four of the five nonhemopoietic cell lines tested, including MCF-, breast adenocarcinoma cells, C-205 colon carcinoma cells, mouse 3T3 fibroblasts, and mouse kidney VERO cells. Hemin did protect human neuroblastoma IMP-32 cells from ADR cytotoxicity; however, this nonhemopoietic cell line undergoes dendrite formation in response to hemin induction. Cytofluorographic analysis of cellular ADR content and labeling studies with [3H]daunomycin demonstrated that hemin decreases the intracellular accumulation of these anthracyclines by more than 50% in K562 erythroleukemia cells. These studies indicate that small doses of hemin prevent intracellular accumulation of anthracyclines and thereby markedly reduce anthracycline toxicity to cells. Since this protective effect is observed preferentially with hemopoietic cells, it is possible that this finding could be exploited to protect the bone marrow from the cytotoxic action of anthracyclines during therapy for nonhemopoietic tumors.

Animals↗
PubMed1985

Normal function of CR1 on affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which affected erythrocytes (E) are abnormally sensitive to lysis by autologous complement. Affected E from patients with PNH (PNH-E) are deficient in an E membrane regulatory protein of complement, decay-accelerating factor (DAF). Because a functional defect in a second membrane regulatory protein of complement, CR1 (C3b receptor), has also been hypothesized, severely affected PNH-E (type III PNH-E) were tested for abnormalities in CR1 by four methods. E from two patients with 100% type III PNH-E had 3201 and 6783 sites per cell for binding of 125I-labeled rabbit polyclonal F(ab')2 anti-CR1. These values fall within the normal range of CR1 antigenic sites per cell (1267 to 7915, mean = 5,014 +/- 155 SEM) established by assaying the E from 113 healthy donors. The Ka of CR1 on type III PNH-E for 125I-labeled C3b dimer was 2.06 X 10(7) M-1, and the Ka values for the binding of the same ligand to the E from two healthy individuals were 2.45 X 10(7) M-1 and 1.58 X 10(7) M-1. In an assay designed to measure the capacity of human E (Eh) to accelerate the decay of the classical C3 convertase deposited on 1 X 10(7) bystander sheep E (EAC1gp,4bh,2agp), the half-life (t 1/2) of this convertase was diminished from 18.1 min (range 15.2 to 22.9) to 8.1 min (range 7.4 to 8.5) by the addition of 1 X 10(7) normal Eh, to 6.2 min by 100% type III PNH-E, and to 7.5 min by Eh pretreated with an IgG fraction of human antiserum directed against the D antigen of the Rh system. In contrast, Eh (t 1/2 = 7.4) pretreated with a saturating dose of F(ab')2 anti-CR1, and CR1-deficient Eh (less than 10 CR1 molecules/E) from a patient with systemic lupus erythematosus, showed a loss of convertase decay-accelerating capacity to t 1/2 = 11.6 and t 1/2 = 12.4, respectively. Type III PNH-E pretreated with anti-CR1 demonstrated a total loss of their decay-accelerating capacity (t 1/2 = 19.9). In an assay of I cofactor activity, soluble C3b was rapidly converted to iC3b by purified I plus Eh or type III PNH-E, whereas CR1-deficient Eh exhibited less than 5% the I cofactor activity of normal Eh.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗
PubMed1985

Analysis of commitment of human leukemia HL-60 cells to terminal granulocytic maturation.

Analysis of commitment of human promyelocytic leukemia HL-60 cells to terminal granulocytic maturation induced by dimethyl sulfoxide (DMSO) or retinoic acid (RA) was accomplished using biochemical measurements and a plasma clot clonal assay system that permits a high plating efficiency of 40 to 60%. Commitment to granulocytic maturation occurs very rapidly. When cells are exposed to these inducers for only 8 to 18 h, an interval much shorter than a single generation time, and are then subcultured in inducer-free plasma clots, they demonstrate a decrease in proliferative capacity and form colonies composed of mature nitroblue tetrazolium (NBT)-positive cells along with occasional colonies containing both NBT-positive and NBT-negative cells; in both types of colony, the NBT-positive cells are widely dispersed. Undifferentiated HL-60 cells give rise to compact NBT-negative colonies of large size without cell migration. HL-60 cell differentiation induced by either DMSO or RA is associated with a progressive decline in both DNA and RNA synthesis; this includes transcriptional inactivation of ribosomal DNA sequences. In contrast to DMSO, which induces development primarily of metamyelocytes, RA treatment leads to the accumulation of more mature band and segmented neutrophils; sequential exposure of cells pretreated with DMSO to RA alone fails to cause rapid appearance of segmented neutrophils. From these studies, we conclude that HL-60 cells become very rapidly committed to terminal maturation and that DMSO and RA appear to induce granulocytic maturation via two different mechanisms.

Cell Differentiation↗
PubMed1985

Relationship of mitochondrial membrane potential to hemoglobin synthesis during Friend cell maturation.

Previous studies have shown that exposure to imidazole dissociates hemoglobin synthesis from other aspects of cell maturation in dimethylsulfoxide (DMSO)-treated mouse erythroleukemia (MEL) cells. In the present study, we have found that imidazole causes hyperpolarization of the mitochondrial membrane in MEL cells exposed to DMSO, in contrast to the depolarization observed with DMSO alone. Like the defect in hemoglobin synthesis, membrane hyperpolarization is reversible upon removal of imidazole and incubation of cells with DMSO alone. These correlations suggest that alterations in the electrostatic properties of the mitochondrial membrane, due directly or indirectly to the effects of imidazole, interfere with heme synthesis but not with other aspects of the maturation process in these developing erythroid cells.

Animals↗
PubMed1984

Chronic immune stimulation by sperm alloantigens. Support for the hypothesis that spermatozoa induce immune dysregulation in homosexual males.

Putative, sperm-induced allogeneic immunization was correlated with immune dysregulation in a study of 30 asymptomatic, monogamously paired homosexual males. Evidence for allogeneic immunization existed among 19 of 26 homosexual males who were anal sperm recipients. No evidence for any form of alloimmunization was found in four exclusive sperm donors. Immune dysregulation in the form of a reduced effector/suppressor T-cell ratio (Te/Ts less than 1.0) was exclusively documented in eight anal-sperm-recipient homosexual males, five of whom also manifested evidence for allogeneic immunization. In three of those, immune dysregulation was further manifested by functional T-cell deficiency in the form of a subnormal (less than 50 cu mm) local graft-v-host reaction. Similar evidence for alloimmunization was associated with a reduced Te/Ts ratio (0.85) in the female of a heterosexual couple who routinely practiced anal intercourse. Based on these findings, we suggest that chronic, repeated exposure to sperm during anal intercourse results in a high frequency of allogeneic immunization and may play an important role in the development of acquired immune dysregulation among homosexual males.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Monoclonal antibodies to immunodeterminants of lipoteichoic acids.

Murine hybrid cell lines producing monoclonal antibodies directed against determinants present on lipoteichoic acids were generated. Hapten inhibition studies showed that one group of monoclonal antibodies was inhibited by deacylated cardiolipin, and the second group was inhibited by kojibiose. Thus, antibodies directed against the polyglycerophosphate chain, which is common to the lipoteichoic acids of many gram-positive species, and against the streptococcal group D antigen were obtained.

Animals↗
PubMed1984

Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts.

Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery.

Adult↗
PubMed1983

Dexamethasone-sensitive and -insensitive responses during in vitro differentiation of Friend erythroleukemia cells.

We have investigated the mechanism(s) by which dexamethasone inhibit DMSO-induced Friend erythroleukemia cell differentiation in vitro. In particular, we examined the effects of dexamethasone on (a) the early events of differentiation such as cell volume alterations and 'memory response' and (b) the onset of biochemical events associated with terminal erythroid cell differentiation. By analysing kinetics of commitment of Friend cells to terminal erythroid differentiation on a clonal basis, we have observed that dexamethasone inhibited the completion of the latent period (time elapsed prior to commitment) and impaired "memory" (ability to inducer-treated cells to continue differentiation after a discontinuous exposure to inducer). Treatment of Friend cells with dexamethasone did not prevent the occurrence of DMSO-induced alterations in cell volume. However, dexamethasone treatment prevented a series of biochemical events associated with terminal Friend cell differentiation. These include the decrease in the rate of both cytoplasmic and nuclear RNA synthesis as well as the induction of cytidine deaminase activity and hemoglobin synthesis. These data indicate that the dexamethasone-sensitive process(es) operate during the early stages of Friend cell differentiation and that they are responsible for the inhibition of terminal erythroid maturation. These dexamethasone-sensitive processes, however, appear to be different from those regulating cell volume alterations during the early steps of DMSO-induced Friend cell differentiation.

Animals↗
PubMed1983

Objective evaluation of local xenogeneic graft-versus-host reaction by computerized radioisotope imaging (CRI).

The local xenogeneic graft-versus-host reaction (GVHR) assay has been used clinically to evaluate cellular immune competence and experimentally to monitor the immunomodulatory effects of several drugs. By employing a computerized radioisotope imaging (CRI) technique, we were able to perform the assay with smaller numbers of mononuclear cells (MNC) and to rid it entirely of any bias. Measuring the local GVHR by CRI compares well with the conventional measurement of the volume (correlation coefficient r = 0.619; P less than 0.001). A clear-cut distinction was documented between normal donors and cancer patients (P less than 0.001) when 10 X 10(6) or more MNC were used in the assay. This is an improvement over the previous, conventional testing of local GVHR which required injection of 20 X 10(6) MNC in order to achieve a similar resolution. The indications for the presence of immune competence have therefore been redefined using the local GVHR index as determined by CRI according to the scale of MNC injected. Thus, immunocompetence is considered present if the CRI index is greater than or equal to 1.2 for 10 X 10(6) MNC, greater than or equal to 2.0 for 15 X 10(6) MNC and greater than or equal to 2.6 for 20 X 10(6) MNC.

Animals↗
PubMed1983

Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs.

The in vitro restorative effect of aqueous extracts from two traditional Chinese medicinal herbs were studied in 19 cancer patients and in 15 normal healthy donors. Using the local graft versus host (GVH) reaction as a test assay for T-cell function, the extract from astragalus membranaceus (10 microgram/ml) induced a restored reaction in nine of ten patients with an increase in local GVH reaction from 18.2 plus/minus 15.8 mm3 to 112.9 plus/minus 94.2 mm3 (P less than 0.01). The extract from ligustrum lucidum, likewise effected an immune restoration in nine of 13 cancer patients with an increase in local GVH reaction from 32.3 plus/minus 36.1 mm3 to 118 plus/minus 104.9 mm3 (P less than 0.01). This degree of immune restoration appears to be complete as it equals the local GVH reaction observed among untreated mononuclear cells from normal healthy donors (82.8 plus/minus 41.1 mm3, P greater than 0.1). These results suggest that both extracts of the traditional Chinese medicinal herbs contain potent immune stimulants which may provide the rational basis for their therapeutic use as biological response modifiers.

Adjuvants, Immunologic↗
PubMed1983

The immune restorative effect of Isoprinosine administration on the local graft-versus-host reaction of cancer patients.

The immunorestorative effect of Isoprinosine (ISO) in vivo on T-cell-induced local graft-versus-host reaction (GVHR) was analyzed in 60 cancer patients randomized into three groups: 20 patients received 1 g/day ISO orally for 7 days, 20 patients received 4 g/day ISO for 7 days, and 20 patients received no treatment for 7 days. The local GVHR was assessed before and after the 7 days of treatment (or no treatment). A significant augmentation of the local GVHR was observed among the ISO-treated patients (44.1 +/- 19.1 vs 61 +/- 37.1 for 1 g ISO, P less than 0.05; 42.1 +/- 20.1 vs 58.9 +/- 23.8 for 4 g of ISO, P less than 0.01). This was not so for patients who received no treatment (38.5 +/- 20.4 vs 38.3 +/- 21.2; P greater than 0.1). Nine patients treated with 1 g of ISO and 5 treated with 4 g of ISO/day, who were initially characterized by a negative local GVHR (less than 50 mm3), converted to a positive reaction (greater than or equal to 50 mm3) compared to none of the patients who received no treatment. Two patients treated with 1 g of ISO and 2 patients treated with 4 g, who initially had a positive GVHR, demonstrated further augmentation (greater than or equal to 50% increase) in the GVHR after 7 days of treatment. In 2 patients (one in each treated group) the ISO induced a suppression of the GVHR from positive to negative. Incubation of the patients' lymphocytes in vitro with ISO (100 micrograms/ml X 1 hr) failed to induce augmentation of the GVHR and did not correlate with the in vivo effect in the same patients. These results demonstrate an immunomodulatory effect of ISO in cancer patients and lend further support to the use of this drug as an immunomodulating therapy among cancer patients.

Animals↗
PubMed1983

Dissociation of iron transport and heme biosynthesis from commitment to terminal maturation of murine erythroleukemia cells.

Treatment of murine erythroleukemia (MEL) cells with imidazole in the presence of dimethyl sulfoxide (Me2SO) has been shown to dissociate hemoglobin accumulation from commitment to terminal maturation. To explore the mechanism(s) of this effect, we studied iron transport and heme and hemoglobin synthesis in Me2SO-induced MEL cells that were then exposed to imidazole. Imidazole treatment (i) causes moderate inhibition of 125I-labeled transferrin binding to both control and Me2SO-treated MEL cells; (ii) markedly suppresses Me2SO-induced activation of iron uptake into MEL cells; (iii) markedly decreases the incorporation of iron into ferritin; and (iv) abolishes heme biosynthesis from [2-14C]glycine and hemoglobin accumulation in Me2SO-treated cells. Imidazole treatment does not inhibit other aspects of cellular maturation; cells treated with Me2SO in the presence or absence of imidazole exhibit similar changes in proliferative activity and protein synthesis and, as shown previously, in cell morphology. Inhibition of hemoglobin accumulation in MEL cells is reversible on withdrawal of imidazole but is not altered by exogenous hemin. These data indicate that commitment to terminal maturation is regulated independently from the systems for iron transport and heme biosynthesis during early phases of erythroid cell differentiation.

Animals↗
PubMed1983

Gangrenous cholecystitis: diagnosis by ultrasound.

Sonographic findings were analyzed in 19 patients with surgically proved gangrenous cholecystitis. In 8 patients (42%), there were no specific features that would allow differentiation from typical uncomplicated acute cholecystitis. However, in 11 patients (58%) atypical findings were present, including intraluminal membranes and/or marked irregularities of the gallbladder wall. These features are unusual in uncomplicated acute cholecystitis and should prompt close clinical observation for possible gangrenous cholecystitis.

Adult↗
PubMed1982

Evidence for the secretion of soluble peptidoglycans by clinical isolates of Staphylococcus aureus.

Four isolates of Staphylococcus aureus from patients with endocarditis and bacteremia were capable of secreting high-molecular-weight soluble peptidoglycans when grown in a minimal cell wall medium containing penicillin G. Vancomycin was not able to substitute for penicillin G in triggering this secretion. Secretion reflected de novo synthesis of soluble peptidoglycan and was strongly dependent on time of incubation (30 to 60 min), and number of bacteria (2 X 10(8) to 5 X 10(8) colony-forming units per ml), but not on penicillin G concentration (10 to 250 micrograms/ml). The incorporation of alanine into the peptidoglycans secreted in vitro by these isolates incubated in the presence of penicillin G under optimal conditions was variable. The least incorporation of alanine into peptidoglycan occurred with an isolate from a patient treated with nafcillin who had no detectable antipeptidoglycan titer.

Alanine↗